Objectives: The authors sought to study the safety of antipsychotic polypharmacy compared with monotherapy in specific dosage categories.
Methods: Patients with schizophrenia (N=61,889; median follow-up, 14.8 years [IQR=7.4-22.0]) were identified from the Finnish nationwide inpatient care register and followed up over the period 1996-2017. Antipsychotic polypharmacy was compared with monotherapy in seven dosage categories (<0.4, 0.4-<0.6, 0.6-<0.9, 0.9-<1.1, 1.1-<1.4, 1.4-<1.6, and ≥1.6 defined daily doses [DDDs] per day) in terms of risk of severe physical morbidity, indicated by nonpsychiatric and cardiovascular hospitalizations (adjusted hazard ratio). Within-individual analysis was used in an effort to eliminate selection bias.
Results: The mean age of the cohort was 46.7 years (SD=16.0), and 50.3% (N=31,104) were men. Among patients who had used both monotherapy and polypharmacy, the risk of nonpsychiatric hospitalization was significantly lower during polypharmacy use at all total dosage categories above 1.1 DDDs/day with differences up to -13% than during monotherapy use of the same dosage category (for 1.1-<1.4 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.87-0.95; for 1.4-<1.6 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.86-0.96; and for ≥1.6 DDDs/day, adjusted hazard ratio=0.87, 95% CI=0.84-0.89). The risk of cardiovascular hospitalization was significantly lower for polypharmacy at the highest total dosage category (-18%, adjusted hazard ratio=0.82, 95% CI=0.72-0.94). The results from the comparisons between monotherapy and no use and between polypharmacy and no use were in line with the primary comparison of polypharmacy and monotherapy within the same individual. Comparison of any polypharmacy use with any monotherapy use showed no significant difference for nonpsychiatric or cardiovascular hospitalization.
Conclusions: The results show that antipsychotic monotherapy is not associated with a lower risk of hospitalization for severe physical health problems when compared with antipsychotic polypharmacy. Treatment guidelines should not encourage use of monotherapy instead of antipsychotic polypharmacy without any existing evidence on the safety issues.
Keywords: Antipsychotics; Polypharmacy; Schizophrenia Spectrum and Other Psychotic Disorders.