Dose of caution: New antipsychotic meds produce muted benefits

The past decade has witnessed a wave of new medications to treat schizophrenia, a debilitating mental disorder that afflicts 1 in 100 people. Armed with results from their own studies, various pharmaceutical companies tout the new drugs, the so-called atypical antipsychotics, as superior to traditional antipsychotic drugs in the battle against schizophrenia.

However, it may be time to lower expectations for atypical antipsychotics. A new investigation, funded largely by the federal government, finds that treatment with any of three of these medications diminishes chronic schizophrenia symptoms only slightly more than a traditional antipsychotic drug does.

Atypical antipsychotics work better than standard medications, but their advantage is relatively modest, at least for chronic schizophrenia, says study coauthor Jeffrey A. Lieberman, a psychiatrist at the University of North Carolina at Chapel Hill. Although atypical antipsychotics often induce a weight gain of 5 to 12 pounds, Lieberman adds, theyre much less likely than traditional antipsychotics to cause severe movement disorders.

The new investigation, led by psychiatrist Jan Volavka of the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, N.Y., sharpens an ongoing debate among physicians about whether to prescribe atypical antipsychotics as a primary schizophrenia treatment. These drugs cost at least 10 times as much as traditional antipsychotic medications, such as haloperidol.

Volavka and his coworkers describe their findings in the February American Journal of Psychiatry.

The scientists recruited 157 patients, most around age 40, from state psychiatric hospitals in North Carolina and New York. Participants had suffered from schizophrenia for up to several decades and had previously taken only traditional antipsychotics, which had not yielded any improvement. Over a 14-week trial, patients were randomly assigned to receive one of three atypical antipsychotics–clozapine, olanzapine, or risperidone–or haloperidol.

The three atypical drugs, but not haloperidol, yielded statistically significant but clinically modest improvements in schizophrenia symptoms, the researchers say. These symptoms included delusions, hallucinations, apathy, and a lack of verbal and emotional expression. Clozapine and olanzapine worked slightly better than risperidone did.

The new study was funded mainly by the National Institute of Mental Health (NIMH) in Bethesda, Md., with about 18 percent of the projects cost assumed by olanzapines manufacturer. Previous trials subsidized by pharmaceutical firms have focused on the particular atypical antipsychotic drug made by the funder.

The modest treatment advantage reported by Volavkas group for atypical antipsychotics clearly underscores the need for identification of more effective [antipsychotic] treatments, remarks psychiatrist David A. Lewis of the University of Pittsburgh in an editorial published with the new study.

Researchers need trials longer than the new study to clarify the relative merits of different atypical antipsychotic drugs, especially as frontline treatments for schizophrenia, holds psychiatrist John M. Kane of Hillside Hospital in Glen Oaks, N.Y.

Such a project is now under way. Researchers in 38 states, led by Lieberman, plan to study 1,600 people with schizophrenia treated for up to 1 year with one of five atypical antipsychotics or a traditional medication. Participants in this NIMH-funded study will also receive standard forms of supportive psychotherapy and education (SN: 4/28/01, p. 268: Back from the Brink).