Abstract Lithium is the gold-standard maintenance treatment for bipolar disorder, yet many patients experience inadequate response or intolerance. Using harmonized nationwide cohorts from Sweden ( n = 105,495) and Finland ( n = 60,045) with an average of 9 years of follow-up, we assessed the comparative effectiveness of mood stabilizers, antipsychotics and their combinations in preventing psychiatric hospitalization. Within-individual analyses revealed that, compared with lithium monotherapy, clozapine plus aripiprazole (adjusted hazard ratio = 0.42; 95% confidence interval, 0.22–0.80), clozapine alone (0.61; 0.49–0.75) and long-acting injectable antipsychotics + lithium (0.70; 0.59–0.84) were associated with lower relapse risk. Among 20,645 lithium discontinuers, long-acting injectable antipsychotics + valproate (0.41; 0.19–0.92), quetiapine + lamotrigine (0.64; 0.51–0.79), olanzapine + valproate (0.65; 0.50–0.84) and risperidone + valproate (0.63; 0.42–0.93) were linked to reduced hospitalization risk. These findings highlight specific regimens that provide potential options for patients in whom lithium is ineffective or discontinued.
Lieslehto et al. (Thu,) studied this question.