Optimal Clozapine Dose for Schizophrenia Remains Elusive

By Reuters Staff

NEW YORK—The existing evidence leaves open the question as to whether a standard-, low-, or very-low-dose regimen of clozapine yields the best results in patients with schizophrenia, according to a new Cochrane review.

Clozapine, an atypical antipsychotic, can improve positive symptoms (delusions and hallucinations) and negative symptoms (withdrawal and poverty of speech) in patients with schizophrenia, but it remains unclear what dose of clozapine is most effective with the least side effects.

Dr. Nick Huband from the University of Nottingham Innovation Park, in the U.K., and colleagues compared the efficacy and tolerability of clozapine at different doses in the treatment of schizophrenia as well as schizophreniform and schizoaffective disorders in their review of five relevant studies.

They divided the doses into very low doses (up to 149 mg/day), low doses (150 to 300 mg/day), and standard doses (301 to 600 mg/day). There were no studies of high or very high doses of clozapine.

There was no evidence of a difference on the effects on mental states between low and very low doses, between very low and standard doses, or between low doses and standard doses of clozapine, the reserachers report in the Cochrane Database of Systematic Reviews, online June 14.

Serum triglyceride levels appeared to be lower with low doses of clozapine versus very low doses of clozapine in the short term.

There appeared to be fewer adverse effects with low doses than with standard doses of clozapine. Weight gain and postprandial glucose levels were lower and total cholesterol levels were higher with very low doses than with standard doses of clozapine.

“We found very little useful data and the evidence available is generally of low or very low quality,” the researchers conclude. “More studies are needed to validate our findings and report on outcomes such as relapse, remission, social functioning, service utilization, cost-effectiveness, satisfaction with care, and quality of life. There is a particular lack of medium- or long-term outcome data, and on dose regimes above the standard rate.”

Dr. Huband did not respond to a request for comments.

SOURCE: https://bit.ly/2sHDhyf

Cochrane Database Syst Rev 2017.

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