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Stanford research finds better results in newer antipsychotic medicines

STANFORD, CALIF., June 17, 2003 -- Nearly five million people in the United States suffer from schizophrenia or manic depression, making antipsychotics the fourth-highest selling class of drugs. But how effectively do the most commonly prescribed medications treat the disorder? And how much better are newer antipsychotics, known as atypicals, compared to their older counterparts?

Ira D. Glick, MD, tackled these questions in a sweeping review of medical literature.

Glick, professor of psychiatry and behavioral sciences at the Stanford School of Medicine, said 90 percent of antipsychotic prescriptions written in the U.S. are for atypicals. He and his colleagues found that their effectiveness, widely considered to be superior over conventional medications, varies from drug to drug. The researchers also found that four of the 10 studied atypicals were more effective than the older ones.

"Some people consider the new antipsychotics a homogenous group, but there are differences," said Glick, senior author of a paper in the June issue of Archives of General Psychiatry. "Some of the drugs are clearly more effective and have fewer side effects than older medications."

Antipsychotics reduce symptoms of psychosis by blocking the neurotransmitter dopamine, which is overabundant in people who have schizophrenia. Although conventional drugs control symptoms, they also cause unpleasant and disabling side effects, such as severe shaking, twisting and trembling. Many patients on these drugs become frustrated with the side effects, stop taking their medication and later relapse.

"Conventional drugs improved lives when they were introduced in the 1950s, but they also left much to be desired," said Glick. "Noncompliance rates for these medications run as high as 50 percent."

Atypicals not only block dopamine less strongly than conventional drugs but they also target other receptors in the brain. As a result, they carry a smaller risk of severe side effects and patients tolerate them better. "Patients on the new drugs are not relapsing and going back to the hospital," said Glick.

But the effectiveness of atypicals has recently come into question with some researchers contending there is little difference between the new and old drugs. The lead author of another recent study said because conventional drugs were previously prescribed in very high doses, making them less effective, historical comparisons of conventional and atypical drugs make the newer drugs appear more effective than they actually are.

To ascertain the effectiveness of atypical antipsychotics, Glick and his colleagues collected literature published between 1953 and 2002. They reviewed 124 controlled, randomized trials that compared conventional medications with 10 atypicals, as well as 18 studies that compared various kinds of atypicals. The studies involved more than 20,000 patients.

The researchers' meta-analysis found that conventional antipsychotics were similar to each other in terms of effectiveness, yet the effectiveness of the newer drugs varied widely. They found that four atypicals (clozapine, amisulpride, risperidone and olanzapine) were more effective in treating psychotic symptoms than conventional drugs. Clozapine, one of the most prescribed antipsychotics, was found most effective. Five of the drugs were equally as effective as conventional drugs and one medication was found to be slightly less effective.

In response to the research asserting that atypicals falsely appear more effective in comparison studies, the scientists conducted a separate analysis on dosage levels. They found that the high dosage level of conventional drugs did not affect results.

Given their popularity and the recent studies questioning their effectiveness, the finding that some atypicals are more effective than conventional antipsychotics is significant, Glick said. He added that it's important for clinicians to know which drugs are most effective and to understand that all atypicals are not the same. Glick said further studies comparing the new drugs head-to-head are needed.

"They're not miracle drugs, but they can certainly help patients socialize, work and function at a higher level," he said. "As clinicians it's important that we prescribe the medications that can most help our patients."

Glick collaborated with John Davis, MD, and Nancy Chen at the University of Illinois-Chicago. The researchers received no financing from pharmaceutical companies for the study.

Source: Stanford University Medical Center

Posted: June 2003