Referencing a 2013 Japanese study,4 Barbui and colleagues suggested that switching from polypharmacy to monotherapy is feasible in a majority of patients with schizophrenia. In the referenced study, H. Tani and colleagues identified and reviewed 17 clinical trials that attempted to reduce the use of AP polypharmacy for patients with schizophrenia. One randomized controlled trial and 2 open-label trials systematically switched patients from AP polypharmacy to monotherapy. The switch was successfully completed by more than two-thirds of the patients in 2 of the 3 studies. In the third trial, whose sample size was small, only 6 of the 14 subjects (42.96%) tolerated the switch.4   

The 14 remaining studies examined the effectiveness of interventions to dissuade physicians from using AP polypharmacy. Interventions were classified as modest or aggressive. Modest intervention consisted mainly of the one-way, passive dissemination of information—via lectures and seminars, for example. Assertive intervention involved more active forms of communication, such as in-person feedback, letters, and phone calls.4 The authors concluded that assertive interventions are more effective than passive education alone in reducing AP polypharmacy, and that carefully switching from polypharmacy to monotherapy seems feasible in a majority of patients with schizophrenia.4



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There are many reasons, in addition to QTc lengthening, for considering a switch from AP polypharmacy to monotherapy, and many factors to take into account when doing so. A 2015 study by Robert Constantine and colleagues casts some doubt on the feasibility of switching.1 This randomized controlled trial demonstrated that, for stable patients with schizophrenia and long histories of AP drug therapy, switching from to 2 agents to 1 may present risks that exceed the benefits. The trial included 104 adult outpatients with schizophrenia from 7 community mental health centers. All were taking 2 AP medications and were clinically stable. The patients were randomly assigned to stay on their current 2-drug regimen (stay group) or switch to monotherapy (switch group). Baseline antipsychotic doses were different for the groups. Participants were then followed for 1 year; during that time, they were assessed for side effects and symptoms every 60 days, for a total of 7 assessments. Adherence was assessed by questionnaire but not confirmed with antipsychotic blood level measurements.1

During the second 6 months of the trial, patients who switched to monotherapy experienced greater increases in symptoms than participants who remained on 2 drugs. Over the one-year trial, all-cause discontinuation rates were higher in the switch group than in the stay group (42% vs. 13%; P <.01). Change in side effects over time was similar for the two groups.1