Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy

Joseph I. Friedman, Jean Pierre Lindenmayer, Frances Alcantara, Stephanie Bowler, Mohan Parak, Leonard White, Adel Iskander, Michael Parrella, David N. Adler, Nicholas D. Tsopelas, Wei Yann Tsai, Vladan Novakovick, Philip D. Harvey, Kenneth L. Davis

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Despite its superior efficacy, clozapine is helpful in only a subset of patients with schizophrenia unresponsive to other antipsychotics. This lack of complete success has prompted the frequent use of various clozapine combination strategies despite a paucity of evidence from randomized controlled trials supporting their efficacy. Pimozide, a diphenylbutylpiperidine, possesses pharmacological and clinical properties distinct from other typical antipsychotics. An open-label trial of pimozide adjunctive treatment to clozapine provided promising pilot data in support of a larger controlled trial. Therefore, we conducted a double-blind, placebo-controlled, parallel-designed 12-week trial of pimozide adjunctive treatment added to ongoing optimal clozapine treatment in 53 patients with schizophrenia and schizoaffective disorder partially or completely unresponsive to clozapine monotherapy. An average dose of 6.48 mg/day of pimozide was found to be no better than placebo in combination with clozapine at reducing Positive and Negative Syndrome Scale total, positive, negative, and general psychopathology scores. There is no suggestion from this rigorously conducted trial to suggest that pimozide is an effective augmenting agent if an optimal clozapine trial is ineffective. However, given the lack of evidence to guide clinicians and patients when clozapine does not work well, more controlled trials of innovative strategies are warranted.

Original languageEnglish (US)
Pages (from-to)1289-1295
Number of pages7
Issue number6
StatePublished - May 2011


  • clozapine
  • combination
  • pimozide
  • schizophrenia
  • treatment non-response

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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