MEDICATIONS: PSYCHOSIS ONSET MAY BE DELAYED BY OLANZAPINE

May 4, 2006 — For young people who seem to be developing early signs of schizophrenia, early treatment with the antipsychotic drug olanzapine appears to delay the rate of conversion to full-blown psychotic disorder, compared to placebo, according to an article in the May issue of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association (APA).

The Prevention Through Risk Identification, Management, and Education (PRIME) study was conducted in two U.S. and two Canadian cities during 1998-2003. Results are presented by Thomas H. McGlashan, M.D., Depart of Psychiatry, Yale University School of Medicine in the article "Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis."

The participants were mostly adolescents who were seeking treatment as a result of having problems with functioning and displaying symptoms resembling those of psychosis, but less severe. The prodromal symptoms included occasional periods of persecutory thoughts, abnormal sensory experiences such as hearing unusual sounds, or brief periods of incoherent thoughts. Earlier studies suggest that many of these individuals will eventually develop the full symptoms of schizophrenia, with persistent paranoia, auditory hallucinations and disability in their lives.

The participants were randomly assigned to olanzapine, a drug often used to treat schizophrenia, or placebo for one year and were then observed for an additional year after treatment was stopped. During the year of treatment, the olanzapine group had greater improvement in these prodromal symptoms. Conversion to full psychosis occurred in 16 percent of the olanzapine patients and 38 percent of the placebo patients. In the year following treatment, when the treatment was discontinued, the rates of conversion to psychosis did not differ, and symptoms increased for the patients formerly treated with olanzapine.

"The delay of the onset of the most severe symptoms of schizophrenia appears to have occurred because of the early recognition and treatment of these young persons. This delay enabled them to be better connected with treatment and to better cope with this devastating illness," said Robert Freedman, M.D., AJP editor-in-chief.

The findings are considered preliminary, as 60 patients began the study and only 17 remained by the end of the posttreatment year. Despite the long recruitment period and multiple study sites, participation was limited by the low natural incidence of prodromal psychotic symptoms in the general population and by treatment dropouts.

Research into the early detection and treatment of schizophrenia has become important to determining whether psychosis and/or some of its disabilities can be prevented. Recent investigations have examined whether a longer duration of untreated psychosis leads to a poorer outcome after treatment begins. The possibility of delaying or preventing schizophrenia has been tested only since improvements in the identification of high-risk individuals and the introduction of antipsychotic medications that do not produce disorders in body movements, which occur with the first generation of antipsychotics.

Weight gain is a frequent side effect of olanzapine, and the patients in the PRIME study who took olanzapine gained an average of 19 pounds. Increases in glucose and cholesterol levels are also common but did not develop in these patients.

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