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
пятница, 30 сентября 2011 г.
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.
четверг, 15 сентября 2011 г.
Patients, Be Patient: Brain Images Suggest New Therapy For Severe Depression Can Take Months To Work
It takes time - between three and 12 months - before a new type of therapy for treatment-resistant depression starts to benefit patients, according to new preliminary brain scan research that confirms earlier observations by psychiatrists about vagal nerve stimulation.
Saint Louis University, working in collaboration with Washington University School of Medicine, conducted a pilot study of brain scans of a small group of depressed patients who received vagal nerve stimulation after failing other therapies.
Positron emission tomography (PET) scans showed significant changes in brain activity starting three months after vagal nerve stimulation treatment began. These changes continued to evolve over the course of the next 21 months.
These changes in brain scans appear to "roughly parallel" the significantly delayed effects that psychiatrists observed in improvement in mood.
"The effects come after a significant period of treatment time," said Charles Conway, M.D., an assistant professor of psychiatry at Saint Louis University School of Medicine and the lead investigator of a vagal nerve stimulation research project conducted between 2000 and 2004.
Psychiatrists are not used to such a long time lag before a treatment begins to be effective, he added.
"This is very different from the delays we see with existing treatments for depression, including pharmacotherapy and electroconvulsive therapy (ECT)," Dr. Conway said. "The biggest changes in the brain that we're noting occur between 12 and 24 months after patients began receiving vagal nerve stimulation. In psychiatry, we're used to seeing results after six to 12 weeks."
Dr. Conway cautioned the findings are preliminary and need replication.
"But they suggest that in this type of therapy, the brain takes a relatively long time to change, perhaps as long as a year or more. In this sense, vagal nerve stimulation may represent a paradigm shift in the way we view depression treatment. Patients may have to be instructed to 'be patient,' with the expectations that the antidepressant effects will be slow to come."
The good news, however, seems to be that those who benefit from the treatment stay better.
"The existing evidence suggests that about 70 percent of patients who get better from vagal nerve stimulation at one year, stay better at two years," Dr. Conway said. "That is unheard of in a depressed population this severe, and suggests that the brain changes induced by this treatment appear to be long-lasting."
Dr. Conway examined the brain scans of patients at three, six, 12 and 24 months intervals after they began receiving vagal nerve stimulation. Eight patients participated in the study for the three and six month scans, six patients at 12 months and four patients at 24 months. The size of the study group grew smaller during the two year investigation.
"This is admittedly a very tiny population and the findings of this study are very preliminary. We need to do more research with a larger group of patients," Dr. Conway said. "That said, I think the findings are real and promising and beg more research."
Vagal nerve stimulation was approved in 2005 by the U.S. Food and Drug Administration to treat severe treatment-resistant depression. A vagal nerve stimulator is similar to a cardiac pacemaker and is implanted in the chest with leads that run under the skin to the vagal nerve in the neck. The device emits electrical pulses to simulate the brain, and also is used to treat epilepsy.
Doctors don't know exactly why vagal nerve therapy works, but Dr. Conway says his new research gives some clues.
When Dr. Conway examined the neuroimages of four patients 24 months after they began receiving vagal nerve stimulation, he found brain activity that was similar to what doctors see in patients who have received ECT.
"There actually appears to be decreased activity in regions of the prefrontal cortex, which is very much parallel to the findings of treatment response in ECT, and the opposite of findings seen in medication-response to depression."
He found unexpected action in the prefrontal cortex of the brain that is similar to brain activity in depressed patients immediately after they have received ECT and before its effect wears off.
"No one knows exactly how vagal nerve stimulation works. This suggests that one way in which it works may parallel ECT," Dr. Conway said.
"ECT had been considered to be the best therapy for treatment-resistant depression, but unfortunately the effects are not long-lasting. The data so far shows that one-third of the depressed patients who are treatment resistant are responsive to vagal nerve simulations and those who respond stay well."
Dr. Conway collaborated with John Chibnall, Ph.D, a psychologist and researcher in Saint Louis University's department of psychiatry; Yvette Sheline, M.D., a psychiatrist and researcher, and Mark Mintun, M.D., a radiologist/neuroimager and researcher, both of Washington University in St. Louis.
Dr. Conway is presenting his research results at the annual meeting of the Society of Biological Psychiatrists on May 18-20, and at the annual meeting of the American Psychiatrists Association in May 20-25.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.
Nancy Solomon
solomonnslu
Saint Louis University
slu/
Saint Louis University, working in collaboration with Washington University School of Medicine, conducted a pilot study of brain scans of a small group of depressed patients who received vagal nerve stimulation after failing other therapies.
Positron emission tomography (PET) scans showed significant changes in brain activity starting three months after vagal nerve stimulation treatment began. These changes continued to evolve over the course of the next 21 months.
These changes in brain scans appear to "roughly parallel" the significantly delayed effects that psychiatrists observed in improvement in mood.
"The effects come after a significant period of treatment time," said Charles Conway, M.D., an assistant professor of psychiatry at Saint Louis University School of Medicine and the lead investigator of a vagal nerve stimulation research project conducted between 2000 and 2004.
Psychiatrists are not used to such a long time lag before a treatment begins to be effective, he added.
"This is very different from the delays we see with existing treatments for depression, including pharmacotherapy and electroconvulsive therapy (ECT)," Dr. Conway said. "The biggest changes in the brain that we're noting occur between 12 and 24 months after patients began receiving vagal nerve stimulation. In psychiatry, we're used to seeing results after six to 12 weeks."
Dr. Conway cautioned the findings are preliminary and need replication.
"But they suggest that in this type of therapy, the brain takes a relatively long time to change, perhaps as long as a year or more. In this sense, vagal nerve stimulation may represent a paradigm shift in the way we view depression treatment. Patients may have to be instructed to 'be patient,' with the expectations that the antidepressant effects will be slow to come."
The good news, however, seems to be that those who benefit from the treatment stay better.
"The existing evidence suggests that about 70 percent of patients who get better from vagal nerve stimulation at one year, stay better at two years," Dr. Conway said. "That is unheard of in a depressed population this severe, and suggests that the brain changes induced by this treatment appear to be long-lasting."
Dr. Conway examined the brain scans of patients at three, six, 12 and 24 months intervals after they began receiving vagal nerve stimulation. Eight patients participated in the study for the three and six month scans, six patients at 12 months and four patients at 24 months. The size of the study group grew smaller during the two year investigation.
"This is admittedly a very tiny population and the findings of this study are very preliminary. We need to do more research with a larger group of patients," Dr. Conway said. "That said, I think the findings are real and promising and beg more research."
Vagal nerve stimulation was approved in 2005 by the U.S. Food and Drug Administration to treat severe treatment-resistant depression. A vagal nerve stimulator is similar to a cardiac pacemaker and is implanted in the chest with leads that run under the skin to the vagal nerve in the neck. The device emits electrical pulses to simulate the brain, and also is used to treat epilepsy.
Doctors don't know exactly why vagal nerve therapy works, but Dr. Conway says his new research gives some clues.
When Dr. Conway examined the neuroimages of four patients 24 months after they began receiving vagal nerve stimulation, he found brain activity that was similar to what doctors see in patients who have received ECT.
"There actually appears to be decreased activity in regions of the prefrontal cortex, which is very much parallel to the findings of treatment response in ECT, and the opposite of findings seen in medication-response to depression."
He found unexpected action in the prefrontal cortex of the brain that is similar to brain activity in depressed patients immediately after they have received ECT and before its effect wears off.
"No one knows exactly how vagal nerve stimulation works. This suggests that one way in which it works may parallel ECT," Dr. Conway said.
"ECT had been considered to be the best therapy for treatment-resistant depression, but unfortunately the effects are not long-lasting. The data so far shows that one-third of the depressed patients who are treatment resistant are responsive to vagal nerve simulations and those who respond stay well."
Dr. Conway collaborated with John Chibnall, Ph.D, a psychologist and researcher in Saint Louis University's department of psychiatry; Yvette Sheline, M.D., a psychiatrist and researcher, and Mark Mintun, M.D., a radiologist/neuroimager and researcher, both of Washington University in St. Louis.
Dr. Conway is presenting his research results at the annual meeting of the Society of Biological Psychiatrists on May 18-20, and at the annual meeting of the American Psychiatrists Association in May 20-25.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.
Nancy Solomon
solomonnslu
Saint Louis University
slu/
понедельник, 12 сентября 2011 г.
AstraZeneca Presents New Depression And Anxiety Results For SEROQUEL XR
The first data from the SEROQUEL XR™ (quetiapine fumarate) Extended Release clinical development programme in major depressive disorder (MDD)1,2 and generalised anxiety disorder (GAD)3 were presented at the 7th International Forum on Mood and Anxiety Disorders (IFMAD) in Budapest, AstraZeneca announced today. The data showed that patients who received SEROQUEL XR once daily experienced significant reductions in symptom severity compared to those on placebo in each of three trials, which investigated SEROQUEL XR as monotherapy in MDD,1 adjunctive therapy in patients with MDD2 with inadequate response to antidepressant therapy, and as monotherapy in GAD.3 These studies are part of a clinical development programme that involved over 7000 patients - one of the largest conducted in depression and anxiety. SEROQUEL® and SEROQUEL XR™ are not approved for the treatment of MDD or GAD.
Reductions in symptom severity were measured by improved (lowered) symptom scale scores. Two randomised, double-blind Phase III studies in MDD reported significantly reduced total scores on the Montgomery-?…sberg Depression Rating Scale (MADRS) after 6 weeks of treatment with once daily SEROQUEL XR. In the MDD monotherapy study, mean MADRS score was significantly improved for patients receiving SEROQUEL XR 150 mg (-14.81; p
Martin Brecher, Executive Director Medical Science, AstraZeneca said: "The data are very encouraging and suggest SEROQUEL XR has the potential to provide a new treatment choice in this area particularly among patients who fail antidepressant therapy with existing treatment. The study program not only covers adjunct treatment but extended also to monotherapy. New therapy options are needed for treating MDD and GAD because currently available antidepressants do not achieve symptom remission in a substantial proportion of patients. Over the coming months and years we will learn more about how far an antipsychotic like SEROQUEL XR may provide a new option for these patients. AstraZeneca plans regulatory submissions in 2008."
Recently presented data may help to explain the study data in MDD and GAD alongside SEROQUEL's known efficacy in bipolar depression. A pre-clinical study used brain imaging with positron emission tomography (PET) to investigate the mechanism of action of SEROQUEL® in non-human primates.4 SEROQUEL (quetiapine fumarate), both directly and indirectly (via its major active metabolite norquetiapine), was found to target the dopamine D2 and the serotonin 5-HT2A receptors in the brain at blood concentrations similar to those during treatment with clinically recommended doses of SEROQUEL in humans. Additionally, SEROQUEL's major active metabolite norquetiapine was shown to target NET - the transporter for norepinephrine (noradrenaline). Inhibition of NET elevates norepinephrine (noradrenaline) levels in specific areas of the brain, an effect that is associated with antidepressant action.
Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 25 million* patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 77 countries for the treatment of bipolar mania, and in 11 countries including the USA for the treatment of bipolar depression. SEROQUEL XR was launched for the treatment of schizophrenia in the US in 2007, and its clinical development program and planned regulatory filings extend through bipolar disorder to major depressive disorder (MDD) and generalised anxiety disorder (GAD).
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
SEROQUEL XR™ and SEROQUEL® are trademarks of the AstraZeneca group of companies.
References
1. Montgomery S, et al. A randomised, placebo-controlled study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
2. Bauer M, et al. Results from a phase III study of extended release quetiapine fumarate (quetiapine XR) as add-on to antidepressants in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
3. Bandelow B, et al. Results from a phase III study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder. Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
4. Nyberg S et al. PET-measured D2, 5-HT2, and NET occupancy by quetiapine and N-desalkyl-quetiapine in non-human primates. Presented at the European Congress of Neuropsychopharmacology, Vienna, Austria, 13-17 October, 2007
*This estimate is based upon: (1) assumptions as to persistence (the number of prescriptions per patient) based upon 2002 market research; and (2) projections of prescriptions since launch based upon information available in the US and 13 of the 50 other countries in which SEROQUEL is marketed.
For further information, please visit astrazeneca or astrazenecapressoffice.
What is Anxiety?
For more information on what anxiety is and what to do about it, please see:
What is Anxiety? What Causes Anxiety? What To Do About It.
View drug information on Seroquel.
Reductions in symptom severity were measured by improved (lowered) symptom scale scores. Two randomised, double-blind Phase III studies in MDD reported significantly reduced total scores on the Montgomery-?…sberg Depression Rating Scale (MADRS) after 6 weeks of treatment with once daily SEROQUEL XR. In the MDD monotherapy study, mean MADRS score was significantly improved for patients receiving SEROQUEL XR 150 mg (-14.81; p
Martin Brecher, Executive Director Medical Science, AstraZeneca said: "The data are very encouraging and suggest SEROQUEL XR has the potential to provide a new treatment choice in this area particularly among patients who fail antidepressant therapy with existing treatment. The study program not only covers adjunct treatment but extended also to monotherapy. New therapy options are needed for treating MDD and GAD because currently available antidepressants do not achieve symptom remission in a substantial proportion of patients. Over the coming months and years we will learn more about how far an antipsychotic like SEROQUEL XR may provide a new option for these patients. AstraZeneca plans regulatory submissions in 2008."
Recently presented data may help to explain the study data in MDD and GAD alongside SEROQUEL's known efficacy in bipolar depression. A pre-clinical study used brain imaging with positron emission tomography (PET) to investigate the mechanism of action of SEROQUEL® in non-human primates.4 SEROQUEL (quetiapine fumarate), both directly and indirectly (via its major active metabolite norquetiapine), was found to target the dopamine D2 and the serotonin 5-HT2A receptors in the brain at blood concentrations similar to those during treatment with clinically recommended doses of SEROQUEL in humans. Additionally, SEROQUEL's major active metabolite norquetiapine was shown to target NET - the transporter for norepinephrine (noradrenaline). Inhibition of NET elevates norepinephrine (noradrenaline) levels in specific areas of the brain, an effect that is associated with antidepressant action.
Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 25 million* patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 77 countries for the treatment of bipolar mania, and in 11 countries including the USA for the treatment of bipolar depression. SEROQUEL XR was launched for the treatment of schizophrenia in the US in 2007, and its clinical development program and planned regulatory filings extend through bipolar disorder to major depressive disorder (MDD) and generalised anxiety disorder (GAD).
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
SEROQUEL XR™ and SEROQUEL® are trademarks of the AstraZeneca group of companies.
References
1. Montgomery S, et al. A randomised, placebo-controlled study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
2. Bauer M, et al. Results from a phase III study of extended release quetiapine fumarate (quetiapine XR) as add-on to antidepressants in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
3. Bandelow B, et al. Results from a phase III study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder. Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
4. Nyberg S et al. PET-measured D2, 5-HT2, and NET occupancy by quetiapine and N-desalkyl-quetiapine in non-human primates. Presented at the European Congress of Neuropsychopharmacology, Vienna, Austria, 13-17 October, 2007
*This estimate is based upon: (1) assumptions as to persistence (the number of prescriptions per patient) based upon 2002 market research; and (2) projections of prescriptions since launch based upon information available in the US and 13 of the 50 other countries in which SEROQUEL is marketed.
For further information, please visit astrazeneca or astrazenecapressoffice.
What is Anxiety?
For more information on what anxiety is and what to do about it, please see:
What is Anxiety? What Causes Anxiety? What To Do About It.
View drug information on Seroquel.
пятница, 9 сентября 2011 г.
Spirituality Protects Against Depression Better Than Church Attendance
Those who worship a higher power often do so in different ways. Whether they are active in their religious community, or prefer to simply pray or meditate, new research out of Temple University suggests that a person's religiousness - also called religiosity - can offer insight into their risk for depression.
Lead researcher Joanna Maselko, Sc.D., characterized the religiosity of 918 study participants in terms of three domains of religiosity: religious service attendance, which refers to being involved with a church; religious well-being, which refers to the quality of a person's relationship with a higher power; and existential well-being, which refers to a person's sense of meaning and their purpose in life.
In a study published on-line this month in Psychological Medicine, Maselko and fellow researchers compared each domain of religiosity to their risk of depression, and were surprised to find that the group with higher levels of religious well-being were 1.5 times more likely to have had depression than those with lower levels of religious well-being.
Maselko theorizes this is because people with depression tend to use religion as a coping mechanism. As a result, they're more closely relating to God and praying more.
Researchers also found that those who attended religious services were 30 percent less likely to have had depression in their lifetime, and those who had high levels of existential well-being were 70 percent less likely to have had depression than those who had low levels of existential well-being.
Maselko says involvement in the church provides the opportunity for community interaction, which could help forge attachments to others, an important factor in preventing depression. She added that those with higher levels of existential-well being have a strong sense of their place in the world.
"People with high levels of existential well-being tend to have a good base, which makes them very centered emotionally," said Maselko. "People who don't have those things are at greater risk for depression, and those same people might also turn to religion to cope."
Maselko admits that researchers have yet to determine which comes first: depression or being religious, but is currently investigating the time sequence of this over people's lives to figure out the answer.
"For doctors, psychiatrists and counselors, it's hard to disentangle these elements when treating mental illness," she said. "You can't just ask a patient if they go to church to gauge their spirituality or coping behaviors. There are other components to consider when treating patients, and its important information for doctors to have."
Other authors on this study are Stephen Gilman, Sc.D., and Stephen Buka, Sc.D., from the department of Public Health at Harvard University and Brown University Medical School. This research was funded by a grant from the National Institutes of Mental Health and by the Jack Shand Award from the Society for the Scientific Study of Religion.
Lead researcher Joanna Maselko, Sc.D., characterized the religiosity of 918 study participants in terms of three domains of religiosity: religious service attendance, which refers to being involved with a church; religious well-being, which refers to the quality of a person's relationship with a higher power; and existential well-being, which refers to a person's sense of meaning and their purpose in life.
In a study published on-line this month in Psychological Medicine, Maselko and fellow researchers compared each domain of religiosity to their risk of depression, and were surprised to find that the group with higher levels of religious well-being were 1.5 times more likely to have had depression than those with lower levels of religious well-being.
Maselko theorizes this is because people with depression tend to use religion as a coping mechanism. As a result, they're more closely relating to God and praying more.
Researchers also found that those who attended religious services were 30 percent less likely to have had depression in their lifetime, and those who had high levels of existential well-being were 70 percent less likely to have had depression than those who had low levels of existential well-being.
Maselko says involvement in the church provides the opportunity for community interaction, which could help forge attachments to others, an important factor in preventing depression. She added that those with higher levels of existential-well being have a strong sense of their place in the world.
"People with high levels of existential well-being tend to have a good base, which makes them very centered emotionally," said Maselko. "People who don't have those things are at greater risk for depression, and those same people might also turn to religion to cope."
Maselko admits that researchers have yet to determine which comes first: depression or being religious, but is currently investigating the time sequence of this over people's lives to figure out the answer.
"For doctors, psychiatrists and counselors, it's hard to disentangle these elements when treating mental illness," she said. "You can't just ask a patient if they go to church to gauge their spirituality or coping behaviors. There are other components to consider when treating patients, and its important information for doctors to have."
Other authors on this study are Stephen Gilman, Sc.D., and Stephen Buka, Sc.D., from the department of Public Health at Harvard University and Brown University Medical School. This research was funded by a grant from the National Institutes of Mental Health and by the Jack Shand Award from the Society for the Scientific Study of Religion.
вторник, 6 сентября 2011 г.
Corcept Therapeutics Completes Enrollment In Second Phase 3 Study For Treating Psychotic Major Depression
Corcept
Therapeutics Incorporated (Nasdaq: CORT) announced today that it completed
patient enrollment in Corcept 09, the second of three Phase 3 clinical
trials in which CORLUX(R) (mifepristone) is being evaluated for treating
the psychotic features of psychotic major depression (PMD).
"We recently announced that patient enrollment was completed in our
first Phase 3 study, Corcept 07, and that we expect to report the results
of that trial in August," said Corcept's Chief Executive Officer Joseph K.
Belanoff, M.D. "In addition, we now expect to report the results from
Corcept 09 in September 2006. We expect to report the results of our third
Phase 3 trial, Corcept 06, in the fourth quarter."
About Psychotic Major Depression
PMD is a serious psychiatric disorder that affects about three million
people in the United States every year. It is more prevalent than either
schizophrenia or manic depression. The disorder is characterized by severe
depression accompanied by delusions, hallucinations or both. People with
PMD are approximately 70 times more likely to commit suicide than the
general population and often require lengthy and expensive hospital stays.
There is no FDA-approved treatment for PMD.
A Description of Study 09
Study 09 is a randomized, double-blind, placebo-controlled study that
is being conducted in Europe. The primary endpoint is the proportion of
patients with at least a 50 percent improvement in the Brief Psychiatric
Rating Scale Positive Symptom Subscale (BPRS PSS) at both Day 7 and Day 28, a responder analysis. A secondary endpoint is the proportion of patients
with at least a 50 percent improvement in the BPRS PSS at both Day 7 and
Day 56. The BPRS is an 18-item rating instrument used to assess
psychopathology, and the PSS includes the four items in the BPRS that
specifically measure psychosis. Patients must have at least mild psychotic
symptoms (BPRS PSS greater than or equal to 12) to enter the study. Study
enrollees may be either inpatients or outpatients. BPRS PSS assessments are
made at Days 14, 42 and 56.
Patients may not take any antidepressant or antipsychotic medication
for at least one week before study randomization. At randomization, they
are placed in a one-to-one distribution into either a treatment group or a
placebo group. Patients in the treatment group receive 600 mg of CORLUX
once daily for a period of seven days. All patients receive antidepressant
therapy starting on Day 1 and through Day 56. Treatment with antipsychotic
medications or electroconvulsive therapy at any time during the study
results in the patient being classified as a non-responder.
Previously Completed Trials
The company has completed four studies of CORLUX for treating the
psychotic features of PMD. In January 2001, a dose-finding clinical trial
evaluated the efficacy, tolerability of and dose response to CORLUX. The
results showed that after one week of treatment, approximately two-thirds
of the patients in the two higher dosage groups (600 mg and 1200 mg)
experienced clinically meaningful reductions in psychosis, as measured by
the BPRS PSS. Based on these encouraging results, Corcept conducted two
double-blind, placebo-controlled safety and efficacy clinical trials (Study
02 and Study 03) in which a total of 429 patients were enrolled.
Study 02 indicated that CORLUX was well tolerated, and there were no
discernible problems with drug interactions between CORLUX and commonly
prescribed antipsychotic and antidepressant medications. Study 03
demonstrated with statistical significance that patients in the CORLUX
group were more likely than patients in the placebo group to achieve a 50
percent reduction in the BPRS PSS at Day 7, sustained to Day 28. At the
request of the FDA, approximately one third of the 221 patients enrolled in
this study had efficacy measures taken at Day 56. Of those patients who
exhibited at least mild psychotic symptoms on Day 0 (BPRS PSS greater than
or equal to 12) Study 03 showed with statistical significance that patients
receiving CORLUX were more likely than patients receiving placebo to
achieve a 50% reduction in the BPRS PSS at day 7 sustained to day 56.
A fourth trial involved an open-label study of the safety of
retreatment in patients with a favorable response to treatment in Studies
02 and 03. The results indicated that patients tolerated their retreatment
well. Twenty-eight patients participated in this study.
About Corcept Therapeutics Incorporated
Corcept Therapeutics Incorporated is a pharmaceutical company focused
on developing drugs for treating severe psychiatric and neurological
diseases. Corcept's lead product, CORLUX, is in Phase 3 clinical trials for
treating the psychotic features of PMD. The drug is administered orally to
PMD patients once per day for seven days. CORLUX, a potent GR-II
antagonist, appears to reduce the effects of the elevated and abnormal
release patterns of cortisol seen in PMD. The company has also initiated a
proof-of-concept study to evaluate the ability of CORLUX to mitigate weight
gain associated with the use of olanzapine. For more information, please
visit corcept.
Forward-looking Statements
Statements made in this news release -- other than statements of
historical fact -- are forward-looking statements. These include
information relating to Corcept's PMD clinical development program, FDA
agreements, and the timing of the completion of pivotal Phase 3 trials.
Forward-looking statements are subject to a number of known and unknown
risks and uncertainties that might cause actual results to differ
materially from those expressed or implied here. For example, there can be
no assurances on the efficacy, safety, completion or success of clinical
trials; the regulatory process or regulatory approvals; or commercial
success; in addition, trial timetables may not be accurate. Risk factors
are explained in the company's SEC filings, all of which are available from
its Web site ( corcept ) or from the SEC's Web site ( sec ).
The company does not have any intention or duty to update forward-looking
statements made in this news release.
Corcept Therapeutics Incorporated
corcept/
Therapeutics Incorporated (Nasdaq: CORT) announced today that it completed
patient enrollment in Corcept 09, the second of three Phase 3 clinical
trials in which CORLUX(R) (mifepristone) is being evaluated for treating
the psychotic features of psychotic major depression (PMD).
"We recently announced that patient enrollment was completed in our
first Phase 3 study, Corcept 07, and that we expect to report the results
of that trial in August," said Corcept's Chief Executive Officer Joseph K.
Belanoff, M.D. "In addition, we now expect to report the results from
Corcept 09 in September 2006. We expect to report the results of our third
Phase 3 trial, Corcept 06, in the fourth quarter."
About Psychotic Major Depression
PMD is a serious psychiatric disorder that affects about three million
people in the United States every year. It is more prevalent than either
schizophrenia or manic depression. The disorder is characterized by severe
depression accompanied by delusions, hallucinations or both. People with
PMD are approximately 70 times more likely to commit suicide than the
general population and often require lengthy and expensive hospital stays.
There is no FDA-approved treatment for PMD.
A Description of Study 09
Study 09 is a randomized, double-blind, placebo-controlled study that
is being conducted in Europe. The primary endpoint is the proportion of
patients with at least a 50 percent improvement in the Brief Psychiatric
Rating Scale Positive Symptom Subscale (BPRS PSS) at both Day 7 and Day 28, a responder analysis. A secondary endpoint is the proportion of patients
with at least a 50 percent improvement in the BPRS PSS at both Day 7 and
Day 56. The BPRS is an 18-item rating instrument used to assess
psychopathology, and the PSS includes the four items in the BPRS that
specifically measure psychosis. Patients must have at least mild psychotic
symptoms (BPRS PSS greater than or equal to 12) to enter the study. Study
enrollees may be either inpatients or outpatients. BPRS PSS assessments are
made at Days 14, 42 and 56.
Patients may not take any antidepressant or antipsychotic medication
for at least one week before study randomization. At randomization, they
are placed in a one-to-one distribution into either a treatment group or a
placebo group. Patients in the treatment group receive 600 mg of CORLUX
once daily for a period of seven days. All patients receive antidepressant
therapy starting on Day 1 and through Day 56. Treatment with antipsychotic
medications or electroconvulsive therapy at any time during the study
results in the patient being classified as a non-responder.
Previously Completed Trials
The company has completed four studies of CORLUX for treating the
psychotic features of PMD. In January 2001, a dose-finding clinical trial
evaluated the efficacy, tolerability of and dose response to CORLUX. The
results showed that after one week of treatment, approximately two-thirds
of the patients in the two higher dosage groups (600 mg and 1200 mg)
experienced clinically meaningful reductions in psychosis, as measured by
the BPRS PSS. Based on these encouraging results, Corcept conducted two
double-blind, placebo-controlled safety and efficacy clinical trials (Study
02 and Study 03) in which a total of 429 patients were enrolled.
Study 02 indicated that CORLUX was well tolerated, and there were no
discernible problems with drug interactions between CORLUX and commonly
prescribed antipsychotic and antidepressant medications. Study 03
demonstrated with statistical significance that patients in the CORLUX
group were more likely than patients in the placebo group to achieve a 50
percent reduction in the BPRS PSS at Day 7, sustained to Day 28. At the
request of the FDA, approximately one third of the 221 patients enrolled in
this study had efficacy measures taken at Day 56. Of those patients who
exhibited at least mild psychotic symptoms on Day 0 (BPRS PSS greater than
or equal to 12) Study 03 showed with statistical significance that patients
receiving CORLUX were more likely than patients receiving placebo to
achieve a 50% reduction in the BPRS PSS at day 7 sustained to day 56.
A fourth trial involved an open-label study of the safety of
retreatment in patients with a favorable response to treatment in Studies
02 and 03. The results indicated that patients tolerated their retreatment
well. Twenty-eight patients participated in this study.
About Corcept Therapeutics Incorporated
Corcept Therapeutics Incorporated is a pharmaceutical company focused
on developing drugs for treating severe psychiatric and neurological
diseases. Corcept's lead product, CORLUX, is in Phase 3 clinical trials for
treating the psychotic features of PMD. The drug is administered orally to
PMD patients once per day for seven days. CORLUX, a potent GR-II
antagonist, appears to reduce the effects of the elevated and abnormal
release patterns of cortisol seen in PMD. The company has also initiated a
proof-of-concept study to evaluate the ability of CORLUX to mitigate weight
gain associated with the use of olanzapine. For more information, please
visit corcept.
Forward-looking Statements
Statements made in this news release -- other than statements of
historical fact -- are forward-looking statements. These include
information relating to Corcept's PMD clinical development program, FDA
agreements, and the timing of the completion of pivotal Phase 3 trials.
Forward-looking statements are subject to a number of known and unknown
risks and uncertainties that might cause actual results to differ
materially from those expressed or implied here. For example, there can be
no assurances on the efficacy, safety, completion or success of clinical
trials; the regulatory process or regulatory approvals; or commercial
success; in addition, trial timetables may not be accurate. Risk factors
are explained in the company's SEC filings, all of which are available from
its Web site ( corcept ) or from the SEC's Web site ( sec ).
The company does not have any intention or duty to update forward-looking
statements made in this news release.
Corcept Therapeutics Incorporated
corcept/
суббота, 3 сентября 2011 г.
Antidepressants may lower risk of recurrent heart attack in depressed heart attack patients
In depressed patients who have experienced a heart attack, use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), was associated with a reduced risk of death and recurrent heart attack, according to an article in the July issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Cardiovascular disease (CVD) is the leading cause of death, major disease and disability among U.S. men and women, according to background information in the article. Major depression was found in approximately 20 percent of patients with a recent myocardial infarction (MI; heart attack); a similar prevalence was found for minor depression. Depression is a risk factor for recurrent non-fatal heart attack and cardiac death in patients who experience an acute MI (AMI), independent of cardiac disease severity. Despite their effectiveness in treating depression, the use of antidepressants in patients with CVD remains controversial.
C. Barr Taylor, M.D., from Stanford Medical Center, Stanford, Calif., and colleagues conducted a secondary analysis of data from the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial to determine the effects of antidepressants on post-MI patients. The ENRICHD trial randomized 2,481 depressed and/or socially isolated patients from October 1, 1996 to October 31, 1999. The analysis in this report is based on 1834 patients (985 men and 849 women) who had depression, with or without low social support. Of these, 446 patients took antidepressants during the study, including 301 who were prescribed SSRIs (a class of drugs that increases the levels of serotonin in the body); and 145 patients who were prescribed other types of antidepressants.
During an average follow-up of 29 months, 457 fatal and non-fatal cardiovascular events occurred. Twenty-six percent (361 of 1,388) of the patients who did not receive antidepressants died or had a recurrent MI, compared to 21.5 percent (96 of 446) of the patients who did take antidepressants. After adjusting for baseline depression and cardiac risk, SSRI use was associated with 43 percent lower risk of death or recurrent non-fatal MI, and 43 percent lower risk of death from all causes, compared with patients not receiving SSRIs. Risk of death or recurrent MI, all-cause death, or recurrent MI was 28 percent, 36 percent, and 27 percent lower, respectively, in patients taking non-SSRI antidepressants, compared with nonusers.
"The main finding of this study is that antidepressant use post-AMI by depressed patients in the ENRICHD clinical trial was associated with significantly lower rates of the study primary end points, death and reinfarction [recurrent heart attack]," the authors write.
(Arch Gen Psychiatry. 2005; 62: 792-798. Available pre-embargo to the media at jamamedia.)
Editor's Note: This study was supported by contracts from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Editorial: Does Treating Post-Myocardial Infarction Depression Reduce Medical Mortality?
In an editorial accompanying this study, Alexander H. Glassman, M.D., of the New York State Psychiatric Institute, writes that in the ENRICHD trial "only the most depressed patients, those known to be at higher risk for cardiac events, were offered antidepressants. In addition, there was no control over when the drug was started or stopped, and even the reported start and stop times were only estimates. However, the sample was large, the number of events reasonable, and the magnitude of the effect is hard to ignore. Had the ENRICHD study observed an uncontrolled 40 percent increase in mortality with antidepressant drug treatment, public advocates would be clamoring for review by the Food and Drug Administration, label changes, or even 'black box' warnings. Yet this observation of a 40 percent decrease in life-threatening outcomes has been in the literature for almost three years with no systematic follow-up and minimal medical or psychiatric awareness."
"There are multiple mechanisms by which depression could increase vascular disease," Dr. Glassman writes. "It increases platelet activation and inflammatory markers, reduces heart variability, and leads to multiple adverse health behaviors; all are associated with increased cardiovascular risk and death. Whatever links depression and heart disease, it is more likely to involve all of the above rather than any single pathway."
"Acknowledging the implications of MDD [major depressive disorder] for cardiac morbidity and mortality would validate depression as a systemic disease with implications for the entire body, and reduce the stigma of this diagnosis for medical professionals, the public, and the patients themselves," Dr. Glassman concludes. "The ENRICHD investigators have made a significant step in that direction."
(Arch Gen Psychiatry. 2005; 62: 711-712. Available pre-embargo to the media at jamamedia.)
For more information, contact JAMA/Archives Media Relations at 312-464-JAMA (5262) or email mediarelationsjama-archives.
JAMA and Archives Journals
jamamedia
Cardiovascular disease (CVD) is the leading cause of death, major disease and disability among U.S. men and women, according to background information in the article. Major depression was found in approximately 20 percent of patients with a recent myocardial infarction (MI; heart attack); a similar prevalence was found for minor depression. Depression is a risk factor for recurrent non-fatal heart attack and cardiac death in patients who experience an acute MI (AMI), independent of cardiac disease severity. Despite their effectiveness in treating depression, the use of antidepressants in patients with CVD remains controversial.
C. Barr Taylor, M.D., from Stanford Medical Center, Stanford, Calif., and colleagues conducted a secondary analysis of data from the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial to determine the effects of antidepressants on post-MI patients. The ENRICHD trial randomized 2,481 depressed and/or socially isolated patients from October 1, 1996 to October 31, 1999. The analysis in this report is based on 1834 patients (985 men and 849 women) who had depression, with or without low social support. Of these, 446 patients took antidepressants during the study, including 301 who were prescribed SSRIs (a class of drugs that increases the levels of serotonin in the body); and 145 patients who were prescribed other types of antidepressants.
During an average follow-up of 29 months, 457 fatal and non-fatal cardiovascular events occurred. Twenty-six percent (361 of 1,388) of the patients who did not receive antidepressants died or had a recurrent MI, compared to 21.5 percent (96 of 446) of the patients who did take antidepressants. After adjusting for baseline depression and cardiac risk, SSRI use was associated with 43 percent lower risk of death or recurrent non-fatal MI, and 43 percent lower risk of death from all causes, compared with patients not receiving SSRIs. Risk of death or recurrent MI, all-cause death, or recurrent MI was 28 percent, 36 percent, and 27 percent lower, respectively, in patients taking non-SSRI antidepressants, compared with nonusers.
"The main finding of this study is that antidepressant use post-AMI by depressed patients in the ENRICHD clinical trial was associated with significantly lower rates of the study primary end points, death and reinfarction [recurrent heart attack]," the authors write.
(Arch Gen Psychiatry. 2005; 62: 792-798. Available pre-embargo to the media at jamamedia.)
Editor's Note: This study was supported by contracts from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Editorial: Does Treating Post-Myocardial Infarction Depression Reduce Medical Mortality?
In an editorial accompanying this study, Alexander H. Glassman, M.D., of the New York State Psychiatric Institute, writes that in the ENRICHD trial "only the most depressed patients, those known to be at higher risk for cardiac events, were offered antidepressants. In addition, there was no control over when the drug was started or stopped, and even the reported start and stop times were only estimates. However, the sample was large, the number of events reasonable, and the magnitude of the effect is hard to ignore. Had the ENRICHD study observed an uncontrolled 40 percent increase in mortality with antidepressant drug treatment, public advocates would be clamoring for review by the Food and Drug Administration, label changes, or even 'black box' warnings. Yet this observation of a 40 percent decrease in life-threatening outcomes has been in the literature for almost three years with no systematic follow-up and minimal medical or psychiatric awareness."
"There are multiple mechanisms by which depression could increase vascular disease," Dr. Glassman writes. "It increases platelet activation and inflammatory markers, reduces heart variability, and leads to multiple adverse health behaviors; all are associated with increased cardiovascular risk and death. Whatever links depression and heart disease, it is more likely to involve all of the above rather than any single pathway."
"Acknowledging the implications of MDD [major depressive disorder] for cardiac morbidity and mortality would validate depression as a systemic disease with implications for the entire body, and reduce the stigma of this diagnosis for medical professionals, the public, and the patients themselves," Dr. Glassman concludes. "The ENRICHD investigators have made a significant step in that direction."
(Arch Gen Psychiatry. 2005; 62: 711-712. Available pre-embargo to the media at jamamedia.)
For more information, contact JAMA/Archives Media Relations at 312-464-JAMA (5262) or email mediarelationsjama-archives.
JAMA and Archives Journals
jamamedia
Подписаться на:
Сообщения (Atom)