title: Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy.
abstract: 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.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. jfriedman1@rcn.com
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Friedman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Frances
authors.initials: F
authors.lastname: Alcantara
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bowler
authors.forename: Mohan
authors.initials: M
authors.lastname: Parak
authors.forename: Leonard
authors.initials: L
authors.lastname: White
authors.forename: Adel
authors.initials: A
authors.lastname: Iskander
authors.forename: Michael
authors.initials: M
authors.lastname: Parrella
authors.forename: David N
authors.initials: DN
authors.lastname: Adler
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Tsopelas
authors.forename: Wei-Yann
authors.initials: WY
authors.lastname: Tsai
authors.forename: Vladan
authors.initials: V
authors.lastname: Novakovic
authors.forename: Vladan
authors.initials: V
authors.lastname: Novakovick
authors.forename: Philip D
authors.initials: PD
authors.lastname: Harvey
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Davis
authors.forename: Saurabh
authors.initials: S
authors.lastname: Kaushik
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000819:agonists; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003024:Clozapine / Q000819:agonists*; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010868:Pimozide / Q000008:administration & dosage*; D010919:Placebos; D011618:Psychotic Disorders / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D010868:Pimozide; D003024:Clozapine