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Discontinuing Neuroleptics in Schizophrenics: Good News or Bad News?

It is well known that neuroleptic drugs prevent relapse in schizophrenia. However, it is equally well known that long-term treatment with neuroleptics carries significant risks of tardive dyskinesia, dysphoria, apathy, and occupational impairment. To help clinicians assess the risks associated with continuing or withdrawing antipsychotic drugs, this article reviewed 66 studies involving 3141 schizophrenic patients withdrawn from neuroleptics and 1224 patients continued on neuroleptic therapy.

During a mean follow-up of 9.7 months, 51.5% of patients withdrawn from neuroleptics relapsed, a rate significantly higher than the 16.2% relapse rate in patients who remained on neuroleptics. Abrupt withdrawal increased the risk of relapse. Patients who relapsed recompensated within three weeks of restarting neuroleptics, although it was not known whether social and behavioral functioning recovered as rapidly as psychotic symptoms abated.

The meaning of these results is debated in a series of accompanying commentaries. The authors and expert commentators recommend a very slow taper of neuroleptics after one to two years of acute neuroleptic therapy to determine whether a lower (or no) dose prevents relapse. They all also recommend increased use of atypical antipsychotic drugs such as clozapine, risperidone, and the still experimental drugs olanzopine and sertindole; careful patient monitoring; and reevaluation of the treatment plan after 5 to 10 years of illness, when schizophrenic patients' functioning seems to naturally stabilize or even improve. Most believe that drug holidays are less effective and have a higher risk of tardive dyskinesia than continuous treatment. However, most disagreement centered on whether recurrent psychotic episodes (such as those that could occur with medication withdrawal) increase the likelihood of future episodes and treatment resistance.

Comment: All schizophrenic patients deserve periodic reevaluation of their neuroleptic dose, especially when they are chronically ill. If an attempt is made to withdraw antipsychotic drugs, it should occur over many months with careful observation and in combination with appropriate psychosocial therapies. Although drug discontinuation may be riskier in patients who are still symptomatic, even patients who seem to be in remission may relapse when the medication is withdrawn.

— S Dubovsky

Published in Journal Watch Psychiatry May 1, 1995

Citation(s):

Gilbert PL et al. Neuroleptic withdrawal in schizophrenic patients. A review of the literature. Arch Gen Psychiatry 1995 Mar 52 173-188.

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Baldessarini RJ; Viguera AC. Neuroleptic withdrawal in schizophrenic patients. Arch Gen Psychiatry 1995 Mar 52 189-192.

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Meltzer HY. Neuroleptic withdrawal in schizophrenic patients. An idea whose time has come. Arch Gen Psychiatry 1995 Mar 52 200-202.

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Wyatt RJ. Risks of withdrawing antipsychotic medications. Arch Gen Psychiatry 1995 Mar 52 205-208.

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