Many biological processes are controlled by small molecules known as microRNAs, which work by suppressing the expression of specific sets of genes. Xiang-Hang Luo and colleagues, at Second Xiangya Hospital of Central South University, People's Republic of China, have now identified a previously unknown microRNA (miR-2861) as crucial to bone maintenance in mice and humans. Of clinical importance, expression of functional miR-2861 was absent in two related adolescents with primary osteoporosis.
Several lines of evidence determined the key role of miR-2861 in maintaining bone. First, miR-2861 promoted the in vitro development of a mouse stromal cell line into the cells responsible for bone formation. Second, in mice, in vivo silencing of miR-2861 inhibited bone formation and decreased bone mass. Last, analysis of ten patients with primary osteoporosis revealed two related adolescents in whom disease was caused by a mutation in the miR-2861 precursor (pre-miR-2861) that blocked expression of miR-2861. These data led the authors to conclude that miR-2861 has an important role in controlling the generation of the cells responsible for bone formation and that defects in the processing of its precursor can cause osteoporosis.
TITLE: A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans
Author: Xiang-Hang Luo
View this article at: jci/articles/view/39832?key=wTvdY50uyZkh8Uji59Po
Source: Karen Honey
Journal of Clinical Investigation
воскресенье, 29 мая 2011 г.
понедельник, 16 мая 2011 г.
Anxiety And Mood Disorders Affect Many Affected By Katrina
A disproportionately high number of pre-Katrina New Orleans residents are affected by anxiety or mood disorders, according to an article published in Archives of General Psychiatry (JAMA/Archives). Approximately one quarter of residents who live in other affected areas also suffer from mood disorders and/or anxiety, the study reveals.
The authors explain "Hurricane Katrina was the worst natural disaster in the United States in the past 75 years, creating a disaster region as large as Great Britain, killing more than 1,000 people, uprooting 500,000 others and causing more than $100 billion in damage. This vast devastation would lead us to expect a high prevalence of mental illness among people who lived through Katrina."
Sandro Galea, M.D., Dr. P.H., University of Michigan School of Public Health, Ann Arbor, and team carried out a telephone survey involving 1,043 residents who lived in the affected areas of Alabama, Mississippi, and Louisiana before Hurricane Katrina struck. The survey took place during Jan 19 - March 31, 2006, approximately 5-7 months after the disaster. The interviewees were asked about stressors related to the hurricane and checked for mood and anxiety disorder symptoms - these included panic disorders, depression, and PTSD (post-traumatic stress disorder), within 30 days of the interview.
The researchers found that;
-- 31.2% of them had an anxiety-mood disorder (49.1% of New Orleans metropolitan area residents and 26.4% of other participants)
-- 16.3% had PTSD (30.3% of New Orleans residents, 12.5% of others)
-- A higher percentage of people suffered from an anxiety-mood disorder if they were under 60, female, non-graduates, unmarried, unemployed, and/or came from a low income home
-- Hispanics had lower rates of anxiety mood disorders
The researchers wrote "The vast majority of respondents both in the New Orleans metro (91.9 percent) and in the remainder of the sample (81.7 percent) reported experiencing at least one of the 10 categories of hurricane-related stressors," including the death of a family member, robbery, injury or property loss.
The researchers explained that the extent of exposure to these stressors was more closely linked to anxiety-mood disorders among New Orleans residents, compared to those from other areas. While New Orleans residents were the most susceptible to experiencing anxiety-mood disorders after physical illness, injury or physical adversity, the other residents were more prone to these disorders following property loss.
The authors found that the rate of these disorders among New Orleans residents was significantly higher than one would expect following a natural disaster in the USA. However, rates for those from other areas who were affected by Katrina were more-or-less equivalent.
"Evidence that avoidable stressors associated with the slow government response to Hurricane Katrina (e.g., physical adversity) had important implications for the mental health of people who lived through Katrina argues strongly for the importance of efficient provision of practical and logistical assistance in future disasters, not only on humanitarian grounds, but also as a way to minimize the adverse mental health effects of disasters," the authors conclude.
The authors explain "Hurricane Katrina was the worst natural disaster in the United States in the past 75 years, creating a disaster region as large as Great Britain, killing more than 1,000 people, uprooting 500,000 others and causing more than $100 billion in damage. This vast devastation would lead us to expect a high prevalence of mental illness among people who lived through Katrina."
Sandro Galea, M.D., Dr. P.H., University of Michigan School of Public Health, Ann Arbor, and team carried out a telephone survey involving 1,043 residents who lived in the affected areas of Alabama, Mississippi, and Louisiana before Hurricane Katrina struck. The survey took place during Jan 19 - March 31, 2006, approximately 5-7 months after the disaster. The interviewees were asked about stressors related to the hurricane and checked for mood and anxiety disorder symptoms - these included panic disorders, depression, and PTSD (post-traumatic stress disorder), within 30 days of the interview.
The researchers found that;
-- 31.2% of them had an anxiety-mood disorder (49.1% of New Orleans metropolitan area residents and 26.4% of other participants)
-- 16.3% had PTSD (30.3% of New Orleans residents, 12.5% of others)
-- A higher percentage of people suffered from an anxiety-mood disorder if they were under 60, female, non-graduates, unmarried, unemployed, and/or came from a low income home
-- Hispanics had lower rates of anxiety mood disorders
The researchers wrote "The vast majority of respondents both in the New Orleans metro (91.9 percent) and in the remainder of the sample (81.7 percent) reported experiencing at least one of the 10 categories of hurricane-related stressors," including the death of a family member, robbery, injury or property loss.
The researchers explained that the extent of exposure to these stressors was more closely linked to anxiety-mood disorders among New Orleans residents, compared to those from other areas. While New Orleans residents were the most susceptible to experiencing anxiety-mood disorders after physical illness, injury or physical adversity, the other residents were more prone to these disorders following property loss.
The authors found that the rate of these disorders among New Orleans residents was significantly higher than one would expect following a natural disaster in the USA. However, rates for those from other areas who were affected by Katrina were more-or-less equivalent.
"Evidence that avoidable stressors associated with the slow government response to Hurricane Katrina (e.g., physical adversity) had important implications for the mental health of people who lived through Katrina argues strongly for the importance of efficient provision of practical and logistical assistance in future disasters, not only on humanitarian grounds, but also as a way to minimize the adverse mental health effects of disasters," the authors conclude.
воскресенье, 15 мая 2011 г.
Warning For Gastric Bypass Patients: Go Easy On The Alcohol
Patients who have had a gastric bypass operation take longer to process alcohol, potentially leading some of them to overindulge when drinking, according to the results of a new study in the February issue of the Journal of the American College of Surgeons.
Previous studies have shown that gastric bypass patients often find it difficult adjusting to physical and psychological changes after the procedure. An increased risk of depression, alcoholism, and other substance abuse issues for this patient population led researchers to take a more in-depth look at how these patients metabolize alcohol after the procedure.
The results of this unique demonstration of alcohol metabolism changes in gastric bypass patients showed that patients who underwent a Roux-en-Y gastric bypass (RYGB) operation had considerably higher breath alcohol content (BAC) and took significantly more time to return to a sober state after drinking, compared with BAC levels tested prior to having their procedure.
"Severe obesity continues to be a public health crisis in the U.S., and bariatric surgery offers a very effective treatment," said senior author John M. Morton, MD, MPH, FACS, associate professor of surgery at Stanford (CA) University. "Despite its benefits, we want to raise the potential concern for RYGB patients who continue to drink after their operation because they may tend to overuse alcohol, which can, in turn, lead to weight regain, nutritional deficiencies, and/or alcohol dependence."
During the study, alcohol metabolism tests were performed on 19 morbidly obese patients before their RYGB operation and then measured again at three and six months post-operation. Patients also reported symptoms experienced when drinking and answered a questionnaire about their drinking habits.
The results showed peak BAC percentage of patients after drinking five ounces of red wine was significantly higher post-operation. BAC was 0.024 percent at pre-operation and 0.059 percent (p = 0.0003) at three months. Tested again at six months post-operation, the patients' BAC was 0.088 percent (p = 0.0008) which is more than the legal driving limit of .08 percent. Additionally, it took 49 minutes for patients to reach a zero BAC prior to their operation compared with 61 minutes at three months and 88 minutes at six months post-operation.
In other studies, researchers have found that a few gastric bypass patients undergo an addiction transfer where they trade one vice, such as overeating, for another, like over consumption of alcohol or drug use. Additionally, patients who display binge eating behavior prior to their operation have the highest likelihood of postoperative alcoholism.
"RYGB patients need to understand that their body will respond to alcohol differently after their operation and they need to exercise caution if they choose to drink alcohol," said Dr. Morton. "Our recommendation to all of our RYGB patients is never drink and drive and to limit consumption of alcohol to one standard drink (one 12-oz beer, 5-oz wine, or 2-oz liquor) for every two hours. The key to safeguarding bariatric surgery benefits is to provide appropriate patient education."
Previous studies have shown that gastric bypass patients often find it difficult adjusting to physical and psychological changes after the procedure. An increased risk of depression, alcoholism, and other substance abuse issues for this patient population led researchers to take a more in-depth look at how these patients metabolize alcohol after the procedure.
The results of this unique demonstration of alcohol metabolism changes in gastric bypass patients showed that patients who underwent a Roux-en-Y gastric bypass (RYGB) operation had considerably higher breath alcohol content (BAC) and took significantly more time to return to a sober state after drinking, compared with BAC levels tested prior to having their procedure.
"Severe obesity continues to be a public health crisis in the U.S., and bariatric surgery offers a very effective treatment," said senior author John M. Morton, MD, MPH, FACS, associate professor of surgery at Stanford (CA) University. "Despite its benefits, we want to raise the potential concern for RYGB patients who continue to drink after their operation because they may tend to overuse alcohol, which can, in turn, lead to weight regain, nutritional deficiencies, and/or alcohol dependence."
During the study, alcohol metabolism tests were performed on 19 morbidly obese patients before their RYGB operation and then measured again at three and six months post-operation. Patients also reported symptoms experienced when drinking and answered a questionnaire about their drinking habits.
The results showed peak BAC percentage of patients after drinking five ounces of red wine was significantly higher post-operation. BAC was 0.024 percent at pre-operation and 0.059 percent (p = 0.0003) at three months. Tested again at six months post-operation, the patients' BAC was 0.088 percent (p = 0.0008) which is more than the legal driving limit of .08 percent. Additionally, it took 49 minutes for patients to reach a zero BAC prior to their operation compared with 61 minutes at three months and 88 minutes at six months post-operation.
In other studies, researchers have found that a few gastric bypass patients undergo an addiction transfer where they trade one vice, such as overeating, for another, like over consumption of alcohol or drug use. Additionally, patients who display binge eating behavior prior to their operation have the highest likelihood of postoperative alcoholism.
"RYGB patients need to understand that their body will respond to alcohol differently after their operation and they need to exercise caution if they choose to drink alcohol," said Dr. Morton. "Our recommendation to all of our RYGB patients is never drink and drive and to limit consumption of alcohol to one standard drink (one 12-oz beer, 5-oz wine, or 2-oz liquor) for every two hours. The key to safeguarding bariatric surgery benefits is to provide appropriate patient education."
During Pregnancy A Deficiency Of Dietary Omega-3 May Explain Depressive Behaviors
Neuroscience of nutrition
How maternal essential fatty acid deficiency impact on its progeny is poorly understood. Dietary insufficiency in omega-3 fatty acid has been implicated in many disorders. Researchers from Inserm and INRA and their collaborators in Spain collaboration, have studied mice fed on a diet low in omega-3 fatty acid. They discovered that reduced levels of omega-3 had deleterious consequences on synaptic functions and emotional behaviours. Details of this work are available in the online version of the journal Nature Neuroscience, which can be accessed here.
In industrialized nations, diets have been impoverished in essential fatty acids since the beginning of the 20th century. The dietary ratio between omega-6 polyunsaturated fatty acid and omega-3 polyunsaturated fatty acid omega-3 increased continuously over the course of the 20th century. These fatty acids are "essential" lipids because the body cannot synthesize them from new. They must therefore be provided through food and their dietary balance is essential to maintain optimal brain functions.
Olivier Manzoni (Head of Research Inserm Unit 862, "Neurocentre Magendie", in Bordeaux and Unit 901 "Institut de Neurobiologie de la M?©diterran?©e" in Marseille), and Sophie Lay?© (Head of Research at INRA Unit 1286, "Nutrition et Neurobiologie Int?©grative" in Bordeaux) and their co-workers hypothesized that chronic malnutrition during intra-uterine development, may later influence synaptic activity involved in emotional behaviour (e.g. depression, anxiety) in adulthood.
To verify their hypotheses, the researchers studied mice fed a life-long diet imbalanced in omega-3 and omega-6 fatty acids. They found that omega-3 deficiency disturbed neuronal communication specifically. The researchers observed that only the cannabinoid receptors, which play a strategic role in neurotransmission, suffer a complete loss of function. This neuronal dysfunction was accompanied by depressive behaviours among the malnourished mice.
Among omega-3 deficient mice, the usual effects produced by cannabinoid receptor activation, on both the synaptic and behavioural levels, no longer appear. Thus, the CB1R receptors lose their synaptic activity and the antioxidant effect of the cannabinoids disappears.
Consequently, the researchers discovered that among mice subjected to an omega-3 deficient dietary regime, synaptic plasticity, which is dependent on the CB1R cannabinoid receptors, is disturbed in at least two structures involved with reward, motivation and emotional regulation: the prefrontal cortex and the nucleus accumbens. These parts of the brain contain a large number of CB1R cannabinoid receptors and have important functional connections with each other.
"Our results can now corroborate clinical and epidemiological studies which have revealed associations between an omega-3/omega-6 imbalance and mood disorders", explain Olivier Manzoni and Sophie Lay?©. "To determine if the omega-3 deficiency is responsible for these neuropsychiatric disorders additional studies are, of course, required".
In conclusion, the authors estimate that their results provide the first biological components of an explanation for the observed correlation between omega-3 poor diets, which are very widespread in the industrialized world, and mood disorders such as depression.
How maternal essential fatty acid deficiency impact on its progeny is poorly understood. Dietary insufficiency in omega-3 fatty acid has been implicated in many disorders. Researchers from Inserm and INRA and their collaborators in Spain collaboration, have studied mice fed on a diet low in omega-3 fatty acid. They discovered that reduced levels of omega-3 had deleterious consequences on synaptic functions and emotional behaviours. Details of this work are available in the online version of the journal Nature Neuroscience, which can be accessed here.
In industrialized nations, diets have been impoverished in essential fatty acids since the beginning of the 20th century. The dietary ratio between omega-6 polyunsaturated fatty acid and omega-3 polyunsaturated fatty acid omega-3 increased continuously over the course of the 20th century. These fatty acids are "essential" lipids because the body cannot synthesize them from new. They must therefore be provided through food and their dietary balance is essential to maintain optimal brain functions.
Olivier Manzoni (Head of Research Inserm Unit 862, "Neurocentre Magendie", in Bordeaux and Unit 901 "Institut de Neurobiologie de la M?©diterran?©e" in Marseille), and Sophie Lay?© (Head of Research at INRA Unit 1286, "Nutrition et Neurobiologie Int?©grative" in Bordeaux) and their co-workers hypothesized that chronic malnutrition during intra-uterine development, may later influence synaptic activity involved in emotional behaviour (e.g. depression, anxiety) in adulthood.
To verify their hypotheses, the researchers studied mice fed a life-long diet imbalanced in omega-3 and omega-6 fatty acids. They found that omega-3 deficiency disturbed neuronal communication specifically. The researchers observed that only the cannabinoid receptors, which play a strategic role in neurotransmission, suffer a complete loss of function. This neuronal dysfunction was accompanied by depressive behaviours among the malnourished mice.
Among omega-3 deficient mice, the usual effects produced by cannabinoid receptor activation, on both the synaptic and behavioural levels, no longer appear. Thus, the CB1R receptors lose their synaptic activity and the antioxidant effect of the cannabinoids disappears.
Consequently, the researchers discovered that among mice subjected to an omega-3 deficient dietary regime, synaptic plasticity, which is dependent on the CB1R cannabinoid receptors, is disturbed in at least two structures involved with reward, motivation and emotional regulation: the prefrontal cortex and the nucleus accumbens. These parts of the brain contain a large number of CB1R cannabinoid receptors and have important functional connections with each other.
"Our results can now corroborate clinical and epidemiological studies which have revealed associations between an omega-3/omega-6 imbalance and mood disorders", explain Olivier Manzoni and Sophie Lay?©. "To determine if the omega-3 deficiency is responsible for these neuropsychiatric disorders additional studies are, of course, required".
In conclusion, the authors estimate that their results provide the first biological components of an explanation for the observed correlation between omega-3 poor diets, which are very widespread in the industrialized world, and mood disorders such as depression.
Sleep Disturbances In Soldiers With Combat PTSD Improved By Bright Light Therapy
Bright light therapy has significant effects on sleep disturbances associated with combat-related post-traumatic stress disorder, according to a research abstract that will be presented Monday, June 7, 2010, in San Antonio, Texas, at SLEEP 2010, the 24th annual meeting of the Associated Professional Sleep Societies LLC.
Results indicate that bright light therapy produced a significantly greater improvement than placebo in sleep disturbances specific to PTSD. Bright light therapy also produced a moderate improvement in PTSD symptoms and depression.
"Results of this ongoing study show significant effects of bright light on disruptive nocturnal behaviors associated with combat PTSD, as well as positive effects of bright light therapy on PTSD symptom severity," said study coordinator Shannon Cornelius, PhD, graduate research assistant for Dr. Shawn D. Youngstedt in the department of exercise science at the University of South Carolina in Columbia, S.C. "Because bright light therapy is a relatively simple, self-administered, inexpensive treatment with few side effects, these results are an important step to further establish the efficacy of bright light therapy as an alternative or adjunct treatment for combat-related PTSD."
The study involved 16 soldiers who returned to the U.S. with combat-related PTSD after serving in Operation Enduring Freedom or Operation Iraqi Freedom. Following a one-week baseline, participants were randomized to one of two four-week treatments. Eight soldiers received 10,000 lux of bright light therapy for 30 minutes each day. The other eight participants were assigned to the placebo group and received sham treatment with an inactivated negative ion generator. The Clinician-Administered PTSD Scale (CAPS-2) was completed at baseline and immediately following completion of the study. At weekly intervals, depression was assessed with the Beck Depression Inventory (BDI-II), and sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) with addendum for PTSD (PSQI-PTSD).
Cornelius noted that sleep disturbance is a commonly reported problem that can play both a precipitating and perpetuating role in PTSD, making it an important target for therapy.
"Disturbed sleep is known to interact with depression and anxiety in a vicious cycle," said Cornelius. "By reducing the severity and occurrence of sleep disturbances, it may be possible to reduce the severity of symptoms such as anxiety and depression in combat-related PTSD."
The study was supported by a U.S. Department of Veterans Affairs Merit Award.
The American Academy of Sleep Medicine reports that 70 to 90 percent of people with PTSD describe subjective sleep disturbance. Recurrent nightmares of the traumatic event represent one of the most problematic and enduring symptoms of PTSD. These nightmares may take the form of a realistic reliving of the traumatic event or depict only some of its elements.
Bright light therapy exposes your eyes to intense but safe amounts of light for a specific and regular length of time. Typically it involves exposure to up to 10,000 lux of light for scheduled periods of 20 minutes or more using a small light box.
In a 2007 study published in the journal BMC Psychiatry, Youngstedt reported that bright light exposure may have an anxiolytic effect. Three hours of exposure to 3,000 lux of bright light for three consecutive days reduced anxiety in a group of low-anxiety adults.
Abstract Title: The effect of bright light therapy on PTSD related sleep disturbances
Abstract ID: 0706
Category: Psychiatric and Behavioral Disorders
Presentation Date: Monday, June 7, 2010
Presentation Type: Poster - #300
Presentation Time: 10:30 a.m. - 12:30 p.m.
Results indicate that bright light therapy produced a significantly greater improvement than placebo in sleep disturbances specific to PTSD. Bright light therapy also produced a moderate improvement in PTSD symptoms and depression.
"Results of this ongoing study show significant effects of bright light on disruptive nocturnal behaviors associated with combat PTSD, as well as positive effects of bright light therapy on PTSD symptom severity," said study coordinator Shannon Cornelius, PhD, graduate research assistant for Dr. Shawn D. Youngstedt in the department of exercise science at the University of South Carolina in Columbia, S.C. "Because bright light therapy is a relatively simple, self-administered, inexpensive treatment with few side effects, these results are an important step to further establish the efficacy of bright light therapy as an alternative or adjunct treatment for combat-related PTSD."
The study involved 16 soldiers who returned to the U.S. with combat-related PTSD after serving in Operation Enduring Freedom or Operation Iraqi Freedom. Following a one-week baseline, participants were randomized to one of two four-week treatments. Eight soldiers received 10,000 lux of bright light therapy for 30 minutes each day. The other eight participants were assigned to the placebo group and received sham treatment with an inactivated negative ion generator. The Clinician-Administered PTSD Scale (CAPS-2) was completed at baseline and immediately following completion of the study. At weekly intervals, depression was assessed with the Beck Depression Inventory (BDI-II), and sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) with addendum for PTSD (PSQI-PTSD).
Cornelius noted that sleep disturbance is a commonly reported problem that can play both a precipitating and perpetuating role in PTSD, making it an important target for therapy.
"Disturbed sleep is known to interact with depression and anxiety in a vicious cycle," said Cornelius. "By reducing the severity and occurrence of sleep disturbances, it may be possible to reduce the severity of symptoms such as anxiety and depression in combat-related PTSD."
The study was supported by a U.S. Department of Veterans Affairs Merit Award.
The American Academy of Sleep Medicine reports that 70 to 90 percent of people with PTSD describe subjective sleep disturbance. Recurrent nightmares of the traumatic event represent one of the most problematic and enduring symptoms of PTSD. These nightmares may take the form of a realistic reliving of the traumatic event or depict only some of its elements.
Bright light therapy exposes your eyes to intense but safe amounts of light for a specific and regular length of time. Typically it involves exposure to up to 10,000 lux of light for scheduled periods of 20 minutes or more using a small light box.
In a 2007 study published in the journal BMC Psychiatry, Youngstedt reported that bright light exposure may have an anxiolytic effect. Three hours of exposure to 3,000 lux of bright light for three consecutive days reduced anxiety in a group of low-anxiety adults.
Abstract Title: The effect of bright light therapy on PTSD related sleep disturbances
Abstract ID: 0706
Category: Psychiatric and Behavioral Disorders
Presentation Date: Monday, June 7, 2010
Presentation Type: Poster - #300
Presentation Time: 10:30 a.m. - 12:30 p.m.
Med Students Not Seeking Mental Health Treatment; The Stigma Associated With Real Depression
Okay, something does not make sense here. Why do med students, who are obviously in a stressful and competitive environment for several years, have a high rate of depression and suicidal tendencies? For some reason, one would think that with all that medicine, therapy and peer training surrounding them, persons would have more outlets and methods to ease depression and anxiety. However, med students are less likely to receive the proper treatment for mental health, more often than not because of the stigma associated with depressive symptoms. In the September 15, 2010 issue of JAMA, which is a special edition dedicated to medical education, this topic is discussed.
Thomas L. Schwenk, M.D., of the University of Michigan, Ann Arbor, and colleagues begin:
Medical students experience depression, burnout, and mental illness at a higher rate than the general population, with mental health deteriorating over the course of medical training. Medical students have a higher risk of suicidal ideation and suicide, higher rates of burnout, and a lower quality of life than age-matched populations. Students may worry that revealing their depression will make them less competitive for residency training positions or compromise their education, and physicians may be reluctant to disclose their diagnosis on licensure and medical staff applications.
Schwenk and others chose to go to the 769 medical students at University of Michigan between September and November 2009, and looked deeper into the levels of self-reported suicidal thoughts and depression, and dove deeper into what students thought others think of them when they make these mental ailments known. A good percentage of students participated in the study (65.7% or 505).
The number of depressed and suicidal students were clear. Depression existed in 14.3% of medical students in 2009 on the Michigan campus. Interestingly, double the number of women reported moderate to severe depression than the men. Twenty-two of the 505 student participants, or 4.4%, reported suicidal thoughts while taking classes. One and two year students were far less likely to report suicidal ideation then their year three and four counterparts (1.4% vs. 7.9%).
It is known that it is of utmost importance for persons to seek help when depressed or suicidal. However, many medical students fear the impression that reaching out will generate.
The authors wrote:
Students with higher depression scores felt more strongly than did those with no to minimal depression that telling a counselor would be risky and that asking for help would mean the student's coping skills were inadequate. Those with moderate to severe depression scores also agreed more strongly that, if depressed, others would find them unable to handle medical school responsibilities (83.1 vs. 55.1%). Medical students with moderate to severe depression scores more frequently reported feeling that, if depressed, fellow medical students would respect their opinions less than did those with no to minimal depression (56 vs. 23.7%).
Male students had the belief that depressed colleagues could potentially endanger patients (36.3%), while women felt this way at a much lower percentage of 20.1%. More early year students (34.1%) felt that if they sought out help, they would feel less intelligent and capable in their studies. Year three and four year students agreed at a rate of 22.9%.
The Michigan University authors conclude:
These results suggest that new approaches may be needed to reduce the stigma of depression and to enhance its prevention, detection, and treatment. The characteristics of medical education emphasizing professional competence and outstanding performance might be explored as reinforcing, rather than potentially sabotaging, factors in the creation of a culture that promotes professional mental health. The effective care of mental illness, the maintenance of mental health and effective emotional function, and the care of professional colleagues with mental illness could be taught as part of the ethical and professional responsibilities of the outstanding physician and become a critical component of the teaching, role modeling, and professional guidance that medical students receive as part of their curriculum in professionalism.
JAMA. 2010;304[11]:1181-1190
Written by: Sy Kraft, B.A. - Journalism - California State University, Northridge (CSUN)
Thomas L. Schwenk, M.D., of the University of Michigan, Ann Arbor, and colleagues begin:
Medical students experience depression, burnout, and mental illness at a higher rate than the general population, with mental health deteriorating over the course of medical training. Medical students have a higher risk of suicidal ideation and suicide, higher rates of burnout, and a lower quality of life than age-matched populations. Students may worry that revealing their depression will make them less competitive for residency training positions or compromise their education, and physicians may be reluctant to disclose their diagnosis on licensure and medical staff applications.
Schwenk and others chose to go to the 769 medical students at University of Michigan between September and November 2009, and looked deeper into the levels of self-reported suicidal thoughts and depression, and dove deeper into what students thought others think of them when they make these mental ailments known. A good percentage of students participated in the study (65.7% or 505).
The number of depressed and suicidal students were clear. Depression existed in 14.3% of medical students in 2009 on the Michigan campus. Interestingly, double the number of women reported moderate to severe depression than the men. Twenty-two of the 505 student participants, or 4.4%, reported suicidal thoughts while taking classes. One and two year students were far less likely to report suicidal ideation then their year three and four counterparts (1.4% vs. 7.9%).
It is known that it is of utmost importance for persons to seek help when depressed or suicidal. However, many medical students fear the impression that reaching out will generate.
The authors wrote:
Students with higher depression scores felt more strongly than did those with no to minimal depression that telling a counselor would be risky and that asking for help would mean the student's coping skills were inadequate. Those with moderate to severe depression scores also agreed more strongly that, if depressed, others would find them unable to handle medical school responsibilities (83.1 vs. 55.1%). Medical students with moderate to severe depression scores more frequently reported feeling that, if depressed, fellow medical students would respect their opinions less than did those with no to minimal depression (56 vs. 23.7%).
Male students had the belief that depressed colleagues could potentially endanger patients (36.3%), while women felt this way at a much lower percentage of 20.1%. More early year students (34.1%) felt that if they sought out help, they would feel less intelligent and capable in their studies. Year three and four year students agreed at a rate of 22.9%.
The Michigan University authors conclude:
These results suggest that new approaches may be needed to reduce the stigma of depression and to enhance its prevention, detection, and treatment. The characteristics of medical education emphasizing professional competence and outstanding performance might be explored as reinforcing, rather than potentially sabotaging, factors in the creation of a culture that promotes professional mental health. The effective care of mental illness, the maintenance of mental health and effective emotional function, and the care of professional colleagues with mental illness could be taught as part of the ethical and professional responsibilities of the outstanding physician and become a critical component of the teaching, role modeling, and professional guidance that medical students receive as part of their curriculum in professionalism.
JAMA. 2010;304[11]:1181-1190
Written by: Sy Kraft, B.A. - Journalism - California State University, Northridge (CSUN)
Hyperactive Nerve Cells May Contribute To Depression
Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory, Cold Spring Harbor Laboratory, and the University of California, San Diego School of Medicine, have identified hyperactive cells in a tiny brain structure that may play an important role in depression. The study, conducted in rats and appearing in the February 24, 2011, issue of Nature, is helping to reveal a cellular mechanism for depressive disorders that could lead to new, effective treatments.
The research provides evidence that inhibition of this particular brain region - the lateral habenula - using implanted electrodes can reverse certain behaviors associated with depression, and also provides a mechanism to explain this effect. These findings lend support to the use of deep brain stimulation as a clinical treatment for people with long-standing, treatment-resistant depression.
"This research identifies a new anatomical circuit in the brain that mediates depression, and shows how it interacts with the brain's reward system to trigger a constant disappointment signal - which certainly would be depressing," said Fritz Henn, a neurobiologist and psychiatrist at Brookhaven and Cold Spring Harbor laboratories and a co-investigator on the research. "But," he added, optimistically, "identifying this circuit and how it works may open new doors to reversing these effects."
For example, said co-investigator Roberto Malinow, a professor of neurosciences at the UCSD School of Medicine, "it's possible that the genes specifically expressed in these neurons could be targeted genetically or pharmacologically in order to manipulate them and reduce depression."
Scientists have known that cells in the lateral habenula are activated by negative or unpleasant events, including punishment and disappointment, such as when you don't get an expected reward. It may seem intuitive that such negative stimuli can lead to depression, but not everyone who experiences disappointment collapses into a state of helplessness. To explore this connection, the scientists wanted to take a closer look at the brain circuits.
They examined the sensitivity of lateral habenula brain cells - particularly those that connect and send signals to the brain's reward centers - in two animal models of "learned helplessness," a form of depression, as well as in control animals that weren't helpless.
Overall, the scientists found that these lateral habenula nerve cells were hyperactive in the depressed animals but not in the controls. Furthermore, the degree of hyperactivity coincided with the degree of helplessness.
"The activation of the lateral habenula is known to influence the release of serotonin and norepinepherine, two targets of current antidepressant medications," said Henn. "The current study looked at the role of the lateral habenula in terms of the dopamine system, the system involved in reward signaling. We found that hyperactivity in the lateral habenula due to stress-induced helplessness shuts off the brain's reward system."
To explore whether electrical stimulation could potentially reverse this reward-dampening effect, the researchers placed a stimulating electrode in the lateral habenula and measured the effects on the brain cells leading to the reward center. This was a study of rat brain cells that simulated the effects of deep brain stimulation, a technique that is currently being explored as a treatment for clinical depression, which has shown promising results. The scientists found that electrical stimulation of hyperactive habenula brain cells markedly decreased excitatory activity leading to the reward center.
Next the scientists tested to see if deep brain stimulation in living rats that exhibited helplessness would affect their behavior. The result was a marked reduction in helpless behavior that was dependent on both placement of the electrode in the lateral habenula (not adjacent brain regions), and the intensity of the stimulation.
"Our results clearly show that suppression of synaptic transmission at the lateral habenula through deep brain stimulation can acutely reverse helpless behavior in rats," said Henn. "It's very likely that this beneficial effect was mediated by a suppression of excitatory nerve cells leading to the brain's reward system, as we observed in the cellular studies."
"Our study provides a cellular mechanism that may explain the hyperactivity of lateral habenula nerve cells observed in depressed humans and animal models of depression, as well as why 'silencing' these circuits, whether surgically or pharmacologically, can reduce depression-like symptoms in animals," Henn said.
Identifying these specific brain circuits and their dysfunction in depression may open the door to new effective treatments, including, potentially, lateral-habenula-targeted deep brain stimulation.
Notes:
This research was supported through Laboratory Directed Research and Development funding at Brookhaven Lab, and by the Simons Foundation, the Dana Foundation, the National Institute of Mental Health, and a Shiley-Marcos endowment at UCSD.
In addition to Henn and Malinow, co-authors include: Bo Li (UCSD and Cold Spring Harbor), Joaquin Piriz (UCSD), Martine Mirrione (Cold Spring Harbor and Brookhaven), Chihye Chung (UCSD), Christophe Proulx (UCSD), and Daniela Schulz (Brookhaven).
The research provides evidence that inhibition of this particular brain region - the lateral habenula - using implanted electrodes can reverse certain behaviors associated with depression, and also provides a mechanism to explain this effect. These findings lend support to the use of deep brain stimulation as a clinical treatment for people with long-standing, treatment-resistant depression.
"This research identifies a new anatomical circuit in the brain that mediates depression, and shows how it interacts with the brain's reward system to trigger a constant disappointment signal - which certainly would be depressing," said Fritz Henn, a neurobiologist and psychiatrist at Brookhaven and Cold Spring Harbor laboratories and a co-investigator on the research. "But," he added, optimistically, "identifying this circuit and how it works may open new doors to reversing these effects."
For example, said co-investigator Roberto Malinow, a professor of neurosciences at the UCSD School of Medicine, "it's possible that the genes specifically expressed in these neurons could be targeted genetically or pharmacologically in order to manipulate them and reduce depression."
Scientists have known that cells in the lateral habenula are activated by negative or unpleasant events, including punishment and disappointment, such as when you don't get an expected reward. It may seem intuitive that such negative stimuli can lead to depression, but not everyone who experiences disappointment collapses into a state of helplessness. To explore this connection, the scientists wanted to take a closer look at the brain circuits.
They examined the sensitivity of lateral habenula brain cells - particularly those that connect and send signals to the brain's reward centers - in two animal models of "learned helplessness," a form of depression, as well as in control animals that weren't helpless.
Overall, the scientists found that these lateral habenula nerve cells were hyperactive in the depressed animals but not in the controls. Furthermore, the degree of hyperactivity coincided with the degree of helplessness.
"The activation of the lateral habenula is known to influence the release of serotonin and norepinepherine, two targets of current antidepressant medications," said Henn. "The current study looked at the role of the lateral habenula in terms of the dopamine system, the system involved in reward signaling. We found that hyperactivity in the lateral habenula due to stress-induced helplessness shuts off the brain's reward system."
To explore whether electrical stimulation could potentially reverse this reward-dampening effect, the researchers placed a stimulating electrode in the lateral habenula and measured the effects on the brain cells leading to the reward center. This was a study of rat brain cells that simulated the effects of deep brain stimulation, a technique that is currently being explored as a treatment for clinical depression, which has shown promising results. The scientists found that electrical stimulation of hyperactive habenula brain cells markedly decreased excitatory activity leading to the reward center.
Next the scientists tested to see if deep brain stimulation in living rats that exhibited helplessness would affect their behavior. The result was a marked reduction in helpless behavior that was dependent on both placement of the electrode in the lateral habenula (not adjacent brain regions), and the intensity of the stimulation.
"Our results clearly show that suppression of synaptic transmission at the lateral habenula through deep brain stimulation can acutely reverse helpless behavior in rats," said Henn. "It's very likely that this beneficial effect was mediated by a suppression of excitatory nerve cells leading to the brain's reward system, as we observed in the cellular studies."
"Our study provides a cellular mechanism that may explain the hyperactivity of lateral habenula nerve cells observed in depressed humans and animal models of depression, as well as why 'silencing' these circuits, whether surgically or pharmacologically, can reduce depression-like symptoms in animals," Henn said.
Identifying these specific brain circuits and their dysfunction in depression may open the door to new effective treatments, including, potentially, lateral-habenula-targeted deep brain stimulation.
Notes:
This research was supported through Laboratory Directed Research and Development funding at Brookhaven Lab, and by the Simons Foundation, the Dana Foundation, the National Institute of Mental Health, and a Shiley-Marcos endowment at UCSD.
In addition to Henn and Malinow, co-authors include: Bo Li (UCSD and Cold Spring Harbor), Joaquin Piriz (UCSD), Martine Mirrione (Cold Spring Harbor and Brookhaven), Chihye Chung (UCSD), Christophe Proulx (UCSD), and Daniela Schulz (Brookhaven).
People With Epilepsy Three Times More Likely To Commit Suicide
There is three times the risk that a person with epilepsy commits suicide when compared to the general population, say the authors of an article published early online and in the August edition of The Lancet Neurology. The study also found that women with epilepsy were more likely to commit suicide than men with the condition, and people diagnosed with epilepsy in the previous six months were at an even higher risk of committing suicide.
Dr Jakob Christensen and Dr Per Sidenius, Aarhus University Hospital, Denmark and colleagues studied 21 169 cases of suicide taken from the Cause of Death Register in Denmark between 1981 and 1997, and also 423 128 controls matched by sex, birth year, and calendar date.
They found that 492 of the suicide cases (2?·32%) had epilepsy, compared with 3140 of the controls (0?·74%), corresponding to a three-times higher risk for people with epilepsy. After exclusion of those with a history of psychiatric disease and adjusting for socioeconomic factors (SEFs), the risk of committing suicide was twice as high for those with epilepsy. SEFs include marital status, job status, annual income, place of residence, and sickness absence from work. People with both epilepsy and comorbid psychiatric disease were nearly 14 times more likely to commit suicide, adjusting for SEFs, compared with those with neither condition.
Further, they found that in individuals with epilepsy, those who had been diagnosed six months ago or less were more than five times more likely to commit suicide, while those diagnosed less than six months ago and with comorbid psychiatric disease were 29 times more likely to take their own lives.
And although the trend in the general population is for incidence of suicide to increase with age, the study found that the risk of suicide after epilepsy decreased with age.
The authors conclude: "Individuals with epilepsy have a higher risk of suicide, even if co-existing psychiatric disease, demographic differences, and socioeconomic factors are taken into account. Our study identifies people with newly diagnosed epilepsy as a vulnerable group that require special attention."
Lancet Neurology
Dr Jakob Christensen and Dr Per Sidenius, Aarhus University Hospital, Denmark and colleagues studied 21 169 cases of suicide taken from the Cause of Death Register in Denmark between 1981 and 1997, and also 423 128 controls matched by sex, birth year, and calendar date.
They found that 492 of the suicide cases (2?·32%) had epilepsy, compared with 3140 of the controls (0?·74%), corresponding to a three-times higher risk for people with epilepsy. After exclusion of those with a history of psychiatric disease and adjusting for socioeconomic factors (SEFs), the risk of committing suicide was twice as high for those with epilepsy. SEFs include marital status, job status, annual income, place of residence, and sickness absence from work. People with both epilepsy and comorbid psychiatric disease were nearly 14 times more likely to commit suicide, adjusting for SEFs, compared with those with neither condition.
Further, they found that in individuals with epilepsy, those who had been diagnosed six months ago or less were more than five times more likely to commit suicide, while those diagnosed less than six months ago and with comorbid psychiatric disease were 29 times more likely to take their own lives.
And although the trend in the general population is for incidence of suicide to increase with age, the study found that the risk of suicide after epilepsy decreased with age.
The authors conclude: "Individuals with epilepsy have a higher risk of suicide, even if co-existing psychiatric disease, demographic differences, and socioeconomic factors are taken into account. Our study identifies people with newly diagnosed epilepsy as a vulnerable group that require special attention."
Lancet Neurology
More Than One In Three Patients Hospitalized For Mental Illness Are Readmitted Within One Year Of Their discharge
Over one in three patients (37%) discharged from a general hospital with a diagnosis of mental illness were readmitted within one year of their discharge, according to a new report released today by the Canadian Institute for Health Information (CIHI). In comparison, 27% of all other patients admitted to a general hospital were readmitted within a year. For the first time, CIHI's annual report Hospital Mental Health Services in Canada, 2003-2004 presents information on general hospital readmissions and their relationship to seven diagnosis categories of mental illness.
"Readmission for a mental illness is often linked to a disruption in outpatient treatment and rehabilitation and may signal instability or a recurrence of severe symptoms of a disease," says Nawaf Madi, CIHI's Program Lead for Mental Health and Addictions. "This is an area of concern for health planners, because, among other things, treating a patient in hospital is significantly more expensive than treatment at the outpatient or community level."
Risk of readmission linked to age, diagnosis
The risk of readmission to general hospital for an individual with a primary diagnosis of mental illness increases with the age of the patient, from a rate of 26.5 per 100 of those aged 0 to 14, to 38.7 per 100 of those aged 65 and over. Among the diagnosis categories, the risk of readmission was higher for individuals with a primary diagnosis of personality disorder (45%), followed by individuals with schizophrenia (41%). Readmissions were similar for women and men (38.3% and 35.5%, respectively) and, overall, the longer the initial general hospital stay, the greater the chance of readmission within one year.
Thirty percent of all general hospital days stayed in 2003-2004 involved a patient diagnosed with mental illness
Patients with a primary diagnosis of mental illness accounted for 6% of all hospitalizations in Canada; another 8% involved patients with a non-psychiatric primary diagnosis and an associated mental illness. But since lengths of stay for patients with mental illness were more than twice as long as for others, these hospitalizations combined accounted for 30% of the total number of days patients spent in Canadian general hospitals in 2003-2004. The average length of stay for a patient with a primary diagnosis of mental illness in a general hospital was 16.9 days in 2003-2004, compared to 7.2 days for those with a non-psychiatric diagnosis.
Schizophrenia accounted for the longest average length of stay (60 days), while mood disorders (depression and bipolar disorder) accounted for the largest proportion (32%) of hospitalizations for mental illness.
Number of patients using general and psychiatric hospital mental health services declining over time
Although the number of psychiatric patients hospitalized in Canada in 2003-2004 was similar to the number reported in 2002-2003, over the last ten years there has been a decline in both the number of patients using general and psychiatric hospital mental health services and in their average length of stay. For 2003-2004, the average length of stay was 35 days; this represents a 47% decrease from 66 days in 1994-1995. Conditions such as depression and bipolar disorder were the most common diagnoses for mental health hospitalizations in 11 of 12 provinces and territories (the exception is the Northwest Territories, where substance-related disorders were most common).
The vast majority (86%) of patients hospitalized because of mental illness in 2003-2004 were cared for in general hospitals, rather than in psychiatric hospitals. Patients with schizophrenia, generally considered the most severe mental health condition, were more likely than any other group to have received treatment from a psychiatric hospital, rather than a general hospital.
One in five patients hospitalized for mental illness also had a substance-related disorder
In 2003-2004, 20% of patients hospitalized in general hospitals with a primary diagnosis of mental illness also had a substance-related disorder (for example, alcoholism). On average, these patients were younger than those without substance-related disorders and they were more likely to be male. Patients hospitalized with personality disorders made up almost one third (27.6%) of those psychiatric patients with a co-occurring substance-related disorder.
About CIHI
The Canadian Institute for Health Information (CIHI) collects and analyzes information on health and health care in Canada and makes it publicly available. Canada's federal, provincial and territorial governments created CIHI as a not-for-profit, independent organization dedicated to forging a common approach to Canadian health information. CIHI's goal: to provide timely, accurate and comparable information. CIHI's data and reports inform health policies, support the effective delivery of health services and raise awareness among Canadians of the factors that contribute to good health.
The report and the following figures and tables are available from CIHI's website at cihi.ca.
Table 1.
Risk of One-Year Readmission per 100 Persons, 2003-2004 (adapted from Table 3.1 in the report)
Table 2.
Characteristics of the Population, 2003-2004 (adapted from Table 1.2 in the report)
Figure 1.
Hospital Separation Rate for Mental Illness by Type of Hospital, 1994-1995 to 2003-2004 (Figure i in the report)
Figure 2.
Average Length of Stay for Mental Illness by Type of Hospital, 1994-1995 to 2003-2004 (Figure ii in the report)
Figure 3.
Percentages of Separations by Diagnosis Category for General Hospitals, 2003-2004 (Figure 1.1 in the report)
Figure 4.
Percentages of Separations by Diagnosis Category for Psychiatric Hospitals, 2003-2004 (Figure 1.2 in the report)
"Readmission for a mental illness is often linked to a disruption in outpatient treatment and rehabilitation and may signal instability or a recurrence of severe symptoms of a disease," says Nawaf Madi, CIHI's Program Lead for Mental Health and Addictions. "This is an area of concern for health planners, because, among other things, treating a patient in hospital is significantly more expensive than treatment at the outpatient or community level."
Risk of readmission linked to age, diagnosis
The risk of readmission to general hospital for an individual with a primary diagnosis of mental illness increases with the age of the patient, from a rate of 26.5 per 100 of those aged 0 to 14, to 38.7 per 100 of those aged 65 and over. Among the diagnosis categories, the risk of readmission was higher for individuals with a primary diagnosis of personality disorder (45%), followed by individuals with schizophrenia (41%). Readmissions were similar for women and men (38.3% and 35.5%, respectively) and, overall, the longer the initial general hospital stay, the greater the chance of readmission within one year.
Thirty percent of all general hospital days stayed in 2003-2004 involved a patient diagnosed with mental illness
Patients with a primary diagnosis of mental illness accounted for 6% of all hospitalizations in Canada; another 8% involved patients with a non-psychiatric primary diagnosis and an associated mental illness. But since lengths of stay for patients with mental illness were more than twice as long as for others, these hospitalizations combined accounted for 30% of the total number of days patients spent in Canadian general hospitals in 2003-2004. The average length of stay for a patient with a primary diagnosis of mental illness in a general hospital was 16.9 days in 2003-2004, compared to 7.2 days for those with a non-psychiatric diagnosis.
Schizophrenia accounted for the longest average length of stay (60 days), while mood disorders (depression and bipolar disorder) accounted for the largest proportion (32%) of hospitalizations for mental illness.
Number of patients using general and psychiatric hospital mental health services declining over time
Although the number of psychiatric patients hospitalized in Canada in 2003-2004 was similar to the number reported in 2002-2003, over the last ten years there has been a decline in both the number of patients using general and psychiatric hospital mental health services and in their average length of stay. For 2003-2004, the average length of stay was 35 days; this represents a 47% decrease from 66 days in 1994-1995. Conditions such as depression and bipolar disorder were the most common diagnoses for mental health hospitalizations in 11 of 12 provinces and territories (the exception is the Northwest Territories, where substance-related disorders were most common).
The vast majority (86%) of patients hospitalized because of mental illness in 2003-2004 were cared for in general hospitals, rather than in psychiatric hospitals. Patients with schizophrenia, generally considered the most severe mental health condition, were more likely than any other group to have received treatment from a psychiatric hospital, rather than a general hospital.
One in five patients hospitalized for mental illness also had a substance-related disorder
In 2003-2004, 20% of patients hospitalized in general hospitals with a primary diagnosis of mental illness also had a substance-related disorder (for example, alcoholism). On average, these patients were younger than those without substance-related disorders and they were more likely to be male. Patients hospitalized with personality disorders made up almost one third (27.6%) of those psychiatric patients with a co-occurring substance-related disorder.
About CIHI
The Canadian Institute for Health Information (CIHI) collects and analyzes information on health and health care in Canada and makes it publicly available. Canada's federal, provincial and territorial governments created CIHI as a not-for-profit, independent organization dedicated to forging a common approach to Canadian health information. CIHI's goal: to provide timely, accurate and comparable information. CIHI's data and reports inform health policies, support the effective delivery of health services and raise awareness among Canadians of the factors that contribute to good health.
The report and the following figures and tables are available from CIHI's website at cihi.ca.
Table 1.
Risk of One-Year Readmission per 100 Persons, 2003-2004 (adapted from Table 3.1 in the report)
Table 2.
Characteristics of the Population, 2003-2004 (adapted from Table 1.2 in the report)
Figure 1.
Hospital Separation Rate for Mental Illness by Type of Hospital, 1994-1995 to 2003-2004 (Figure i in the report)
Figure 2.
Average Length of Stay for Mental Illness by Type of Hospital, 1994-1995 to 2003-2004 (Figure ii in the report)
Figure 3.
Percentages of Separations by Diagnosis Category for General Hospitals, 2003-2004 (Figure 1.1 in the report)
Figure 4.
Percentages of Separations by Diagnosis Category for Psychiatric Hospitals, 2003-2004 (Figure 1.2 in the report)
Paroxetine linked to higher rate of suicide attempts in adults
Adult patients taking the antidepressant drug paroxetine are at higher risk of attempting to commit suicide than those not taking medication. A new analysis, published in BMC Medicine, of previous clinical data on paroxetine use adds the antidepressant to the list of Selective Serotonin Reuptake Inhibitors (SSRIs) that have been shown to increase suicidal tendencies in adult patients with depression.
Ivar Aursnes and colleagues from the University of Oslo, Norway, reanalysed data from 16 selected paroxetine trials. In the trials, patients diagnosed with depression had been randomly given either paroxetine or a placebo drug. Neither the participants nor the researchers conducting the initial studies knew what the participants had been given. Aursnes et al. did a new statistical analysis of the results of these studies, to evaluate the incidence of suicide attempts in both groups. In their analysis, they took into account the amount of time the participants had been exposed to paroxetine. Their results show that there were seven suicide attempts in the group on paroxetine, and only one among the patients on placebo.
Paroxetine has been shown to increase suicidal attempt rates in children and teenagers, but previous studies have failed to reach a conclusion as regards the effects of the drug on suicide attempt rates in adult patients. Gunnell et al., in the February 19th 2005 issue of the BMJ, warned doctors about an increased risk of suicidal behaviour in patients treated with SSRIs. Their conclusion was based on analyses of clinical data submitted by the pharmaceutical companies that produce SSRIs to the Medicine and Healthcare products Regulatory Agency. But Gunnell et al.'s study had not properly included data on paroxetine.
Aursnes et al. conclude that "the recommendation of restrictions in the use of paroxetine in children and adolescents conveyed by regulatory agencies lately should include usage in adults". They confirm that all SSRIs increase suicidal tendencies in depressed adults, "the data strongly suggest that the use of SSRIs are connected with increased intensity per year of suicidal attempts".
Article:
Suicidal attempts in clinical trials with paroxetine randomised against placebo
Ivar Aursnes, Ingunn Fride Tvete, Jorund Gaasemyr, Bent Natvig
BMC Medicine 2005, 3:14
Juliette Savin
juliette.savinbiomedcentral
44-207-631-99-31
BioMed Central
biomedcentral
Ivar Aursnes and colleagues from the University of Oslo, Norway, reanalysed data from 16 selected paroxetine trials. In the trials, patients diagnosed with depression had been randomly given either paroxetine or a placebo drug. Neither the participants nor the researchers conducting the initial studies knew what the participants had been given. Aursnes et al. did a new statistical analysis of the results of these studies, to evaluate the incidence of suicide attempts in both groups. In their analysis, they took into account the amount of time the participants had been exposed to paroxetine. Their results show that there were seven suicide attempts in the group on paroxetine, and only one among the patients on placebo.
Paroxetine has been shown to increase suicidal attempt rates in children and teenagers, but previous studies have failed to reach a conclusion as regards the effects of the drug on suicide attempt rates in adult patients. Gunnell et al., in the February 19th 2005 issue of the BMJ, warned doctors about an increased risk of suicidal behaviour in patients treated with SSRIs. Their conclusion was based on analyses of clinical data submitted by the pharmaceutical companies that produce SSRIs to the Medicine and Healthcare products Regulatory Agency. But Gunnell et al.'s study had not properly included data on paroxetine.
Aursnes et al. conclude that "the recommendation of restrictions in the use of paroxetine in children and adolescents conveyed by regulatory agencies lately should include usage in adults". They confirm that all SSRIs increase suicidal tendencies in depressed adults, "the data strongly suggest that the use of SSRIs are connected with increased intensity per year of suicidal attempts".
Article:
Suicidal attempts in clinical trials with paroxetine randomised against placebo
Ivar Aursnes, Ingunn Fride Tvete, Jorund Gaasemyr, Bent Natvig
BMC Medicine 2005, 3:14
Juliette Savin
juliette.savinbiomedcentral
44-207-631-99-31
BioMed Central
biomedcentral
A Link Between Antidepressants And Type 2 Diabetes
While analyzing data from Saskatchewan health databases, Lauren Brown, researcher with the U of A's School of Public Health, found people with a history of depression had a 30 per cent increased risk of type 2 Diabetes.
Brown then studied the medical history of 2,400 people who were diagnosed with depression and were taking antidepressants to determine whether there was a clear correlation between that disease and type 2 Diabetes.
Brown divided the group into four categories: those who took antidepressants that were considered older therapies, patients who were using newer treatments, those using a combination of both an old and new treatments and people who were switching medications.
What she found was the risk of diabetes almost doubled for the patients who were using two types of therapies at the same time, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Brown says people are usually prescribed multiple medications "if they have severe depression or if they are having a problem finding the right therapy."
Brown believes these results, and results of previous studies demonstrating an increased risk of type 2 diabetes in people with depression, emphasize the need for regular screening for type 2 diabetes in people with depression, particularly those taking more than one antidepressant. She also encourages diabetes and depression organizations to educate their members about this link.
This study was recently published in Diabetes Research & Clinical Practice.
University of Alberta
685 General Services Bldg.
Edmonton, Alberta T6E 2H1
Canada
ualberta.ca
Brown then studied the medical history of 2,400 people who were diagnosed with depression and were taking antidepressants to determine whether there was a clear correlation between that disease and type 2 Diabetes.
Brown divided the group into four categories: those who took antidepressants that were considered older therapies, patients who were using newer treatments, those using a combination of both an old and new treatments and people who were switching medications.
What she found was the risk of diabetes almost doubled for the patients who were using two types of therapies at the same time, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Brown says people are usually prescribed multiple medications "if they have severe depression or if they are having a problem finding the right therapy."
Brown believes these results, and results of previous studies demonstrating an increased risk of type 2 diabetes in people with depression, emphasize the need for regular screening for type 2 diabetes in people with depression, particularly those taking more than one antidepressant. She also encourages diabetes and depression organizations to educate their members about this link.
This study was recently published in Diabetes Research & Clinical Practice.
University of Alberta
685 General Services Bldg.
Edmonton, Alberta T6E 2H1
Canada
ualberta.ca
Girls At Risk For Depression May Not Process Reward And Loss Properly
Young girls at high risk for depression, but who have not experienced any symptoms, show differences in neural response patterns when processing the possibility of receiving a reward or sustaining a loss, according to a report in the April issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
"A hallmark characteristic of major depressive disorder is the diminished experience of pleasure or reward," the authors write as background information in the article. "For example, compared with non-depressed persons, depressed individuals have been found to be characterized by attenuated [decreased] reactivity to slides depicting pleasant scenes, to amusing film clips, to pleasant drinks and to monetary reward contingencies." Recent research has suggested that these variations are reflected in underlying differences in the way the brain processes pleasant stimuli.
To begin assessing whether these deficits precede the onset of depression or are a consequence of the disorder, Ian H. Gotlib, Ph.D., of Stanford University, Calif., and colleagues studied 13 10- to 14-year-old girls who did not have depression themselves but whose mothers had recurrent depression (high-risk group). They were compared with 13 girls who were the same age but had no personal or family history of depression (low-risk group).
All 26 participants underwent functional magnetic resonance imaging (fMRI) while completing a task involving the possibility of reward and punishment. They were first shown a target and told that if a circle appeared, they could gain points by being fast enough to hit the target. If a square appeared, they could avoid losing points by hitting the target quickly. If a triangle appeared, they could neither win nor lose points and should avoid responding. The task consisted of 100 six-second trials, each of which contained an anticipation phase and a feedback phase, during which the girls were told whether they gained or lost points. The points could be redeemed for prizes at the end of the task.
The images revealed important differences in the way the two groups responded to the task. The high-risk group displayed diminished neural responses during both anticipation and receipt of the reward when compared with the low-risk group. Specifically, they did not show any activation in a brain area known as the dorsal anterior cingulate cortex, which appears to be involved in reinforcing past experiences to facilitate learning. However, compared with low-risk girls, high-risk girls showed an increased activation in this area when receiving punishment. This suggests they may more easily integrate information about loss and punishment than reward and pleasure over time.
"Considered together with reduced activation in the striatal areas commonly observed during reward, it seems that the reward processing system is critically impaired in daughters who are at elevated risk for depression, although they have not yet experienced a depressive episode," the authors conclude. "Clearly, longitudinal studies are needed to determine whether the anomalous activations observed in this study during the processing of rewards and losses are associated with the subsequent onset of depression."
Arch Gen Psychiatry.
2010;67[4]:380-387.
Source
Archives of General Psychiatry
"A hallmark characteristic of major depressive disorder is the diminished experience of pleasure or reward," the authors write as background information in the article. "For example, compared with non-depressed persons, depressed individuals have been found to be characterized by attenuated [decreased] reactivity to slides depicting pleasant scenes, to amusing film clips, to pleasant drinks and to monetary reward contingencies." Recent research has suggested that these variations are reflected in underlying differences in the way the brain processes pleasant stimuli.
To begin assessing whether these deficits precede the onset of depression or are a consequence of the disorder, Ian H. Gotlib, Ph.D., of Stanford University, Calif., and colleagues studied 13 10- to 14-year-old girls who did not have depression themselves but whose mothers had recurrent depression (high-risk group). They were compared with 13 girls who were the same age but had no personal or family history of depression (low-risk group).
All 26 participants underwent functional magnetic resonance imaging (fMRI) while completing a task involving the possibility of reward and punishment. They were first shown a target and told that if a circle appeared, they could gain points by being fast enough to hit the target. If a square appeared, they could avoid losing points by hitting the target quickly. If a triangle appeared, they could neither win nor lose points and should avoid responding. The task consisted of 100 six-second trials, each of which contained an anticipation phase and a feedback phase, during which the girls were told whether they gained or lost points. The points could be redeemed for prizes at the end of the task.
The images revealed important differences in the way the two groups responded to the task. The high-risk group displayed diminished neural responses during both anticipation and receipt of the reward when compared with the low-risk group. Specifically, they did not show any activation in a brain area known as the dorsal anterior cingulate cortex, which appears to be involved in reinforcing past experiences to facilitate learning. However, compared with low-risk girls, high-risk girls showed an increased activation in this area when receiving punishment. This suggests they may more easily integrate information about loss and punishment than reward and pleasure over time.
"Considered together with reduced activation in the striatal areas commonly observed during reward, it seems that the reward processing system is critically impaired in daughters who are at elevated risk for depression, although they have not yet experienced a depressive episode," the authors conclude. "Clearly, longitudinal studies are needed to determine whether the anomalous activations observed in this study during the processing of rewards and losses are associated with the subsequent onset of depression."
Arch Gen Psychiatry.
2010;67[4]:380-387.
Source
Archives of General Psychiatry
The Lingering Psychological Impact Of The Disaster In Japan
The psychological impact of natural disasters such as the Japan earthquake can be revealed in the way people inherently respond to unpredictable situations, according to a psychology expert at Queen Mary, University of London.
Dr Magda Osman, Psychology Lecturer at Queen Mary, University of London, and author of Controlling Uncertainty: Decision-making and Learning in Complex Worlds, said the disaster had a devastating immediate effect on tens of thousands of people in Japan but the true psychological impact will be felt "for some time to come".
"A disaster like the Japan earthquake has such wide-ranging implications, especially on the psychological well-being of those affected," Dr Osman said.
"After a disaster, typically small communities become incredibly co-operative and pull together to help each other and start the rebuilding process. There's an immediate response where people start to take control of the situation, begin to deal with it and assess and respond to the devastation around them.
"The problem is that we aren't very good at calculating the long-term effects of disasters. After about two months of re-building and cleaning up we tend to experience a second major slump when we realise the full severity of the situation in the longer term. This is what we need to be wary of because this triggers severe depression."
Dr Osman, who works in Queen Mary's School of Biological and Chemical Sciences, said as soon as there is a disaster, there is often a rapid increase of mental health problems in the people who have been affected. This is because natural disasters threaten our sense of control in the world.
"Our sense of control is like a mental engine, it's like an adaptive driving force that helps us stay motivated. When bad, unpredictable events happen we don't feel we have any effect over anything and this is when we start to lose self esteem," she said.
People who live in areas which are prone to disasters such as in Japan are often prepared through simulation exercises. The importance of this is not only to rehearse what to do in the event of a disaster, but also to increase our sense of control over the situation. This is can be a powerful way to create resilience, according to Dr Osman.
The lab experiments Dr Osman has conducted show that even when a situation is unpredictable and seems to be spiralling out of control, and when people are encouraged to believe they have control over the situation, they tend to be better able to exert control. She said: "Ironically, the illusion of control can actually help to generate a real sense of control."
"Setting goals is the best way of helping to exert or take back control. Working towards goals helps us to gain a lot of information about a situation. Goals act like a yardstick to compare future events against. This helps to reduce our feelings of insecurity because it gives us a way of interpreting the good and bad experiences that happen.
"Evidence from the lab suggests that we don't always do what is best to gain information and gain control in the long term; typically we overreact to massive changes, when the best thing to do is be steadfast."
Notes:
Dr Magda Osman's book Controlling Uncertainty: Decision-making and Learning in Complex Worlds is published by Wiley-Blackwell in 2010.
Dr Magda Osman, Psychology Lecturer at Queen Mary, University of London, and author of Controlling Uncertainty: Decision-making and Learning in Complex Worlds, said the disaster had a devastating immediate effect on tens of thousands of people in Japan but the true psychological impact will be felt "for some time to come".
"A disaster like the Japan earthquake has such wide-ranging implications, especially on the psychological well-being of those affected," Dr Osman said.
"After a disaster, typically small communities become incredibly co-operative and pull together to help each other and start the rebuilding process. There's an immediate response where people start to take control of the situation, begin to deal with it and assess and respond to the devastation around them.
"The problem is that we aren't very good at calculating the long-term effects of disasters. After about two months of re-building and cleaning up we tend to experience a second major slump when we realise the full severity of the situation in the longer term. This is what we need to be wary of because this triggers severe depression."
Dr Osman, who works in Queen Mary's School of Biological and Chemical Sciences, said as soon as there is a disaster, there is often a rapid increase of mental health problems in the people who have been affected. This is because natural disasters threaten our sense of control in the world.
"Our sense of control is like a mental engine, it's like an adaptive driving force that helps us stay motivated. When bad, unpredictable events happen we don't feel we have any effect over anything and this is when we start to lose self esteem," she said.
People who live in areas which are prone to disasters such as in Japan are often prepared through simulation exercises. The importance of this is not only to rehearse what to do in the event of a disaster, but also to increase our sense of control over the situation. This is can be a powerful way to create resilience, according to Dr Osman.
The lab experiments Dr Osman has conducted show that even when a situation is unpredictable and seems to be spiralling out of control, and when people are encouraged to believe they have control over the situation, they tend to be better able to exert control. She said: "Ironically, the illusion of control can actually help to generate a real sense of control."
"Setting goals is the best way of helping to exert or take back control. Working towards goals helps us to gain a lot of information about a situation. Goals act like a yardstick to compare future events against. This helps to reduce our feelings of insecurity because it gives us a way of interpreting the good and bad experiences that happen.
"Evidence from the lab suggests that we don't always do what is best to gain information and gain control in the long term; typically we overreact to massive changes, when the best thing to do is be steadfast."
Notes:
Dr Magda Osman's book Controlling Uncertainty: Decision-making and Learning in Complex Worlds is published by Wiley-Blackwell in 2010.
A Second Pathway For Antidepressants: Berkeley Lab Reports New Fluorescent Assay Reveals TREK1 Mechanism
Using a unique and relatively simple cell-based fluorescent assay they developed, scientists with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC), Berkeley have identified a means by which fluoxetine, the active ingredient in Prozac, suppresses the activity of the TREK1 potassium channel. TREK1 activity has been implicated in mood regulation and could be an important target for fluoxetine and other antidepressant drugs.
"Whereas the inhibiting of serotonin re-uptake remains fluoxetine's primary antidepression mechanism, many pharmacological agents have more than one target," says Ehud Isacoff, a neurobiophysicist who holds joint appointments with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Department of Molecular and Cell Biology. "Our study shows that the inhibition of TREK1 by fluoxetine, which was found in earlier studies, is accompanied by an unbinding of the protein's C-terminal domain from the membrane. This is the first observation of the mechanism by which TREK1 might be regulated by antidepressant drugs."
Isacoff is the corresponding author on a paper reporting the results of this study that appears in the Proceedings of the National Academy of Science (PNAS). The paper is titled "Optical probing of a dynamic membrane interaction that regulates the TREK1 channel." Co-authoring this paper were Guillaume Sandoz, a TREK1 specialist with France's National Center for Scientific Research at the Institute for Molecular and Cellular Physiology, and PhD student Sarah Bell, both of whom were with Isacoff's research group at the time the work was done.
Neurons in the human brain are like high-speed transistors, controlling the flow of electrical current through channels in their membranes by the opening and closing of molecular "gates" that control the flow of ions through selective pores. TREK1 is one of the most ubiquitous of these transmembrane proteins, gating the passage of potassium ions through neural membranes, which sets the excitability of the neuron. Earlier studies had shown that when the TREK1 gene is "knocked out" of mice, the mice display a depression-resistant phenotype that mimics the behavior of mice treated with fluoxetine and that the antidepressant inhibits the activity of the TREK1 channel. While these results pointed to a possible role for the TREK1 ion channel in the beneficial response to fluoxetine, the mechanism behind this activity was unclear.
"Studying what the different protein parts of an ion channel do is a huge challenge," Isacoff says. "Over the years, my group has developed techniques by which the domains of channel proteins can be labeled with site-specific fluorescent dyes. Structural rearrangements of the labeled sites in the channel can then be detected through changes in the fluorescence."
Isacoff and his group separated the C-terminal domain from the rest of the protein and tagged it with a green fluorescent protein (GFP) - a fluorescent protein from jellyfish commonly used to paint cells green for biological studies. Whereas the pore of the TREK1 ion channel is embedded in the plasma membrane of a neuron, the C-terminal is a short tail that protrudes out into the surrounding cytoplasm.
Using voltage clamps to measure electrical currents through the channel and fluorescence to monitor the disposition of the C-terminal domain, Isacoff and his group found that when the C-terminal tail is fully bound to the plasma membrane, the TREK1 potassium channel opens more; when the tail is unbound from the plasma membrane, the ion channel tends to close.
"We found that fluoxetine causes the isolated C-terminal domain to unbind from the membrane and also causes an inhibition of current from the full TREK1 channel," Isacoff says.
The next step will be to see how the C-terminal tail is affected by the presence of fluoxetine when the tail is still attached to the rest of the TREK1 protein. In the meantime, Isacoff and his team feel they now have a valuable assay that can be used to monitor the reversible plasma membrane association of protein domains without the need for scanning, optical slicing or imaging.
"Pharmaceutical companies screening for potential new drugs, such as improved antidepressants, prefer assays that are fast and simple," Isacoff says. "Our technique can be used to follow changes in lipid composition that result from membrane signaling events, or to study the binding to membranes by cytoplasmic regulatory domains of ion channels. This could be very useful for pharmaceutical research."
Notes:
This research was primarily supported by the National Institutes of Health.
The PNAS paper: "Optical probing of a dynamic membrane interaction that regulates the TREK1 channel" can be viewed as a pdf here.
"Whereas the inhibiting of serotonin re-uptake remains fluoxetine's primary antidepression mechanism, many pharmacological agents have more than one target," says Ehud Isacoff, a neurobiophysicist who holds joint appointments with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Department of Molecular and Cell Biology. "Our study shows that the inhibition of TREK1 by fluoxetine, which was found in earlier studies, is accompanied by an unbinding of the protein's C-terminal domain from the membrane. This is the first observation of the mechanism by which TREK1 might be regulated by antidepressant drugs."
Isacoff is the corresponding author on a paper reporting the results of this study that appears in the Proceedings of the National Academy of Science (PNAS). The paper is titled "Optical probing of a dynamic membrane interaction that regulates the TREK1 channel." Co-authoring this paper were Guillaume Sandoz, a TREK1 specialist with France's National Center for Scientific Research at the Institute for Molecular and Cellular Physiology, and PhD student Sarah Bell, both of whom were with Isacoff's research group at the time the work was done.
Neurons in the human brain are like high-speed transistors, controlling the flow of electrical current through channels in their membranes by the opening and closing of molecular "gates" that control the flow of ions through selective pores. TREK1 is one of the most ubiquitous of these transmembrane proteins, gating the passage of potassium ions through neural membranes, which sets the excitability of the neuron. Earlier studies had shown that when the TREK1 gene is "knocked out" of mice, the mice display a depression-resistant phenotype that mimics the behavior of mice treated with fluoxetine and that the antidepressant inhibits the activity of the TREK1 channel. While these results pointed to a possible role for the TREK1 ion channel in the beneficial response to fluoxetine, the mechanism behind this activity was unclear.
"Studying what the different protein parts of an ion channel do is a huge challenge," Isacoff says. "Over the years, my group has developed techniques by which the domains of channel proteins can be labeled with site-specific fluorescent dyes. Structural rearrangements of the labeled sites in the channel can then be detected through changes in the fluorescence."
Isacoff and his group separated the C-terminal domain from the rest of the protein and tagged it with a green fluorescent protein (GFP) - a fluorescent protein from jellyfish commonly used to paint cells green for biological studies. Whereas the pore of the TREK1 ion channel is embedded in the plasma membrane of a neuron, the C-terminal is a short tail that protrudes out into the surrounding cytoplasm.
Using voltage clamps to measure electrical currents through the channel and fluorescence to monitor the disposition of the C-terminal domain, Isacoff and his group found that when the C-terminal tail is fully bound to the plasma membrane, the TREK1 potassium channel opens more; when the tail is unbound from the plasma membrane, the ion channel tends to close.
"We found that fluoxetine causes the isolated C-terminal domain to unbind from the membrane and also causes an inhibition of current from the full TREK1 channel," Isacoff says.
The next step will be to see how the C-terminal tail is affected by the presence of fluoxetine when the tail is still attached to the rest of the TREK1 protein. In the meantime, Isacoff and his team feel they now have a valuable assay that can be used to monitor the reversible plasma membrane association of protein domains without the need for scanning, optical slicing or imaging.
"Pharmaceutical companies screening for potential new drugs, such as improved antidepressants, prefer assays that are fast and simple," Isacoff says. "Our technique can be used to follow changes in lipid composition that result from membrane signaling events, or to study the binding to membranes by cytoplasmic regulatory domains of ion channels. This could be very useful for pharmaceutical research."
Notes:
This research was primarily supported by the National Institutes of Health.
The PNAS paper: "Optical probing of a dynamic membrane interaction that regulates the TREK1 channel" can be viewed as a pdf here.
The Occurence Of Depression Increasing During Financial Crisis Due To Income Inequalities
Due to the recent economic crisis, an increase of health inequalities between socio-economic groups has been noticed in both developed and developing countries.
The World Health Organization, the World Bank and the United Nations Development Programme have all reported these inequalities and emphasized its importance and made this issue a priority.
There is evidence that such inequalities not only affect general health, but have a particular impact on mental health.
A new study, published in World Psychiatry, the official journal of the World Psychiatric Association (WPA), examined the data of the Korea National Health and Nutrition Examination Survey (KHANES), for the period between 1998 and 2007. The aim of the study was to measure income-related inequalities in depression, suicidal ideation and suicide attempts in South Korea and to trace their changes over a 10-year period (1998-2007).
The study data was obtained from a representative sample of the South Korean population through face-to-face interviews, gathering information about socio-economic status, health condition, and health behaviour (e.g. exercise, smoking, alcohol consumption). Information on depression and suicidal behaviour was obtained through self-report of whether the respondents had (a) been diagnosed with depression, (b) had ever felt like dying in the past 12 months, and (c) had ever attempted suicides in the past 12 months.
This study shows that the three psychopathologies (depression, suicidal ideation and suicide attempts) were more highly concentrated in lower income groups across years. This inequality observed was more pronounced in recent years, especially for suicide attempt. This means that the lowest income groups have the highest risk of depression, suicidal ideation and suicidal attempt.
Moreover, during this period, the suicide rate rose dramatically from an average of 13.0 per 100,000 to 26.0. This is the highest rate among countries belonging to the Organization for Economic Cooperation and Development (OECD). This may reflect an acute response to the economic crisis in the late 1990s.
This study showed clear existence of significant pro-rich inequalities in the prevalence of depression, suicidal ideation and suicide attempts. These inequalities have doubled over the past 10 years, in parallel to the widening income inequalities following the economic crisis.
The World Health Organization, the World Bank and the United Nations Development Programme have all reported these inequalities and emphasized its importance and made this issue a priority.
There is evidence that such inequalities not only affect general health, but have a particular impact on mental health.
A new study, published in World Psychiatry, the official journal of the World Psychiatric Association (WPA), examined the data of the Korea National Health and Nutrition Examination Survey (KHANES), for the period between 1998 and 2007. The aim of the study was to measure income-related inequalities in depression, suicidal ideation and suicide attempts in South Korea and to trace their changes over a 10-year period (1998-2007).
The study data was obtained from a representative sample of the South Korean population through face-to-face interviews, gathering information about socio-economic status, health condition, and health behaviour (e.g. exercise, smoking, alcohol consumption). Information on depression and suicidal behaviour was obtained through self-report of whether the respondents had (a) been diagnosed with depression, (b) had ever felt like dying in the past 12 months, and (c) had ever attempted suicides in the past 12 months.
This study shows that the three psychopathologies (depression, suicidal ideation and suicide attempts) were more highly concentrated in lower income groups across years. This inequality observed was more pronounced in recent years, especially for suicide attempt. This means that the lowest income groups have the highest risk of depression, suicidal ideation and suicidal attempt.
Moreover, during this period, the suicide rate rose dramatically from an average of 13.0 per 100,000 to 26.0. This is the highest rate among countries belonging to the Organization for Economic Cooperation and Development (OECD). This may reflect an acute response to the economic crisis in the late 1990s.
This study showed clear existence of significant pro-rich inequalities in the prevalence of depression, suicidal ideation and suicide attempts. These inequalities have doubled over the past 10 years, in parallel to the widening income inequalities following the economic crisis.
Cymbalta Provided Sustained Pain Relief for Women with Fibromyalgia
Study shows improvement in pain unrelated to effect on mood and presence of major depression
The antidepressant Cymbalta® (duloxetine HCl; pronounced sim-BAWL'-tuh), a dual-reuptake inhibitor of serotonin and
norepinephrine, 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia,
with and without major depression, according to 12-week data presented this week at the annual meeting of the American
College of Rheumatology.
These data are being presented one month after another study, in which Cymbalta also significantly reduced pain in women with
fibromyalgia versus placebo, was published in Arthritis and Rheumatism.
"The results in these study patients were very striking in the degree of reduction of pain, which is the primary symptom of
fibromyalgia. In addition, Cymbalta significantly improved these patients' quality of life and overall functioning, as
measured by quality of life and disability scales," said Lesley M. Arnold, M.D., University of Cincinnati College of
Medicine, Cincinnati, Ohio, who presented the study. "For many, the pain of fibromyalgia makes them so sensitive to being
touched that even a hug from a loved-one can be intolerable."
In the study, Cymbalta's effect on pain was independent of any effect on mood, and there was no significant difference in
response rates between patients in the study with and without major depression.
Fibromyalgia is a chronic disorder that causes widespread pain and tenderness in the muscles and soft tissue of nearly 6
million Americans, predominantly women.1 According to the National Fibromyalgia Association, patients often experience a deep
muscular aching, throbbing, twitching, stabbing and shooting pain that "knows no boundaries, migrating to all parts of the
body and varying in intensity." Neurological complaints, such as numbness, tingling and burning, are often present and add to
the discomfort of the patient.
While the cause of fibromyalgia remains unknown, it has been linked to abnormalities in the brain's neurotransmitters,
serotonin and norepinephrine, the same neurotransmitters believed to play a role in major depressive disorder, diabetic
peripheral neuropathic pain and stress urinary incontinence.1
There is no approved treatment for fibromyalgia. Cymbalta, a balanced and potent serotonin and norepinephrine reuptake
inhibitor, is proven to help treat the emotional and painful physical symptoms of depression. It also is the only approved
treatment for management of pain caused by diabetic peripheral neuropathy, a type of nerve damage. Cymbalta is not approved
for the treatment of fibromyalgia.
Study Findings
More than half of patients treated with 60 mg of Cymbalta, once or twice daily, responded to treatment after 12
weeks, compared with one-third of those taking a sugar pill.
Patients treated with 60 mg of Cymbalta, once or twice daily, were significantly more likely to experience a
sustained treatment response than those treated with a sugar pill (44 percent, 43 percent and 19 percent, respectively).
Patients treated with 60 mg of Cymbalta, once or twice daily, had functional improvements on the Sheehan Disability
Scale which measures disability at work, in family life and in social life, that were significantly greater than those of
patients taking a sugar pill.
Cymbalta 60 mg once or twice daily directly reduced pain (75.7 and 87.5 percent, respectively) more than the indirect
effect attributed to improvement in depressive symptoms (24.4 percent and 12.5 percent, respectively).
Cymbalta 60 mg twice a day also relieved the pain associated with tender points often associated with fibromyalgia.
Treatment-emergent adverse events were more common in patients treated with Cymbalta 60 mg once or twice daily, than
in those treated with a sugar pill (79.2 percent). Events were typically mild to moderate in severity.
Patients taking Cymbalta 60 mg once or twice daily were more likely to discontinue because of side effects than those
taking placebo (21.2 percent, 23.3 percent and 11.7 percent respectively).
The most common side effects for patients taking Cymbalta (occurring in at least 5 percent of patients and at twice
the rate for those receiving placebo) were nausea, dry mouth, constipation, diarrhea, decreased appetite, nasopharyngitis,
increased sweating and anorexia. In addition, for patients taking Cymbalta 60 mg twice daily, sleepiness and feeling jittery
were common side effects.
Methodology
In a 12-week, double blind study, patients were randomized to receive Cymbalta 60 mg once (n=118) or twice daily (n=116), or
placebo (n=120). The primary outcome measure was Brief Pain Inventory (BPI) 24-hour average pain severity score (score
range: 0 [no pain] -10 [pain as bad as you can imagine]). Response to treatment was defined as a 30 percent reduction in the
BPI 24-hour average pain score. Secondary outcome measures included remaining BPI pain and interference scores, Fibromyalgia
Impact Questionnaire (FIQ), the tender point pain threshold and tender point number, Clinical Global Impression of Severity
(CGI-Severity), Patient Global Impression of Improvement (PGI-Improvement), and the 17-item Hamilton Rating Scale for
Depression.
About Cymbalta
Cymbalta is indicated for the treatment of major depression and the management of diabetic peripheral neuropathic pain, both
in adults. As Cymbalta has not been studied in children, Lilly discourages its use in those under 18.
Cymbalta should not be confused with Symbyax® (pronounced SIMM-bee-ax), a medicine for bipolar depression also marketed by
Lilly. Symbyax is a combination of olanzapine, the active ingredient in Zyprexa®, and fluoxetine, the active ingredient in
Prozac®. Symbyax is available in capsules of 6 mg/25 mg (olanzapine/fluoxetine), 12 mg/25 mg, 6 mg/50 mg and 12 mg/50 mg.
Cymbalta is available in 20 mg, 30 mg and 60 mg capsules.
Important Safety Information
Patients being treated with antidepressants should be observed closely for clinical worsening of depressive symptoms and
suicidality. Patients and their families should watch for these as well as for anxiety, agitation, panic, difficulty
sleeping, irritability, hostility, aggressiveness, impulsivity, restlessness, or overexcitement and hyperactivity. Call the
doctor if any of these are severe or occur suddenly. Be especially observant when starting any antidepressant therapy and
whenever there is a change in dose.
Prescription Cymbalta is not for everyone. People who are allergic to duloxetine hydrochloride or the other ingredients in
Cymbalta should not take it. If you have recently taken a type of antidepressant called a monoamine oxidase inhibitor
(MAOI), are taking thioridazine or have uncontrolled narrow-angle glaucoma, you should not take Cymbalta. Talk with your
doctor before taking Cymbalta if you have serious liver or kidney problems, glaucoma or consume large quantities of alcohol.
Women who are pregnant should talk with their doctor before taking Cymbalta. Nursing while taking Cymbalta is not
recommended.
In the fibromyalgia study of Cymbalta, the most common side effects were nausea, dry mouth, constipation, decreased appetite
and anorexia. In clinical studies of Cymbalta for depression, the most common side effects were nausea, dry mouth,
constipation, decreased appetite, fatigue, sleepiness, and increased sweating. Cymbalta is also approved for the management
of neuropathic pain associated with diabetic peripheral neuropathy. In clinical studies of Cymbalta in these patients, the
most common side effects were nausea, sleepiness, dizziness, constipation, dry mouth, increased sweating, decreased appetite,
and muscle weakness. In all clinical trials, most people were not bothered enough by side effects to stop taking Cymbalta.
Your doctor may periodically check your blood pressure. Don't stop taking Cymbalta without talking to your doctor.
For full patient information, visit Cymbalta.
About Lilly
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class
pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with
eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and
information - for some of the world's most urgent medical needs. Additional information about Lilly is available at lilly.
This press release contains forward-looking statements about the potential of Cymbalta for the treatment of fibromyalgia and
reflects Lilly's current beliefs. However, as with any pharmaceutical product under development, there are substantial risks
and uncertainties in the process of development and regulatory review. There is no guarantee that the company will apply for
or receive regulatory approval for this indication. There is also no guarantee that the product with be commercially
successful. For further discussion of these and other risks and uncertainties, see Lilly's filings with the United States
Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.
1. American College of Rheumatology. Fibromyalgia Fact Sheet. Available at: rheumatology/public/factsheets/fibromya.asp. Accessed October 4, 2004.
View drug information on Cymbalta; Prozac Weekly; Zyprexa.
The antidepressant Cymbalta® (duloxetine HCl; pronounced sim-BAWL'-tuh), a dual-reuptake inhibitor of serotonin and
norepinephrine, 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia,
with and without major depression, according to 12-week data presented this week at the annual meeting of the American
College of Rheumatology.
These data are being presented one month after another study, in which Cymbalta also significantly reduced pain in women with
fibromyalgia versus placebo, was published in Arthritis and Rheumatism.
"The results in these study patients were very striking in the degree of reduction of pain, which is the primary symptom of
fibromyalgia. In addition, Cymbalta significantly improved these patients' quality of life and overall functioning, as
measured by quality of life and disability scales," said Lesley M. Arnold, M.D., University of Cincinnati College of
Medicine, Cincinnati, Ohio, who presented the study. "For many, the pain of fibromyalgia makes them so sensitive to being
touched that even a hug from a loved-one can be intolerable."
In the study, Cymbalta's effect on pain was independent of any effect on mood, and there was no significant difference in
response rates between patients in the study with and without major depression.
Fibromyalgia is a chronic disorder that causes widespread pain and tenderness in the muscles and soft tissue of nearly 6
million Americans, predominantly women.1 According to the National Fibromyalgia Association, patients often experience a deep
muscular aching, throbbing, twitching, stabbing and shooting pain that "knows no boundaries, migrating to all parts of the
body and varying in intensity." Neurological complaints, such as numbness, tingling and burning, are often present and add to
the discomfort of the patient.
While the cause of fibromyalgia remains unknown, it has been linked to abnormalities in the brain's neurotransmitters,
serotonin and norepinephrine, the same neurotransmitters believed to play a role in major depressive disorder, diabetic
peripheral neuropathic pain and stress urinary incontinence.1
There is no approved treatment for fibromyalgia. Cymbalta, a balanced and potent serotonin and norepinephrine reuptake
inhibitor, is proven to help treat the emotional and painful physical symptoms of depression. It also is the only approved
treatment for management of pain caused by diabetic peripheral neuropathy, a type of nerve damage. Cymbalta is not approved
for the treatment of fibromyalgia.
Study Findings
More than half of patients treated with 60 mg of Cymbalta, once or twice daily, responded to treatment after 12
weeks, compared with one-third of those taking a sugar pill.
Patients treated with 60 mg of Cymbalta, once or twice daily, were significantly more likely to experience a
sustained treatment response than those treated with a sugar pill (44 percent, 43 percent and 19 percent, respectively).
Patients treated with 60 mg of Cymbalta, once or twice daily, had functional improvements on the Sheehan Disability
Scale which measures disability at work, in family life and in social life, that were significantly greater than those of
patients taking a sugar pill.
Cymbalta 60 mg once or twice daily directly reduced pain (75.7 and 87.5 percent, respectively) more than the indirect
effect attributed to improvement in depressive symptoms (24.4 percent and 12.5 percent, respectively).
Cymbalta 60 mg twice a day also relieved the pain associated with tender points often associated with fibromyalgia.
Treatment-emergent adverse events were more common in patients treated with Cymbalta 60 mg once or twice daily, than
in those treated with a sugar pill (79.2 percent). Events were typically mild to moderate in severity.
Patients taking Cymbalta 60 mg once or twice daily were more likely to discontinue because of side effects than those
taking placebo (21.2 percent, 23.3 percent and 11.7 percent respectively).
The most common side effects for patients taking Cymbalta (occurring in at least 5 percent of patients and at twice
the rate for those receiving placebo) were nausea, dry mouth, constipation, diarrhea, decreased appetite, nasopharyngitis,
increased sweating and anorexia. In addition, for patients taking Cymbalta 60 mg twice daily, sleepiness and feeling jittery
were common side effects.
Methodology
In a 12-week, double blind study, patients were randomized to receive Cymbalta 60 mg once (n=118) or twice daily (n=116), or
placebo (n=120). The primary outcome measure was Brief Pain Inventory (BPI) 24-hour average pain severity score (score
range: 0 [no pain] -10 [pain as bad as you can imagine]). Response to treatment was defined as a 30 percent reduction in the
BPI 24-hour average pain score. Secondary outcome measures included remaining BPI pain and interference scores, Fibromyalgia
Impact Questionnaire (FIQ), the tender point pain threshold and tender point number, Clinical Global Impression of Severity
(CGI-Severity), Patient Global Impression of Improvement (PGI-Improvement), and the 17-item Hamilton Rating Scale for
Depression.
About Cymbalta
Cymbalta is indicated for the treatment of major depression and the management of diabetic peripheral neuropathic pain, both
in adults. As Cymbalta has not been studied in children, Lilly discourages its use in those under 18.
Cymbalta should not be confused with Symbyax® (pronounced SIMM-bee-ax), a medicine for bipolar depression also marketed by
Lilly. Symbyax is a combination of olanzapine, the active ingredient in Zyprexa®, and fluoxetine, the active ingredient in
Prozac®. Symbyax is available in capsules of 6 mg/25 mg (olanzapine/fluoxetine), 12 mg/25 mg, 6 mg/50 mg and 12 mg/50 mg.
Cymbalta is available in 20 mg, 30 mg and 60 mg capsules.
Important Safety Information
Patients being treated with antidepressants should be observed closely for clinical worsening of depressive symptoms and
suicidality. Patients and their families should watch for these as well as for anxiety, agitation, panic, difficulty
sleeping, irritability, hostility, aggressiveness, impulsivity, restlessness, or overexcitement and hyperactivity. Call the
doctor if any of these are severe or occur suddenly. Be especially observant when starting any antidepressant therapy and
whenever there is a change in dose.
Prescription Cymbalta is not for everyone. People who are allergic to duloxetine hydrochloride or the other ingredients in
Cymbalta should not take it. If you have recently taken a type of antidepressant called a monoamine oxidase inhibitor
(MAOI), are taking thioridazine or have uncontrolled narrow-angle glaucoma, you should not take Cymbalta. Talk with your
doctor before taking Cymbalta if you have serious liver or kidney problems, glaucoma or consume large quantities of alcohol.
Women who are pregnant should talk with their doctor before taking Cymbalta. Nursing while taking Cymbalta is not
recommended.
In the fibromyalgia study of Cymbalta, the most common side effects were nausea, dry mouth, constipation, decreased appetite
and anorexia. In clinical studies of Cymbalta for depression, the most common side effects were nausea, dry mouth,
constipation, decreased appetite, fatigue, sleepiness, and increased sweating. Cymbalta is also approved for the management
of neuropathic pain associated with diabetic peripheral neuropathy. In clinical studies of Cymbalta in these patients, the
most common side effects were nausea, sleepiness, dizziness, constipation, dry mouth, increased sweating, decreased appetite,
and muscle weakness. In all clinical trials, most people were not bothered enough by side effects to stop taking Cymbalta.
Your doctor may periodically check your blood pressure. Don't stop taking Cymbalta without talking to your doctor.
For full patient information, visit Cymbalta.
About Lilly
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class
pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with
eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and
information - for some of the world's most urgent medical needs. Additional information about Lilly is available at lilly.
This press release contains forward-looking statements about the potential of Cymbalta for the treatment of fibromyalgia and
reflects Lilly's current beliefs. However, as with any pharmaceutical product under development, there are substantial risks
and uncertainties in the process of development and regulatory review. There is no guarantee that the company will apply for
or receive regulatory approval for this indication. There is also no guarantee that the product with be commercially
successful. For further discussion of these and other risks and uncertainties, see Lilly's filings with the United States
Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.
1. American College of Rheumatology. Fibromyalgia Fact Sheet. Available at: rheumatology/public/factsheets/fibromya.asp. Accessed October 4, 2004.
View drug information on Cymbalta; Prozac Weekly; Zyprexa.
Elderly Depression And Dementia
When senior citizens become depressed, agitated, or show signs of dementia, it is often difficult to know what the best ways to keep them healthy and happy are. Before you consider long-term care as a solution, there are things you can do to keep your loved ones in their homes.
According to the American Association for Geriatric Psychiatry (AAGP), nearly 20 percent of those who are 55 years and older have mental disorders that are not part of normal aging. Some of the most common illnesses are anxiety, severe cognitive impairment and mood disorders.
Jeffery Lafferman, M.D., a psychiatrist at Levindale Hebrew Geriatric Center and Hospital's Partial Hospitalization Program and Outpatient Services, says that too often mental health illnesses are underreported. "As people age, their health needs become more complicated. Medical problems, such as high blood pressure and arthritis, are common and can mask the emotional challenges that the elderly face, until it has reached a critical stage."
But there is help and hope available. One of the ways to keep an elderly loved one at home for as long as possible when they are experiencing depression, dementia, agitation and other emotional challenges is through day treatment programs.
"Some adult day services programs are specifically designed to help elders relearn how to again be a useful part of their communities. The programs have group and individual therapy sessions in a stimulating environment. In addition, participants can reminisce with people their own age, take part in activities designed to renew their enthusiasm for life and be in their own homes in the evening," says Dr. Lafferman.
Many people do not understand that clinical depression and other mental illnesses are treatable. Some of the symptoms to look for are a change in personality, a decline in memory, isolation from friends and family, excessive feelings of guilt or hopelessness, frequent crying, sleep problems, unexplained physical illnesses, loss of function, changes in appetite, loss of interest in personal hygiene and irritability, and anxiety.
However, Dr. Lafferman advises, "Before you entrust your loved one to any program, try to visit to see with your own eyes what the program is like. Although your elder loved one needs supervision, his or her dignity must be preserved. In addition, check to see if there are medical professionals on site, and if there are different therapies to engage them."
When a loved one is experiencing emotional issues, it can also affect the whole family, so giving caregivers a break during the day is also important.
According to the American Association for Geriatric Psychiatry (AAGP), nearly 20 percent of those who are 55 years and older have mental disorders that are not part of normal aging. Some of the most common illnesses are anxiety, severe cognitive impairment and mood disorders.
Jeffery Lafferman, M.D., a psychiatrist at Levindale Hebrew Geriatric Center and Hospital's Partial Hospitalization Program and Outpatient Services, says that too often mental health illnesses are underreported. "As people age, their health needs become more complicated. Medical problems, such as high blood pressure and arthritis, are common and can mask the emotional challenges that the elderly face, until it has reached a critical stage."
But there is help and hope available. One of the ways to keep an elderly loved one at home for as long as possible when they are experiencing depression, dementia, agitation and other emotional challenges is through day treatment programs.
"Some adult day services programs are specifically designed to help elders relearn how to again be a useful part of their communities. The programs have group and individual therapy sessions in a stimulating environment. In addition, participants can reminisce with people their own age, take part in activities designed to renew their enthusiasm for life and be in their own homes in the evening," says Dr. Lafferman.
Many people do not understand that clinical depression and other mental illnesses are treatable. Some of the symptoms to look for are a change in personality, a decline in memory, isolation from friends and family, excessive feelings of guilt or hopelessness, frequent crying, sleep problems, unexplained physical illnesses, loss of function, changes in appetite, loss of interest in personal hygiene and irritability, and anxiety.
However, Dr. Lafferman advises, "Before you entrust your loved one to any program, try to visit to see with your own eyes what the program is like. Although your elder loved one needs supervision, his or her dignity must be preserved. In addition, check to see if there are medical professionals on site, and if there are different therapies to engage them."
When a loved one is experiencing emotional issues, it can also affect the whole family, so giving caregivers a break during the day is also important.
A New Approach To Exploring The Genetics Of Suicidal Behaviour
"A deeper understanding of the biology of suicidal behavior may facilitate the development of new pharmacological interventions that could be targeted at vulnerable individuals, potentially saving thousands of lives," say Jonathan Savitz and colleagues from the University of Cape Town. Identifying the genes that contribute to the risk for suicidal behavior is an integral part of this process, say the authors.
While "tantalizing genetic clues" are beginning to emerge on the genetics of suicide, they say, research on this topic has been hindered by problems such as the difficulty in replicating data. They outline a new approach to exploring the genetics of suicidal behavior--"endophenotyping."
Endophenotyping involves trying to identify an intermediate trait that lies somewhere on the developmental pathway from genes to phenotype. If suicide is the phenotype of interest--the final product of different genetic and environmental factors--then the "endophenotype" is a more elementary trait that is tightly correlated with suicide. "An understanding of the molecular basis of the endophenotype," say Savitz and colleagues, "should theoretically be the first step towards the larger prize: uncovering the molecular basis of the phenotype itself." The authors discuss the possibility that personality traits could be an endophenotype for investigating the genetic basis of suicidal behavior.
Citation: Savitz JB, Cupido C-L, Ramesar RS (2006) Trends in suicidology: Personality as an endophenotype for molecular genetic investigations. PLoS Med 3(5): e107.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: dx.doi/10.1371/journal.pmed.0030107
CONTACT:
Jonathan Savitz
University of Cape Town
Institute of Infectious Disease and Molecular Medicine
UCT/MRC Human Genetics Research Unit
Observatory 7925
Cape Town, South Africa
jscormack.uct.ac.za
PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS MEDICINE (plosmedicine/) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY-AVAILABLE TEXT. THANK YOU.
All works published in PLoS Medicine are open access. Everything is immediately available without cost to anyone, anywhere--to read, download, redistribute, include in databases, and otherwise use--subject only to the condition that the original authorship is properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
About PLoS Medicine
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit plosmedicine/
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit plos/
Contact: Andrew Hyde
Public Library of Science
While "tantalizing genetic clues" are beginning to emerge on the genetics of suicide, they say, research on this topic has been hindered by problems such as the difficulty in replicating data. They outline a new approach to exploring the genetics of suicidal behavior--"endophenotyping."
Endophenotyping involves trying to identify an intermediate trait that lies somewhere on the developmental pathway from genes to phenotype. If suicide is the phenotype of interest--the final product of different genetic and environmental factors--then the "endophenotype" is a more elementary trait that is tightly correlated with suicide. "An understanding of the molecular basis of the endophenotype," say Savitz and colleagues, "should theoretically be the first step towards the larger prize: uncovering the molecular basis of the phenotype itself." The authors discuss the possibility that personality traits could be an endophenotype for investigating the genetic basis of suicidal behavior.
Citation: Savitz JB, Cupido C-L, Ramesar RS (2006) Trends in suicidology: Personality as an endophenotype for molecular genetic investigations. PLoS Med 3(5): e107.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: dx.doi/10.1371/journal.pmed.0030107
CONTACT:
Jonathan Savitz
University of Cape Town
Institute of Infectious Disease and Molecular Medicine
UCT/MRC Human Genetics Research Unit
Observatory 7925
Cape Town, South Africa
jscormack.uct.ac.za
PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS MEDICINE (plosmedicine/) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY-AVAILABLE TEXT. THANK YOU.
All works published in PLoS Medicine are open access. Everything is immediately available without cost to anyone, anywhere--to read, download, redistribute, include in databases, and otherwise use--subject only to the condition that the original authorship is properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
About PLoS Medicine
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit plosmedicine/
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit plos/
Contact: Andrew Hyde
Public Library of Science
Pregnant Women, Those Planning Pregnancy Should Avoid Taking Antidepressant Paxil, ACOG Opinion Says
Pregnant women or those who are planning for pregnancy should avoid taking GlaxoSmithKline's antidepressant Paxil because it can increase the risk of birth defects, according to an opinion published by an American College of Obstetricians and Gynecologists committee in the December issue of ACOG's journal Obstetrics & Gynecology, the AP/Seattle Post-Intelligencer reports (AP/Seattle Post-Intelligencer, 11/30). ACOG's Committee on Obstetric Practice's opinion recommends that women who were exposed to Paxil in early pregnancy should consider having a fetal echocardiography, which detects heart trouble HealthDay News/Forbes reports (HealthDay News/Forbes, 11/29). FDA in December 2005 issued a public health advisory warning pregnant women and physicians about an increased risk of fetal heart defects from taking Paxil -- known generically as paroxetine -- during the first three months of pregnancy. The warning moved Paxil to Category D, FDA's second-highest category for risk of birth defects. According to FDA, Category D means that either "controlled or observational" studies of pregnant women "have demonstrated a risk to the fetus." The advisory was based on previous studies that questioned the safety of using Paxil during pregnancy. One study found an increased risk of an infant experiencing a potentially fatal lung disorder if the woman takes a group of antidepressants called selective serotonin reuptake inhibitors during pregnancy, and two other studies found that use of Paxil during pregnancy could cause cardiac fetal heart defects. Before the advisory, Paxil had been classified as a Category C drug for pregnant women, which means comprehensive studies of its effects during pregnancy have not been performed (Kaiser Daily Women's Health Policy Report, 12/9/05).
ACOG Committee Opinion
ACOG's Committee on Obstetric Practice's opinion also recommends physicians make decisions on treating pregnant women with other SSRIs -- such as Pfizer's Zoloft, Eli Lilly's Prozac and Forest Pharmaceuticals' Lexapro -- on an individual basis (AP/Seattle Post-Intelligencer, 11/30). The opinion says the committee "recommends that treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible." ACOG also acknowledged another study that found pregnant women who stopped taking their antidepressant regimen were five times more likely to relapse into depression than women who continued their medication, HealthDay News/Forbes reports. "Untreated depression has its own risks, including low weight gain, alcohol and substance abuse, and sexually transmitted diseases, all of which have negative maternal and fetal health implications," the opinion says. ACOG estimates that about one in 10 women of reproductive age will experience a period of major or minor depression sometime during or after pregnancy or the postpartum period (HealthDay News/Forbes, 11/29).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
View drug information on Lexapro; Paxil CR; Prozac Weekly.
Alaska Northern Lights Offers Bright Light Therapy To Combat Common Health Problems
Alaska Northern Lights manufactures a bright light therapy box that aids in treating chronic health problems such as seasonal affective disorder (SAD), depression, bipolar disorder and sleep problems. Sufferers of SAD, a form of clinical depression, include up to 25 percent of those living in northern latitudes who experience varying degrees of SAD during winter months when there is less natural light. Night shift workers are also susceptible to SAD which affects over one third of the population, or about 10.8 million Americans.
"Our bright light box treatment affects the pineal gland's production of melatonin, a hormone that is believed to help prevent and relieve symptoms of depression," says Alaska Northern Lights President Cort Christie. "We find that our bright light box treatment, prescribed by physicians for SAD, also works extremely well for insomnia and other health problems." Christie says that daily use can reduce time lost from work and reduced productivity.
"Many people subscribe to 'I'll just deal with it' thinking when it comes to SAD, depression or insomnia," said Christie. "But these illnesses may lead to more serious health problems and put a tremendous strain on relationships." The bright light therapy box is a healthy and inexpensive alternative to prescription drugs which can make users groggy and lead to bizarre side effects such as sleep eating and sleep driving. We believe that people should try a safe, non-prescription treatment first to alleviate problems."
Source
Alaska Northern Lights
"Our bright light box treatment affects the pineal gland's production of melatonin, a hormone that is believed to help prevent and relieve symptoms of depression," says Alaska Northern Lights President Cort Christie. "We find that our bright light box treatment, prescribed by physicians for SAD, also works extremely well for insomnia and other health problems." Christie says that daily use can reduce time lost from work and reduced productivity.
"Many people subscribe to 'I'll just deal with it' thinking when it comes to SAD, depression or insomnia," said Christie. "But these illnesses may lead to more serious health problems and put a tremendous strain on relationships." The bright light therapy box is a healthy and inexpensive alternative to prescription drugs which can make users groggy and lead to bizarre side effects such as sleep eating and sleep driving. We believe that people should try a safe, non-prescription treatment first to alleviate problems."
Source
Alaska Northern Lights
ADHD In Children Linked To Depression And Higher Suicide Risk During Teens
Children who are diagnosed with ADHD (attention-deficit/hyperactivity disorder) have a higher chance of developing depression and/or attempting suicide during their teenage years, or 5 to 13 years after being diagnosed, say researchers in a new article published in Archives of General Psychiatry. A person with ADHD finds it much harder to focus on something without being distracted. They have greater difficulty in controlling what they are doing or saying and are less able to control how much physical activity is appropriate for a particular situation compared to somebody without ADHD. A person with ADHD is much more impetuous and agitated.
The researchers explain that between 16% and 37% of adults diagnosed with ADHD also suffer from dysthymia (a mild form of depression) and/or major depressive disorder.
The authors add:
When major depressive disorder occurs concurrently with ADHD, major depressive disorder has an earlier age of onset, has a longer duration and results in greater impairment.
Andrea Chronis-Tuscano, Ph.D., the University of Maryland, College Park, and team assessed 125 children who met the diagnosed criteria for ADHD; they were aged from 4 to 6 years. They also studied 123 children without ADHD in the Chicago and Pittsburgh areas. All children were demographically matched. Their aim was to find out whether young children who were diagnosed with ADHD had a higher chance or developing depression or attempting suicide during their teen years.
Follow-up sessions took place in both groups until the children were 18 years old.
The writers report that it does appear that a child who is diagnosed with ADHD at the age of 4 to 6 years has a higher risk of developing depression between the ages of 9 and 18. Seventeen of the 248 children said they had had a specific suicide plan at least once between the ages of 8 and 18.
They also found that 18.4% of the children who had been diagnosed with ADHD made at least one attempt at suicide by the age of 14, compared to 5.7% in the control group.
The authors wrote:
Our findings indicate that young children with ADHD are at high risk for both single and recurrent episodes of adolescent depression and for suicidal behavior, even controlling for a history of major depression in their mothers and other demographic and methodologic predictors of these outcomes.
If the mother had depression and the child had emotional/behavioral problems at the ages of 4 to 6 years, the risk of suicidal behaviors and behaviors for that child later on appeared to be greater. The investigators report that the risk is even larger for girls.
They researchers broke down ADHD into three subtypes, and found that each one predicted different outcomes:
Inattentiveness - the greater risk later on appeared to be only depression
Hyperactivity - the greater risk later on appeared to be only suicide attempts
Both inattentiveness and hyperactivity - the greater risk appeared to be for both depression and attempted suicide later on
The authors concluded:
These findings suggest that it is possible to identify children with ADHD at very young ages who are at very high risk for later depression and suicidal behavior. Considered in light of what is already known about the antisocial outcomes of childhood ADHD and their risk for unintentional injury, it would not be premature to test early prevention programs designed to reduce both serious behavioral and affective sequelae of ADHD in early childhood.
"Very Early Predictors of Adolescent Depression and Suicide Attempts in Children With Attention-Deficit/Hyperactivity Disorder"
Andrea Chronis-Tuscano, PhD; Brooke S. G. Molina, PhD; William E. Pelham, PhD; Brooks Applegate, PhD; Allison Dahlke, BA; Meghan Overmyer, AM; Benjamin B. Lahey, PhD
Arch Gen Psychiatry. 2010;67(10):1044-1051. doi:10.1001/archgenpsychiatry.2010.127
The researchers explain that between 16% and 37% of adults diagnosed with ADHD also suffer from dysthymia (a mild form of depression) and/or major depressive disorder.
The authors add:
When major depressive disorder occurs concurrently with ADHD, major depressive disorder has an earlier age of onset, has a longer duration and results in greater impairment.
Andrea Chronis-Tuscano, Ph.D., the University of Maryland, College Park, and team assessed 125 children who met the diagnosed criteria for ADHD; they were aged from 4 to 6 years. They also studied 123 children without ADHD in the Chicago and Pittsburgh areas. All children were demographically matched. Their aim was to find out whether young children who were diagnosed with ADHD had a higher chance or developing depression or attempting suicide during their teen years.
Follow-up sessions took place in both groups until the children were 18 years old.
The writers report that it does appear that a child who is diagnosed with ADHD at the age of 4 to 6 years has a higher risk of developing depression between the ages of 9 and 18. Seventeen of the 248 children said they had had a specific suicide plan at least once between the ages of 8 and 18.
They also found that 18.4% of the children who had been diagnosed with ADHD made at least one attempt at suicide by the age of 14, compared to 5.7% in the control group.
The authors wrote:
Our findings indicate that young children with ADHD are at high risk for both single and recurrent episodes of adolescent depression and for suicidal behavior, even controlling for a history of major depression in their mothers and other demographic and methodologic predictors of these outcomes.
If the mother had depression and the child had emotional/behavioral problems at the ages of 4 to 6 years, the risk of suicidal behaviors and behaviors for that child later on appeared to be greater. The investigators report that the risk is even larger for girls.
They researchers broke down ADHD into three subtypes, and found that each one predicted different outcomes:
Inattentiveness - the greater risk later on appeared to be only depression
Hyperactivity - the greater risk later on appeared to be only suicide attempts
Both inattentiveness and hyperactivity - the greater risk appeared to be for both depression and attempted suicide later on
The authors concluded:
These findings suggest that it is possible to identify children with ADHD at very young ages who are at very high risk for later depression and suicidal behavior. Considered in light of what is already known about the antisocial outcomes of childhood ADHD and their risk for unintentional injury, it would not be premature to test early prevention programs designed to reduce both serious behavioral and affective sequelae of ADHD in early childhood.
"Very Early Predictors of Adolescent Depression and Suicide Attempts in Children With Attention-Deficit/Hyperactivity Disorder"
Andrea Chronis-Tuscano, PhD; Brooke S. G. Molina, PhD; William E. Pelham, PhD; Brooks Applegate, PhD; Allison Dahlke, BA; Meghan Overmyer, AM; Benjamin B. Lahey, PhD
Arch Gen Psychiatry. 2010;67(10):1044-1051. doi:10.1001/archgenpsychiatry.2010.127
Mutant gene linked to treatment-resistant depression
A mutant gene that starves the brain of serotonin, a mood-regulating chemical messenger, has been discovered and found to
be 10 times more prevalent in depressed patients than in control subjects, report researchers funded by the National
Institutes of Health's National Institute of Mental Health (NIMH) and National Heart Lung and Blood Institute (NHLBI).
Patients with the mutation failed to respond well to the most commonly prescribed class of antidepressant medications, which
work via serotonin, suggesting that the mutation may underlie a treatment-resistant subtype of the illness.
The mutant gene codes for the brain enzyme, tryptophan hydroxylase-2, that makes serotonin, and results in 80 percent less of
the neurotransmitter. It was carried by nine of 87 depressed patients, three of 219 healthy controls and none of 60 bipolar
disorder patients. Drs. Marc Caron, Xiaodong Zhang and colleagues at Duke Unversity announced their findings in the January
2005 Neuron, published online in mid-December.
"If confirmed, this discovery could lead to a genetic test for vulnerability to depression and a way to predict which
patients might respond best to serotonin-selective antidepressants," noted NIMH Director Thomas Insel, M.D.
The Duke researchers had previously reported in the July 9, 2004 Science that some mice have a tiny, one-letter variation in
the sequence of their tryptophan hydroxylase gene (Tph2) that results in 50-70 percent less serotonin. This suggested that
such a variant gene might also exist in humans and might be involved in mood and anxiety disorders, which often respond to
serotonin selective reuptake inhibitors (SSRIs) - antidepressants that block the re-absorption of serotonin, enhancing its
availability to neurons.
In the current study, a similar variant culled from human subjects produced 80 percent less serotonin in cell cultures than
the common version of the enzyme. More than 10 percent of the 87 patients with unipolar major depression carried the
mutation, compared to only one percent of the 219 controls. Among the nine SSRI-resistant patient carriers, seven had a
family history of mental illness or substance abuse, six had been suicidal and four had generalized anxiety.
Although they fell short of meeting criteria for major depression, the three control group carriers also had family histories
of psychiatric problems and experienced mild depression and anxiety symptoms. This points up the complexity of these
disorders, say the researchers. For example, major depression is thought to be 40-70 percent heritable, but likely involves
an interaction of several genes with environmental events. Previous studies have linked depression with the same region of
chromosome 12, where the tryptophan hydroxylase-2 gene is located. Whether the absence of the mutation among 60 patients with
bipolar disorder proves to be evidence of a different underlying biology remains to be investigated in future studies.
The researchers say their finding provides a potential molecular mechanism for aberrant serotonin function in
neuropsychiatric disorders.
Also participating in the study were: Raul Gainetdinov, Jean-Marin Beaulieu, Tatyana Sotnikova, Lauranell Burch, Redford
Williams, David Schwartz, and Ranga Krishnan, Duke University.
In addition to grants from NIMH and NHLBI, the study was also funded by the Human Frontiers Science Program and the Canadian
Institute of Health Research.
NIMH and NHLBI are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical
and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
To learn more, visit the following links:
Depression nimh.nih/HealthInformation/Depressionmenu.cfm
Bipolar Disorder nimh.nih/healthinformation/bipolarmenu.cfm
PubMed abstract of July 9, 2004 Science article ncbi.nlm.nih/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247473
Contact: Jules Asher
NIMHpressnih
301-443-4536
NIH/National Institute of Mental Health
be 10 times more prevalent in depressed patients than in control subjects, report researchers funded by the National
Institutes of Health's National Institute of Mental Health (NIMH) and National Heart Lung and Blood Institute (NHLBI).
Patients with the mutation failed to respond well to the most commonly prescribed class of antidepressant medications, which
work via serotonin, suggesting that the mutation may underlie a treatment-resistant subtype of the illness.
The mutant gene codes for the brain enzyme, tryptophan hydroxylase-2, that makes serotonin, and results in 80 percent less of
the neurotransmitter. It was carried by nine of 87 depressed patients, three of 219 healthy controls and none of 60 bipolar
disorder patients. Drs. Marc Caron, Xiaodong Zhang and colleagues at Duke Unversity announced their findings in the January
2005 Neuron, published online in mid-December.
"If confirmed, this discovery could lead to a genetic test for vulnerability to depression and a way to predict which
patients might respond best to serotonin-selective antidepressants," noted NIMH Director Thomas Insel, M.D.
The Duke researchers had previously reported in the July 9, 2004 Science that some mice have a tiny, one-letter variation in
the sequence of their tryptophan hydroxylase gene (Tph2) that results in 50-70 percent less serotonin. This suggested that
such a variant gene might also exist in humans and might be involved in mood and anxiety disorders, which often respond to
serotonin selective reuptake inhibitors (SSRIs) - antidepressants that block the re-absorption of serotonin, enhancing its
availability to neurons.
In the current study, a similar variant culled from human subjects produced 80 percent less serotonin in cell cultures than
the common version of the enzyme. More than 10 percent of the 87 patients with unipolar major depression carried the
mutation, compared to only one percent of the 219 controls. Among the nine SSRI-resistant patient carriers, seven had a
family history of mental illness or substance abuse, six had been suicidal and four had generalized anxiety.
Although they fell short of meeting criteria for major depression, the three control group carriers also had family histories
of psychiatric problems and experienced mild depression and anxiety symptoms. This points up the complexity of these
disorders, say the researchers. For example, major depression is thought to be 40-70 percent heritable, but likely involves
an interaction of several genes with environmental events. Previous studies have linked depression with the same region of
chromosome 12, where the tryptophan hydroxylase-2 gene is located. Whether the absence of the mutation among 60 patients with
bipolar disorder proves to be evidence of a different underlying biology remains to be investigated in future studies.
The researchers say their finding provides a potential molecular mechanism for aberrant serotonin function in
neuropsychiatric disorders.
Also participating in the study were: Raul Gainetdinov, Jean-Marin Beaulieu, Tatyana Sotnikova, Lauranell Burch, Redford
Williams, David Schwartz, and Ranga Krishnan, Duke University.
In addition to grants from NIMH and NHLBI, the study was also funded by the Human Frontiers Science Program and the Canadian
Institute of Health Research.
NIMH and NHLBI are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical
and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
To learn more, visit the following links:
Depression nimh.nih/HealthInformation/Depressionmenu.cfm
Bipolar Disorder nimh.nih/healthinformation/bipolarmenu.cfm
PubMed abstract of July 9, 2004 Science article ncbi.nlm.nih/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247473
Contact: Jules Asher
NIMHpressnih
301-443-4536
NIH/National Institute of Mental Health
Researchers To Study Depression And Disability In Age-Related Macular Degeneration Patients
Researchers at the Farber Institute for Neurosciences at Thomas Jefferson University and the Department of Psychiatry and Human Behavior at Jefferson Medical College of Thomas Jefferson University were recently awarded a $3.7 million grant from The National Eye Institute to study depression in patients diagnosed with age-related macular degeneration (AMD). Barry W. Rovner, M.D., director of Clinical Alzheimer's Disease Research at the Farber Institute for Neurosciences and professor of Psychiatry and Neurology at Jefferson Medical College; and Robin Casten, Ph.D., associate professor of Psychiatry and Human Behavior at Jefferson Medical College, will lead the single site study of 200 AMD patients, who will be followed for 12 months, to determine the effectiveness of a treatment program designed to prevent depression and disability in these patients.
AMD is the leading cause of vision loss in Americans 60 years of age and older. It gradually destroys sharp, central vision, which is needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD affects the macula, the part of the eye that allows you to see fine detail. In some cases, the disease advances so slowly that people notice little change in their vision. In others, it progresses faster and may lead to a loss of vision in both eyes.
"Vision loss in the elderly is a major risk factor for depression. The disease robs older persons of their ability to perform everyday activities and limits their independence," said Dr. Rovner. "The loss of these abilities and having to give up valued activities can lead to depression. We want to find ways to improve the vision skills of people with AMD and thereby prevent depression."
The Low Vision Depression Prevention Trial will test a combined treatment to prevent depression and disability associated with AMD. It will test the efficacy of a low vision rehabilitation and psychological intervention program designed to treat/prevent depression in patients diagnosed with the disease by helping them maintain their independence and participation in enjoyable activities. The study consists of two low vision optometry visits, in which specially trained optometrists will evaluate visual function and develop a rehabilitative plan; and six in-home occupational therapy visits where low-vision occupational therapists will teach compensatory strategies to improve visual ability and administer a behavioral treatment to activate subjects and enable them to remain engaged in valued activities.
"Vision loss in the elderly is extremely distressing, significantly impacts quality of life, and is a risk factor for nursing home placement," said Dr. Casten. "Finding ways to help these patients maintain their independence and engagement with life is key to promoting successful aging."
AMD is the leading cause of vision loss in Americans 60 years of age and older. It gradually destroys sharp, central vision, which is needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD affects the macula, the part of the eye that allows you to see fine detail. In some cases, the disease advances so slowly that people notice little change in their vision. In others, it progresses faster and may lead to a loss of vision in both eyes.
"Vision loss in the elderly is a major risk factor for depression. The disease robs older persons of their ability to perform everyday activities and limits their independence," said Dr. Rovner. "The loss of these abilities and having to give up valued activities can lead to depression. We want to find ways to improve the vision skills of people with AMD and thereby prevent depression."
The Low Vision Depression Prevention Trial will test a combined treatment to prevent depression and disability associated with AMD. It will test the efficacy of a low vision rehabilitation and psychological intervention program designed to treat/prevent depression in patients diagnosed with the disease by helping them maintain their independence and participation in enjoyable activities. The study consists of two low vision optometry visits, in which specially trained optometrists will evaluate visual function and develop a rehabilitative plan; and six in-home occupational therapy visits where low-vision occupational therapists will teach compensatory strategies to improve visual ability and administer a behavioral treatment to activate subjects and enable them to remain engaged in valued activities.
"Vision loss in the elderly is extremely distressing, significantly impacts quality of life, and is a risk factor for nursing home placement," said Dr. Casten. "Finding ways to help these patients maintain their independence and engagement with life is key to promoting successful aging."
Health Visitors Can Prevent Postnatal Depression Says Pioneering New Study
The world's first ever analysis of data from a full scale clinical trial in adults shows that training Health Visitors to assess and psychologically support mothers after childbirth can prevent the development of depression over the following year.
But the substantial reduction in the number of NHS health visitors was identified by researchers as a key issue for the health and well-being of mums.
The prevention study was led at the University of Leicester by Professor Terry Brugha with researchers from the universities of Nottingham and Sheffield. It is being published in the Cambridge University Press journal Psychological Medicine.
While small scale studies have been carried out into the prevention of depression among adults, this peer refereed scientific report is the first sufficiently large scale randomised trial to clearly show a statistically significant reduction in future cases of depression in women living in the community who were not depressed when they joined the study.
Intervention women, who had a Health Visitor with additional mental health training, were 30% less likely to have developed depression six months after child birth compared to control women receiving usual care.
The results suggest that these improvements continued throughout the eighteen month follow-up. Even women who had few or no complaints of depression at six weeks following child birth appeared to benefit later if their Health Visitor had additional training.
If the Health Visitor with additional training discussed the results of depression screening with the mother at six weeks it appears there was even more benefit and less risk of developing later depression.
There was evidence that the training programme was also cost effective even when the cost of extra training was taken into account. Health visitors with the new training were found to spend less general time with mothers but more time with those who needed emotional support.
In discussing the findings the investigators considered that the quality of the ongoing relationship between the Health Visitor and mother, which can continue until the child starts to attend school, may have provided the mother with a reliable confidant she knew she could turn to later if necessary. It may also have helped to know that she would not have to discuss emotional concerns with a different person such as her doctor or a psychologist and that access to help would be easy and non stigmatizing.
The investigators were successful in obtaining further funding to undertake similar research in Leicestershire and Northamptonshire but were unable to do so because of the critical reduction in the number of Health Visitor Staff available. Health Visitors told them that they wanted to receive such training and to support such research but they were struggling to provide a minimum of one home visit for each new childbirth.
Depression is thought to affect about one in ten women following child birth, depending on the definition and method used to assess depression. The consequences for the child and family are even more profound and concerning than when depression affects adults at other times.
The World Health Organisation has predicted that depression will be a leading cause of disability due to ill health by the year 2020. Although depression can be treated effectively with medication and psychological approaches there is no evidence that rates of depression have fallen since these treatments became available. It is also often the case that once treatment is stopped the condition can relapse.
The prevention study involved analysing data already collected as part of the PoNDER clinical trial originally designed to test the effectiveness of health visitors identifying and managing postnatal depression following child birth. Dr Jane Morrell, now at the University of Nottingham, was Principal Investigator for the PoNDER trial with a team of researchers at the Universities of Sheffield (Jane Morrell, Pauline Slade, Stephen Walters), Leicester and Leeds, with funding from the NIHR Health Technology Assessment programme , London.
While the PoNDER treatment trial was published in the BMJ in 2009, the research into prevention of depression required additional collaborative analysis by the authors of this new scientific paper which is now published separately in the Cambridge University Press journal Psychological Medicine.
Notes:
"Universal prevention of depression in women postnatally: cluster randomized trial evidence in primary care", appears in the journal Psychological Medicine (2010) Vol 40. Cambridge University Press, doi:10.1017/S0033291710001467 at (dx.doi/10.1017/S0033291710001467)
But the substantial reduction in the number of NHS health visitors was identified by researchers as a key issue for the health and well-being of mums.
The prevention study was led at the University of Leicester by Professor Terry Brugha with researchers from the universities of Nottingham and Sheffield. It is being published in the Cambridge University Press journal Psychological Medicine.
While small scale studies have been carried out into the prevention of depression among adults, this peer refereed scientific report is the first sufficiently large scale randomised trial to clearly show a statistically significant reduction in future cases of depression in women living in the community who were not depressed when they joined the study.
Intervention women, who had a Health Visitor with additional mental health training, were 30% less likely to have developed depression six months after child birth compared to control women receiving usual care.
The results suggest that these improvements continued throughout the eighteen month follow-up. Even women who had few or no complaints of depression at six weeks following child birth appeared to benefit later if their Health Visitor had additional training.
If the Health Visitor with additional training discussed the results of depression screening with the mother at six weeks it appears there was even more benefit and less risk of developing later depression.
There was evidence that the training programme was also cost effective even when the cost of extra training was taken into account. Health visitors with the new training were found to spend less general time with mothers but more time with those who needed emotional support.
In discussing the findings the investigators considered that the quality of the ongoing relationship between the Health Visitor and mother, which can continue until the child starts to attend school, may have provided the mother with a reliable confidant she knew she could turn to later if necessary. It may also have helped to know that she would not have to discuss emotional concerns with a different person such as her doctor or a psychologist and that access to help would be easy and non stigmatizing.
The investigators were successful in obtaining further funding to undertake similar research in Leicestershire and Northamptonshire but were unable to do so because of the critical reduction in the number of Health Visitor Staff available. Health Visitors told them that they wanted to receive such training and to support such research but they were struggling to provide a minimum of one home visit for each new childbirth.
Depression is thought to affect about one in ten women following child birth, depending on the definition and method used to assess depression. The consequences for the child and family are even more profound and concerning than when depression affects adults at other times.
The World Health Organisation has predicted that depression will be a leading cause of disability due to ill health by the year 2020. Although depression can be treated effectively with medication and psychological approaches there is no evidence that rates of depression have fallen since these treatments became available. It is also often the case that once treatment is stopped the condition can relapse.
The prevention study involved analysing data already collected as part of the PoNDER clinical trial originally designed to test the effectiveness of health visitors identifying and managing postnatal depression following child birth. Dr Jane Morrell, now at the University of Nottingham, was Principal Investigator for the PoNDER trial with a team of researchers at the Universities of Sheffield (Jane Morrell, Pauline Slade, Stephen Walters), Leicester and Leeds, with funding from the NIHR Health Technology Assessment programme , London.
While the PoNDER treatment trial was published in the BMJ in 2009, the research into prevention of depression required additional collaborative analysis by the authors of this new scientific paper which is now published separately in the Cambridge University Press journal Psychological Medicine.
Notes:
"Universal prevention of depression in women postnatally: cluster randomized trial evidence in primary care", appears in the journal Psychological Medicine (2010) Vol 40. Cambridge University Press, doi:10.1017/S0033291710001467 at (dx.doi/10.1017/S0033291710001467)
Higher Risk Of Depression For Diabetic Women During And After Pregnancy
A study in the February 25 issue of JAMA reveals that low- income diabetic women who are pregnant or new mothers, have almost double the risk of suffering from depression during and after pregnancy, than women without diabetes.
In the perinatal period, usually known as the last few months of pregnancy and the year following childbirth, at least 10 to 12 percent of new mothers are affected by depression, according to the article, and about 2 to 9 percent of pregnancies are complicated by diabetes. A connection between depressive disorders and diabetes in general adult populations has been confirmed in previous research.
The link between depression in the perinatal period among low-income women and diabetes was analyzed by Katy Backes Kozhimannil, M.P.A., Harvard Medical School and Harvard Pilgrim Health Care, Boston, and team. Information from New Jersey??s Medicaid administrative claims database was used by the researchers. The study examined 11,024 women enrolled in Medicaid six months prior and one year after delivery. The births occurred between July 2004 and September 2006.
Women suffering from any type of diabetes were considerably more inclined to show signs of depression during pregnancy or postpartum, according to the researchers. Following an analysis on the effects of age, race, year of delivery, and preterm birth, it appears that the probability of having a depression diagnosis doubles for women with diabetes. The prescribing of an antidepressant drug during the perinatal period was of 15.2 percent for women with diabetes compared to 8.5 percent for women with no signs of diabetes. For all forms of diabetes, this connection persisted.
For women with diabetes who had no signs of depression during pregnancy, the probability of suffering from new episodes of a depressive disorder was increased (9.6 percent) compared with those without diabetes (5.9 percent).
The authors write "Pregnancy and the postpartum period represent a time of increased vulnerability to depression. Treatable, perinatal depression is underdiagnosed, and it is important to target detection and support efforts toward women at high risk."
".. studies designed to test the impact of interventions that target those most vulnerable to depression during the perinatal period could provide helpful input to policy making. Among all women with depression, diabetes, or other mental or physical health conditions that complicate the normal course of pregnancy and postpartum recovery, careful monitoring and appropriate treatment are critical to ensuring the health of the mother and her child."
JAMA. 2009;301[8]:842-847.
jama.ama-assn
Written by Stephanie Brunner (B.A.)
In the perinatal period, usually known as the last few months of pregnancy and the year following childbirth, at least 10 to 12 percent of new mothers are affected by depression, according to the article, and about 2 to 9 percent of pregnancies are complicated by diabetes. A connection between depressive disorders and diabetes in general adult populations has been confirmed in previous research.
The link between depression in the perinatal period among low-income women and diabetes was analyzed by Katy Backes Kozhimannil, M.P.A., Harvard Medical School and Harvard Pilgrim Health Care, Boston, and team. Information from New Jersey??s Medicaid administrative claims database was used by the researchers. The study examined 11,024 women enrolled in Medicaid six months prior and one year after delivery. The births occurred between July 2004 and September 2006.
Women suffering from any type of diabetes were considerably more inclined to show signs of depression during pregnancy or postpartum, according to the researchers. Following an analysis on the effects of age, race, year of delivery, and preterm birth, it appears that the probability of having a depression diagnosis doubles for women with diabetes. The prescribing of an antidepressant drug during the perinatal period was of 15.2 percent for women with diabetes compared to 8.5 percent for women with no signs of diabetes. For all forms of diabetes, this connection persisted.
For women with diabetes who had no signs of depression during pregnancy, the probability of suffering from new episodes of a depressive disorder was increased (9.6 percent) compared with those without diabetes (5.9 percent).
The authors write "Pregnancy and the postpartum period represent a time of increased vulnerability to depression. Treatable, perinatal depression is underdiagnosed, and it is important to target detection and support efforts toward women at high risk."
".. studies designed to test the impact of interventions that target those most vulnerable to depression during the perinatal period could provide helpful input to policy making. Among all women with depression, diabetes, or other mental or physical health conditions that complicate the normal course of pregnancy and postpartum recovery, careful monitoring and appropriate treatment are critical to ensuring the health of the mother and her child."
JAMA. 2009;301[8]:842-847.
jama.ama-assn
Written by Stephanie Brunner (B.A.)
A Blood Test For Depression?
Blood tests have been extremely important tools aiding doctors in making medical diagnoses and in guiding the treatment of many diseases. However, psychiatry is one area of medicine where there are few diagnostic blood tests.
New scientific fields may someday generate blood tests that can be used for these purposes. Some of the areas under increasingly intensive study are genetics, the study of variations in the genes (DNA) that can be extracted from blood cells, and genomics like proteomics, the measurement of the levels of specific proteins in the blood, and gene expression profiling, which measures the levels of RNA produced from DNA as an indication of the level of the "activity" of particular genes.
Using the latter approach, Dutch researchers evaluated blood gene expression profiles in healthy individuals and patients diagnosed with major depressive disorder, or MDD. They identified a set of seven genes in whole blood that was able to distinguish un-medicated MDD patients from healthy controls.
"This is a first, but major step in providing a molecular diagnostic tool for depression," explained Dr. Sabine Spijker, corresponding author of this study. Although psychiatry already has specific criteria for diagnosing mental health disorders, this type of diagnosis would be unbiased and particularly valuable for those with whom it is more difficult to have a conversation. It may also eventually assist in reducing the stigma associated with mental health problems.
"It is far too early to be confident that gene expression profiling will lead us to diagnostic or prognostic tests for depression. However, the objective of this line of research is extremely important," cautions Dr. John Krystal, Editor of Biological Psychiatry. "In the past, many types of tests have been explored as potential diagnostic markers, but they all have failed to have sufficient sensitivity and specificity to guide doctors in making psychiatric diagnoses or choosing between treatments. I look forward to seeing whether the patterns of gene expression profiling are replicable and diagnostically specific as multiple groups report their findings."
Most importantly, the authors hope that this study is a stepping stone for finding markers that might predict treatment outcome and recurrence.
New scientific fields may someday generate blood tests that can be used for these purposes. Some of the areas under increasingly intensive study are genetics, the study of variations in the genes (DNA) that can be extracted from blood cells, and genomics like proteomics, the measurement of the levels of specific proteins in the blood, and gene expression profiling, which measures the levels of RNA produced from DNA as an indication of the level of the "activity" of particular genes.
Using the latter approach, Dutch researchers evaluated blood gene expression profiles in healthy individuals and patients diagnosed with major depressive disorder, or MDD. They identified a set of seven genes in whole blood that was able to distinguish un-medicated MDD patients from healthy controls.
"This is a first, but major step in providing a molecular diagnostic tool for depression," explained Dr. Sabine Spijker, corresponding author of this study. Although psychiatry already has specific criteria for diagnosing mental health disorders, this type of diagnosis would be unbiased and particularly valuable for those with whom it is more difficult to have a conversation. It may also eventually assist in reducing the stigma associated with mental health problems.
"It is far too early to be confident that gene expression profiling will lead us to diagnostic or prognostic tests for depression. However, the objective of this line of research is extremely important," cautions Dr. John Krystal, Editor of Biological Psychiatry. "In the past, many types of tests have been explored as potential diagnostic markers, but they all have failed to have sufficient sensitivity and specificity to guide doctors in making psychiatric diagnoses or choosing between treatments. I look forward to seeing whether the patterns of gene expression profiling are replicable and diagnostically specific as multiple groups report their findings."
Most importantly, the authors hope that this study is a stepping stone for finding markers that might predict treatment outcome and recurrence.
In New Study, Duloxetine Was Equally Effective, Regardless Of Switch Method, In Reducing Painful Symptoms In SSRI
The antidepressant duloxetine hydrochloride was equally effective in reducing painful symptoms in depressed patients who did not respond, or responded only partially, to treatment with a selective serotonin reuptake inhibitor (SSRI), regardless of whether those patients were switched from an SSRI abruptly or gradually.1 This new data was presented today at the American Psychiatric Association??s 160th Annual Meeting in San Diego, Calif.
Between 30-50 percent of individuals treated with a given antidepressant do not respond to that treatment.2,3 As a result, physicians often need to switch patients from one antidepressant to another. Although this is a common clinical scenario, there are relatively few published studies to guide physicians on how to switch patients from one antidepressant to another.
Recent data suggests the more antidepressants an individual has tried, the less likely they are to benefit from a new antidepressant.4 Therefore it is important to maximise the chance of remission earlier in the treatment pathway, said Prof. Angel L. Montejo, Psychiatry Research Coordinator, University Hospital of Salamanca, Spain. These results demonstrate that a switch to duloxetine results in a significant decrease in the painful symptoms in patients with depression and was well tolerated regardless of the switch method used.
The new results are based on several secondary endpoints from a study comparing the efficacy, safety and tolerability of two switch methods in 368 patients who remained depressed despite taking an SSRI for at least six weeks.5 Participants were randomized to either abrupt discontinuation of their SSRI (the Direct Switch, or DS group) or to a gradual/tapered discontinuation of their SSRI (the Start-Taper Switch, or STS group). Both groups began taking duloxetine 60 mg/day at the beginning of the study. The dosage could be increased to a maximum of 120 mg/day based on the investigators discretion.1
The primary data disclosure took place at a major medical conference in December 2006.5 The primary objective of the overall study was to demonstrate the non-inferiority of Direct Switch (DS) compared with Start-taper Switch (STS) based on changes in HAMD17 total scores. Overall, that initial data disclosure showed that switch to duloxetine was associated with significant improvements in the emotional symptoms of depression, and was well tolerated and safe, regardless of which SSRI the patient was taking at study entry.
This new analysis focused on the prevalence and severity of painful symptoms following the switch to duloxetine and in relation to switch method. The study participants, as a group, had average pain scores indicating clinically significant physical pain. Ten weeks after switching to duloxetine, patients made significant improvements on all pain measures evaluated, regardless of which switch method was used.1
Efficacy, safety, and tolerability outcomes following Direct Switch (DS) from SSRI to duloxetine were similar to those observed for Start-taper Switch (STS). The most commonly reported adverse events in the study were headache (13.1 percent for DS vs. 9.7 percent STS), dry mouth (10.4 percent DS vs. 11.9 percent STS), and nausea (8.2 percent DS vs. 8.1 percent STS). No adverse event was reported by significantly more patients in one group compared with the other. An excess of adverse events was not evident following switch from any particular SSRI.1
This study provides some much-needed clinical evidence to help physicians successfully switch patients from one antidepressant to another when they remain depressed,??? Montejo said. ???It also highlights the continued prevalence and severity of painful symptoms among patients who are not adequately responding to SSRI therapy, he said.
Duloxetine, a member of a class of drugs commonly referred to as serotonin and norepinephrine reuptake inhibitors (SNRI)5, is approved in more than 70 countries for the treatment of major depression.
There is a possibility of an increased risk of suicidal thoughts or behaviour in children and young adults treated with antidepressants. Patients should call their doctor right away if they experience worsening depression symptoms, unusual changes in behaviour or thoughts of suicide, especially at the beginning of treatment or after a change in dose.
About the Study1
Methodology
Subjects were outpatients who met criteria for MDD despite having taken an SSRI antidepressant for at least 6 weeks, and who had a Hamilton Depression Rating Scale (HAMD17) total score of ?‰?15 and a Clinical Global Impression of Severity (CGI-S) score of ?‰?3. Eligible patients were randomized to either abrupt discontinuation of their SSRI immediately followed by initiation of duloxetine (Direct Switch) or to tapered discontinuation of their SSRI over 2 weeks and simultaneous administration of duloxetine (Start-taper Switch). Painful physical symptoms were assessed at baseline and at the 10-week study endpoint via a variety of measures including 6 Visual Analogue Scales (VAS) for pain, and the Symptom Questionnaire-Somatic Subscale (SQ-SS).
Results included:1
Clinically significant levels of pain (mean baseline VAS scores >30 mm) were seen across all VAS pain measures prior to switching.
Switch to duloxetine resulted in significant improvements on all pain measures in both treatment groups.
Mean improvements in each of the VAS pain scores, expressed as a percentage of baseline VAS scores for the Direct-Switch and Start-Taper-Switch groups respectively, were:
-- Overall Pain 20.3 percent, 17.9 percent;
-- Headache 25.6 percent, 15.6 percent;
-- Back Pain 18.2 percent, 20.2 percent;
-- Shoulder Pain 17.9 percent, 16.2 percent;
-- Interference with Daily Activities 29.5 percent, 23.2 percent;
-- Time in Pain While Awake 28.8 percent, 26.3 percent.
Efficacy, safety, and tolerability outcomes following direct switch from SSRI to duloxetine were similar to those observed for start-taper switch. Few patients experienced a serious adverse event (5 patients during the 10 weeks of treatment and 1 during the taper period), and there was a low rate of discontinuations due to adverse events (6.6 percent DS vs. 3.8 percent STS).
This was an open-label study, so biases inherent in open-label studies could have been a factor in the observed outcomes. Due to the large number of possible SSRI/dose possibilities for patients entering the study, it was necessary for study investigators to use their clinical judgment to devise an appropriate 2-week down-titration regimen for patients in the STS group. Although general guidance was provided to investigators within the study protocol, the taper was nevertheless not rigidly standardized.
About Duloxetine
While duloxetine??s mechanism of action in humans is not fully known, it is believed to affect both serotonin and norepinephrine/noradrenaline mediated nerve signalling in the brain and the spinal cord. Based on pre-clinical studies, duloxetine is a balanced and potent reuptake inhibitor of serotonin and norepinephrine/noradrenaline. Scientists believe its effect on pain perception is due to increasing the activity of serotonin and norepinephrine in the central nervous system.
Duloxetine is approved for the treatment of depression and diabetic peripheral neuropathic pain in many countries and is approved in some countries for the treatment of stress urinary incontinence. Duloxetine is approved only for adults 18 and over. There is a possibility of an increased risk of suicidal thoughts or behaviour in children and young adults treated with antidepressants. Patients should call their doctor right away if they experience worsening depression symptoms, unusual changes in behaviour or thoughts of suicide, especially at the beginning of treatment or after a change in dose.
Patients taking Cymbalta may experience dizziness or fainting upon standing. The most common side effects of Cymbalta include:
-- For depression: Nausea, dry mouth, headache, insomnia, diarrhea
-- For diabetic peripheral neuropathic pain: Nausea, somnolence (sleepiness), fatigue, headache, dizziness
-- For stress urinary incontinence: Nausea, dry mouth, fatigue
This is not a complete list of side effects.
Duloxetine is contraindicated in patients who are allergic to it, who have liver disease resulting in hepatic impairment, who are taking a monoamine oxidase inhibitor (MAOI), fluvoxamine, ciprofloxacin or enoxacine or who have severe kidney disease. The initiation of treatment with duloxetine also is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis.
About Depression
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide.7 The World Health Organization estimates depression will be among the highest-ranking causes of disability in developed countries by 2020, second only to ischemic heart disease worldwide.8 It can happen to anyone of any age, race or ethnicity; however, women are nearly twice as likely to experience depression as men.9 Although it is one of the most frequently seen psychiatric disorders in the primary care setting,10,11 it often goes undiagnosed or is under-treated.7,12 This might be because depressed people often present with physical symptoms rather than emotional complaints; in one large study, 69 percent of patients with MDD reported only physical symptoms as the reason for visiting their physician.13
Complete elimination of symptoms, or remission, is the primary goal of depression treatment. Treating the full spectrum of emotional and physical symptoms to remission significantly decreases a patient???s risk of relapse.14
Eli Lilly and Company and Boehringer Ingelheim
In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a long-term agreement to jointly develop and commercialize duloxetine hydrochloride. This partnership covers neuroscience indications in most countries outside of the United States and Japan, with few exceptions.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers through medicines and information for some of the world`s most urgent medical needs.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world??s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 137 affiliates in 47 countries and 38,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2006, Boehringer Ingelheim posted net sales of 10.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
Please be advised
This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for all international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.
Duloxetine for depression and diabetic peripheral neuropathic pain is marketed by Lilly and Boehringer Ingelheim in all countries included in the partnership under the brand name Cymbalta, except for Greece, Italy and Spain. In Greece, Italy and Spain Lilly markets the product as Cymbalta and Boehringer Ingelheim markets the product as Xeristar. In the United States, Cymbalta is marketed by Lilly and Quintiles. In Japan, duloxetine will be co-developed and co-marketed by Lilly and Shionogi & Co., Ltd.
Duloxetine for stress urinary incontinence is marketed by Lilly under the brand name Yentreve.
References:
1 Perahia, DGS, Quail, D, Desaiah D, Montejo, A-L. Switch to Duloxetine in SSRI non- and partial-responders: Effects on painful physical symptoms of depression. Presented at the American Psychiatric Association 160th Annual Meeting, San Diego, 23 May 2007
2 Baghai, TC., Moller, HJ, Rupprecht, R. (2006) Recent progress in pharmacological and non-pharmacological treatment options of major depression. Curr Pharm Des. ;12(4):503-15.
3 Ruhe HG, Huyser J, Swinkels JA, Schene AH. (2006) Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. Dec;67(12):1836-55.
4 Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg A, Stewart JW, et al (2006). Acute and Longer-term Outcomes in Depressed Outpatients Who Required One or Several Treatment Steps: A STAR*D Report. Am J of Psych Oct; 163(11):1905-1917
5 Perahia, DGS, Quail, D, Desaiah D, Rasmussen K. Switching to Duloxetine From Other Antidepressants: A Regional Multicenter Trial Comparing Two Switching Techniques. Presented at the American College of Neuropsychopharmacology45th Annual Meeting, Hollywood, FL December 2006
6 Bymaster, FP et al. The Dual Transporter Inhibitor Duloxetine: A Review of its Preclinical Pharmacology, Pharmacokinetic Profile, and Clinical Results in Depression.??? Current Pharmaceutical Design. 2005; 11: 1475-1493.
7 World Health Organization. Factsheet - Depression, 2005. Available at: who.int/mental_health/management/depression/definition/en/. Last visited 26 April 2007
8 Murray CJL, Lopez AD, eds. The Global Burden of Disease; 1996.
9 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision. Washington DC: American Psychiatric Association; 2000:345-428.
10 Ormel J, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA. 1994;272:1741 1748.
11 Spitzer RL, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994;272:1749 1756.
12 Ormel J, Koeter MWJ, van den Brink W, van de Willige G. Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry. 1991;48:700 706.
13 Simon GE et al. An International Study of the Relation Between Somatic Symptoms and Depression. New Engl J Med. 1999;341(18):1329-35.
14 Paykel ES, et al. Psychol Med. 1995;25(6):1171-1180.
1999 - 2007 Boehringer Ingelheim GmbH, Germany. All rights reserved.
View drug information on Cymbalta.
Between 30-50 percent of individuals treated with a given antidepressant do not respond to that treatment.2,3 As a result, physicians often need to switch patients from one antidepressant to another. Although this is a common clinical scenario, there are relatively few published studies to guide physicians on how to switch patients from one antidepressant to another.
Recent data suggests the more antidepressants an individual has tried, the less likely they are to benefit from a new antidepressant.4 Therefore it is important to maximise the chance of remission earlier in the treatment pathway, said Prof. Angel L. Montejo, Psychiatry Research Coordinator, University Hospital of Salamanca, Spain. These results demonstrate that a switch to duloxetine results in a significant decrease in the painful symptoms in patients with depression and was well tolerated regardless of the switch method used.
The new results are based on several secondary endpoints from a study comparing the efficacy, safety and tolerability of two switch methods in 368 patients who remained depressed despite taking an SSRI for at least six weeks.5 Participants were randomized to either abrupt discontinuation of their SSRI (the Direct Switch, or DS group) or to a gradual/tapered discontinuation of their SSRI (the Start-Taper Switch, or STS group). Both groups began taking duloxetine 60 mg/day at the beginning of the study. The dosage could be increased to a maximum of 120 mg/day based on the investigators discretion.1
The primary data disclosure took place at a major medical conference in December 2006.5 The primary objective of the overall study was to demonstrate the non-inferiority of Direct Switch (DS) compared with Start-taper Switch (STS) based on changes in HAMD17 total scores. Overall, that initial data disclosure showed that switch to duloxetine was associated with significant improvements in the emotional symptoms of depression, and was well tolerated and safe, regardless of which SSRI the patient was taking at study entry.
This new analysis focused on the prevalence and severity of painful symptoms following the switch to duloxetine and in relation to switch method. The study participants, as a group, had average pain scores indicating clinically significant physical pain. Ten weeks after switching to duloxetine, patients made significant improvements on all pain measures evaluated, regardless of which switch method was used.1
Efficacy, safety, and tolerability outcomes following Direct Switch (DS) from SSRI to duloxetine were similar to those observed for Start-taper Switch (STS). The most commonly reported adverse events in the study were headache (13.1 percent for DS vs. 9.7 percent STS), dry mouth (10.4 percent DS vs. 11.9 percent STS), and nausea (8.2 percent DS vs. 8.1 percent STS). No adverse event was reported by significantly more patients in one group compared with the other. An excess of adverse events was not evident following switch from any particular SSRI.1
This study provides some much-needed clinical evidence to help physicians successfully switch patients from one antidepressant to another when they remain depressed,??? Montejo said. ???It also highlights the continued prevalence and severity of painful symptoms among patients who are not adequately responding to SSRI therapy, he said.
Duloxetine, a member of a class of drugs commonly referred to as serotonin and norepinephrine reuptake inhibitors (SNRI)5, is approved in more than 70 countries for the treatment of major depression.
There is a possibility of an increased risk of suicidal thoughts or behaviour in children and young adults treated with antidepressants. Patients should call their doctor right away if they experience worsening depression symptoms, unusual changes in behaviour or thoughts of suicide, especially at the beginning of treatment or after a change in dose.
About the Study1
Methodology
Subjects were outpatients who met criteria for MDD despite having taken an SSRI antidepressant for at least 6 weeks, and who had a Hamilton Depression Rating Scale (HAMD17) total score of ?‰?15 and a Clinical Global Impression of Severity (CGI-S) score of ?‰?3. Eligible patients were randomized to either abrupt discontinuation of their SSRI immediately followed by initiation of duloxetine (Direct Switch) or to tapered discontinuation of their SSRI over 2 weeks and simultaneous administration of duloxetine (Start-taper Switch). Painful physical symptoms were assessed at baseline and at the 10-week study endpoint via a variety of measures including 6 Visual Analogue Scales (VAS) for pain, and the Symptom Questionnaire-Somatic Subscale (SQ-SS).
Results included:1
Clinically significant levels of pain (mean baseline VAS scores >30 mm) were seen across all VAS pain measures prior to switching.
Switch to duloxetine resulted in significant improvements on all pain measures in both treatment groups.
Mean improvements in each of the VAS pain scores, expressed as a percentage of baseline VAS scores for the Direct-Switch and Start-Taper-Switch groups respectively, were:
-- Overall Pain 20.3 percent, 17.9 percent;
-- Headache 25.6 percent, 15.6 percent;
-- Back Pain 18.2 percent, 20.2 percent;
-- Shoulder Pain 17.9 percent, 16.2 percent;
-- Interference with Daily Activities 29.5 percent, 23.2 percent;
-- Time in Pain While Awake 28.8 percent, 26.3 percent.
Efficacy, safety, and tolerability outcomes following direct switch from SSRI to duloxetine were similar to those observed for start-taper switch. Few patients experienced a serious adverse event (5 patients during the 10 weeks of treatment and 1 during the taper period), and there was a low rate of discontinuations due to adverse events (6.6 percent DS vs. 3.8 percent STS).
This was an open-label study, so biases inherent in open-label studies could have been a factor in the observed outcomes. Due to the large number of possible SSRI/dose possibilities for patients entering the study, it was necessary for study investigators to use their clinical judgment to devise an appropriate 2-week down-titration regimen for patients in the STS group. Although general guidance was provided to investigators within the study protocol, the taper was nevertheless not rigidly standardized.
About Duloxetine
While duloxetine??s mechanism of action in humans is not fully known, it is believed to affect both serotonin and norepinephrine/noradrenaline mediated nerve signalling in the brain and the spinal cord. Based on pre-clinical studies, duloxetine is a balanced and potent reuptake inhibitor of serotonin and norepinephrine/noradrenaline. Scientists believe its effect on pain perception is due to increasing the activity of serotonin and norepinephrine in the central nervous system.
Duloxetine is approved for the treatment of depression and diabetic peripheral neuropathic pain in many countries and is approved in some countries for the treatment of stress urinary incontinence. Duloxetine is approved only for adults 18 and over. There is a possibility of an increased risk of suicidal thoughts or behaviour in children and young adults treated with antidepressants. Patients should call their doctor right away if they experience worsening depression symptoms, unusual changes in behaviour or thoughts of suicide, especially at the beginning of treatment or after a change in dose.
Patients taking Cymbalta may experience dizziness or fainting upon standing. The most common side effects of Cymbalta include:
-- For depression: Nausea, dry mouth, headache, insomnia, diarrhea
-- For diabetic peripheral neuropathic pain: Nausea, somnolence (sleepiness), fatigue, headache, dizziness
-- For stress urinary incontinence: Nausea, dry mouth, fatigue
This is not a complete list of side effects.
Duloxetine is contraindicated in patients who are allergic to it, who have liver disease resulting in hepatic impairment, who are taking a monoamine oxidase inhibitor (MAOI), fluvoxamine, ciprofloxacin or enoxacine or who have severe kidney disease. The initiation of treatment with duloxetine also is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis.
About Depression
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide.7 The World Health Organization estimates depression will be among the highest-ranking causes of disability in developed countries by 2020, second only to ischemic heart disease worldwide.8 It can happen to anyone of any age, race or ethnicity; however, women are nearly twice as likely to experience depression as men.9 Although it is one of the most frequently seen psychiatric disorders in the primary care setting,10,11 it often goes undiagnosed or is under-treated.7,12 This might be because depressed people often present with physical symptoms rather than emotional complaints; in one large study, 69 percent of patients with MDD reported only physical symptoms as the reason for visiting their physician.13
Complete elimination of symptoms, or remission, is the primary goal of depression treatment. Treating the full spectrum of emotional and physical symptoms to remission significantly decreases a patient???s risk of relapse.14
Eli Lilly and Company and Boehringer Ingelheim
In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a long-term agreement to jointly develop and commercialize duloxetine hydrochloride. This partnership covers neuroscience indications in most countries outside of the United States and Japan, with few exceptions.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers through medicines and information for some of the world`s most urgent medical needs.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world??s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 137 affiliates in 47 countries and 38,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2006, Boehringer Ingelheim posted net sales of 10.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
Please be advised
This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for all international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.
Duloxetine for depression and diabetic peripheral neuropathic pain is marketed by Lilly and Boehringer Ingelheim in all countries included in the partnership under the brand name Cymbalta, except for Greece, Italy and Spain. In Greece, Italy and Spain Lilly markets the product as Cymbalta and Boehringer Ingelheim markets the product as Xeristar. In the United States, Cymbalta is marketed by Lilly and Quintiles. In Japan, duloxetine will be co-developed and co-marketed by Lilly and Shionogi & Co., Ltd.
Duloxetine for stress urinary incontinence is marketed by Lilly under the brand name Yentreve.
References:
1 Perahia, DGS, Quail, D, Desaiah D, Montejo, A-L. Switch to Duloxetine in SSRI non- and partial-responders: Effects on painful physical symptoms of depression. Presented at the American Psychiatric Association 160th Annual Meeting, San Diego, 23 May 2007
2 Baghai, TC., Moller, HJ, Rupprecht, R. (2006) Recent progress in pharmacological and non-pharmacological treatment options of major depression. Curr Pharm Des. ;12(4):503-15.
3 Ruhe HG, Huyser J, Swinkels JA, Schene AH. (2006) Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. Dec;67(12):1836-55.
4 Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg A, Stewart JW, et al (2006). Acute and Longer-term Outcomes in Depressed Outpatients Who Required One or Several Treatment Steps: A STAR*D Report. Am J of Psych Oct; 163(11):1905-1917
5 Perahia, DGS, Quail, D, Desaiah D, Rasmussen K. Switching to Duloxetine From Other Antidepressants: A Regional Multicenter Trial Comparing Two Switching Techniques. Presented at the American College of Neuropsychopharmacology45th Annual Meeting, Hollywood, FL December 2006
6 Bymaster, FP et al. The Dual Transporter Inhibitor Duloxetine: A Review of its Preclinical Pharmacology, Pharmacokinetic Profile, and Clinical Results in Depression.??? Current Pharmaceutical Design. 2005; 11: 1475-1493.
7 World Health Organization. Factsheet - Depression, 2005. Available at: who.int/mental_health/management/depression/definition/en/. Last visited 26 April 2007
8 Murray CJL, Lopez AD, eds. The Global Burden of Disease; 1996.
9 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision. Washington DC: American Psychiatric Association; 2000:345-428.
10 Ormel J, et al. Common mental disorders and disability across cultures: results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA. 1994;272:1741 1748.
11 Spitzer RL, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994;272:1749 1756.
12 Ormel J, Koeter MWJ, van den Brink W, van de Willige G. Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry. 1991;48:700 706.
13 Simon GE et al. An International Study of the Relation Between Somatic Symptoms and Depression. New Engl J Med. 1999;341(18):1329-35.
14 Paykel ES, et al. Psychol Med. 1995;25(6):1171-1180.
1999 - 2007 Boehringer Ingelheim GmbH, Germany. All rights reserved.
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