Public Release:  Onset of psychosis may be delayed by medication

Yale University

New Haven, Conn.--For young people who clearly seem to be developing early signs of schizophrenia, treatment with the antipsychotic drug olanzapine appears to lower or delay the rate of conversion to full-blown psychosis, according to an article by a Yale School of Medicine researcher in the May issue of The American Journal of Psychiatry.

The findings are preliminary since 60 patients began the study and 17 completed it. Despite the long recruitment period and multiple study sites, participation was limited by the low incidence of pre-psychotic, or "prodromal," symptoms in the general population.

Schizophrenia affects about one percent of the population, or three million people, and is one of the most disabling medical disorders.

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

The study, "The Prevention Through Risk Identification, Management, and Education (PRIME)," was conducted in two U.S. cities and two Canadian cities during 1998-2003. Senior author of the study was Thomas McGlashan, M.D., professor in the Department of Psychiatry at Yale.

The participants were mostly adolescents. The individuals or their parents sought treatment because the adolescents had symptoms resembling those of psychosis, but less severe. Symptoms included occasional periods of persecutory thoughts, abnormal sensory experiences such as hearing unusual sounds, and brief periods of incoherent thoughts, among other symptoms. Earlier studies suggest that many of these individuals would eventually develop the full symptoms of schizophrenia--persistent paranoia, auditory hallucinations and disability.

The participants were randomly assigned for one year to olanzapine, a drug often used to treat schizophrenia, or placebo, and then were observed for an additional year after treatment was stopped.

During the year of treatment the olanzapine group had greater improvement in prodromal symptoms with conversion to full psychosis in 16 percent of the olanzapine patients and 38 percent of the placebo patients. In following year, after the treatment was discontinued, the rates of conversion to psychosis did not differ and symptoms increased for the patients previously treated with olanzapine.

Research into the early detection and treatment of schizophrenia has become important to determine whether psychosis and/or some of its disabilities can be prevented. Recent investigations have examined whether a long duration of untreated psychosis leads to a poorer outcome after treatment begins. Clinical trials to determine whether schizophrenia can be delayed or prevented are now possible due to improvements in antipsychotic medications and in identification of high-risk individuals.

Weight gain is a frequent side effect of olanzapine, although it does not cause body tremors as did the first generation of antipsychotic medications. The patients in the PRIME study who took olanzapine gained an average of 19 pounds. Increases in glucose and cholesterol levels are also common in patients taking antipsychotic medications, but the patients in this study did not develop these symptoms.

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Eli Lilly Company and the National Institute of Mental Health funded the study.

The American Journal of Psychiatry 163: 790-799 (May 1, 2006)

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