Research paperReducing the rehospitalization risk after a manic episode: A population based cohort study of lithium, valproate, olanzapine, quetiapine and aripiprazole in monotherapy and combinations

•Real-world rehospitalization risks after a manic episode are largely unknown.•78% of patients initiated pharmacologic relapse prevention after a manic episode.•Out of these, 40% were rehospitalized within one year.•Patients combining olanzapine with lithium or valproate had the lowest risk.

BackgroundData on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited.MethodsWe conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18-75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors.ResultsThe study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62-0.93) and 0.83 (95% CI 0.70-0.98), compared to lithium monotherapy).LimitationsRegister data does not provide information on all clinical parameters affecting treatment choices.ConclusionsOne-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode.