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Dr. Bob is Robert Hsiung, MD,
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Posted by e789 on January 24, 2003, at 20:24:18
What do you all think about the new indication of Clozaril for the treatment of recurrent suicidal behavior in patients with schizophrenia and schizoaffective disorder. Just ran across this and thought that this was pretty interesting especially for those who have a family member who attempted suidice.
Study Shows Clozaril Reduces Risk of Suicidal Behavior Among Patients with Schizophrenia and Schizoaffective Disorder by 26 Percent
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First Prospective and Randomized Study to Demonstrate Efficacy on Suicidal Behavior
EAST HANOVER, NJ, January 13, 2003 - A landmark two-year study published today in the Archives of General Psychiatry finds that a widely prescribed antipsychotic medication, Clozaril® (clozapine) can reduce by up to 26 percent, the risk of recurrent suicidal behavior and suicide attempts among people suffering from schizophrenia or schizoaffective disorder. Nearly 1,000 individuals participated in the International Suicide Prevention Trial (InterSePTTM), at more than 60 health centers in the Americas, Europe and the Middle East. The study is the first ever to prospectively demonstrate efficacy of a medication to affect suicidal behavior in any patient group.
In December 2002, the US Food and Drug Administration (FDA) approved Clozaril® for treatment of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are at chronic risk. Clozaril® is the first medication ever approved for this use. Although generic versions of Clozaril® are available, FDA regulations provide Novartis with exclusive rights to market the new indication for a period of 36 months.
Dr. Herbert Meltzer, Bixler Chair of Psychiatry and Professor of Pharmacology at Vanderbilt University, and lead author of the study report said, "The risk of suicide attempts in people with schizophrenia-- and especially schizoaffective disorder-- is appallingly high. About 30 to 40 percent will make a suicide attempt during their lifetime, and 10 percent of people with schizophrenia will actually die from suicide. The risk is especially high for males in the first decade of their illness and is further exacerbated by substance abuse which is present in about 50 percent of people with schizophrenia in the United States."
The InterSePTTM trial, a multi-center, randomized study was initiated in 1998 to compare the efficacy of two antipsychotic compounds, Clozaril® (clozapine) and Zyprexa®* (olanzapine) in reducing the risk of suicide and self-destructive behavior among patients with schizophrenia or schizoaffective disorder. For several years, epidemiological evidence has suggested that Clozaril® may reduce the rate of suicide among patients with schizophrenia.
Paulo Costa, President and Chief Executive Officer of Novartis Pharmaceuticals Corporation, the InterSePT sponsor, said "More than half a century ago, Novartis introduced one of the first effective antipsychotic drugs. Since that time our medications have improved the lives of millions of individuals with schizophrenia and various other mental illnesses. We are very proud that knowledge gained from the InterSePT study may now help to prevent the tragic death of some of these most vulnerable people."
InterSePTTM was conducted under a unique protocol developed collaboratively with academic experts and with feedback from the FDA. One powerful aspect of the study design combined un-blinded psychiatrists with blinded raters. With this design, investigators knew which study medication their patients received and were able to make any clinical interventions necessary to prevent suicide attempts.
Changes in suicide risk were assessed with a validated clinical scale, the Clinical Global Impression of Suicide Severity (CGI-SS), and a semi-structured interview which were administered by blinded raters. All patients were initially assessed on the CGI-SS at baseline and subsequently at eight-week intervals throughout the trial. All deaths, suicide attempts and hospitalizations to prevent suicide were reviewed by a blinded expert Suicide Monitoring Board (SMB) that identified study endpoints.
Results show that the risk for a suicide attempt or hospitalization to prevent suicide was significantly lower in patients treated with Clozaril® compared to Zyprexa®* (hazard ratio=0.74, p=0.02, 95% CI = (0.57, 0.95)). In addition, patients treated with Clozaril® made fewer suicide attempts (p=0.03); required fewer rescue interventions to prevent suicide (p=0.01); experienced fewer hospitalizations to prevent suicide (p=0.05); and needed fewer concomitant medications such as antidepressants (p=0.02) and anxiolytics/soporifics (p=0.03). The most common adverse events associated with Clozaril use in this trial were salivary hypersecretion, somnolence, dizziness, and constipation, which is consistent with current prescribing information.
"Overall, this study demonstrated that Clozaril® is superior to Zyprexa®* for the prevention of suicide attempts in patients with schizophrenia and schizoaffective disorder who are at risk for suicide," Dr. Meltzer said. "Wider use of Clozaril® in this population could very well help to save many lives each year. I think that InterSePT will fundamentally change the care that suicidal patients with psychosis receive in the future."
Dr. John M. Kane, Vice President for Behavioral Health Services at the North Shore Long Island Jewish Health System, and a co-author of the study report offered a clinical context for the results, "To put this into perspective, we can translate the InterSePT data into a number needed to treat analysis. That means that over a two year period if we treat 13 at risk patients with Clozaril® instead of Zyprexa®*, we would prevent one suicide attempt or one hospitalization to prevent suicide."
Since being introduced in the United States in 1990, Clozaril® has established a unique role in the treatment of patients with refractory schizophrenia, and serves as a standard of comparison for the efficacy of most other antipsychotic medications. The compound is classified as an atypical antipsychotic because its profile of binding to certain dopamine receptors and its effects on various dopamine mediated behaviors, differs from those exhibited by older or "typical" antipsychotic drugs. In particular, Clozaril® is recognized for a unique binding profile which is associated with a particularly low propensity for movement disorders (extrapyramidal side effects) seen with the typical antipsychotic medications.
In addition to the new indication for treatment of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are at chronic risk; Clozaril® is also indicated for the treatment of severely ill schizophrenic patients who fail to respond adequately to standard antipsychotic drug therapies. For complete prescribing information, please call Harry Rohme at 973 781-5151 or, refer to the Clozaril® package insert at: http://www.pharma.us.novartis.com/product/pi/pdf/Clozaril.pdf.
Clozaril® use is associated with a substantial risk of seizure affecting 1% to 2% of patients at low doses (below 300 mg/day), 3% to 4% at moderate doses (300 mg/day to 600 mg/day), and 5% at high doses (600 mg/day to 900 mg/day). In clinical trials, Clozaril® was associated with a 1% to 2% incidence of agranulocytosis, a potentially fatal blood disorder, which, if caught early, can be reversed. Mandatory weekly white blood cell counts and weekly drug dispensing provide an efficient means of determining developing agranulocytosis. Analysis of post-marketing safety databases suggests that Clozaril® is associated with an increased risk of fatal myocarditis, especially during, but not limited to, the first month of therapy. Orthostatic hypotension may occur in some patients, especially during the initial phases of treatment, and can, in rare cases (approximate incidence of 1/3,000), be accompanied by collapse and/or cardiac arrest.
This release contains certain "forward-looking statements," relating to the Company's business, which can be identified by the use of forward-looking terminology such as "if," "could very well," "would," "will," or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the potential benefit of Clozaril® as evidenced by initial clinical trial results. Those statements reflect the current views of the Company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the Company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements.
There are no guarantees that the aforementioned clinical trial will result in the commercialization of Clozaril® to reduce suicidal behavior in any market. Any such commercialization can be affected by, among other things, uncertainties relating to regulatory actions, delays in or government regulation generally, competition in general and other risks and factors referred to in the Company's current Form 20-F on file with the Securities and Exchange Commission of the United States.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in healthcare with core businesses in pharmaceuticals, consumer health, generics, eye-care, and animal health. In 2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1 billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 74,000 people and operate in over 140 countries around the world.
For further information about Novartis Pharmaceuticals Corporation please consult http://www.pharma.us.novartis.com/. For further information about Novartis AG, please consult www.novartis.com.
* Zyprexa® is a trademark of Eli Lilly and Company
Press Contact: Harry Rohme, 862-778-5151
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Posted by BrittPark on January 25, 2003, at 16:27:24
In reply to Clozaril for suicide?, posted by e789 on January 24, 2003, at 20:24:18
Thanks for posting the article. It was interesting but I'd like to point out a couple of things. The study was funded by the manufacturer of Clozaril. The P scores for Clozaril's superiority are quite poor. I would not consider this a conclusive study. It's quite possible that some APs may be better than others. But I would imagine that differences in individual response to APs swamps any statistical superiority of one AP over another. I hope that in time there are demonstrably superior APs, but as with ADs we don't seem to be there yet.
Cheers,Britt
Posted by e789 on January 25, 2003, at 19:46:31
In reply to Re: Clozaril for suicide? » e789, posted by BrittPark on January 25, 2003, at 16:27:24
This is the end of the thread.
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