More than half of people with chronic cough-a nagging cough that can last for months or even years-suffer from depressive
symptoms, according to a study to be presented at the American Thoracic Society International Conference on May 23.
The study of 100 people with chronic cough that had lasted an average of 9 years found that 53% suffered from depressive
symptoms. The percentage of men and women with chronic cough who suffered from depressive symptoms was similar, according to
study author Peter V. Dicpinigaitis, M.D., Director of the Montefiore Cough Center in the Bronx, NY.
Three months after the initial study, researchers have so far conducted a follow-up with two-thirds of the patients and found
that those whose cough had improved had significant reduction in depressive symptoms, while those whose cough did not improve
did not have any corresponding improvement in their depressive symptoms.
"A lot of people don't realize that cough is the single most common complaint for which patients seek medical attention in
the U.S.," said Dr. Dicpinigaitis, who is also Professor of Clinical Medicine at Albert Einstein College of Medicine and
Director of the ICU at Montefiore Medical Center. "This is the first study to look at the link between cough and depression."
Dr. Dicpinigaitis has seen more than 300 chronic cough patients in his practice, and was struck by how their cough has
affected their quality of life. "They are socially isolated and miserable. They are afraid to go out in public, go to church
or to a restaurant. Their cough affects their relationship and their jobs," he said. "Since cough doesn't kill people it
doesn't get the attention that other conditions get, but it is a tremendous quality of life issue."
Chronic cough has three main causes, either alone or in combination, Dr. Dicpinigaitis said: post-nasal drip, asthma and
gastroesophageal reflux (GERD), commonly known as acid reflux. "Often the diagnosis is difficult because in many patients,
cough is their only symptom."
Treatments include older antihistamines combined with decongestant for cough from post-nasal drip; asthma medicines for
asthmatic cough; and high doses of drugs called proton-pump inhibitors for several months, sometimes combined with other
drugs, for GERD-related cough.
By the time patients have come to see him, they generally have already seen several other doctors and have been told they
simply have to live with the cough, Dr. Dicpinigaitis said. "My message for patients with chronic cough is, 'Don't give up,'"
he said. "Continue to seek out help. Once the cause of the cough is diagnosed, it can be treated." He noted that treatment
guidelines for chronic cough will be published later this year for physicians, and he is hopeful that this will improve the
treatment of the problem.
Contact: Jim Augustine
619-525-6216
American Thoracic Society
thoracic
вторник, 30 августа 2011 г.
суббота, 27 августа 2011 г.
Clinical hypnosis can be used to treat depression
Dr Michael Yapko has, for the last thirty years, specialized in the treatment of depression with clinical hypnosis. In a climate where anti-depressant medication is still physicians' first treatment choice, Dr. Yapko's approach to clinical practice still represents cutting-edge work.
Clinical hypnosis has been directly influenced by the current push for empirically supported treatments, and in recent years substantial high-quality research has assessed the effectiveness of hypnosis and its contribution to improving therapeutic outcome.
There is also a growing body of evidence demonstrating that, when hypnosis is part of the treatment process, it catalyses positive clinical outcomes and generally increases the benefits of established treatments.
"Hypnosis offers a way to conceptualise how human beings construct their individual realities, and how to interact more effectively with others; in clinical hypnosis hypnotic processes are employed as agents of effective communication and change," says Dr. Yapko, who was chosen to write the sections on Treating Depression and Brief Therapy for the Encyclopaedia Britannica Medical and Health Annuals. "Our knowledge of depression has greatly improved in recent years, firmly establishing the essential role of psychotherapy in treatment. Whenever psychotherapy is indicated, so are specific identifiable patterns of hypnotic influence, since the two are fundamentally inseparable."
It is estimated that at any one time almost 10% of the UK general population are suffering from depression. Worldwide the figure rises to over 100 million (Paul Gilbert, Overcoming Depression 1997), and the World Health Organisation estimates that by the year 2020 depression will be the second most burdensome illness in the world.
Financially, depression costs the British nation more than ?8 billion annually; included in this cost is provision of health and medical care, lost production and social security benefits." (Depression Alliance 1999).
BIOGRAPHY
Michael Yapko, Ph.D. is a clinical psychologist and marriage and family therapist based in Solana Beach, California. He is internationally recognised for his work in depression and outcome-focused psychotherapy, and has had a special interest spanning nearly a quarter century in the intricacies of brief therapy, the clinical applications of directive methods, and in training therapists to treat the disorder of major depression. He is the author of numerous books, book chapters, and articles on these subjects, including Treating Depression With Hypnosis: Integrating Cognitive-Behavioral and Strategic Approaches; Psychological 911: Depression; Hand-Me-Down Blues: How to Stop Depression From Spreading in Families; Breaking the Patterns of Depression; and Hypnosis and the Treatment of Depressions. Dr. Yapko is a member of the American Psychological Association, a clinical member of the American Association for Marriage and Family Therapy, and a Fellow of the Royal Society of Medicine.
Dr Yapko is a charismatic and engaging speaker, whose recent London masterclasses (February 2004) elicited high praise from delegates.
Formal Education
* Doctoral: Ph.D. in Professional Psychology, Clinical Specialization, United States International University, San Diego (1980).
* Masters: M.A. in Psychology. United States International University, San Diego (1978)
* Bachelors: B.A. in Psychology. University of Michigan, Ann Arbor (1976). Received academic class honors.
ABOUT CSCT
CSCT is the UK's main provider of counselling training programmes, having trained over 50,000 students over more than two decades working in the UK, Eire and Gibraltar with the education, charity, health and private sectors. The organisation specialises in creating, administering and supporting nationally approved programmes for counselling trainees, as well as delivering continuing professional development courses to already qualified counsellors, and counselling skills training to practitioners of a range of allied health professions and the private sector. With a proven track record in its field, CSCT is committed to providing high quality training that reflects current thinking and research in the field, and meets the changing needs of the marketplace.
After hosting Dr Yapko's successful masterclasses in London in February 2004, CSCT Events will be sponsoring his renowned Six-Day Comprehensive Training Course in Clinical Hypnosis, 6-8 May and 13-15 May 2005.
Zo? Fitzgerald-Pool, a UKCP registered psychotherapist who integrates hypnosis in her clinical practice, is CSCT's Director of Training and Development.
This article comes from counsellingtraining
Contact:
CSCT Ltd
9 Telfords Yard
6-8 The Highway
London, UK
E1W 2BS
t: 020 7977 7999
f: 020 7977 7990
e: infocounsellingtraining
Clinical hypnosis has been directly influenced by the current push for empirically supported treatments, and in recent years substantial high-quality research has assessed the effectiveness of hypnosis and its contribution to improving therapeutic outcome.
There is also a growing body of evidence demonstrating that, when hypnosis is part of the treatment process, it catalyses positive clinical outcomes and generally increases the benefits of established treatments.
"Hypnosis offers a way to conceptualise how human beings construct their individual realities, and how to interact more effectively with others; in clinical hypnosis hypnotic processes are employed as agents of effective communication and change," says Dr. Yapko, who was chosen to write the sections on Treating Depression and Brief Therapy for the Encyclopaedia Britannica Medical and Health Annuals. "Our knowledge of depression has greatly improved in recent years, firmly establishing the essential role of psychotherapy in treatment. Whenever psychotherapy is indicated, so are specific identifiable patterns of hypnotic influence, since the two are fundamentally inseparable."
It is estimated that at any one time almost 10% of the UK general population are suffering from depression. Worldwide the figure rises to over 100 million (Paul Gilbert, Overcoming Depression 1997), and the World Health Organisation estimates that by the year 2020 depression will be the second most burdensome illness in the world.
Financially, depression costs the British nation more than ?8 billion annually; included in this cost is provision of health and medical care, lost production and social security benefits." (Depression Alliance 1999).
BIOGRAPHY
Michael Yapko, Ph.D. is a clinical psychologist and marriage and family therapist based in Solana Beach, California. He is internationally recognised for his work in depression and outcome-focused psychotherapy, and has had a special interest spanning nearly a quarter century in the intricacies of brief therapy, the clinical applications of directive methods, and in training therapists to treat the disorder of major depression. He is the author of numerous books, book chapters, and articles on these subjects, including Treating Depression With Hypnosis: Integrating Cognitive-Behavioral and Strategic Approaches; Psychological 911: Depression; Hand-Me-Down Blues: How to Stop Depression From Spreading in Families; Breaking the Patterns of Depression; and Hypnosis and the Treatment of Depressions. Dr. Yapko is a member of the American Psychological Association, a clinical member of the American Association for Marriage and Family Therapy, and a Fellow of the Royal Society of Medicine.
Dr Yapko is a charismatic and engaging speaker, whose recent London masterclasses (February 2004) elicited high praise from delegates.
Formal Education
* Doctoral: Ph.D. in Professional Psychology, Clinical Specialization, United States International University, San Diego (1980).
* Masters: M.A. in Psychology. United States International University, San Diego (1978)
* Bachelors: B.A. in Psychology. University of Michigan, Ann Arbor (1976). Received academic class honors.
ABOUT CSCT
CSCT is the UK's main provider of counselling training programmes, having trained over 50,000 students over more than two decades working in the UK, Eire and Gibraltar with the education, charity, health and private sectors. The organisation specialises in creating, administering and supporting nationally approved programmes for counselling trainees, as well as delivering continuing professional development courses to already qualified counsellors, and counselling skills training to practitioners of a range of allied health professions and the private sector. With a proven track record in its field, CSCT is committed to providing high quality training that reflects current thinking and research in the field, and meets the changing needs of the marketplace.
After hosting Dr Yapko's successful masterclasses in London in February 2004, CSCT Events will be sponsoring his renowned Six-Day Comprehensive Training Course in Clinical Hypnosis, 6-8 May and 13-15 May 2005.
Zo? Fitzgerald-Pool, a UKCP registered psychotherapist who integrates hypnosis in her clinical practice, is CSCT's Director of Training and Development.
This article comes from counsellingtraining
Contact:
CSCT Ltd
9 Telfords Yard
6-8 The Highway
London, UK
E1W 2BS
t: 020 7977 7999
f: 020 7977 7990
e: infocounsellingtraining
среда, 24 августа 2011 г.
What Does Prozac Target?
Researchers at Cold Spring Harbor Laboratory on Long Island have identified which among several different kinds of cells in the brain is the chief target of the widely prescribed antidepressant Prozac. This discovery might enable a new generation of more specific treatments for depression, with fewer side effects, to be developed.
The findings also lay the foundation for many studies of the factors that control how, when, and where new neurons are generated from stem cells in the brain. Such work could eventually lead to cell replacement therapies for neurodegenerative and other brain disorders including Alzheimer's and Parkinson's disease.
It has been known for some years that Prozac (fluoxetine) is likely to relieve the symptoms of depression by somehow causing more neurons to be present in a particular region of the brain (the "dentate gyrus"). But the origins of these neurons, and how Prozac promotes their existence, have been a mystery until now.
By profiling the telltale marker proteins produced by different kinds of cells in the brains of adult mice, the researchers first defined discrete steps in the complex process, called neurogenesis, that converts unspecialized stem cells into mature, specialized neurons.
Next, knowing that Prozac treatment somehow increases the number of neurons in the brain, the researchers tested which step in the neurogenesis pathway might be stimulated by Prozac. They found that Prozac treatment specifically stimulates the generation of a kind of cells they dubbed "amplifying neural progenitors" or ANPs--the second step in the neurogenesis pathway from stem cells to mature neurons. (Illustration available on request)
The study is published in the published in the Proceedings of the National Academy of Sciences (advance on-line this week, in print on May 23). It was led by Grigori Enikolopov and spearheaded by postdoctoral fellow Juan Manuel Encinas.
To address the controversy surrounding the use of Prozac in children and in pregnant women, Enikolopov's group is currently testing the effects of the drug on brain neurogenesis in juvenile and pregnant mice. The results of those experiments may provide valuable information for assessing the possible effects of Prozac and related drugs on fetal and adolescent brain development.
The researchers are currently using the approach and tools they've developed to explore whether other treatments for depression--including other drugs and deep brain stimulation--act in the same way as Prozac or in different ways. In addition, the scientists are screening for new drugs that expand the production of brain neurons by stimulating ANP cells to multiply.
In collaboration with NASA researchers, experiments are also under way at Cold Spring Harbor Laboratory to assess how neurogenesis in the adult brain might be influenced by long-term, Mission-to-Mars levels of exposure to a particular kind of damaging radiation that's prevalent in space.
Peter Sherwood
sherwoodcshl
Cold Spring Harbor Laboratory
cshl
View drug information on Prozac Weekly.
The findings also lay the foundation for many studies of the factors that control how, when, and where new neurons are generated from stem cells in the brain. Such work could eventually lead to cell replacement therapies for neurodegenerative and other brain disorders including Alzheimer's and Parkinson's disease.
It has been known for some years that Prozac (fluoxetine) is likely to relieve the symptoms of depression by somehow causing more neurons to be present in a particular region of the brain (the "dentate gyrus"). But the origins of these neurons, and how Prozac promotes their existence, have been a mystery until now.
By profiling the telltale marker proteins produced by different kinds of cells in the brains of adult mice, the researchers first defined discrete steps in the complex process, called neurogenesis, that converts unspecialized stem cells into mature, specialized neurons.
Next, knowing that Prozac treatment somehow increases the number of neurons in the brain, the researchers tested which step in the neurogenesis pathway might be stimulated by Prozac. They found that Prozac treatment specifically stimulates the generation of a kind of cells they dubbed "amplifying neural progenitors" or ANPs--the second step in the neurogenesis pathway from stem cells to mature neurons. (Illustration available on request)
The study is published in the published in the Proceedings of the National Academy of Sciences (advance on-line this week, in print on May 23). It was led by Grigori Enikolopov and spearheaded by postdoctoral fellow Juan Manuel Encinas.
To address the controversy surrounding the use of Prozac in children and in pregnant women, Enikolopov's group is currently testing the effects of the drug on brain neurogenesis in juvenile and pregnant mice. The results of those experiments may provide valuable information for assessing the possible effects of Prozac and related drugs on fetal and adolescent brain development.
The researchers are currently using the approach and tools they've developed to explore whether other treatments for depression--including other drugs and deep brain stimulation--act in the same way as Prozac or in different ways. In addition, the scientists are screening for new drugs that expand the production of brain neurons by stimulating ANP cells to multiply.
In collaboration with NASA researchers, experiments are also under way at Cold Spring Harbor Laboratory to assess how neurogenesis in the adult brain might be influenced by long-term, Mission-to-Mars levels of exposure to a particular kind of damaging radiation that's prevalent in space.
Peter Sherwood
sherwoodcshl
Cold Spring Harbor Laboratory
cshl
View drug information on Prozac Weekly.
воскресенье, 21 августа 2011 г.
STAR*D Depression Study Finds Cognitive Therapy Equivalent To Medication But Selected By Fewer Patients
In the federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, outcomes for cognitive therapy as a second-step treatment were not different from outcomes of medication therapy. However, random assignment in this STAR*D level was based on each patient's treatment preferences, and only 26 percent of the patients accepted cognitive therapy as an option. These findings are reported in two articles in the May issue of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association (APA).
The treatment results are presented in "Cognitive Therapy as a Second-Step Treatment: A STAR*D Report," by Michael E. Thase, M.D., of the University of Pittsburgh, and other STAR*D investigators. The patients in the second treatment step had discontinued citalopram in the first treatment phase, either because it was not effective for them or because the side effects were too burdensome.
In the second step, 36 patients were switched from citalopram to cognitive therapy and 65 received cognitive therapy in addition to citalopram. The first group was compared with patients switched from citalopram to another medication, and the second group was compared with participants receiving citalopram plus a second medication.
The rates of remission over 12 weeks were 25 percent for the patients who switched to cognitive therapy and 23 percent for those who received it as augmentation. These rates were not significantly different from those for the comparison groups assigned to medication. Cognitive therapy produced remission more slowly than medication, but it produced fewer side effects.
Patients' preferences for the second treatment step in STAR*D are examined in "Which Second Step Treatments Are Acceptable to Depressed Outpatients? A STAR*D Report," by Stephen R. Wisniewski, Ph.D., of the University of Pittsburgh, and other STAR*D investigators. Patients were asked which treatments they found acceptable after the initial citalopram trial and whether they had a preference regarding a switch to a new treatment or augmentation of citalopram with another treatment. Patients' preferred treatments were considered in the random assignment of patients to the different treatment conditions.
Of the 1,439 participants who entered second-step treatment, only one percent accepted all treatment options. The 26 percent who accepted cognitive therapy were found to have more education and to be more likely to have a family history of mood disorder than patients who did not include cognitive therapy among their possible treatments. Patients with panic disorder were less likely to accept cognitive therapy. A switch from citalopram to a new treatment, rather than augmentation, was more likely to be accepted by participants in a primary care setting. Cognitive therapy was also less likely to accepted by patients with greater side effects or less reduction in depressive symptoms in the first treatment step. Those with concurrent drug abuse or recurrent depression were less likely to accept a switch strategy.
These findings are discussed in an editorial by Myrna Weissman, Ph.D., of Columbia University.
AJP Editor in Chief Robert Freedman, M.D., stated, "The lower rate of selection of cognitive therapy, despite its effectiveness and freedom from side effects, suggests that rapid, convenient treatment was foremost on patients' minds. Re-thinking psychotherapy to provide more assurance of early effect may improve its appeal to depressed people."
The STAR*D study was funded by the National Institute of Mental Health. Medications were provided at no cost by Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer and Wyeth Pharmaceuticals. Additional financial disclosures appear at the end of the article.
(Am J Psychiatry 2007; 164:790-799; 800-804)
About the American Journal of Psychiatry
The American Journal of Psychiatry, the official journal of the American Psychiatric Association, publishes a monthly issue with scientific articles submitted by psychiatrists and other scientists worldwide. The peer review and editing process is conducted independently of any other American Psychiatric Association components. Therefore, statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association. The Journal's editorial policies conform to the Uniform Requirements of the International Committee of Medical Journal Editors, of which it is a member. For further information about the Journal visit ajp.psychiatryonline.
About the American Psychiatric Association
The American Psychiatric Association is a national medical specialty society whose more than 38,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders. Visit the APA at psych and HealthyMinds.
The treatment results are presented in "Cognitive Therapy as a Second-Step Treatment: A STAR*D Report," by Michael E. Thase, M.D., of the University of Pittsburgh, and other STAR*D investigators. The patients in the second treatment step had discontinued citalopram in the first treatment phase, either because it was not effective for them or because the side effects were too burdensome.
In the second step, 36 patients were switched from citalopram to cognitive therapy and 65 received cognitive therapy in addition to citalopram. The first group was compared with patients switched from citalopram to another medication, and the second group was compared with participants receiving citalopram plus a second medication.
The rates of remission over 12 weeks were 25 percent for the patients who switched to cognitive therapy and 23 percent for those who received it as augmentation. These rates were not significantly different from those for the comparison groups assigned to medication. Cognitive therapy produced remission more slowly than medication, but it produced fewer side effects.
Patients' preferences for the second treatment step in STAR*D are examined in "Which Second Step Treatments Are Acceptable to Depressed Outpatients? A STAR*D Report," by Stephen R. Wisniewski, Ph.D., of the University of Pittsburgh, and other STAR*D investigators. Patients were asked which treatments they found acceptable after the initial citalopram trial and whether they had a preference regarding a switch to a new treatment or augmentation of citalopram with another treatment. Patients' preferred treatments were considered in the random assignment of patients to the different treatment conditions.
Of the 1,439 participants who entered second-step treatment, only one percent accepted all treatment options. The 26 percent who accepted cognitive therapy were found to have more education and to be more likely to have a family history of mood disorder than patients who did not include cognitive therapy among their possible treatments. Patients with panic disorder were less likely to accept cognitive therapy. A switch from citalopram to a new treatment, rather than augmentation, was more likely to be accepted by participants in a primary care setting. Cognitive therapy was also less likely to accepted by patients with greater side effects or less reduction in depressive symptoms in the first treatment step. Those with concurrent drug abuse or recurrent depression were less likely to accept a switch strategy.
These findings are discussed in an editorial by Myrna Weissman, Ph.D., of Columbia University.
AJP Editor in Chief Robert Freedman, M.D., stated, "The lower rate of selection of cognitive therapy, despite its effectiveness and freedom from side effects, suggests that rapid, convenient treatment was foremost on patients' minds. Re-thinking psychotherapy to provide more assurance of early effect may improve its appeal to depressed people."
The STAR*D study was funded by the National Institute of Mental Health. Medications were provided at no cost by Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer and Wyeth Pharmaceuticals. Additional financial disclosures appear at the end of the article.
(Am J Psychiatry 2007; 164:790-799; 800-804)
About the American Journal of Psychiatry
The American Journal of Psychiatry, the official journal of the American Psychiatric Association, publishes a monthly issue with scientific articles submitted by psychiatrists and other scientists worldwide. The peer review and editing process is conducted independently of any other American Psychiatric Association components. Therefore, statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association. The Journal's editorial policies conform to the Uniform Requirements of the International Committee of Medical Journal Editors, of which it is a member. For further information about the Journal visit ajp.psychiatryonline.
About the American Psychiatric Association
The American Psychiatric Association is a national medical specialty society whose more than 38,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders. Visit the APA at psych and HealthyMinds.
четверг, 18 августа 2011 г.
Parkinson's Disease Alters Patient's Ability To Learn From Rewards While Treatment Affects Ability To Learn From Negative Outcomes
A new neuropsychological memory test is helping to uncover how Parkinson's disease can alter people's ability to learn about the consequences of the choices they make. The test was developed by Dr. Mark Gluck, professor of neuroscience at the Center for Molecular and Behavioral Neuroscience at Rutgers University, Newark, working with co-researchers at Rutgers, New York University, and in Hungary.
As reported in a forthcoming article in the journal Brain (advanced access published May 4, 2009 -- doi:10.1093/brain/awp094), Gluck and co-researchers Nikoletta Bodi and Szabolcs Keri of Semmelweis University, Hungary, found that non-medicated patients in the early stages of Parkinson's were selectively impaired at learning from reward.
Patients in Hungary were tested using a novel feedback-learning task developed by Gluck and his colleagues: Catherine E. Myers, research professor, Rutgers University, Newark; and Nathaniel Daw, assistant professor, New York University. The research was supported by a Dekker Foundation Award from the Bachman-Strauss Dystonia and Parkinson Foundation.
"What we are seeing in recently diagnosed patients is that prior to being put on any medications, they exhibit a selective impairment in their ability to learn from positive (rewarding) outcomes while their sensitivity to learning from negative (or punishing) outcomes is normal," says Gluck, director of Rutgers' Center for Collaborative Research on Cognition and Parkinson's Disease.
This selective deficit in learning from reward is not surprising, says Gluck, because scientists have long known that dopamine is used to carry reward information throughout the brain. Parkinson's patients, however, have lost most of their dopamine-producing cells by the time they are first diagnosed with the disease. This decrease in their ability to process rewarding outcomes could be one reason why many Parkinson's patients experience depression, says Gluck. "It's not just that they have an awful disease, but they have lost the ability to process the rewarding aspects of life."
Gluck and colleagues found that this reward-learning deficit in un-medicated Parkinson's patients is in direct contrast to what is seen in patients once they begin treatment with dopamine agonists, a standard therapy for treating the disease's motor symptoms. On dopamine agonists, a patient's ability to learn from positive rewarding outcomes improved to normal levels. But there was a catch - their ability to learn from negative (or punishing) outcomes, which had previously been normal, was now impaired.
Gluck explains that an increased sensitivity to learning from events that results in positive outcomes, coupled with a decrease in the ability to learn from negative outcomes, could explain why some Parkinson patients treated with dopamine agonists develop impulse-control disorders, including pathological gambling, hypersexuality, alcoholism, and compulsive eating and shopping. All of these behaviors can be understood as reward-seeking behaviors in the absence of appropriate sensitivity to their negative consequences.
"For example," notes Gluck, "if your ability to learn from negative outcomes is reduced and you play the slot machines and win $10 for a few rounds but lose many more times in between, what you may recall best is the thrill of winning. As such, you will be hampered in your ability to learn that gambling can also have negative consequences."
The ability to test the effects on feedback learning in early onset Parkinson's disease could provide additional insight into the impact of dopamine loss on cognition and behavior. It also could pave the way for identifying which Parkinson's patients are most likely to experience agonist-related feedback problems so they can be treated with alternate medications.
Other ongoing research by Gluck and his clinical collaborators in New Jersey, New York, Europe and the Middle East aims to further understand how and why learning and decision making is impaired by Parkinson's disease and how the medications used to treat motor symptoms can impair or remediate these essential cognitive abilities.
Feedback Learning, Dementia, Depression and Drug Addiction
In addition to providing new insight into the effects of Parkinson's disease and dopamine agonists on learning and personality, the new feedback-learning tasks developed at Rutgers University are being used to study learning and decision-making deficits in people suffering from fronto-temporal dementia (FTD), a degenerative condition involving the front part of the brain's cortex. FTD is associated with dramatic changes in personality, behavior and thought processes, which can include inhibition, social withdrawal and compulsive behaviors.
With co-investigator Murray Grossman of the University of Pennsylvania, Gluck is studying changes in positive and negative feedback learning in those diagnosed with FTD. That research, funded with a grant from the Association for Frontotemporal Dementia, has the potential to help in identifying methods to aid in correcting behavior for FTD patients.
"If, for example, FTD patients learn better from reward then punishment, this would mean caregivers might be advised to avoid reacting negatively to inappropriate behaviors and to focus instead on rewarding patients for not engaging in inappropriate behaviors," says Gluck.
In related research, Gluck is working with Palestinian and Israel doctors, as part of a joint Rutgers-sponsored Israeli-Palestinian brain research project, to study cognitive deficits in Israeli and Palestinian patients suffering from Parkinson's disease and depression.
As reported in a forthcoming article in the journal Brain (advanced access published May 4, 2009 -- doi:10.1093/brain/awp094), Gluck and co-researchers Nikoletta Bodi and Szabolcs Keri of Semmelweis University, Hungary, found that non-medicated patients in the early stages of Parkinson's were selectively impaired at learning from reward.
Patients in Hungary were tested using a novel feedback-learning task developed by Gluck and his colleagues: Catherine E. Myers, research professor, Rutgers University, Newark; and Nathaniel Daw, assistant professor, New York University. The research was supported by a Dekker Foundation Award from the Bachman-Strauss Dystonia and Parkinson Foundation.
"What we are seeing in recently diagnosed patients is that prior to being put on any medications, they exhibit a selective impairment in their ability to learn from positive (rewarding) outcomes while their sensitivity to learning from negative (or punishing) outcomes is normal," says Gluck, director of Rutgers' Center for Collaborative Research on Cognition and Parkinson's Disease.
This selective deficit in learning from reward is not surprising, says Gluck, because scientists have long known that dopamine is used to carry reward information throughout the brain. Parkinson's patients, however, have lost most of their dopamine-producing cells by the time they are first diagnosed with the disease. This decrease in their ability to process rewarding outcomes could be one reason why many Parkinson's patients experience depression, says Gluck. "It's not just that they have an awful disease, but they have lost the ability to process the rewarding aspects of life."
Gluck and colleagues found that this reward-learning deficit in un-medicated Parkinson's patients is in direct contrast to what is seen in patients once they begin treatment with dopamine agonists, a standard therapy for treating the disease's motor symptoms. On dopamine agonists, a patient's ability to learn from positive rewarding outcomes improved to normal levels. But there was a catch - their ability to learn from negative (or punishing) outcomes, which had previously been normal, was now impaired.
Gluck explains that an increased sensitivity to learning from events that results in positive outcomes, coupled with a decrease in the ability to learn from negative outcomes, could explain why some Parkinson patients treated with dopamine agonists develop impulse-control disorders, including pathological gambling, hypersexuality, alcoholism, and compulsive eating and shopping. All of these behaviors can be understood as reward-seeking behaviors in the absence of appropriate sensitivity to their negative consequences.
"For example," notes Gluck, "if your ability to learn from negative outcomes is reduced and you play the slot machines and win $10 for a few rounds but lose many more times in between, what you may recall best is the thrill of winning. As such, you will be hampered in your ability to learn that gambling can also have negative consequences."
The ability to test the effects on feedback learning in early onset Parkinson's disease could provide additional insight into the impact of dopamine loss on cognition and behavior. It also could pave the way for identifying which Parkinson's patients are most likely to experience agonist-related feedback problems so they can be treated with alternate medications.
Other ongoing research by Gluck and his clinical collaborators in New Jersey, New York, Europe and the Middle East aims to further understand how and why learning and decision making is impaired by Parkinson's disease and how the medications used to treat motor symptoms can impair or remediate these essential cognitive abilities.
Feedback Learning, Dementia, Depression and Drug Addiction
In addition to providing new insight into the effects of Parkinson's disease and dopamine agonists on learning and personality, the new feedback-learning tasks developed at Rutgers University are being used to study learning and decision-making deficits in people suffering from fronto-temporal dementia (FTD), a degenerative condition involving the front part of the brain's cortex. FTD is associated with dramatic changes in personality, behavior and thought processes, which can include inhibition, social withdrawal and compulsive behaviors.
With co-investigator Murray Grossman of the University of Pennsylvania, Gluck is studying changes in positive and negative feedback learning in those diagnosed with FTD. That research, funded with a grant from the Association for Frontotemporal Dementia, has the potential to help in identifying methods to aid in correcting behavior for FTD patients.
"If, for example, FTD patients learn better from reward then punishment, this would mean caregivers might be advised to avoid reacting negatively to inappropriate behaviors and to focus instead on rewarding patients for not engaging in inappropriate behaviors," says Gluck.
In related research, Gluck is working with Palestinian and Israel doctors, as part of a joint Rutgers-sponsored Israeli-Palestinian brain research project, to study cognitive deficits in Israeli and Palestinian patients suffering from Parkinson's disease and depression.
понедельник, 15 августа 2011 г.
Rexahn To Use MedAvante Centralized Ratings In MDD Phase 2b Study
MedAvante, Inc., the leader in centralized expert evaluation of central nervous system (CNS) disorders, and Rexahn Pharmaceuticals, Inc. (NYSE Amex: RNN) a clinical stage pharmaceutical company developing and commercializing potential best in class oncology and CNS therapeutics, announced that Rexahn will use MedAvante 's Remote Centralized Ratings™ in their randomized, double-blind, placebo-controlled Phase 2b clinical study assessing the efficacy of Serdaxin® in patients with major depressive disorder (MDD). MedAvante's centralized ratings were chosen to reduce bias and variability associated with CNS trials.
Rexahn is the latest in a growing number of pharmaceutical companies deciding to use centralized raters, who are free of study biases, for CNS trials. This approach has empirically demonstrated the ability to reduce rater variability and the placebo effect.
Centralized assessments in other therapeutic areas, including oncology, imaging and cardiovascular, are used to reduce bias and minimize variability and have been described affirmatively in regulatory guidance documents. Now centralized calibrated raters conducting real-time psychiatric assessments are achieving the same benefits for sponsors of CNS studies.
Rexahn's Serdaxin is a well characterized chemical entity tested for multiple CNS indications. Data from a Phase 2a study in MDD has shown that Serdaxin has the potential to improve symptoms of depression, without the side effects commonly associated with currently marketed antidepressants.
"As a company seeking to develop and deliver new treatments for CNS disorders, it is vital that we design and conduct clinical trials that maximize rater objectivity and standardization," said Rick Soni, President and Chief Operating Officer of Rexahn.
"By their nature, depression trial results can be affected by any number of variables, especially when subjective assessments are used. That is why having central raters who are continuously monitored and calibrated can minimize rater bias," said Soni. "We carefully evaluated different methodologies and found MedAvante Remote Centralized Ratings far superior to traditional methods."
"Centralized ratings are the wave of the future in clinical testing of CNS drugs," said Paul M. Gilbert, Chief Executive Officer of MedAvante. "Our centralized ratings are backed with extensive clinical operations experience, professional project management capabilities, and proprietary infrastructure all working together to fit seamlessly into Rexahn's existing study research design.
"We are confident that our unique ability to deliver 'true' centralized ratings can significantly reduce the bias and ratings variability associated with typical CNS trials thereby providing a true reflection of both treatment and placebo effect," said Gilbert.
MedAvante's centralized raters diagnose subjects and evaluate symptom severity to ensure appropriate patient ascertainment and post-baseline standardization, the most difficult challenges to signal detection in CNS studies. The raters are mental health professionals with deep clinical and rating scale expertise, carefully selected through an intensive qualification process, and continuously trained and calibrated to ensure optimal inter-rater reliability and minimize rater drift, a factor leading to inconclusive results in CNS trials.
Having set up over 600 remote sites worldwide, MedAvante supports each with a robust rater scheduling system to ensure blinding, and 24/7 global technology support. MedAvante automated systems are 21CFR (part 11) certified and data privacy protection is US/EU Safe Harbor compliant.
Rexahn is the latest in a growing number of pharmaceutical companies deciding to use centralized raters, who are free of study biases, for CNS trials. This approach has empirically demonstrated the ability to reduce rater variability and the placebo effect.
Centralized assessments in other therapeutic areas, including oncology, imaging and cardiovascular, are used to reduce bias and minimize variability and have been described affirmatively in regulatory guidance documents. Now centralized calibrated raters conducting real-time psychiatric assessments are achieving the same benefits for sponsors of CNS studies.
Rexahn's Serdaxin is a well characterized chemical entity tested for multiple CNS indications. Data from a Phase 2a study in MDD has shown that Serdaxin has the potential to improve symptoms of depression, without the side effects commonly associated with currently marketed antidepressants.
"As a company seeking to develop and deliver new treatments for CNS disorders, it is vital that we design and conduct clinical trials that maximize rater objectivity and standardization," said Rick Soni, President and Chief Operating Officer of Rexahn.
"By their nature, depression trial results can be affected by any number of variables, especially when subjective assessments are used. That is why having central raters who are continuously monitored and calibrated can minimize rater bias," said Soni. "We carefully evaluated different methodologies and found MedAvante Remote Centralized Ratings far superior to traditional methods."
"Centralized ratings are the wave of the future in clinical testing of CNS drugs," said Paul M. Gilbert, Chief Executive Officer of MedAvante. "Our centralized ratings are backed with extensive clinical operations experience, professional project management capabilities, and proprietary infrastructure all working together to fit seamlessly into Rexahn's existing study research design.
"We are confident that our unique ability to deliver 'true' centralized ratings can significantly reduce the bias and ratings variability associated with typical CNS trials thereby providing a true reflection of both treatment and placebo effect," said Gilbert.
MedAvante's centralized raters diagnose subjects and evaluate symptom severity to ensure appropriate patient ascertainment and post-baseline standardization, the most difficult challenges to signal detection in CNS studies. The raters are mental health professionals with deep clinical and rating scale expertise, carefully selected through an intensive qualification process, and continuously trained and calibrated to ensure optimal inter-rater reliability and minimize rater drift, a factor leading to inconclusive results in CNS trials.
Having set up over 600 remote sites worldwide, MedAvante supports each with a robust rater scheduling system to ensure blinding, and 24/7 global technology support. MedAvante automated systems are 21CFR (part 11) certified and data privacy protection is US/EU Safe Harbor compliant.
пятница, 12 августа 2011 г.
USA Today Examines Effect Of Depression During Pregnancy
USA Today on Monday examined the risks pregnant women face when continuing or stopping treatment for depression during pregnancy. Two recent studies, one published in February in the New England Journal of Medicine and another published in the Feb. 1 edition of the Journal of the American Medical Association, led to "mixed conclusions" about the benefits and risks associated with taking antidepressants during pregnancy, USA Today reports. The NEJM study finds that women who take certain types of antidepressants, called selective serotonin reuptake inhibitors, during the second half of pregnancy are six times as likely as women not taking SSRIs to have an infant with a rare, but severe, heart and lung condition. Meanwhile, the JAMA study finds that 68% of pregnant women who stopped taking antidepressants during pregnancy relapsed compared with 26% of pregnant women who continued taking the drugs. "There are potentially risks on both sides of the fence," University of Michigan psychiatrist Sheila Marcus said, adding. "You really have to look at the severity of the maternal illness, the desire of the mother [and] the medicine you're thinking about using." Data suggest that more that 10% of pregnant women experience depression (Rubin, USA Today, 3/13).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . ?© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . ?© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
вторник, 9 августа 2011 г.
Aplenzin(TM), The Only Single Tablet Once-Daily Treatment For Depression At All Doses, Now Available In The United States
Sanofi-Aventis U.S. announced that Aplenzin(TM) (bupropion hydrobromide) extended-release tablets, an effective bupropion therapy for the treatment of major depressive disorder (MDD), is now available by prescription in the United States for adults ages 18 and older. Aplenzin differs from other generic and branded bupropion antidepressants because it provides a unique HBr salt extended-release formulation, offering prescribers and their patients the benefit of convenience with simple one tablet, once-daily dosing at all doses.
"For patients who show little clinical improvement on lower doses of bupropion, there is a need to take higher doses to treat major depressive disorder," said Prakash Masand, M.D., Consulting Professor of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC. "Aplenzin offers patients and physicians an alternative option which only requires one tablet, once a day at the highest bupropion dose. This provides a simple, convenient option for patients that currently need to take two to three tablets daily."
For those patients in whom no clinical improvement is noted after several weeks of treatment at the target dose of 348 mg per day, Aplenzin offers physicians and their patients the ability to titrate up to the 522 mg strength. The Aplenzin 522 mg dose is the only FDA-approved single-tablet, once daily treatment equivalent to 450 mg of bupropion HCl therapy, requiring two or three tablets daily.
"With major depressive disorder affecting about 14 million Americans, we are excited to offer patients an effective treatment option that hopefully addresses existing unmet needs," said Brent Ragans, Vice President and Head of the General Therapeutics Business Unit, sanofi-aventis.
Bupropion, the active ingredient in Aplenzin, offers comparable efficacy to fluoxetine, an SSRI. Bupropion also has low incidence of weight gain compared to placebo. Research suggests that MDD may be caused by an imbalance of brain chemicals called neurotransmitters. The mechanism of action of Aplenzin is unknown; however, it is believed that bupropion, the active ingredient of Aplenzin, may help restore the balance of neurotransmitters, by inhibiting the reuptake of norepinephrine and dopamine.
Aplenzin was approved by the U.S. Food and Drug Administration (FDA) in April 2008. Sanofi-aventis U.S., which licensed Aplenzin from Biovail Corporation in December 2008, markets the product in the United States and Puerto Rico.
About Major Depressive Disorder
In the United States, it is estimated that between 10 percent and 25 percent of women and five percent and 12 percent of men will experience a major depressive episode at some point in their lives. Unlike normal emotional experiences of sadness, loss or passing mood states, MDD is persistent (it may last, on average, up to 16 weeks) and is usually associated with substantial symptom severity and role impairment, contributing to reduced productivity. According to one study, people with MDD reported an average of 35 days in the past year when they were unable to work or carry out their normal activities. MDD is associated with comorbid anxiety and substance abuse, and evidence suggests it is a significant risk factor for stroke, hypertension, heart disease, and death due to heart attack. The costs associated with MDD are greater than those from hypertension and equivalent to those of heart disease, diabetes and back problems combined.
Research shows that only 57 percent of patients with MDD are treated for depression in the primary care setting each year, with only one in five of these patients receiving adequate treatment. The most common treatments for MDD are antidepressants and psychotherapy.
About Aplenzin
Indication:
APLENZIN is indicated for the treatment of major depressive disorder in adults aged 18 years and older.
Important Safety Information:
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of APLENZIN or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. APLENZIN is not approved for use in pediatric patients.
APLENZIN is contraindicated in patients who have a seizure disorder, patients being treated with Zyban(R) (bupropion HCl) Sustained-Release Tablets, WELLBUTRIN(R) (bupropion HCl), WELLBUTRIN SR(R) (bupropion HCl) Sustained-Release Tablets, or any other medications that contain bupropion, patients who have or had bulimia or anorexia nervosa, patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines), patients who have shown an allergic response to bupropion and patients taking MAO inhibitors. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of APLENZIN.
Physicians should be aware that bupropion is associated with a risk of seizure, which is dose related. The incidence of seizure may be similar to that of the sustained-release formulations of bupropion, since APLENZIN has demonstrated bioequivalence. To reduce the risk of seizures, please see WARNINGS and PRECAUTIONS in the Prescribing Information for patient selection considerations, including concomitant medications and dosing recommendations.
Physicians, families, and caregivers should monitor patients for suicidality as well as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, and other unusual changes in behavior. All patients should be closely monitored for these symptoms, especially at the beginning of therapy, or with changes in dose and reported immediately to the patient's healthcare provider. Please consult prescribing information for APLENZIN for additional monitoring recommendations. There is concern that such symptoms may be precursors to suicidality, although a causal link has not been proven. If such symptoms occur, prescribers should consider changing or discontinuing treatment. Patients should be screened for bipolar disorder prior to initiating treatment with an antidepressant.
When treating patients with severe hepatic cirrhosis, extreme caution should be exercised, and a reduced dosage and/or frequency is required to avoid accumulation. Increased restlessness, agitation, anxiety, and insomnia, especially shortly after initiation of treatment, have been associated with treatment with bupropion. Neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion have been reported with bupropion. Anaphylactoid reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. There have been reports of hypertension, in some cases severe, in patients receiving bupropion alone and in combination with nicotine replacement therapy.
The most common adverse reactions reported are dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency and rash. Please see the full prescribing information for additional safety information.
About Sanofi Aventis
Sanofi-aventis U.S. is an affiliate of sanofi-aventis, a leading global pharmaceutical company that discovers, develops and distributes therapeutic solutions to help improve the lives of patients. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2008. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
"For patients who show little clinical improvement on lower doses of bupropion, there is a need to take higher doses to treat major depressive disorder," said Prakash Masand, M.D., Consulting Professor of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC. "Aplenzin offers patients and physicians an alternative option which only requires one tablet, once a day at the highest bupropion dose. This provides a simple, convenient option for patients that currently need to take two to three tablets daily."
For those patients in whom no clinical improvement is noted after several weeks of treatment at the target dose of 348 mg per day, Aplenzin offers physicians and their patients the ability to titrate up to the 522 mg strength. The Aplenzin 522 mg dose is the only FDA-approved single-tablet, once daily treatment equivalent to 450 mg of bupropion HCl therapy, requiring two or three tablets daily.
"With major depressive disorder affecting about 14 million Americans, we are excited to offer patients an effective treatment option that hopefully addresses existing unmet needs," said Brent Ragans, Vice President and Head of the General Therapeutics Business Unit, sanofi-aventis.
Bupropion, the active ingredient in Aplenzin, offers comparable efficacy to fluoxetine, an SSRI. Bupropion also has low incidence of weight gain compared to placebo. Research suggests that MDD may be caused by an imbalance of brain chemicals called neurotransmitters. The mechanism of action of Aplenzin is unknown; however, it is believed that bupropion, the active ingredient of Aplenzin, may help restore the balance of neurotransmitters, by inhibiting the reuptake of norepinephrine and dopamine.
Aplenzin was approved by the U.S. Food and Drug Administration (FDA) in April 2008. Sanofi-aventis U.S., which licensed Aplenzin from Biovail Corporation in December 2008, markets the product in the United States and Puerto Rico.
About Major Depressive Disorder
In the United States, it is estimated that between 10 percent and 25 percent of women and five percent and 12 percent of men will experience a major depressive episode at some point in their lives. Unlike normal emotional experiences of sadness, loss or passing mood states, MDD is persistent (it may last, on average, up to 16 weeks) and is usually associated with substantial symptom severity and role impairment, contributing to reduced productivity. According to one study, people with MDD reported an average of 35 days in the past year when they were unable to work or carry out their normal activities. MDD is associated with comorbid anxiety and substance abuse, and evidence suggests it is a significant risk factor for stroke, hypertension, heart disease, and death due to heart attack. The costs associated with MDD are greater than those from hypertension and equivalent to those of heart disease, diabetes and back problems combined.
Research shows that only 57 percent of patients with MDD are treated for depression in the primary care setting each year, with only one in five of these patients receiving adequate treatment. The most common treatments for MDD are antidepressants and psychotherapy.
About Aplenzin
Indication:
APLENZIN is indicated for the treatment of major depressive disorder in adults aged 18 years and older.
Important Safety Information:
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of APLENZIN or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. APLENZIN is not approved for use in pediatric patients.
APLENZIN is contraindicated in patients who have a seizure disorder, patients being treated with Zyban(R) (bupropion HCl) Sustained-Release Tablets, WELLBUTRIN(R) (bupropion HCl), WELLBUTRIN SR(R) (bupropion HCl) Sustained-Release Tablets, or any other medications that contain bupropion, patients who have or had bulimia or anorexia nervosa, patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines), patients who have shown an allergic response to bupropion and patients taking MAO inhibitors. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of APLENZIN.
Physicians should be aware that bupropion is associated with a risk of seizure, which is dose related. The incidence of seizure may be similar to that of the sustained-release formulations of bupropion, since APLENZIN has demonstrated bioequivalence. To reduce the risk of seizures, please see WARNINGS and PRECAUTIONS in the Prescribing Information for patient selection considerations, including concomitant medications and dosing recommendations.
Physicians, families, and caregivers should monitor patients for suicidality as well as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, and other unusual changes in behavior. All patients should be closely monitored for these symptoms, especially at the beginning of therapy, or with changes in dose and reported immediately to the patient's healthcare provider. Please consult prescribing information for APLENZIN for additional monitoring recommendations. There is concern that such symptoms may be precursors to suicidality, although a causal link has not been proven. If such symptoms occur, prescribers should consider changing or discontinuing treatment. Patients should be screened for bipolar disorder prior to initiating treatment with an antidepressant.
When treating patients with severe hepatic cirrhosis, extreme caution should be exercised, and a reduced dosage and/or frequency is required to avoid accumulation. Increased restlessness, agitation, anxiety, and insomnia, especially shortly after initiation of treatment, have been associated with treatment with bupropion. Neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion have been reported with bupropion. Anaphylactoid reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. There have been reports of hypertension, in some cases severe, in patients receiving bupropion alone and in combination with nicotine replacement therapy.
The most common adverse reactions reported are dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency and rash. Please see the full prescribing information for additional safety information.
About Sanofi Aventis
Sanofi-aventis U.S. is an affiliate of sanofi-aventis, a leading global pharmaceutical company that discovers, develops and distributes therapeutic solutions to help improve the lives of patients. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2008. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
суббота, 6 августа 2011 г.
SLaM's Self-Harm Service Uses Animation To Aid Recovery
Residents at Dower House, South London and Maudsley NHS Foundation Trust's (SLaM) adult Self-harm service, have developed an animated short film. To watch via YouTube: click here.
Titled 'The Perspex Human', the short film was developed by patients and staff on the unit and in the Occupational Therapy department, under the guidance of experienced animator Assaf Hayut. The animation project asked participants the question 'what is in a human?' The theme provided residents with an enjoyable creative project which enabled them to explore both the literal interpretations as well as exploring deeper meanings and emotions such as anxiety and depression.
The four-and-a-half-minute animation was developed over a five-month period. Six residents from Dower House took part in the project, along with staff members from the Self-harm Service and members of Bethlem Royal Hospital's Occupational Therapy department.
Residents were encouraged to make their own fictional or biographical stories, and to produce a storyboard. A great deal of time was devoted to the project, and residents displayed sensitivity and emotion as the animation was developed. More than 2000 images were produced over 16 sessions, and edited down into the final film.
Assaf Hayut has worked with SLaM before, delivering collaborative creative projects for residents in ward environments and within the specialised technical environment of the Bethlem's Occupational Therapy department. The animated films produced have been screened in the Bethlem Gallery during exhibitions for World Mental Health Day (2009 and 2010) and are hosted on the SLaM website.
Mr Hayut said the detailed nature of animation meant it was not like standard therapeutic tools, but in time, residents took great pride and satisfaction in the project. Participants learnt basic animation techniques, and the project also encouraged better communication between patients and staff members.
"The project offered residents a non-judgemental and open environment that supported their emotional expression", Mr Hayut said. "During the animation workshops, patients were communicating issues relevant to their treatment, and many opened up more in the less formal environment.
"The patients had a story to tell, and wanted to share it. I was amazed by the care, the companionship, the pace and the creativity the people involved had expressed. Participants laughed, enjoyed, learnt, explored and shared."
The feedback from Dower House residents on the animation project has been overwhelmingly positive, with one resident saying it had boosted morale within the house.
Another participant said, "it was an amazing experience to see the final animation take shape. There was such a community feel to the process; it brought us together in a way that I'd never thought it possible. There we were, discussing self-harm and creating a unique perspective."
One patient said, "it was almost liberating to be able to express ourselves in a visual way and to explain our journey with self-harm, something which for me, has been kept a secret for so long. Just knowing that there are other people who understand self-harm can make a difference and I really hope that this animation can make this difference for others who self-harm."
SLaM's Self-harm Service is for people who repeatedly self-harm and who have chronic interpersonal difficulties. The service has been designed to work with people whom other services have found difficult to help and who make frequent use of emergency services or multiple care agencies. Treatment is offered on both an inpatient and outpatient basis.
Dr Paul Moran, Consultant Psychiatrist for the Self-harm Service, said the animation project had provided residents with a creative outlet and aided recovery.
"The Perspex Human makes very compelling viewing. It powerfully captures the emotional turbulence associated with self-harm and also the struggles associated with learning to cope without self-harming. The service users who put this together should be very proud of their achievement."
Peter O'Hare, Head of Occupational Therapy for SLaM, said "the animation project tapped into the powerful potential of modern creative media to empower individuals in their quest to make sense of their lived experience, and as part of their recovery to share that experience, on their own terms, with a wider audience."
Many residents at Dower House have been diagnosed with a Borderline Personality Disorder and also have a range of other mental health problems, including eating disorders, anxiety, depression, and alcohol or drug misuse. They often have enduring emotional problems linked to severe and adverse experiences during their early life.
Self-harm Service inpatient residents are offered a range of treatments, including individual safety planning sessions, occupational therapy, group sessions on topics such as coping strategies, movement psychotherapy and family therapy, all aimed to reduce the number of self-harm incidents. Patients leave SLaM with reduced anxiety and depression, and enhanced self-esteem.
Jane Bunclark, Clinical Service Lead said "Creative media like this animation project enable the residents to communicate their pain, distress and powerful emotions in a healthier way, than through using their bodies via self-harm as a canvass for communication."
Dower House regularly receives appreciative and positive feedback from departing residents, as illustrated by the comments from this former patient:
"Thanks for the space to explore my emotions and for tolerating my stubbornness. Not only have I learnt valuable lessons to take with me, I also have valuable memories of trust, care and friendship to keep. My admission to the unit has allowed me to discover who I am and has given me a lot more optimism for the future. It has been a struggle at times, but I wouldn't have changed any part of it, because it has got me to this point. I feel I'm leaving here, and going on to bigger and better things."
Notes
- For a case study of a former Self-Harm Service patient who repeatedly self-harmed and is now in recovery see here.
Titled 'The Perspex Human', the short film was developed by patients and staff on the unit and in the Occupational Therapy department, under the guidance of experienced animator Assaf Hayut. The animation project asked participants the question 'what is in a human?' The theme provided residents with an enjoyable creative project which enabled them to explore both the literal interpretations as well as exploring deeper meanings and emotions such as anxiety and depression.
The four-and-a-half-minute animation was developed over a five-month period. Six residents from Dower House took part in the project, along with staff members from the Self-harm Service and members of Bethlem Royal Hospital's Occupational Therapy department.
Residents were encouraged to make their own fictional or biographical stories, and to produce a storyboard. A great deal of time was devoted to the project, and residents displayed sensitivity and emotion as the animation was developed. More than 2000 images were produced over 16 sessions, and edited down into the final film.
Assaf Hayut has worked with SLaM before, delivering collaborative creative projects for residents in ward environments and within the specialised technical environment of the Bethlem's Occupational Therapy department. The animated films produced have been screened in the Bethlem Gallery during exhibitions for World Mental Health Day (2009 and 2010) and are hosted on the SLaM website.
Mr Hayut said the detailed nature of animation meant it was not like standard therapeutic tools, but in time, residents took great pride and satisfaction in the project. Participants learnt basic animation techniques, and the project also encouraged better communication between patients and staff members.
"The project offered residents a non-judgemental and open environment that supported their emotional expression", Mr Hayut said. "During the animation workshops, patients were communicating issues relevant to their treatment, and many opened up more in the less formal environment.
"The patients had a story to tell, and wanted to share it. I was amazed by the care, the companionship, the pace and the creativity the people involved had expressed. Participants laughed, enjoyed, learnt, explored and shared."
The feedback from Dower House residents on the animation project has been overwhelmingly positive, with one resident saying it had boosted morale within the house.
Another participant said, "it was an amazing experience to see the final animation take shape. There was such a community feel to the process; it brought us together in a way that I'd never thought it possible. There we were, discussing self-harm and creating a unique perspective."
One patient said, "it was almost liberating to be able to express ourselves in a visual way and to explain our journey with self-harm, something which for me, has been kept a secret for so long. Just knowing that there are other people who understand self-harm can make a difference and I really hope that this animation can make this difference for others who self-harm."
SLaM's Self-harm Service is for people who repeatedly self-harm and who have chronic interpersonal difficulties. The service has been designed to work with people whom other services have found difficult to help and who make frequent use of emergency services or multiple care agencies. Treatment is offered on both an inpatient and outpatient basis.
Dr Paul Moran, Consultant Psychiatrist for the Self-harm Service, said the animation project had provided residents with a creative outlet and aided recovery.
"The Perspex Human makes very compelling viewing. It powerfully captures the emotional turbulence associated with self-harm and also the struggles associated with learning to cope without self-harming. The service users who put this together should be very proud of their achievement."
Peter O'Hare, Head of Occupational Therapy for SLaM, said "the animation project tapped into the powerful potential of modern creative media to empower individuals in their quest to make sense of their lived experience, and as part of their recovery to share that experience, on their own terms, with a wider audience."
Many residents at Dower House have been diagnosed with a Borderline Personality Disorder and also have a range of other mental health problems, including eating disorders, anxiety, depression, and alcohol or drug misuse. They often have enduring emotional problems linked to severe and adverse experiences during their early life.
Self-harm Service inpatient residents are offered a range of treatments, including individual safety planning sessions, occupational therapy, group sessions on topics such as coping strategies, movement psychotherapy and family therapy, all aimed to reduce the number of self-harm incidents. Patients leave SLaM with reduced anxiety and depression, and enhanced self-esteem.
Jane Bunclark, Clinical Service Lead said "Creative media like this animation project enable the residents to communicate their pain, distress and powerful emotions in a healthier way, than through using their bodies via self-harm as a canvass for communication."
Dower House regularly receives appreciative and positive feedback from departing residents, as illustrated by the comments from this former patient:
"Thanks for the space to explore my emotions and for tolerating my stubbornness. Not only have I learnt valuable lessons to take with me, I also have valuable memories of trust, care and friendship to keep. My admission to the unit has allowed me to discover who I am and has given me a lot more optimism for the future. It has been a struggle at times, but I wouldn't have changed any part of it, because it has got me to this point. I feel I'm leaving here, and going on to bigger and better things."
Notes
- For a case study of a former Self-Harm Service patient who repeatedly self-harmed and is now in recovery see here.
среда, 3 августа 2011 г.
Efficacy And Safety Of Aripiprazole As Adjunctive Therapy In Major Depressive Disorder
In adults with major depressive disorder, adding aripiprazole to antidepressant therapy (ADT) resulted in significant improvement in the primary endpoint, the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. In this six-week, randomized, placebo-controlled study presented here at the 160th Annual Meeting of the American Psychiatric Association, the Bristol-Myers Squibb Company (NYSE: BMY) and Otsuka Pharmaceutical Co., Ltd. atypical antipsychotic aripiprazole was added to antidepressants in patients who did not have an adequate response to ADT alone. (1)(Berman, 2007, APA Poster) These findings are from one of two completed studies evaluating adjunctive aripiprazole with ADT.
"Investigational studies are important because many patients with major depressive disorder do not achieve adequate symptom response," said study investigator Arif Khan, M.D., Medical Director, Northwest Clinical Research Center, Bellevue, Wash., and Adjunct Professor, Psychiatry, Duke University, Durham, N.C. "The findings from this study contribute more information about the potential use of add-on medications to antidepressant therapy in patients who inadequately respond to antidepressants alone."
Study Design and Findings
This double-blind, randomized, placebo-controlled, multi-center, six-week study enrolled adults diagnosed with major depressive disorder who had an inadequate response to one or more ADTs. After a seven to 28-day screening phase, adults in this study underwent an eight-week prospective treatment phase with one ADT plus single-blind placebo to confirm their inadequate response to ADT. The ADTs included escitalopram, fluoxetine, paroxetine controlled release, sertraline or venlafaxine extended release, dosed per label guidelines. A total of 362 adults with inadequate response then entered the six-week randomized treatment phase during which they continued their ADT plus double-blind adjunctive placebo or adjunctive aripiprazole (2-20 mg/day).
The primary efficacy endpoint was the mean change from baseline - the end of the prospective treatment phase - to the end of the randomized treatment phase in a standard measure called the MADRS Total Score, which can range from 0 (no symptoms) to 60 points (most severe symptoms). A reduction in MADRS Total Score represents improvement in depressive symptoms. Some of the secondary endpoints included Sheehan Disability Scale (SDS), MADRS-measured remission and response rates and Clinical Global Impression-Severity of Illness (CGI-S) score.
For the primary endpoint, the study showed that adults taking adjunctive aripiprazole had a greater reduction in MADRS Total Score from baseline compared to placebo (-8.8 vs. -5.8 points, p-value less than 0.001).
The discontinuation rate due to an adverse event for adults taking add-on aripiprazole was 3.3 percent and 2.3 percent for placebo. The most common adverse events in the add-on aripiprazole and add-on placebo groups, respectively, (greater than or equal to 5 percent and at least twice the incidence of placebo) were akathisia (23.1 percent vs. 4.5 percent), insomnia (7.7 percent vs. 2.3 percent), restlessness (14.3 percent vs. 3.4 percent), upper respiratory tract infection (8.2 percent vs. 4 percent), and blurred vision (6.6 percent vs. 1.7 percent).
About Major Depressive Disorder
Major depressive disorder (MDD) is characterized by one or more major depressive episodes, (i.e., at least two weeks of depressed mood or loss of interest accompanied by at least four additional symptoms of depression.) (2)(DSM IV) It affects 6.7 percent of American adults (approximately 15 million individuals) in a given year (3)(Kessler, 2005, p. 620, Table 1) and is the most common mental health disorder after anxiety. (4)(Merck Manual, 1995-2005, p. 1, paragraph 2)
About Aripiprazole
Aripiprazole is indicated for the treatment of schizophrenia including maintaining stability in adults who had been symptomatically stable on other antipsychotic medications for periods of three months or longer and observed for relapse during a period of up to 26 weeks. Aripiprazole is also indicated for the treatment of acute manic and mixed episodes associated with Bipolar I Disorder, and for maintaining efficacy in adults with Bipolar I Disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least six (6) weeks. Physicians who elect to use aripiprazole for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual. Aripiprazole Injection is indicated for the treatment of agitation in adults with schizophrenia or bipolar disorder, manic or mixed.
Initially approved in November 2002, over 10 million prescriptions have been written for aripiprazole in the U.S.(5)
Aripiprazole is available by prescription only. Aripiprazole is available in tablets, orally disintegrating tablets, oral solution, and injection for intramuscular use.
Patients should talk to their healthcare professional for more information about aripiprazole.
IMPORTANT SAFETY INFORMATION:
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death compared to placebo (4.5% vs 2.6%, respectively). Aripiprazole is not approved for the treatment of patients with dementia-related psychosis (see Boxed WARNING).
??? Neuroleptic malignant syndrome (NMS) - As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with aripiprazole. NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status. If signs and symptoms appear, immediate discontinuation is recommended
??? Tardive dyskinesia (TD) - The risk of developing TD and the potential for it to become irreversible may increase as the duration of treatment and the total cumulative dose increase. Prescribing should be consistent with the need to minimize TD. If signs and symptoms appear, discontinuation should be considered since TD may remit, partially or completely
??? Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, have been reported at an increased incidence in clinical trials of elderly patients with dementia-related psychosis treated with aripiprazole
??? Hyperglycemia and diabetes mellitus - Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes should be monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. There have been few reports of hyperglycemia with aripiprazole
Aripiprazole may be associated with orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.
As with other antipsychotic drugs, aripiprazole should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Like other antipsychotics, aripiprazole may have the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are certain aripiprazole does not affect them adversely.
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotics. Appropriate care is advised for patients who may exercise strenuously, be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or be subject to dehydration.
As antipsychotics have been associated with esophageal dysmotility and aspiration, aripiprazole should be used cautiously in patients at risk for aspiration pneumonia.
As the possibility of a suicide attempt is inherent in psychotic illness and bipolar disorder, close supervision of high-risk patients should accompany drug therapy. Prescriptions for aripiprazole should be written for the smallest quantity consistent with good patient management to reduce the risk of overdose.
Physicians should determine if a patient is pregnant or intends to become pregnant while taking aripiprazole. Patients should be advised not to breast-feed while taking aripiprazole.
Physicians should advise patients to avoid alcohol while taking aripiprazole.
Both CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4 (eg, carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.
Commonly observed adverse events (greater than or equal to 5% incidence and at a rate at least twice the rate of placebo for aripiprazole vs placebo, respectively):
Aripiprazole Oral
In 3-week bipolar mania trials the following were reported: akathisia (15% vs 3%), constipation (13% vs 6%), sedation (8% vs 3%), tremor (7% vs 3%), restlessness (6% vs 3%), and extrapyramidal disorder (5% vs 2%).
In 4- to 6-week schizophrenia trials the following was reported: akathisia (8% vs 4%).
A similar adverse event profile was observed in a 26-week trial in schizophrenia except for a higher incidence of tremor (aripiprazole 8% vs placebo 2%).
Aripiprazole Injection
In short-term (24 hour) trials in patients with agitation associated with schizophrenia or bipolar mania the following was reported: nausea (9% vs 3%).
Treatment-emergent adverse events reported with:
Aripiprazole Oral
In short-term trials of patients with schizophrenia (up to 6 weeks) or bipolar disorder (up to 3 weeks), the following were reported at an incidence greater than or equal to 10% and greater than placebo, respectively: headache (30% vs 25%), anxiety (20% vs 17%), insomnia (19% vs 14%), nausea (16% vs 12%), vomiting (12% vs 6%), dizziness (11% vs 8%), constipation (11% vs 7%), dyspepsia (10% vs 8%), and akathisia (10% vs 4%).
Aripiprazole Injection
In short-term (24 hour) trials, the following were reported at an incidence greater than or equal to 5% and greater than placebo, respectively: headache (12% vs 7%), nausea (9% vs 3%), dizziness (8% vs 5%), and somnolence (7% vs 4%).
About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.
Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in the development and commercialization of aripiprazole in the United States and major European countries.
Aripiprazole was discovered by Otsuka Pharmaceutical Co., Ltd. Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a healthcare company with the mission statement: "Otsuka - people creating new products for better health worldwide." Otsuka researches, develops, manufactures and markets innovative, original products, focusing its core businesses on pharmaceutical products for the treatment of disease and consumer products for the maintenance of everyday health. The Otsuka Pharmaceutical Group comprises 87 companies and employs approximately 27,000 people in 17 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned US $6.8 billion in consolidated annual revenues in fiscal 2005.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
Visit Bristol-Myers Squibb at: bms/
Visit Otsuka Pharmaceutical Co., Ltd. at: otsuka-global/
Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. There can be no guarantee that a registrational submission will be made to the FDA based on the data described in this press release or if such registrational submission is made, that it would receive FDA approval. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2006 and in our Quarterly Reports on Form 10-Q. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
References
1 Berman RM, Marcus RN, Swanink R, Carson Jr WH, McQuade RD, Khan A. Efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study (study cn138-139).
2 Diagnostic and Statistical Manual of Mental Disorders. Fourth ed-TR. Psychiatry Online Web site. Available at: psychiatryonline/content.aspx"aID=2016. Accessed April 9, 2007.
3 Kessler RC, Chiu WT, Demler OD, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62:617-627.
4 Merck Manual of Medical Information - Second Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; Copyright © 1995-2005 Merck & Co.
5 IMS Auditrac NGPS: Abilify total monthly retail prescriptions: Data accessed 11/2006.
570US07PG16301 April 2007 AB07N-0079
Contact: David Rosen
Bristol-Myers Squibb
View drug information on Abilify.
"Investigational studies are important because many patients with major depressive disorder do not achieve adequate symptom response," said study investigator Arif Khan, M.D., Medical Director, Northwest Clinical Research Center, Bellevue, Wash., and Adjunct Professor, Psychiatry, Duke University, Durham, N.C. "The findings from this study contribute more information about the potential use of add-on medications to antidepressant therapy in patients who inadequately respond to antidepressants alone."
Study Design and Findings
This double-blind, randomized, placebo-controlled, multi-center, six-week study enrolled adults diagnosed with major depressive disorder who had an inadequate response to one or more ADTs. After a seven to 28-day screening phase, adults in this study underwent an eight-week prospective treatment phase with one ADT plus single-blind placebo to confirm their inadequate response to ADT. The ADTs included escitalopram, fluoxetine, paroxetine controlled release, sertraline or venlafaxine extended release, dosed per label guidelines. A total of 362 adults with inadequate response then entered the six-week randomized treatment phase during which they continued their ADT plus double-blind adjunctive placebo or adjunctive aripiprazole (2-20 mg/day).
The primary efficacy endpoint was the mean change from baseline - the end of the prospective treatment phase - to the end of the randomized treatment phase in a standard measure called the MADRS Total Score, which can range from 0 (no symptoms) to 60 points (most severe symptoms). A reduction in MADRS Total Score represents improvement in depressive symptoms. Some of the secondary endpoints included Sheehan Disability Scale (SDS), MADRS-measured remission and response rates and Clinical Global Impression-Severity of Illness (CGI-S) score.
For the primary endpoint, the study showed that adults taking adjunctive aripiprazole had a greater reduction in MADRS Total Score from baseline compared to placebo (-8.8 vs. -5.8 points, p-value less than 0.001).
The discontinuation rate due to an adverse event for adults taking add-on aripiprazole was 3.3 percent and 2.3 percent for placebo. The most common adverse events in the add-on aripiprazole and add-on placebo groups, respectively, (greater than or equal to 5 percent and at least twice the incidence of placebo) were akathisia (23.1 percent vs. 4.5 percent), insomnia (7.7 percent vs. 2.3 percent), restlessness (14.3 percent vs. 3.4 percent), upper respiratory tract infection (8.2 percent vs. 4 percent), and blurred vision (6.6 percent vs. 1.7 percent).
About Major Depressive Disorder
Major depressive disorder (MDD) is characterized by one or more major depressive episodes, (i.e., at least two weeks of depressed mood or loss of interest accompanied by at least four additional symptoms of depression.) (2)(DSM IV) It affects 6.7 percent of American adults (approximately 15 million individuals) in a given year (3)(Kessler, 2005, p. 620, Table 1) and is the most common mental health disorder after anxiety. (4)(Merck Manual, 1995-2005, p. 1, paragraph 2)
About Aripiprazole
Aripiprazole is indicated for the treatment of schizophrenia including maintaining stability in adults who had been symptomatically stable on other antipsychotic medications for periods of three months or longer and observed for relapse during a period of up to 26 weeks. Aripiprazole is also indicated for the treatment of acute manic and mixed episodes associated with Bipolar I Disorder, and for maintaining efficacy in adults with Bipolar I Disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least six (6) weeks. Physicians who elect to use aripiprazole for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual. Aripiprazole Injection is indicated for the treatment of agitation in adults with schizophrenia or bipolar disorder, manic or mixed.
Initially approved in November 2002, over 10 million prescriptions have been written for aripiprazole in the U.S.(5)
Aripiprazole is available by prescription only. Aripiprazole is available in tablets, orally disintegrating tablets, oral solution, and injection for intramuscular use.
Patients should talk to their healthcare professional for more information about aripiprazole.
IMPORTANT SAFETY INFORMATION:
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death compared to placebo (4.5% vs 2.6%, respectively). Aripiprazole is not approved for the treatment of patients with dementia-related psychosis (see Boxed WARNING).
??? Neuroleptic malignant syndrome (NMS) - As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with aripiprazole. NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status. If signs and symptoms appear, immediate discontinuation is recommended
??? Tardive dyskinesia (TD) - The risk of developing TD and the potential for it to become irreversible may increase as the duration of treatment and the total cumulative dose increase. Prescribing should be consistent with the need to minimize TD. If signs and symptoms appear, discontinuation should be considered since TD may remit, partially or completely
??? Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, have been reported at an increased incidence in clinical trials of elderly patients with dementia-related psychosis treated with aripiprazole
??? Hyperglycemia and diabetes mellitus - Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes should be monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. There have been few reports of hyperglycemia with aripiprazole
Aripiprazole may be associated with orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.
As with other antipsychotic drugs, aripiprazole should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Like other antipsychotics, aripiprazole may have the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are certain aripiprazole does not affect them adversely.
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotics. Appropriate care is advised for patients who may exercise strenuously, be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or be subject to dehydration.
As antipsychotics have been associated with esophageal dysmotility and aspiration, aripiprazole should be used cautiously in patients at risk for aspiration pneumonia.
As the possibility of a suicide attempt is inherent in psychotic illness and bipolar disorder, close supervision of high-risk patients should accompany drug therapy. Prescriptions for aripiprazole should be written for the smallest quantity consistent with good patient management to reduce the risk of overdose.
Physicians should determine if a patient is pregnant or intends to become pregnant while taking aripiprazole. Patients should be advised not to breast-feed while taking aripiprazole.
Physicians should advise patients to avoid alcohol while taking aripiprazole.
Both CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4 (eg, carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.
Commonly observed adverse events (greater than or equal to 5% incidence and at a rate at least twice the rate of placebo for aripiprazole vs placebo, respectively):
Aripiprazole Oral
In 3-week bipolar mania trials the following were reported: akathisia (15% vs 3%), constipation (13% vs 6%), sedation (8% vs 3%), tremor (7% vs 3%), restlessness (6% vs 3%), and extrapyramidal disorder (5% vs 2%).
In 4- to 6-week schizophrenia trials the following was reported: akathisia (8% vs 4%).
A similar adverse event profile was observed in a 26-week trial in schizophrenia except for a higher incidence of tremor (aripiprazole 8% vs placebo 2%).
Aripiprazole Injection
In short-term (24 hour) trials in patients with agitation associated with schizophrenia or bipolar mania the following was reported: nausea (9% vs 3%).
Treatment-emergent adverse events reported with:
Aripiprazole Oral
In short-term trials of patients with schizophrenia (up to 6 weeks) or bipolar disorder (up to 3 weeks), the following were reported at an incidence greater than or equal to 10% and greater than placebo, respectively: headache (30% vs 25%), anxiety (20% vs 17%), insomnia (19% vs 14%), nausea (16% vs 12%), vomiting (12% vs 6%), dizziness (11% vs 8%), constipation (11% vs 7%), dyspepsia (10% vs 8%), and akathisia (10% vs 4%).
Aripiprazole Injection
In short-term (24 hour) trials, the following were reported at an incidence greater than or equal to 5% and greater than placebo, respectively: headache (12% vs 7%), nausea (9% vs 3%), dizziness (8% vs 5%), and somnolence (7% vs 4%).
About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.
Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in the development and commercialization of aripiprazole in the United States and major European countries.
Aripiprazole was discovered by Otsuka Pharmaceutical Co., Ltd. Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a healthcare company with the mission statement: "Otsuka - people creating new products for better health worldwide." Otsuka researches, develops, manufactures and markets innovative, original products, focusing its core businesses on pharmaceutical products for the treatment of disease and consumer products for the maintenance of everyday health. The Otsuka Pharmaceutical Group comprises 87 companies and employs approximately 27,000 people in 17 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned US $6.8 billion in consolidated annual revenues in fiscal 2005.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
Visit Bristol-Myers Squibb at: bms/
Visit Otsuka Pharmaceutical Co., Ltd. at: otsuka-global/
Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. There can be no guarantee that a registrational submission will be made to the FDA based on the data described in this press release or if such registrational submission is made, that it would receive FDA approval. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2006 and in our Quarterly Reports on Form 10-Q. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
References
1 Berman RM, Marcus RN, Swanink R, Carson Jr WH, McQuade RD, Khan A. Efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study (study cn138-139).
2 Diagnostic and Statistical Manual of Mental Disorders. Fourth ed-TR. Psychiatry Online Web site. Available at: psychiatryonline/content.aspx"aID=2016. Accessed April 9, 2007.
3 Kessler RC, Chiu WT, Demler OD, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62:617-627.
4 Merck Manual of Medical Information - Second Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; Copyright © 1995-2005 Merck & Co.
5 IMS Auditrac NGPS: Abilify total monthly retail prescriptions: Data accessed 11/2006.
570US07PG16301 April 2007 AB07N-0079
Contact: David Rosen
Bristol-Myers Squibb
View drug information on Abilify.
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