Antipsychotic Polypharmacy in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      The literature suggests that when a patient is prescribed more than one antipsychotic for at
      least 30 days, he or she is likely to continue on that combination. In this 12 week study 100
      adult patients being treated on more than one antipsychotic medication for at least 30 days
      will be recruited. In order to control for the natural course of the illness, patients will
      be randomly assigned to one of two groups: the first group will continue the second
      medication hidden in a capsule at the same dose, while the second group will be given an
      inactive capsule (placebo) - the capsules in both group will be identical such that neither
      the patient nor the treating doctor will be able to identify the group assignment.
    

Detailed description: 
      There is no evidence that using more than one antipsychotic drug enhances clinical efficacy.
      Nonetheless, this practice is highly prevalent (up to 1/3 of our patient population), and
      physicians are reluctant to reduce patients' treatment to a single antipsychotic drug for
      fear of precipitating relapse. This study therefore seeks to evaluate the effectiveness of
      continued treatment with more than one antipsychotic drug using a rigorous placebo-controlled
      design. The results of this study will subsequently serve to guide physicians in making
      appropriately informed decisions regarding the continuation of multiple antipsychotic drugs.

      Our primary hypothesis is that we expect to find no difference in the primary variable of
      interest (BPRS) following reduction to antipsychotic monotherapy (placebo group) versus
      continuing antipsychotic polypharmacy.

      This proposed study is the first study to systematically address the reduction of
      antipsychotic polypharmacy to monotherapy in patients with primary psychotic disorders in a
      prospective, double-blind, placebo-controlled design. The results of this study will have
      important implications for the clinical practice of physicians treating the severely mentally
      ill who are often constrained to practice beyond the limits of available clinical guidelines
      and evidence based medicine. Thus, in light of the high and growing prevalence of this
      practice, the proposed study speaks to a real and practical clinical dilemma within this
      field. Furthermore, as a university-based, tertiary care psychiatric centre serving thousands
      of severely ill patients suffering from primary psychotic disorders and with an established
      track record for innovative clinical research, we are uniquely placed to address these
      critical questions.

      Male or female subjects aged ≥ 18 years suffering from a primary psychotic disorder treated
      with two antipsychotic drugs for at least 30 days (excluding "prn" or "as needed"
      antipsychotic prescriptions) will be eligible to participate in this study. Subjects with a
      history of treatment with a depot antipsychotic within 6-months of enrollment will be
      excluded form the study unless the depot antipsychotic is considered the "main" antipsychotic
      drug in this study. The "main" antipsychotic drug will be determined by the treating
      physician, except for the case of clozapine which will be considered the 'main'
      antipsychotic. Eligible subjects will be randomly allocated to two groups: Group 1 will
      continue taking the concomitant antipsychotic drug; Group 2 will be allocated to placebo in
      place of the concomitant antipsychotic drug. The dose of the "main" antipsychotic drug will
      remain open and flexible at the discretion of the attending physician. The dose of the
      "second" antipsychotic drug will remain fixed throughout the study period.
    

Intervention name(s): 2 antipsychotic medications (combinations of olanzapine, risperidone, clozapine, seroquel, haldol, perphenazine); main antipsychotic medication and placebo
Intervention type(s): Drug; Drug
Intervention description(s): Primary antipsychotic medication (olanzapine, oral risperidone, seroquel, clozapine, haldol, perphenazine) will be determined by the treating physician and participants will continue taking the concomitant antipsychotic drug. The dose of the main antipsychotic drug will remain open and flexible at the discretion of the attending physician. The dose of the "second" antipsychotic drug will remain fixed throughout the study period.; The "main" antipsychotic drug will be determined by the treating physician. Participants will be allocated to placebo in place of the concomitant antipsychotic drug. The dose of the "main" antipsychotic drug will remain open and flexible at the discretion of the attending physician.
Intervention MeSH terms: Olanzapine; Risperidone; Quetiapine Fumarate; Antipsychotic Agents; Clozapine; Perphenazine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: schizophrenia; antipsychotics; polypharmacy; double-blind; randomized