The Choice of Antipsychotic Drugs for Schizophrenia

A large study funded by NIH's National Institute of Mental Health (NIMH) provides, for the first time, detailed information comparing the effectiveness and side effects of five medications -- both new and older medications -- that are currently used to treat people with schizophrenia. Overall, the medications were comparably effective but were associated with high rates of discontinuation due to intolerable side effects or failure to adequately control symptoms. One new medication, olanzapine, was slightly better than the other drugs but also was associated with significant weight-gain and metabolic changes. Surprisingly, the older, less expensive medication used in the study generally performed as well as the newer medications. The study, which included more than 1,400 people, supplies important new information that will help doctors and patients choose the most appropriate medication according to the patients' individual needs. The study results are published in the September 22 issue of the New England Journal of Medicine.

Since the discovery of the effects of chlorpromazinein the 1950s, treatment of schizophrenia has relied on antipsychotic drugs that target dopamine D2 receptors. The effectiveness of these agents in reducing the intensity of patients' delusions and hallucinations permitted outpatient treatment instead of life long institutionalization in state mental hospitals. The many antipsychotic drugs introduced during the next decade were increasingly potent, as medicinal chemists improved the drugs' affinity for theD2receptor. However, the efficacy of the drugs was similar, since all had the same mechanism of ac-tion.1A troubling problem was that the blockade of dopaminergic neurotransmission in the basal ganglia caused parkinsonian syndromes. A long-lasting movement disorder, tardive dyskinesia, also occurred with prolonged treatment. More fundamentally, the early promise that these drugs might dramatically improve patients' psychosocial and cognitive disabilities was only partially fulfilled.2Al-though many mental hospitals were closed, mental health centers were filled with outpatients who could not live successfully in their communities.

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