Conversion to Antipsychotic Monotherapy

Background: Often, treatment resistant schizophrenia patients are treated with high doses of, or polypharmacy with, antipsychotics, or both. There is a lack of systematic evidence for either practice, and this is not recommended by most treatment guidelines. Often polypharmacy results in dosages well above the recommended upper limit of dosage. Recent studies of antipsychotic utilization, have reported that approximately 10-60% of patients are prescribed at least two antipsychotics. Moreover, antipsychotic treatment carries substantial risks, including the potential development of tardive dyskinesia or metabolic syndrome. Higher doses may expose patients to more adverse events or consequences without any additional therapeutic benefit. Clear benefits of long-term treatment with antipsychotic polypharmacy have rarely been reported, and there is a void of long term double blind, placebo controlled trials. Antipsychotic polypharmacy remains common, including patients receiving atypical antipsychotics. To our knowledge, no one has published a study of a systematic, randomized controlled conversion to antipsychotic monotherapy for patients with chronic schizophrenia or schizoaffective disorder receiving atypical antipsychotic polypharmacy. Design: Hospitalized patients with DSM-IV-TR schizophrenia or schizoaffective disorder meeting the following criteria: (1) at least two antipsychotics, (2) stable dosages for at least one month prior to baseline, (3) baseline dosages of at least one of the antipsychotics are at least olanzapine 15 mg, ziprasidone 120 mg, quetiapine 500 mg, risperidone 4 mg, aripiprazole 10 mg, paliperidone 6 mg, any dose of clozapine, or any first generation antipsychotic \>300 chlorpromazine equivalents. After a baseline assessment, patients will be randomized to conversion to antipsychotic monotherapy of one of their two antipsychotics or continued on their combination antipsychotic treatment. Other psychotropics will be left unchanged from baseline, and the prescription of a new psychotropic will not be permitted, excepting lorazepam and benztropine as detailed below. If a patient is randomized to conversion to monotherapy, then the decision of which of the two baseline antipsychotics to continue will occur as follows: 1. If one is clozapine, then clozapine will be continued. 2. In all other cases: 1. If only one of the antipsychotics is at a dose greater than the above noted doses, then that is one that will be continued. 2. If both doses are greater than the above noted doses, then there will be a flip of a coin to determine which to continue, with heads equal the one with the higher alphabetic letter and tails equal to the lower.