Clinical rationale of mood stabilizers in treating depression: Insights from prescriptions and adherence patterns

ImportanceMood stabilizers are typically reserved for bipolar disorders, yet their role in treating unipolar depression remains underexplored despite clinical need and theoretical rationale. ObjectiveTo evaluate the association between low-dose mood stabilizer use and 6-month treatment retention in patients with unipolar and bipolar depression. Design, Setting, and ParticipantsThis retrospective cohort study analyzed medical records from a single outpatient psychiatric clinic in Japan between 2016 and 2022, including 300 patients with unipolar or bipolar depression initiating pharmacotherapy (100 patients per year). ExposuresPrescription of mood stabilizers (e.g., lithium, valproate), antidepressants, or both. Main Outcomes and MeasuresThe primary outcome was 6-month treatment retention, used as a proxy for pharmacotherapy adherence, reflecting long-term drug tolerability and real-world clinical effectiveness. Retention rates were compared across treatment types using Kaplan-Meier and Cox regression analyses adjusted for demographic and clinical variables. ResultsMood stabilizer prescriptions increased from 27% in 2016 to 89% in 2022. Patients with unipolar depression treated with mood stabilizers exhibited significantly higher 6-month retention compared to those on antidepressants alone (adjusted HR: 0.44; 95% CI, 0.24-0.80; p <.01). Side effects were mild and manageable, with high continuation rates observed for low-dose regimens. Conclusions and RelevanceLow-dose mood stabilizers, particularly lithium and valproate, were associated with significantly higher treatment retention rates in unipolar depression compared to antidepressants alone. These findings suggest the potential role of mood stabilizers in enhancing treatment adherence and highlight the need for confirmatory prospective studies to evaluate their comparative effectiveness. Key PointsO_ST_ABSQuestionC_ST_ABSCan low-dose mood stabilizers improve 6-month treatment retention among patients with unipolar depression? FindingsIn this retrospective cohort study of 185 patients with unipolar depression, treatment with low-dose lithium or valproate was associated with significantly higher 6-month treatment retention compared to antidepressants alone (adjusted HR: 0.44; 95% CI, 0.24-0.80; p <.01). MeaningLow-dose mood stabilizers may improve treatment adherence in unipolar depression, warranting reconsideration of their role in treatment guidelines.