FDA approves anti-psychotic, clozapine, to treat suicide

December 20, 2002

The first of the so-called atypical antipsychotic drugs, clozapine (Clozaril), has been approved by the FDA as a treatment against suicide in patients with schizophrenia.

The drug has been hailed as a miracle for some, but deadly for others. The New York Times failed to inform readers about the severe adverse side-effects linked to the atypical antipsychotic drugs, including clozapine. See: NY Presbyterian Hospital website: http://www.noah-health.org/english/illness/mentalhealth/cornell/medications/clozsideff.html

Among the common adverse side effects are: sedation, weight gain, irregular heart beat, dizziness, and drooling (12% to 40%).

In addition to the fatal risk of agranulocytosis (which occurs in 1% to 2% of patients who take the drug), clozapine (and any of the other atypicals) are linked to risks of disabling chronic side effects including: liver damage, cardiac abnormalities, high blood pressure, diabetes, not to mention myocarditis (inflamation of the heart) and neuroleptic malignant syndrome (NMS), both potentially fatal (NMS occurs in 2% of patients).

FDA posted a Dear Doctor Warning, Feb, 2002: Post-marketing surveillance data from four countries that monitor clozapine-treated patients revealed: 30 reports of myocarditis with 17 fatalities in 205,493 U.S. patients; 7 reports of myocarditis with 1 fatality in 15,600 Canadian patients; 30 reports of myocarditis with 8 fatalities in 24,108 U.K. patients; 15 reports of myocarditis with 5 fatalities in 8,000 Australian patients http://www.fda.gov/medwatch/SAFETY/2002/Clozaril_deardoc.pdf

The Times quotes Dr. Herbert Meltzer suggesting “clozapine might turn out to be effective for suicidal patients with other illnesses like manic depression…or depression.” Such a suggestion would of course, expand clozapine’s market exponentially–but it would also increase patient fatalities.

The Times reporter neglected to inform readers about Dr. Meltzer’s financial ties to Novartis, clozapine’s current manufacturer.

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http://www.nytimes.com/2002/12/20/health/20SUIC.html?pagewanted=print&position=top
THE NEW YORK TIMES
December 20, 2002
Anti-Psychotics Approved to Treat Suicidal Behavior
By ERICA GOODE
A-30

Clozapine, one of a new generation of anti-psychotic drugs, has become the first psychiatric medication to win federal approval as a treatment for suicidal behavior.

The Food and Drug Administration announced yesterday that the agency had approved the drug for treating recurrent suicidal thoughts or suicide attempts in patients with schizophrenia, a devastating illness that afflicts 1 of 100 Americans.

Clozapine was first marketed in 1989 by Novartis under the brand name Clozaril. But the company’s exclusive rights to sell the drug expired in 1994, and the medication is also available in generic form.

A clinical trial conducted by Novartis found that over two years, suicidal patients who took clozapine made fewer suicide attempts and required fewer hospitalizations to prevent suicide than similar patients taking olanzapine, another of the new generation drugs.

The study involved 980 patients with schizophrenia, 490 taking each drug. Paulo Costa, the president and chief executive of Novartis, said, “For a long time, the incidence of suicide in schizophrenic patients has been of concern to caregivers and to patients themselves and to the psychiatric community.”

Dr. Herbert Y. Meltzer, a professor of psychiatry at the Vanderbilt University School of Medicine and the principal investigator for the clinical trial, said that about 1 in 10 patients with schizophrenia committed suicide. Many more try to kill themselves.

Clozapine was the first of the so-called atypicals, a class of anti-psychotic drugs that had fewer side effects than their predecessors and that helped patients who did not respond to older drugs like thorazine or haloperidol.

But clozapine has been less popular than its competitors because patients who take the medication must have frequent blood tests for agranulocytosis, a blood disorder that is an infrequent but potentially fatal side effect.

One to two percent of people taking clozapine develop agranulocytosis and about 1 in 10,000 die from the disorder. But Dr. Meltzer said that given the far higher rate of suicide in schizophrenia, the drug might be lifesaving for patients at high risk.

“There has always been a reluctance to use clozapine because of the side effects,” he said. “This will be a major motivation for clinicians and patients to give clozapine a try.”

Dr. Jeffrey Lieberman, a professor of psychiatry and pharmacology at the University of North Carolina, said the study that led to the F.D.A.’s approval made clear “that clozapine has the ability to alleviate the symptoms which impel patients to suicidal behaviors.”

But Dr. Lieberman added that other newer anti-psychotics might also prove effective in reducing suicide.

He said that the difference in suicide rates between the two groups in the study was statistically significant but small and that the clinical trial did not compare the newer drugs with older generation medications.

“It’s reasonable to think that this effect may be also shared by other clozapine-like drugs,” Dr. Lieberman said.

In a press release announcing the drug’s approval for use in treating suicidal behavior, the food and drug agency said that clozapine might help patients “who are judged to be at chronic risk” for such behavior, based on a history of attempted suicide, hospitalization or suicidal thoughts.

Dr. Lieberman and other researchers speculated that clozapine might help lessen suicidal behavior because it acted on serotonin, a messenger chemical in the brain. Studies have linked abnormalities in serotonin production to suicide.

Dr. Meltzer said clozapine might turn out to be effective for suicidal patients with other illnesses like manic depression, now called bipolar disorder, or psychotic depression.

He said the indicators of a high risk of suicide included feelings of hopelessness, depression, a history of previous suicide attempts and, in men, alcohol or drug abuse.

Novartis said patients who take clozapine must be monitored by weekly blood tests for the first six months they are taking the drug and then every other week after that.

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