Adverse effect MonoPoly: Antipsychotic monopharmacy vs antipsychotic polypharmacy in the treatment of schizophrenia

Although antipsychotic polypharmacy (APP) is not recommended for the treatment of schizophrenia, it remains a common clinical practice. While APP is generally presumed to be associated with a higher burden of adverse effects, the current evidence remains inconclusive.

This study compared the adverse effects experienced by patients with schizophrenia (excluding those receiving clozapine) treated with antipsychotic monopharmacy (APM) or APP using both subjective and objective assessments.

This cross-sectional study included 114 patients with schizophrenia (56 receiving APM and 58 receiving APP). Spontaneously reported adverse effects, including their number and type, were recorded. Objective adverse effects were assessed using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS).

No significant differences were observed between the APM and APP groups on the overall subjective or objective measures of adverse effects. However, headache (P = 0.04), difficulty concentrating (P = 0.01), constipation (P = 0.01), restlessness (P = 0.01), and insomnia (P = 0.006) were reported significantly more frequently in the APP group. Compared with the APM group, patients receiving APP had a significantly longer duration of illness (P = 0.004; d = 0.55), lower treatment adherence (P = 0.02; d = 0.25), a higher total chlorpromazine-equivalent dose (P < 0.001; d = 1.21), and a higher rate of trihexyphenidyl use (P = 0.01; φ = 0.23).

Overall adverse effects were comparable between the APM and APP groups. However, APP was associated with higher antipsychotic and trihexyphenidyl use; more insomnia, restlessness, constipation, and difficulty concentrating; and poorer treatment adherence.