Dropping antipsychotic polypharmacy looks safe, effective when 1 drug is clozapine or an injectable

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  • Patients receiving clozapine (Clozaril, FazaClo, Versacloz) or a long-acting injectable antipsychotic experienced no worsening of symptoms or side effects when switched to monotherapy.
  • Patients who switched to oral, nonclozapine antipsychotic (NCAP) experienced reduced side effects but also increased symptoms.

Why this matters

  • Chronically ill patients may face some symptom risks when switching from polypharmacy to monotherapy, but benefits are also possible.
  • In chronically ill patients switching to monotherapy, clozapine or an injectable antipsychotic may be the best choice.

Study design

  • Patients with schizophrenia or schizoaffective disorder earlier treated with oral NCAP (n=45) or clozapine/injectable antipsychotics (C/IAP; n=45) were switched to monotherapy (n=43) or continued with polypharmacy (n=47).
  • Funding: Florida Agency for Health Care Administration.

Key results

  • Overall trajectory of change (using The Positive and Negative Syndrome score [PANSS]) with C/IAP showed significant increase on PANSS Negative Syndrome Scale scores (18.53; P<.001).
  • Switch patients showed no significant time-by-condition interactions for any symptom or side effects (except Simpson Angus scale, P=.037) in C/IAP.
  • Overall trajectory was positive with oral NCAP, indicating increased symptoms over time.
  • Oral NCAP had significant interactions for BMI (P=.034), HbA1c (P=.035), and Abnormal Involuntary Movement Scale total score (P=.043).


  • Requires cautious interpretation.

Coauthored with Chitra Ravi, M.Pharm