In a nationwide cohort of 61,889 people with schizophrenia in Finland, the risk of hospitalization for severe physical health problems was no lower with monotherapy than with multiple agents. “Treatment guidelines should not encourage use of monotherapy instead of antipsychotic polypharmacy without any existing evidence on the safety issues,” the authors conclude.
Over a median follow-up period of 14.8 years in the 1996 to 2017 period, antipsychotic polypharmacy was compared with monotherapy in 7 dosage categories based on defined daily doses (DDDs) per day. The risk of severe physical morbidity as indicated by nonpsychiatric and cardiovascular hospitalizations was as follows: “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.”