Male veterans are three times more likely than female veterans to commit suicide. Also, whites have a much higher rate of suicide compared with patients of other races.
Researchers examined associations between demographic and clinical characteristics and risk of suicide among veterans treated for depression in the Veteran's Health Administration (VA) system. Out of 807,694 veterans included in the study, 1,683 - or 0.21 percent - committed suicide during the study period. Data suggests that the rate of suicide among male veterans is three times higher than the rate among female veterans, less than the 4:1 ratio reported for the general population. In addition, the rate of suicide among whites was 95.01 per 100,000 person-years, much higher than the 27.08 per 100,000 person-years for blacks and 56.17 per 100,000 person-years for other races. Younger veterans aged 18-44 had moderately higher suicide rates than did middle-aged patients aged 45-65 and modestly higher rates than elderly patients (94.98, 77.93 and 90.06 per 100,000 person-years, respectively). Surprisingly, veterans diagnosed with posttraumatic stress disorder (PTSD) had a lower rate of suicide than those without PTSD.
"These findings can help identify depressed veterans at greatest risk of suicide, allowing providers in the VA health care system to more closely monitor these patients and can provide policy-makers with valuable information about high-risk veterans," the study's authors said. [From: "Suicide Mortality Among Individuals Receiving Treatment for Depression in the Veterans Affairs Health System: Associations with Patient and Treatment Setting Characteristics." Contact: Kara Gavin, kegavinumich.]
The American Journal of Public Health is the monthly journal of the American Public Health Association (APHA), the oldest organization of public health professionals in the world. APHA is a leading publisher of books and periodicals promoting sound scientific standards, action programs and public policy to enhance health.
American Journal of Public Health .
четверг, 6 октября 2011 г.
понедельник, 3 октября 2011 г.
Antidepressants May Be Associated With Modestly Increased Risk Of Suicidality In Children
An analysis of data from 24 clinical trials suggests that antidepressant medications may be linked to a modest increase in the risk of suicidal thoughts and behaviors in children, according to an article in the March issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
For decades, some physicians have suspected that patients' risk of suicidality (suicidal thoughts and behavior) increased when pediatric patients first began taking antidepressants, according to background information in the article. Research indicates that there is no such association in adults. In 2003, a report submitted to the Food and Drug Administration (FDA) suggested a link between the antidepressant paroxetine and suicidality in pediatric patients. The FDA then requested pediatric data from the manufacturers of eight other antidepressant drugs, the authors report.
Tarek A. Hammad, M.D., Ph.D., and colleagues at the FDA performed a meta-analysis of data from 23 short-term clinical trials received in response to the request, as well as one trial funded by the National Institute of Mental Health (NIMH). The 24 studies included 4,582 pediatric patients taking one of nine antidepressant medications for depression, anxiety or other psychiatric disorder.
No children committed suicide in any of the trials. Although the NIMH-funded trial was the only individual trial to show a significant increase in suicidality among children taking antidepressants, the analysis of all the trials together showed a higher risk of suicidal ideation and behavior for children taking the drugs compared with those who were not. "When considering 100 treated patients, we might expect one to three patients to have an increase in suicidality beyond the risk that occurs with depression itself owing to short-term treatment with an antidepressant," the authors write.
The FDA now requires warnings regarding the risk of suicidality in children on antidepressant labeling and the distribution of a patient medication guide to patients, families and caregivers, the authors write. "Although there remain differences of opinion in the clinical community about the strength of this signal for antidepressant drug??"induced suicidality in pediatric patients and the implications for clinical practice, it is important to be clear that the FDA has not contraindicated any of the antidepressant drugs for pediatric use," they conclude. "The FDA recognizes that depression and other psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated. The new warning language recognizes this need but advises close monitoring of patients as a way of managing the risk of suicidality."
(Arch Gen Psychiatry. 2006;63:332-339. Available pre-embargo to the media at jamamedia/.)
Editorial: Suicidal Behavior Different from Suicide Attempts The small number of suicide attempts across the trials make the results of the meta-analysis difficult for physicians and policymakers to use, write Ross J. Baldessarini, M.D., of McLean Hospital, Belmont, Mass., and colleagues in an accompanying editorial.
Measuring suicidality rather than suicides or suicide attempts may not paint an accurate picture of the risk associated with the drugs, they continue. "Only a small fraction of patients with suicidal thoughts attempt suicide, few attempts prove to be fatal and risk factors for suicide attempts (e.g., younger, female) and completions (e.g., older, male) differ markedly," they write. "Moreover, suicidal ideation, but usually not suicidal behavior, has been reduced with antidepressant drug treatment."
"When adverse responses do occur, they are often detectable with close clinical follow-up and psychological support, especially early in treatment, as recommended in recent FDA clinical advisories," they conclude. "Moreover, they may be reversed with appropriately modified treatment."
(Arch Gen Psychiatry. 2006;63:127-128. Available pre-embargo to the media at jamamedia/.)
Editor's Note: This commentary was supported, in part, by a grant from the Bruce J. Anderson Foundation, Boston, and the McLean Private Donors Bipolar Disorders and Psychopharmacology Research Fund, Boston (Dr. Baldessarini), by a University of Rome fellowship and by National Alliance for Research on Schizophrenia and Depression, Great Neck, N.Y. Full financial disclosures are available in the article.
To contact corresponding editorialist Ross J. Baldessarini, M.D., call Cynthia Lepore at 617-855-2110.
Contact: Susan Cruzan
JAMA and Archives Journals
For decades, some physicians have suspected that patients' risk of suicidality (suicidal thoughts and behavior) increased when pediatric patients first began taking antidepressants, according to background information in the article. Research indicates that there is no such association in adults. In 2003, a report submitted to the Food and Drug Administration (FDA) suggested a link between the antidepressant paroxetine and suicidality in pediatric patients. The FDA then requested pediatric data from the manufacturers of eight other antidepressant drugs, the authors report.
Tarek A. Hammad, M.D., Ph.D., and colleagues at the FDA performed a meta-analysis of data from 23 short-term clinical trials received in response to the request, as well as one trial funded by the National Institute of Mental Health (NIMH). The 24 studies included 4,582 pediatric patients taking one of nine antidepressant medications for depression, anxiety or other psychiatric disorder.
No children committed suicide in any of the trials. Although the NIMH-funded trial was the only individual trial to show a significant increase in suicidality among children taking antidepressants, the analysis of all the trials together showed a higher risk of suicidal ideation and behavior for children taking the drugs compared with those who were not. "When considering 100 treated patients, we might expect one to three patients to have an increase in suicidality beyond the risk that occurs with depression itself owing to short-term treatment with an antidepressant," the authors write.
The FDA now requires warnings regarding the risk of suicidality in children on antidepressant labeling and the distribution of a patient medication guide to patients, families and caregivers, the authors write. "Although there remain differences of opinion in the clinical community about the strength of this signal for antidepressant drug??"induced suicidality in pediatric patients and the implications for clinical practice, it is important to be clear that the FDA has not contraindicated any of the antidepressant drugs for pediatric use," they conclude. "The FDA recognizes that depression and other psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated. The new warning language recognizes this need but advises close monitoring of patients as a way of managing the risk of suicidality."
(Arch Gen Psychiatry. 2006;63:332-339. Available pre-embargo to the media at jamamedia/.)
Editorial: Suicidal Behavior Different from Suicide Attempts The small number of suicide attempts across the trials make the results of the meta-analysis difficult for physicians and policymakers to use, write Ross J. Baldessarini, M.D., of McLean Hospital, Belmont, Mass., and colleagues in an accompanying editorial.
Measuring suicidality rather than suicides or suicide attempts may not paint an accurate picture of the risk associated with the drugs, they continue. "Only a small fraction of patients with suicidal thoughts attempt suicide, few attempts prove to be fatal and risk factors for suicide attempts (e.g., younger, female) and completions (e.g., older, male) differ markedly," they write. "Moreover, suicidal ideation, but usually not suicidal behavior, has been reduced with antidepressant drug treatment."
"When adverse responses do occur, they are often detectable with close clinical follow-up and psychological support, especially early in treatment, as recommended in recent FDA clinical advisories," they conclude. "Moreover, they may be reversed with appropriately modified treatment."
(Arch Gen Psychiatry. 2006;63:127-128. Available pre-embargo to the media at jamamedia/.)
Editor's Note: This commentary was supported, in part, by a grant from the Bruce J. Anderson Foundation, Boston, and the McLean Private Donors Bipolar Disorders and Psychopharmacology Research Fund, Boston (Dr. Baldessarini), by a University of Rome fellowship and by National Alliance for Research on Schizophrenia and Depression, Great Neck, N.Y. Full financial disclosures are available in the article.
To contact corresponding editorialist Ross J. Baldessarini, M.D., call Cynthia Lepore at 617-855-2110.
Contact: Susan Cruzan
JAMA and Archives Journals
пятница, 30 сентября 2011 г.
New FDA-Approved Device Offers Hope to Depressed Patients
The Saint Louis University Health Sciences Center medical team involved in the research and development of an innovative therapy for depression - vagal nerve stimulation (VNS) - is starting a new clinic for patients who have treatment-resistant depression.
The vagal nerve stimulator was approved Friday by the Food and Drug Administration for treatment-resistant depression following clinical trials around the United States, including Saint Louis University.
"This important service could dramatically improve the quality of life for some of the sickest patients, patients who had been on seven to 10 medications and continued to be depressed for years," says Dr. Charles Conway, who researched vagal nerve stimulation and now will lead the Saint Louis University Vagal Nerve Stimulation Clinic.
The small device is implanted in front of the armpit and has leads that run under the skin to the vagal nerve in the neck. It has been used for and is FDA-approved to treat epilepsy as well.
Charles Donovan, who had participated in the clinical research at Saint Louis University and written a book about his experience, says vagal nerve stimulation changed his life.
"I feel giddy that I've gone from the depths of despair to a normal life," he says. "For over 20 years I had tried every available treatment to give me some relief from the unbearable suffering I experienced from chronic depression.
"When I was implanted with the vagus nerve stimulator in April of 2001, I was desperate. I didn't want to continue to live a life of utter despair. I had absolutely no idea that my life was about to be completely changed."
Conway was the principal investigator at the Saint Louis University study site, one of 20 sites across the country to participate in a 200-patient clinical trial between 2000 and 2003.
"One of the most rewarding things I've done as a psychiatrist is to conduct research that shows we can help people who have lived essentially all of their lives with severe depression get better," says Conway, an assistant professor of psychiatry at Saint Louis University School of Medicine and a SLUCare psychiatrist. "Dr. George Grossberg, who directs our division of geriatric psychiatry, and I have found the treatment is successful in helping numerous patients who have failed all other existing therapies.
"Now, with a new treatment option on the horizon, I am excited we will reach more patients through the Saint Louis University Vagal Nerve Stimulation Clinic. These are patients who had given up hope of ever feeling better."
Richard Bucholz, M.D., director of the division of neurosurgery at Saint Louis University, brings his experience surgically implanting the device during the study to SLU's Vagal Nerve Stimulation Clinic. He also was involved in studies that led to the FDA's approval of vagal nerve stimulation to treat epilepsy.
Patients who are interested in the service will receive an initial consultation to see if the treatment is appropriate; a surgical consultation if they are eligible; and follow-up appointments to monitor and adjust the device settings.
The Saint Louis University Vagal Nerve Stimulation Clinic is located at the Wohl Memorial Institute, 1221 S. Grand Blvd. For information about the service, call 314-268-5385.
Saint Louis University Health Sciences Center
St. Louis, MO 63103
United States
slu/pr
The vagal nerve stimulator was approved Friday by the Food and Drug Administration for treatment-resistant depression following clinical trials around the United States, including Saint Louis University.
"This important service could dramatically improve the quality of life for some of the sickest patients, patients who had been on seven to 10 medications and continued to be depressed for years," says Dr. Charles Conway, who researched vagal nerve stimulation and now will lead the Saint Louis University Vagal Nerve Stimulation Clinic.
The small device is implanted in front of the armpit and has leads that run under the skin to the vagal nerve in the neck. It has been used for and is FDA-approved to treat epilepsy as well.
Charles Donovan, who had participated in the clinical research at Saint Louis University and written a book about his experience, says vagal nerve stimulation changed his life.
"I feel giddy that I've gone from the depths of despair to a normal life," he says. "For over 20 years I had tried every available treatment to give me some relief from the unbearable suffering I experienced from chronic depression.
"When I was implanted with the vagus nerve stimulator in April of 2001, I was desperate. I didn't want to continue to live a life of utter despair. I had absolutely no idea that my life was about to be completely changed."
Conway was the principal investigator at the Saint Louis University study site, one of 20 sites across the country to participate in a 200-patient clinical trial between 2000 and 2003.
"One of the most rewarding things I've done as a psychiatrist is to conduct research that shows we can help people who have lived essentially all of their lives with severe depression get better," says Conway, an assistant professor of psychiatry at Saint Louis University School of Medicine and a SLUCare psychiatrist. "Dr. George Grossberg, who directs our division of geriatric psychiatry, and I have found the treatment is successful in helping numerous patients who have failed all other existing therapies.
"Now, with a new treatment option on the horizon, I am excited we will reach more patients through the Saint Louis University Vagal Nerve Stimulation Clinic. These are patients who had given up hope of ever feeling better."
Richard Bucholz, M.D., director of the division of neurosurgery at Saint Louis University, brings his experience surgically implanting the device during the study to SLU's Vagal Nerve Stimulation Clinic. He also was involved in studies that led to the FDA's approval of vagal nerve stimulation to treat epilepsy.
Patients who are interested in the service will receive an initial consultation to see if the treatment is appropriate; a surgical consultation if they are eligible; and follow-up appointments to monitor and adjust the device settings.
The Saint Louis University Vagal Nerve Stimulation Clinic is located at the Wohl Memorial Institute, 1221 S. Grand Blvd. For information about the service, call 314-268-5385.
Saint Louis University Health Sciences Center
St. Louis, MO 63103
United States
slu/pr
вторник, 27 сентября 2011 г.
Children And Teens Taking Antidepressants Might Be More Likely To Attempt, Complete Suicide
Antidepressant medications may be associated with suicide attempts and death in severely depressed children and adolescents but not in adults, according to an article in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
The U.S. Food and Drug Administration (FDA) recently began requiring drug manufacturers to include a warning regarding the risk of suicidal behavior among children and teens treated with antidepressants after a large analysis of clinical trials revealed a potential link. It is uncertain whether there is an association between treatment with antidepressants and suicidal behavior in adults, according to background information in the article. Because relatively few completed suicides occur, suicidal behavior is used instead in studies assessing the risks associated with antidepressant medications and few studies have examined the risk of suicide attempts or deaths in patients treated with antidepressants.
Mark Olfson, M.D., M.P.H., College of Physicians and Surgeons of Columbia University Medical Center and New York State Psychiatric Institute, New York, and colleagues analyzed the medical records of 5,469 Medicaid patients who were hospitalized for depression at least once in 1999 or 2000. The researchers first selected all cases of completed suicides (eight children and adolescents and 86 adults) and suicide attempts (263 children and adolescents, 521 adults). They then matched each case with one to five controls based on demographic information, period following hospital discharge, presence or absence of a suicide attempt prior to hospital admission, state of residence, other medication use and presence or absence of a substance abuse disorder.
Severely depressed children and adolescents ages 6 to 18 years were 1.5 times as likely to attempt suicide and also significantly more likely to complete suicide if they were treated with an antidepressant medication than if they were not treated with an antidepressant. More specifically, children and adolescents who died from suicide (eight cases) were more likely to have been treated with an SSRI antidepressant than their matched controls (39 controls, 37.5 percent vs. 7.7 percent). Among adults age 19 to 64 years, however, treatment with antidepressants was not associated with either suicide attempts or suicide deaths.
The link between completed suicides and antidepressants in young patients was based on only eight cases, and it is possible that the sickest children were more likely to be treated with such medications, skewing the results, the authors write. "With these caveats in mind, the present findings are consistent with the recommendations for careful clinical monitoring during the treatment of depressed children and adolescents with antidepressant medications," they conclude. "In practice, physicians face the difficult challenge of balancing safety concerns against evidence that depression is a key risk factor for adult and adolescent suicide and that antidepressant agents are effective for adult and adolescent depression." (Arch Gen Psychiatry. 2006;63:865-872.)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelationsjama-archives.
Contact: Craig LeMoult
JAMA and Archives Journals
The U.S. Food and Drug Administration (FDA) recently began requiring drug manufacturers to include a warning regarding the risk of suicidal behavior among children and teens treated with antidepressants after a large analysis of clinical trials revealed a potential link. It is uncertain whether there is an association between treatment with antidepressants and suicidal behavior in adults, according to background information in the article. Because relatively few completed suicides occur, suicidal behavior is used instead in studies assessing the risks associated with antidepressant medications and few studies have examined the risk of suicide attempts or deaths in patients treated with antidepressants.
Mark Olfson, M.D., M.P.H., College of Physicians and Surgeons of Columbia University Medical Center and New York State Psychiatric Institute, New York, and colleagues analyzed the medical records of 5,469 Medicaid patients who were hospitalized for depression at least once in 1999 or 2000. The researchers first selected all cases of completed suicides (eight children and adolescents and 86 adults) and suicide attempts (263 children and adolescents, 521 adults). They then matched each case with one to five controls based on demographic information, period following hospital discharge, presence or absence of a suicide attempt prior to hospital admission, state of residence, other medication use and presence or absence of a substance abuse disorder.
Severely depressed children and adolescents ages 6 to 18 years were 1.5 times as likely to attempt suicide and also significantly more likely to complete suicide if they were treated with an antidepressant medication than if they were not treated with an antidepressant. More specifically, children and adolescents who died from suicide (eight cases) were more likely to have been treated with an SSRI antidepressant than their matched controls (39 controls, 37.5 percent vs. 7.7 percent). Among adults age 19 to 64 years, however, treatment with antidepressants was not associated with either suicide attempts or suicide deaths.
The link between completed suicides and antidepressants in young patients was based on only eight cases, and it is possible that the sickest children were more likely to be treated with such medications, skewing the results, the authors write. "With these caveats in mind, the present findings are consistent with the recommendations for careful clinical monitoring during the treatment of depressed children and adolescents with antidepressant medications," they conclude. "In practice, physicians face the difficult challenge of balancing safety concerns against evidence that depression is a key risk factor for adult and adolescent suicide and that antidepressant agents are effective for adult and adolescent depression." (Arch Gen Psychiatry. 2006;63:865-872.)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelationsjama-archives.
Contact: Craig LeMoult
JAMA and Archives Journals
суббота, 24 сентября 2011 г.
Does Depression Predict Mortality In Heart Attacks?
A group of Danish investigators, headed by Per Bech (Hillerod) surveyed the literature on depression in patients with
myocardial infarction to assess the methodological quality and to test whether depression leads to an increased
postmyocardial infarction mortality.
Medline, Psycinfo, and UMI were searched, and researchers were contacted in the autumn of 2003. Thirty-one articles
were reviewed. Only seven articles scored above a predefined level of 75% for acceptable quality. The articles lack
description of non-responders, recall period for depressive symptoms, validation of applied instrument on target population,
and sample size large enough to show differences between groups.
The prevalence rates of depression ranged from 1.6 to 50%. In eight articles, a diagnostic test was applied, in the rest of
the studies, questionnaires were used. The prevalence of depression was highest in those using patient-completed
questionnaires. A significant positive association was shown between depression and postmyocardial infarction mortality in 15
studies, a non-significant association in 14, and in two articles, this was not reported. In articles with data collection
starting after 1994, a non-significant relation tended to be reported. The studies were generally not of acceptable quality.
They lacked sufficient power to show differences in stated end points between groups. Application of non-validated
instruments caused large differences in prevalence rates of depression. Future studies should include a minimum of 1,000
patients, use a validated instrument, re-examine the patients, and describe participants and non-participants in detail.
The conclusion of their analysis is that the data are not conclusive and it is premature o suggest a massive use of
antidepressant drugs with hear attacks.
Reference URL
karger
alphagalileo
myocardial infarction to assess the methodological quality and to test whether depression leads to an increased
postmyocardial infarction mortality.
Medline, Psycinfo, and UMI were searched, and researchers were contacted in the autumn of 2003. Thirty-one articles
were reviewed. Only seven articles scored above a predefined level of 75% for acceptable quality. The articles lack
description of non-responders, recall period for depressive symptoms, validation of applied instrument on target population,
and sample size large enough to show differences between groups.
The prevalence rates of depression ranged from 1.6 to 50%. In eight articles, a diagnostic test was applied, in the rest of
the studies, questionnaires were used. The prevalence of depression was highest in those using patient-completed
questionnaires. A significant positive association was shown between depression and postmyocardial infarction mortality in 15
studies, a non-significant association in 14, and in two articles, this was not reported. In articles with data collection
starting after 1994, a non-significant relation tended to be reported. The studies were generally not of acceptable quality.
They lacked sufficient power to show differences in stated end points between groups. Application of non-validated
instruments caused large differences in prevalence rates of depression. Future studies should include a minimum of 1,000
patients, use a validated instrument, re-examine the patients, and describe participants and non-participants in detail.
The conclusion of their analysis is that the data are not conclusive and it is premature o suggest a massive use of
antidepressant drugs with hear attacks.
Reference URL
karger
alphagalileo
среда, 21 сентября 2011 г.
New Preclinical Data Confirm Naurex's Novel Antidepressant GLYX-13 Appears Free Of The Behavioral Impairment And Abuse Potential Seen With Ketamine
Naurex Inc., a clinical-stage company developing innovative treatments to address unmet needs in psychiatry and neurology, reported that data being presented at the 49th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) further confirm that its lead antidepressant candidate GLYX-13 appears free of the behavioral impairment and abuse potential that have limited the clinical utility of other NMDA receptor (NMDAR) modulator drugs such as ketamine.
Ketamine and similar NMDAR-modulating agents act very rapidly to alleviate the symptoms of depression and bipolar disorder, but their clinical utility has been hampered by their potential for abuse and behavioral impairment, including schizophrenia-like effects, at doses near the therapeutic dose. GLYX-13 is Naurex's lead glycine-site functional partial agonist (GFPA) selective modulator of the NMDA receptor. The novel GFPA class of compounds has been specifically designed to achieve the well-documented efficacy of classic NMDAR-modulating drugs, while avoiding their serious side effects.
In previously reported preclinical studies, GLYX-13 demonstrated the robust antidepressant-like activity of ketamine, including its rapid onset and long duration of effect, with no signs of side effects. In preclinical studies, GLYX-13 has demonstrated the widest therapeutic ratio between efficacy and side effects (>500:1) of any known NMDAR modulator.
In the new study, researchers employed a sophisticated preclinical model measuring whether subjects detect and respond to the presence of a specific drug. Rats were trained to accurately discriminate whether ketamine or saline was present in a routine injection, by choosing one of two levers that delivers a reward when correctly matched to the injected substance. The tests were run using increasing doses of ketamine and GLYX-13, including doses that are known to produce antidepressant effects in preclinical models. The rats receiving ketamine selected the "ketamine trained" lever over the "saline trained" lever as the dose was increased, until they were overcome by impairment from the drug. In contrast, the rats receiving increasing doses of GLYX-13 did not preferentially select the "ketamine" lever over the "saline" lever and continued responding until the end of the experiment.*
"This well-validated model shows dramatically different responses in rats dosed with ketamine and with GLYX-13," said Robert Balster, Ph.D., professor of Pharmacology and Toxicology and director of the Institute for Drug and Alcohol Studies at Virginia Commonwealth University, an author of the study and a recognized expert on drug dependence. "Despite its therapeutic potential, the NMDAR modulator ketamine is a well-known drug of abuse with sedative and dissociative effects. GLYX-13 also acts at the NMDA receptor, but it has a different pharmacology and appears to be devoid of these effects, making it a promising candidate for development as a medication."
Numerous studies have shown that ketamine has a markedly faster onset of action than other antidepressants (within hours, instead of weeks) and alleviates depression symptoms in a greater proportion of patients. In studies in preclinical models of depression, GLYX-13 demonstrates antidepressant-like effects consistent with those of ketamine, with antidepressant-like efficacy that was evident within minutes of administering a single dose and lasted more than two weeks post-dosing. No ketamine-like side effects were observed.
J. David Leander, Ph.D., chief scientific adviser to Naurex and an author of the study, commented, "These new data produced by experts in the pharmacology of drug dependence further confirm the clean side effect profile we have seen to date with GLYX-13. In our Phase I trial, there was no sign of any behavioral impairment or ketamine-like subjective effects at drug exposures that exceeded the 'therapeutic range' established in our animal studies. We are currently initiating a Phase II trial of GLYX-13 in patients who are not achieving an adequate response to their current antidepressant agents."
In addition to GLYX-13, Naurex is developing the NRX-1050 series of GFPAs, including numerous second-generation, orally available molecules with structures and mechanisms of action similar to GLYX-13.
The 49th Annual Meeting of the American College of Neuropsychopharmacology is being held at the Fontainebleau Resort, Miami Beach, Florida, December 5-9, 2010.
*Lack of ketamine-like discriminative effects of GLYX-13: A novel NMDA receptor glycine site functional partial agonist with antidepressant-like preclinical effects, J. David Leander, Katherine Nicholson, Robert Balster, Jeffrey Burgdorf, Joseph Moskal.
About NMDA Receptor Modulators and Depression
The glutamate receptor subtype known as NMDA plays a central role in modulating aspects of brain activity. The antidepressant effects of known NMDAR modulators, such as ketamine, have been confirmed in multiple clinical studies over the last decade. These studies have shown dramatic efficacy in patients with treatment-resistant and bipolar depression, demonstrating response rates greater than 50%, fast onset of action within hours of a single dose and a long duration of effect. The antidepressant efficacy of ketamine has been underscored in recent studies published in Science and the Archives of General Psychiatry. But ketamine and other known NMDAR blockers are also associated with significant toxicities at or near their therapeutic doses. These side effects, which include schizophrenia-like effects, behavioral impairment and abuse liability, have limited the therapeutic potential of these agents.
About Glycine-Site Functional Partial Agonists
GFPAs modulate the NMDA receptor in a novel and selective way that results in the largest therapeutic index of any known NMDAR modulator. GFPAs are being developed with the goal of achieving the antidepressant efficacy and rapid onset seen with conventional NMDAR modulators, but without their limiting side effects. The efficacy potential of GFPAs has been demonstrated in animal models in a number of CNS disorders, including major depressive disorder, neuropathic pain, schizophrenia, anxiety, Alzheimer's disease and other cognition disorders. In these studies, GFPAs did not exhibit the schizophrenia-like effects associated with conventional NMDAR-modulating drugs.
Ketamine and similar NMDAR-modulating agents act very rapidly to alleviate the symptoms of depression and bipolar disorder, but their clinical utility has been hampered by their potential for abuse and behavioral impairment, including schizophrenia-like effects, at doses near the therapeutic dose. GLYX-13 is Naurex's lead glycine-site functional partial agonist (GFPA) selective modulator of the NMDA receptor. The novel GFPA class of compounds has been specifically designed to achieve the well-documented efficacy of classic NMDAR-modulating drugs, while avoiding their serious side effects.
In previously reported preclinical studies, GLYX-13 demonstrated the robust antidepressant-like activity of ketamine, including its rapid onset and long duration of effect, with no signs of side effects. In preclinical studies, GLYX-13 has demonstrated the widest therapeutic ratio between efficacy and side effects (>500:1) of any known NMDAR modulator.
In the new study, researchers employed a sophisticated preclinical model measuring whether subjects detect and respond to the presence of a specific drug. Rats were trained to accurately discriminate whether ketamine or saline was present in a routine injection, by choosing one of two levers that delivers a reward when correctly matched to the injected substance. The tests were run using increasing doses of ketamine and GLYX-13, including doses that are known to produce antidepressant effects in preclinical models. The rats receiving ketamine selected the "ketamine trained" lever over the "saline trained" lever as the dose was increased, until they were overcome by impairment from the drug. In contrast, the rats receiving increasing doses of GLYX-13 did not preferentially select the "ketamine" lever over the "saline" lever and continued responding until the end of the experiment.*
"This well-validated model shows dramatically different responses in rats dosed with ketamine and with GLYX-13," said Robert Balster, Ph.D., professor of Pharmacology and Toxicology and director of the Institute for Drug and Alcohol Studies at Virginia Commonwealth University, an author of the study and a recognized expert on drug dependence. "Despite its therapeutic potential, the NMDAR modulator ketamine is a well-known drug of abuse with sedative and dissociative effects. GLYX-13 also acts at the NMDA receptor, but it has a different pharmacology and appears to be devoid of these effects, making it a promising candidate for development as a medication."
Numerous studies have shown that ketamine has a markedly faster onset of action than other antidepressants (within hours, instead of weeks) and alleviates depression symptoms in a greater proportion of patients. In studies in preclinical models of depression, GLYX-13 demonstrates antidepressant-like effects consistent with those of ketamine, with antidepressant-like efficacy that was evident within minutes of administering a single dose and lasted more than two weeks post-dosing. No ketamine-like side effects were observed.
J. David Leander, Ph.D., chief scientific adviser to Naurex and an author of the study, commented, "These new data produced by experts in the pharmacology of drug dependence further confirm the clean side effect profile we have seen to date with GLYX-13. In our Phase I trial, there was no sign of any behavioral impairment or ketamine-like subjective effects at drug exposures that exceeded the 'therapeutic range' established in our animal studies. We are currently initiating a Phase II trial of GLYX-13 in patients who are not achieving an adequate response to their current antidepressant agents."
In addition to GLYX-13, Naurex is developing the NRX-1050 series of GFPAs, including numerous second-generation, orally available molecules with structures and mechanisms of action similar to GLYX-13.
The 49th Annual Meeting of the American College of Neuropsychopharmacology is being held at the Fontainebleau Resort, Miami Beach, Florida, December 5-9, 2010.
*Lack of ketamine-like discriminative effects of GLYX-13: A novel NMDA receptor glycine site functional partial agonist with antidepressant-like preclinical effects, J. David Leander, Katherine Nicholson, Robert Balster, Jeffrey Burgdorf, Joseph Moskal.
About NMDA Receptor Modulators and Depression
The glutamate receptor subtype known as NMDA plays a central role in modulating aspects of brain activity. The antidepressant effects of known NMDAR modulators, such as ketamine, have been confirmed in multiple clinical studies over the last decade. These studies have shown dramatic efficacy in patients with treatment-resistant and bipolar depression, demonstrating response rates greater than 50%, fast onset of action within hours of a single dose and a long duration of effect. The antidepressant efficacy of ketamine has been underscored in recent studies published in Science and the Archives of General Psychiatry. But ketamine and other known NMDAR blockers are also associated with significant toxicities at or near their therapeutic doses. These side effects, which include schizophrenia-like effects, behavioral impairment and abuse liability, have limited the therapeutic potential of these agents.
About Glycine-Site Functional Partial Agonists
GFPAs modulate the NMDA receptor in a novel and selective way that results in the largest therapeutic index of any known NMDAR modulator. GFPAs are being developed with the goal of achieving the antidepressant efficacy and rapid onset seen with conventional NMDAR modulators, but without their limiting side effects. The efficacy potential of GFPAs has been demonstrated in animal models in a number of CNS disorders, including major depressive disorder, neuropathic pain, schizophrenia, anxiety, Alzheimer's disease and other cognition disorders. In these studies, GFPAs did not exhibit the schizophrenia-like effects associated with conventional NMDAR-modulating drugs.
воскресенье, 18 сентября 2011 г.
Minnesota Health Care Group To Launch Pilot 'Pay-for-Performance' Initiative To Reduce Treatment Costs For Depression
The Buyers Health Care Action Group, a health care purchasing coalition in Minnesota for large employers, on Wednesday announced a pay-for-performance pilot program that will reward physicians who effectively treat depressed patients, the St. Paul Pioneer Press reports. The program will start in 2009 (Forster, St. Paul Pioneer Press, 5/28). The program is modeled after similar pay-for-performance initiatives launched in recent years to improve treatment of diabetes and cardiovascular problems (Lerner, Minneapolis Star Tribune, 5/29). Some of the employers participating in the new program include the state of Minnesota, 3M, Wells Fargo, the University of Minnesota, Target, Medtronic and Carlson (St. Paul Pioneer Press, 5/28).
Under the program, patients will complete a nine-question survey to help primary care physicians determine whether a patient is depressed and gauge the severity of his or her condition. Patients will be reassessed at six months and throughout the course of treatment (Minneapolis Star Tribune, 5/29). The goal of the program is to reduce depression within the first six months and achieve full recovery in one year. Physicians who meet the goal would receive a $100 bonus per patient. Insurance companies participating in the program have committed to paying the bonuses through 2010.
Participating employers also plan to share information next year about which physicians provided the most effective treatment for patients with depression. In addition, the program will evaluate how better depression management affects health care costs (St. Paul Pioneer Press, 5/28). Francois de Brantes -- CEO of Bridges to Excellence, a national pay-for-performance group working with the Minnesota project -- said, "Ultimately, we're not about dictating to physicians how they should practice medicine but rather holding them accountable for the results of how they practice."
Opponents of the initiative say it could have an adverse effect on patient care. Sue Abderholden, executive director of the National Alliance on Mental Illness, said, "Anytime we tie pay for performance to people getting better in terms of a mental illness, I always worry that there's going to be an incentive not to treat the hard-to-treat," adding, "Some people are harder to treat than others. So what happens with those folks?" (Minneapolis Star Tribune, 5/29).
Reprinted with kind 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.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
Under the program, patients will complete a nine-question survey to help primary care physicians determine whether a patient is depressed and gauge the severity of his or her condition. Patients will be reassessed at six months and throughout the course of treatment (Minneapolis Star Tribune, 5/29). The goal of the program is to reduce depression within the first six months and achieve full recovery in one year. Physicians who meet the goal would receive a $100 bonus per patient. Insurance companies participating in the program have committed to paying the bonuses through 2010.
Participating employers also plan to share information next year about which physicians provided the most effective treatment for patients with depression. In addition, the program will evaluate how better depression management affects health care costs (St. Paul Pioneer Press, 5/28). Francois de Brantes -- CEO of Bridges to Excellence, a national pay-for-performance group working with the Minnesota project -- said, "Ultimately, we're not about dictating to physicians how they should practice medicine but rather holding them accountable for the results of how they practice."
Opponents of the initiative say it could have an adverse effect on patient care. Sue Abderholden, executive director of the National Alliance on Mental Illness, said, "Anytime we tie pay for performance to people getting better in terms of a mental illness, I always worry that there's going to be an incentive not to treat the hard-to-treat," adding, "Some people are harder to treat than others. So what happens with those folks?" (Minneapolis Star Tribune, 5/29).
Reprinted with kind 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.
© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
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