Older schizophrenia drug safer than more widely prescribed ones, study says
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Schizophrenics taking the first -- and cheapest -- of a new generation of antipsychotic medications, clozapine, were less likely to suffer premature death than patients taking the newer, costlier and more widely prescribed antipsychotic drugs Seroquel, Risperdal and Zyprexa, says a study published in the British medical journal Lancet.
Researchers in Finland, where clozapine is still widely prescribed for schizophrenia patients, found that users of the drug were less likely to die than those who took any one of three other second-generation (also called ‘atypical’) antipsychotics -- Seroquel, Risperdal and Zyprexa -- or those who took the first generation schizophrenia medication pherphenazine (once marketed as Trilafon).
Clozapine, sold now as a generic medication but also marketed as Clozaril, is currently recommended for use only when a patient’s schizophrenia symptoms -- most notably hallucinations, confused thinking and emotional reactions -- fail to improve with use oftwo other antipsychotic medications. Clozapine was briefly taken off the European market -- and has been the subject of strong warnings in the United States -- because its use raises a patient’s risk of a potentially deadly blood disorder called agranulocytosis. Patients taking Clozaril are to undergo routine blood checks to ensure they do not develop the decrease in white blood cells.
Finnish researchers reviewed the 1996-2006 death records of 66,881 patients who had taken one of the studied antipsychotic drugs, and compared them withpatients taking pherphenazine, an older drug considered one of the safest of the first generation. Patients taking Seroquel (also known as quetiapine) were 41% more likely to die prematurely; those taking Risperdal (risperidone) were 34% more likely to die early; those taking Zyprexa (olanzapine) were 13% more likely to die early.
Patients on Clozaril were 26% less likely than those on pherphenazine to die an early death. That finding led the researchers to urge that physicians and drug-safety agencies reconsider their warnings against Clozaril’s use as a first-line drug.
Sufferers of schizophrenia have long been known to die earlier than the general population, markedly more often by suicide and by complications of diabetes. They are far more likely to engage in behaviors that lead to earlier death as well, including tobacco use, substance abuse and sedentary lifestyles. The Lancet article found that a schizophrenia patient who took any of the studied medications for seven to 11 years was less likely to die prematurely. And the longer she took it, the less likely she was to die an early death.
American physicians have largely abandoned Clozaril, which has been on the U.S. market since 1989, in favor of Zyprexa, Seroquel, Risperdal and Abilify -- all newer drugs that have been aggressively marketed to doctors and patients as safer and more effective than the first-generation of antipsychotic drugs, including pherphenazine and haliperidol (better known by its commercial name, Haldol).
Meanwhile, the numbers of people being prescribed these powerful psychiatric drugs have skyrocketed. In 2008, 50 million prescriptions for antipsychotic drugs -- overwhelmingly the newer ones -- were filled. The FDA is now considering whether to allow Seroquel to be prescribed for treatment-resistant depression, and to older children diagnosed with schizophrenia or bipolar disorder. You can read the proceedings of an FDA advisory panel considering both proposals here.
It’s not the first time that the newer drugs’ claims to superiority have been cast into doubt. Many studies comparing the safety and effectiveness of the newest atypical antipsychotics with older drugs were detailed in the Health section recently. Their results, and the controversies surrounding the increased use of these drugs, are detailed here.
-- Melissa Healy
