(AH) Antipsychotic Polytherapy Versus Monotherapy in Specific Dose Categories in The Maintenance Treatment of Schizophrenia

Publication Number: 324

Background: Very little is known about the safety and effectiveness of antipsychotic polytherapy compared with monotherapy, and most schizophrenia treatment guidelines recommend use of monotherapy instead of polytherapy.

Objectives: Objective of this study was to investigate safety, indicated by non-psychiatric hospitalization and hospitalization due to cardiovascular reasons, as well as the risk of relapse, indicated by psychiatric re-hospitalization, during antipsychotic polytherapy versus monotherapy in specified total dose categories in persons with schizophrenia.

Methods: We conducted nationwide register-based cohort study. The study cohort included all patients diagnosed in inpatient care with schizophrenia during 1972-2014 in Finland. They were followed up from January 1, 1996 or their first date of diagnosis if diagnosed later than that, and until death or end of data linkage (December 31, 2017). Exposures were antipsychotic polytherapy (use of ≥2 antipsychotics concomitantly) and monotherapy, and those were further categorized into 7 total dose 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) which were modelled as time-varying exposures (dose re-calculated at each dispensing event). Outcomes were non-psychiatric hospitalization, hospitalization due to cardiovascular reasons, and psychiatric hospitalization (a marker of relapse). Within-individual study design was utilized and all comparisons were conducted by using the individual as his or her own control to minimize selection bias.

Results: The study cohort included N=61,889 persons with schizophrenia and median follow-up time was 15.3 years. Antipsychotic polytherapy was associated with lower risk of non-psychiatric hospitalization than monotherapy at total doses above 1.1 DDDs/day (the lowest aHR 0.87, 0.84-0.89 for >1.6 DDDs/day) and the risk of cardiovascular hospitalization was also lower at the highest total dose >1.6 DDDs/day (aHR 0.82, 95% CI 0.72–0.94). Antipsychotic polytherapy was associated with lower risk of psychiatric hospitalization than monotherapy at all total antipsychotic dose categories except standard dose (0.9- < 1.1 DDDs/day), the lowest for >1.6 DDDs/day (aHR 0.86, 95% CI 0.84-0.88). Monotherapy was not statistically significantly superior to corresponding polypharmacy in any comparison in any dose category.

Conclusions: Antipsychotic polytherapy was associated with lower risk of psychiatric and somatic hospitalization than monotherapy at most total dose categories. The lower risk of somatic hospitalizations during high total dose treatment indicates better tolerability for polytherapy than monotherapy.