Researchers, led by Kerri Boutelle, PhD, associate professor of pediatrics and psychiatry at the University of California, San Diego School of Medicine have found that obesity is a risk factor for depressive symptoms, but not for clinical depression, suggesting that weight status could play a part in the development of depression in some adolescent girls.
"This is important, because depressive symptoms are considered a precursor to major depression," said Boutelle.
According to the Centers for Disease and Prevention, childhood obesity has more than tripled in the past 30 years. The prevalence of obesity among adolescents aged 12 to 19 years increased from 5.0 percent to 18.1 percent in 2008. Similarly, the National Survey on Drug Use and Health, an annual survey sponsored by the Substance Abuse and Mental Health Services Administration, found that 2.0 million youths aged 12 to 17 experienced at least one major depressive episode in 2007.
Knowing that the teenage years are often a tumultuous period in a young person's life, Boutelle and her colleagues set out to determine whether obesity contributes to the development of depression among youth. This is in contrast to the well-documented conclusion that depression increases the risk of obesity. Results of their study will appear in the May 21st issue of Health Psychology.
Using a structured psychiatric interview test the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) assessors gathered responses from almost 500 girls between the ages of 13 and 16 years, of various ethnicities. To receive a diagnosis of depression, the girls had to report the presence and severity of at least five symptoms. At each of four yearly assessments, the girls were weighed and measured. Data from the interviews indicated that obese status was associated with an increase in depressive symptoms, but not Major Depression.
"Based on our findings, I would encourage parents, teachers and physicians to monitor overweight and obese girls for depressive symptoms, and refer them for evaluation if they are concerned," said Boutelle.
Additional contributors are Peter Hannan and Jayne A. Fulkerson, Scott J. Crow University of Minnesota, and Eric Stice, Oregon Research Institute.
This study was funded by a grant from the National Institute of Mental Health.
суббота, 14 мая 2011 г.
New Target For Antidepressants Revealed By Animal Study
University of Michigan scientists have provided the most detailed picture yet of a key receptor in the brain that influences the effectiveness of serotonin-related antidepressants, such as Prozac.
The findings, which appeared online Monday ahead of print in the journal Proceedings of the National Academy of Sciences, open the door to providing a more targeted treatment of depression and anxiety with fewer side effects.
Depressive disorders change a person's mood, emotions and physical well-being and can co-occur with anxiety disorders and substance abuse.
"There are big drawbacks in the current therapies for depression," says senior author John Traynor, Ph.D., professor of pharmacology at the U-M Medical School and director of the U-M Substance Abuse Research Center. "Therapeutic benefits are delayed, there are unwanted side effects, and it's not unusual for depressive symptoms to return."
Authors say the high relapse rate indicates a need for additional treatment options for the estimated 20.9 million Americans with depression.
The best current treatments for depression are selective serotonin reuptake inhibitors, or SSRIs. These drugs work by flooding the brain's synapses with serotonin, a neurotransmitter linked with mood, and increasing signaling through the more than 20 serotonin receptors in the brain.
However the team of researchers showed that one particular pathway, the serotonin 5HT1a receptor is linked with antidepressive and antianxiety behavior in mice.
"Rather than activating all serotonin receptors as SSRIs do, one could increase signaling through the one critical serotonin receptor that our research shows is important for anti-depressant behavior," says co-author Richard R. Neubig, M.D., Ph.D., co-director of the U-M Center for Chemical Genomics and professor of pharmacology at the U-M Medical School.
The new research details the complex actions of a family of proteins, known as RGS proteins, that act as brakes on neurotransmitter signaling.
Researchers created a mutant mouse to boost serotonin signaling at the 5HT1a receptor. This was done by genetically inhibiting the activity of braking proteins. Without the normal brake on serotonin signaling, these mutant mice showed antidepressive behavior even without being given antidepressant drugs. The mice were also more responsive to SSRIs.
Authors say that further research could lead to drugs capable of inhibiting the RGS proteins and which would target the antidepressant signal where it is required on critical 5HT1a receptors.
Additional authors in the study are: Jeffrey Talbot, Ph.D., Ohio Northern University, formerly of U-M who continued parts of this work with Crystal Clemans and Melanie Nicol, Pharm. D. Other U-M authors are Emily Jutkiewicz, Ph.D., Steven Graves, B.S., and Xinyan Huang, Ph.D., from the Department of Pharmacology and Richard Mortensen, M.D., Ph.D., from the Department of Molecular and Integrative Physiology.
Funding:
National Institute of General Medical Sciences; National Institute on Drug Abuse.
Reference:
Proceedings of the National Academy of Sciences, "RGS inhibition at Gai2 selectively potentiates 5-HT1A-mediated antidepressant effects," doi 10.1073/pnas.1000003107
The findings, which appeared online Monday ahead of print in the journal Proceedings of the National Academy of Sciences, open the door to providing a more targeted treatment of depression and anxiety with fewer side effects.
Depressive disorders change a person's mood, emotions and physical well-being and can co-occur with anxiety disorders and substance abuse.
"There are big drawbacks in the current therapies for depression," says senior author John Traynor, Ph.D., professor of pharmacology at the U-M Medical School and director of the U-M Substance Abuse Research Center. "Therapeutic benefits are delayed, there are unwanted side effects, and it's not unusual for depressive symptoms to return."
Authors say the high relapse rate indicates a need for additional treatment options for the estimated 20.9 million Americans with depression.
The best current treatments for depression are selective serotonin reuptake inhibitors, or SSRIs. These drugs work by flooding the brain's synapses with serotonin, a neurotransmitter linked with mood, and increasing signaling through the more than 20 serotonin receptors in the brain.
However the team of researchers showed that one particular pathway, the serotonin 5HT1a receptor is linked with antidepressive and antianxiety behavior in mice.
"Rather than activating all serotonin receptors as SSRIs do, one could increase signaling through the one critical serotonin receptor that our research shows is important for anti-depressant behavior," says co-author Richard R. Neubig, M.D., Ph.D., co-director of the U-M Center for Chemical Genomics and professor of pharmacology at the U-M Medical School.
The new research details the complex actions of a family of proteins, known as RGS proteins, that act as brakes on neurotransmitter signaling.
Researchers created a mutant mouse to boost serotonin signaling at the 5HT1a receptor. This was done by genetically inhibiting the activity of braking proteins. Without the normal brake on serotonin signaling, these mutant mice showed antidepressive behavior even without being given antidepressant drugs. The mice were also more responsive to SSRIs.
Authors say that further research could lead to drugs capable of inhibiting the RGS proteins and which would target the antidepressant signal where it is required on critical 5HT1a receptors.
Additional authors in the study are: Jeffrey Talbot, Ph.D., Ohio Northern University, formerly of U-M who continued parts of this work with Crystal Clemans and Melanie Nicol, Pharm. D. Other U-M authors are Emily Jutkiewicz, Ph.D., Steven Graves, B.S., and Xinyan Huang, Ph.D., from the Department of Pharmacology and Richard Mortensen, M.D., Ph.D., from the Department of Molecular and Integrative Physiology.
Funding:
National Institute of General Medical Sciences; National Institute on Drug Abuse.
Reference:
Proceedings of the National Academy of Sciences, "RGS inhibition at Gai2 selectively potentiates 5-HT1A-mediated antidepressant effects," doi 10.1073/pnas.1000003107
SSRIs May Pack More Punch At The Cellular Level Than Believed
A new discovery about selective serotonin reuptake inhibitors (SSRIs) suggests that these drugs, which are used to treat mental health disorders like depression and anxiety, have multiple effects on our cells. In a research report published in the August 2010 issue of Genetics, researchers used yeast cells to identify secondary drug targets or pathways affected by SSRIs. Such secondary pathways could help explain why different people taking the same drug may experience different effects, and could also lead to new types of drugs altogether.
"We hope that our study begins to illuminate the full breadth of pharmacological effects of antidepressants on cellular physiology starting with the simple unicellular eukaryote, budding yeast," said Ethan O. Perlstein, Ph.D, a researcher involved in the work from the Lewis-Sigler Institute for Integrative Genomics at Princeton University in New Jersey. "Furthermore, our work validates the notion that simple model organisms may be useful for the study of complex human disease."
Knowing that a high concentration of sertraline (Zoloft®) is toxic to yeast cells, scientists applied a lethal dose to millions of these cells and fished out a few cells that became resistant to the drug. Researchers then identified the underlying mutations in those cells and applied genetic, biochemical, and electron microscopic imaging techniques to characterize the molecular basis of resistance. Their results suggest that SSRIs may actually affect more than one process in a cell, including non-protein targets such as phospholipid membranes. Additionally, the study's results demonstrate that sertraline targets intracellular membranes and modulate pathways involved in vesicle trafficking that are present in both yeast and human cells. Vesicle trafficking plays an important role in how neural synapses develop and function. More work is necessary, however, to determine the exact clinical relevance of this secondary drug target.
"There's no question that SSRIs help thousands of people with mental health problems," said Mark Johnston, Editor-in-Chief of the journal GENETICS, "but as this research shows, there is still some mystery about how they help us. This study a key first-step toward giving us a comprehensive answer to how SSRI's work, and it may open doors to entirely new therapies."
"We hope that our study begins to illuminate the full breadth of pharmacological effects of antidepressants on cellular physiology starting with the simple unicellular eukaryote, budding yeast," said Ethan O. Perlstein, Ph.D, a researcher involved in the work from the Lewis-Sigler Institute for Integrative Genomics at Princeton University in New Jersey. "Furthermore, our work validates the notion that simple model organisms may be useful for the study of complex human disease."
Knowing that a high concentration of sertraline (Zoloft®) is toxic to yeast cells, scientists applied a lethal dose to millions of these cells and fished out a few cells that became resistant to the drug. Researchers then identified the underlying mutations in those cells and applied genetic, biochemical, and electron microscopic imaging techniques to characterize the molecular basis of resistance. Their results suggest that SSRIs may actually affect more than one process in a cell, including non-protein targets such as phospholipid membranes. Additionally, the study's results demonstrate that sertraline targets intracellular membranes and modulate pathways involved in vesicle trafficking that are present in both yeast and human cells. Vesicle trafficking plays an important role in how neural synapses develop and function. More work is necessary, however, to determine the exact clinical relevance of this secondary drug target.
"There's no question that SSRIs help thousands of people with mental health problems," said Mark Johnston, Editor-in-Chief of the journal GENETICS, "but as this research shows, there is still some mystery about how they help us. This study a key first-step toward giving us a comprehensive answer to how SSRI's work, and it may open doors to entirely new therapies."
Does It Help To Continue Antidepressant Drug Treatment For Preventing Recurrence In Depression?
Apparently not very much, according to a study by Dutch investigators published in the Jan 2008 issue of Psychotherapy and Psychosomatics.
Maintenance antidepressant (AD) medication is the most commonly used preventive strategy in a highly recurrent disease, i.e. depression. Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice. The purpose of this study was to examine the discontinuation rate of maintenance AD in daily clinical practice in recurrently depressed patients and the associated risk of recurrence.
Prospectively AD maintenance medication and recurrence were examined in 172 euthymic patients with recurrent depression. AD user profiles before recurrence (nonusers, intermittent users, continuous users) were examined and related to recurrence over a 2-year follow-up period.
Less than half of the patients (42%) used AD continuously. Taking into account the minimal required adequate used dosage (20 mg fluoxetine equivalent), only 26% of the patients used AD as recommended by international guidelines. Despite continuous use of AD, 60.4% relapsed in 2 years. This relapse rate was comparable to the rate of the intermittent users (63.6%). In patients who stopped taking AD after remission and who received additional preventive CT, the recurrence rates were significantly lower than in non-AD-using patients treated with usual care (8 vs. 46%).
The majority of recurrently depressed patients treated with AD discontinue maintenance AD therapy in daily primary and secondary clinical practice. AD seems to offer poor protection against relapse in this patient group. Patients who stopped using AD experienced less relapse, especially if they were treated with preventive CT. Alternative maintenance treatments (including preventive cognitive therapy after discontinuation of AD) should be studied in recurrently depressed patients with intermittent good remission, not only in secondary but also in primary care.
PSYCHOTHERAPY AND PSYCHOSOMATICS
karger/pps
Maintenance antidepressant (AD) medication is the most commonly used preventive strategy in a highly recurrent disease, i.e. depression. Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice. The purpose of this study was to examine the discontinuation rate of maintenance AD in daily clinical practice in recurrently depressed patients and the associated risk of recurrence.
Prospectively AD maintenance medication and recurrence were examined in 172 euthymic patients with recurrent depression. AD user profiles before recurrence (nonusers, intermittent users, continuous users) were examined and related to recurrence over a 2-year follow-up period.
Less than half of the patients (42%) used AD continuously. Taking into account the minimal required adequate used dosage (20 mg fluoxetine equivalent), only 26% of the patients used AD as recommended by international guidelines. Despite continuous use of AD, 60.4% relapsed in 2 years. This relapse rate was comparable to the rate of the intermittent users (63.6%). In patients who stopped taking AD after remission and who received additional preventive CT, the recurrence rates were significantly lower than in non-AD-using patients treated with usual care (8 vs. 46%).
The majority of recurrently depressed patients treated with AD discontinue maintenance AD therapy in daily primary and secondary clinical practice. AD seems to offer poor protection against relapse in this patient group. Patients who stopped using AD experienced less relapse, especially if they were treated with preventive CT. Alternative maintenance treatments (including preventive cognitive therapy after discontinuation of AD) should be studied in recurrently depressed patients with intermittent good remission, not only in secondary but also in primary care.
PSYCHOTHERAPY AND PSYCHOSOMATICS
karger/pps
Groundbreaking Kansas City Depression Initiative lauded by American Psychiatric Association
The American Psychiatric Association (APA) commends the Kansas City region for launching a bold and innovative depression
initiative: "Depression in the Workplace: What Does It Mean to Our Community?" A town hall meeting on March 29, sponsored by
the Greater Kansas City Chamber of Commerce, showcased the Mid-America Coalition on Health Care's Community Initiative on
Depression (CID). This first-of-its-kind community initiative addresses undiagnosed and untreated depression and brings
together the key stakeholders in the healthcare system: business and other employers, employees and their dependents,
governmental and educational organizations, and physicians and health plans.
The initiative is an unprecedented approach that attracted representatives from nearly two dozen other metropolitan regions -
including New York City, Chicago, Atlanta and Minneapolis - to Kansas City for a private APA-sponsored National Invitational
to discuss how to replicate the program in their communities.
"If the Community Initiative on Depression were implemented across the country, the impact on the health and wellness of the
American people would be profound," said Norman A. Clemens, M.D., chair of the APA's Committee on Business Relations and a
Cleveland, Ohio-based psychiatrist. "Not only would it alleviate a great deal of unnecessary suffering, but it would also
produce significant economic benefits."
He continued: "We expect the CID to have a continuing and positive impact on both the residents and business community of
Kansas City, and that's why other communities are so interested. The simple truth is that depression is a real medical
illness - not just a 'bad day' or a character weakness - and it can be effectively treated."
The APA and its National Partnership for Workplace Mental Health have been involved with the CID for almost three years.
Early on, the APA recognized the CID's potential and was particularly impressed with both the community's commitment and the
outstanding staff and leadership of the Mid-America Coalition on Health Care.
The National Partnership, which is a collaboration of the APA and America's employers, was created to address mental health
issues in the workplace. The Partnership does this through a variety of free programs and materials, many of which are being
used in the CID, and all of which can be found at workplacementalhealth.
"If there's one thing we have learned, it's that employers need to understand the enormous cost of depression in the
workplace, through its impact on productivity, absenteeism, disability and other medical costs," said William L. Bruning,
J.D., M.B.A., president of the Mid-America Coalition on Healthcare, the employer partnership that developed and runs the CID.
"Once they understand what undiagnosed and untreated depression is doing to their bottom line, business becomes the engine
for change since they're the major purchaser of health care in the community."
A U.S. Surgeon General report reveals that untreated depression costs businesses as much as $79 billion per year. Moreover,
recent research shows that depression is among the most treatable of all medical illnesses, said Dr. Clemens. Between 70 and
80 percent of people with depression respond well to treatment, which may include talk therapy, medication or a combination
of both. Depression can strike at any time, he said, but most often it appears for the first time during the prime "working
years" of life.
The American Psychiatric Association is a national medical specialty society, founded in 1844, whose more than 35,000
physician members specialize in the diagnosis, treatment and prevention of mental illnesses including substance use
disorders. For more information, visit the APA Web site at psych.
Don't miss APA's 2005 Annual Meeting: Psychosomatic Medicine: Integrating Psychiatry & Medicine in Atlanta, May 21-26, 2005.
Please visit APA's online press room for news releases, press policies, and media registration information - psych/news_room/virtual_pressrms/am2005.
psych
initiative: "Depression in the Workplace: What Does It Mean to Our Community?" A town hall meeting on March 29, sponsored by
the Greater Kansas City Chamber of Commerce, showcased the Mid-America Coalition on Health Care's Community Initiative on
Depression (CID). This first-of-its-kind community initiative addresses undiagnosed and untreated depression and brings
together the key stakeholders in the healthcare system: business and other employers, employees and their dependents,
governmental and educational organizations, and physicians and health plans.
The initiative is an unprecedented approach that attracted representatives from nearly two dozen other metropolitan regions -
including New York City, Chicago, Atlanta and Minneapolis - to Kansas City for a private APA-sponsored National Invitational
to discuss how to replicate the program in their communities.
"If the Community Initiative on Depression were implemented across the country, the impact on the health and wellness of the
American people would be profound," said Norman A. Clemens, M.D., chair of the APA's Committee on Business Relations and a
Cleveland, Ohio-based psychiatrist. "Not only would it alleviate a great deal of unnecessary suffering, but it would also
produce significant economic benefits."
He continued: "We expect the CID to have a continuing and positive impact on both the residents and business community of
Kansas City, and that's why other communities are so interested. The simple truth is that depression is a real medical
illness - not just a 'bad day' or a character weakness - and it can be effectively treated."
The APA and its National Partnership for Workplace Mental Health have been involved with the CID for almost three years.
Early on, the APA recognized the CID's potential and was particularly impressed with both the community's commitment and the
outstanding staff and leadership of the Mid-America Coalition on Health Care.
The National Partnership, which is a collaboration of the APA and America's employers, was created to address mental health
issues in the workplace. The Partnership does this through a variety of free programs and materials, many of which are being
used in the CID, and all of which can be found at workplacementalhealth.
"If there's one thing we have learned, it's that employers need to understand the enormous cost of depression in the
workplace, through its impact on productivity, absenteeism, disability and other medical costs," said William L. Bruning,
J.D., M.B.A., president of the Mid-America Coalition on Healthcare, the employer partnership that developed and runs the CID.
"Once they understand what undiagnosed and untreated depression is doing to their bottom line, business becomes the engine
for change since they're the major purchaser of health care in the community."
A U.S. Surgeon General report reveals that untreated depression costs businesses as much as $79 billion per year. Moreover,
recent research shows that depression is among the most treatable of all medical illnesses, said Dr. Clemens. Between 70 and
80 percent of people with depression respond well to treatment, which may include talk therapy, medication or a combination
of both. Depression can strike at any time, he said, but most often it appears for the first time during the prime "working
years" of life.
The American Psychiatric Association is a national medical specialty society, founded in 1844, whose more than 35,000
physician members specialize in the diagnosis, treatment and prevention of mental illnesses including substance use
disorders. For more information, visit the APA Web site at psych.
Don't miss APA's 2005 Annual Meeting: Psychosomatic Medicine: Integrating Psychiatry & Medicine in Atlanta, May 21-26, 2005.
Please visit APA's online press room for news releases, press policies, and media registration information - psych/news_room/virtual_pressrms/am2005.
psych
Older women with depression may have an increased risk of heart disease
New research shows older women with depression may have an increased risk of heart disease and death. Researchers in New York studied more than 93,600 older women who participated in the Women's Health Initiative Observational Study (WHI-OS).
The WHI-OS is a long-term program designed to determine how biological and lifestyle factors influence the risk of heart disease, cancer, osteoporosis, and other health conditions. For this study, participants were evaluated for depression and cardiovascular disease and were followed for about four years.
Researchers found nearly 16 percent of women reported experiencing symptoms of depression. They say depression was significantly linked to cardiovascular disease risk.
Women with depression were 12 percent more likely to have hypertension and 60 percent more likely to have a history of stroke. Women with depression were also 50 percent more likely to die from cardiovascular disease and about 30 percent more likely to die from another cause.
From the study it was concluded that a large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD [cardiovascular disease] death and all-cause mortality, even after controlling for established CVD risk factors. However whether an early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.
The WHI-OS is a long-term program designed to determine how biological and lifestyle factors influence the risk of heart disease, cancer, osteoporosis, and other health conditions. For this study, participants were evaluated for depression and cardiovascular disease and were followed for about four years.
Researchers found nearly 16 percent of women reported experiencing symptoms of depression. They say depression was significantly linked to cardiovascular disease risk.
Women with depression were 12 percent more likely to have hypertension and 60 percent more likely to have a history of stroke. Women with depression were also 50 percent more likely to die from cardiovascular disease and about 30 percent more likely to die from another cause.
From the study it was concluded that a large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD [cardiovascular disease] death and all-cause mortality, even after controlling for established CVD risk factors. However whether an early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.
Sildenafil Treatment Of Women With Antidepressant-Associated Sexual Dysfunction: A Randomized Controlled Trial
UroToday - Treatment emergent sexual dysfunction is a frequent adverse effect occurring with medication use and is a major influence for premature treatment discontinuation, which leads to treatment failure and costly disease management outcomes.
Sexual dysfunction is recognized as being associated with selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants, the most frequently prescribed medications for outpatients aged 18 to 65 years in the United States, and is estimated to occur in 30% to 70% of men and women treated for major depression. Although numerous strategies have been proposed for managing sexual dysfunction associated with SRI treatment, the selective type 5 phosphodiesterase inhibitors, limited to studies involving men, have demonstrated the best evidence-based data to support broad based and clinically meaningful treatment efficacy. No randomized controlled trial (RCT) has demonstrated effectiveness for women, who compared with men, are prescribed antidepressants at rates of 2 to 1 and can be expected to represent the larger number of patients needing relief from sexual dysfunction associated with SRI treatment. Without evidence-based data to treat sexual function associated with SRIs in women, clinicians lack the confidence to manage it effectively, which leaves patients exposed to excess random pharmacology.
The objective of the current trial was to use a protocol similar to our previous study involving men with sexual dysfunction associated with SRI treatment to assess the efficacy of sildenafil in the treatment of women, specifically women whose major depressive disorder in remission while taking a stable dose of SRI antidepressants and who did not have a preexisting sexual dysfunction but due to the treatment had sexual dysfunction manifest as dysfunction of orgasm (delay) or arousal (lubrication). Recognizing the potential importance of hormonal factors on nitric oxide signaling involved in sexual function in women with depression, endocrine measures were examined.
The prevalence of sexual problems was high, with 96% of women reporting more than one complaint. They reported disturbances in desire (88%), subjective arousal (81%), lubrication (80%), orgasm delay (99%), and other difficulties (24%), which included anorgasmia, pain, and lack of pleasure. The difference in the Clinical Global Impression scale sexual function improvement showed a significant difference between groups (P=.03). Clinically, 72% of women taking sildenafil reported improvement compared with 27% on placebo. On the secondary outcome measures, the sildenafil group had a higher mean (SD) improvement on orgasm (p=.01) than women taking placebo. These findings are important not only because women experience major depressive disorder at nearly double the rate of men, and because they experience greater sexual dysfunction than men, but also because it establishes that selective phosphodiesterase type 5 inhibitors are effective in both sexes for treating this bothersome treatment-associated adverse effect in patients who have been effectively treated for depression, but need to continue on their medication to avoid relapse or recurrence, and reduce the current high rates of premature medication discontinuation.
Written by H. George Nurnberg, MD, as part of Beyond the Abstract on UroToday.
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to:
urotoday
Copyright © 2008 - UroToday
Sexual dysfunction is recognized as being associated with selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants, the most frequently prescribed medications for outpatients aged 18 to 65 years in the United States, and is estimated to occur in 30% to 70% of men and women treated for major depression. Although numerous strategies have been proposed for managing sexual dysfunction associated with SRI treatment, the selective type 5 phosphodiesterase inhibitors, limited to studies involving men, have demonstrated the best evidence-based data to support broad based and clinically meaningful treatment efficacy. No randomized controlled trial (RCT) has demonstrated effectiveness for women, who compared with men, are prescribed antidepressants at rates of 2 to 1 and can be expected to represent the larger number of patients needing relief from sexual dysfunction associated with SRI treatment. Without evidence-based data to treat sexual function associated with SRIs in women, clinicians lack the confidence to manage it effectively, which leaves patients exposed to excess random pharmacology.
The objective of the current trial was to use a protocol similar to our previous study involving men with sexual dysfunction associated with SRI treatment to assess the efficacy of sildenafil in the treatment of women, specifically women whose major depressive disorder in remission while taking a stable dose of SRI antidepressants and who did not have a preexisting sexual dysfunction but due to the treatment had sexual dysfunction manifest as dysfunction of orgasm (delay) or arousal (lubrication). Recognizing the potential importance of hormonal factors on nitric oxide signaling involved in sexual function in women with depression, endocrine measures were examined.
The prevalence of sexual problems was high, with 96% of women reporting more than one complaint. They reported disturbances in desire (88%), subjective arousal (81%), lubrication (80%), orgasm delay (99%), and other difficulties (24%), which included anorgasmia, pain, and lack of pleasure. The difference in the Clinical Global Impression scale sexual function improvement showed a significant difference between groups (P=.03). Clinically, 72% of women taking sildenafil reported improvement compared with 27% on placebo. On the secondary outcome measures, the sildenafil group had a higher mean (SD) improvement on orgasm (p=.01) than women taking placebo. These findings are important not only because women experience major depressive disorder at nearly double the rate of men, and because they experience greater sexual dysfunction than men, but also because it establishes that selective phosphodiesterase type 5 inhibitors are effective in both sexes for treating this bothersome treatment-associated adverse effect in patients who have been effectively treated for depression, but need to continue on their medication to avoid relapse or recurrence, and reduce the current high rates of premature medication discontinuation.
Written by H. George Nurnberg, MD, as part of Beyond the Abstract on UroToday.
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to:
urotoday
Copyright © 2008 - UroToday
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