Association of Low-Dose Mood Stabilizers With Treatment Retention in Unipolar Depression: A Retrospective Cohort Study

Importance

Mood stabilizers are typically reserved for bipolar disorders, yet their role in treating unipolar depression remains underexplored despite clinical need and theoretical rationale.

Objective

To evaluate the association between low-dose mood stabilizer use and 6-month treatment retention in patients with unipolar and bipolar depression.

Design, Setting, and Participants

This 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).

Exposures

Prescription of mood stabilizers (e.g., lithium, valproate), antidepressants, or both.

Main Outcomes and Measures

The 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.

Results

Mood 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 Relevance

Low-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 Points