An open-label, flexible-dose study of memantine in major depressive disorder

To assess the efficacy and safety of flexible-dose memantine in patients with major depressive disorder (MDD).

In this 12-week, single-center, open-label study, 8 patients with MDD were titrated for 4 weeks to 20 mg/d memantine. Nonresponsive patients were titrated to 30 mg/d (at week 8) or 40 mg/d (at week 10), provided that no dose-limiting adverse events were observed. Outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale, the Clinical Global Impression-Severity of Illness and the Clinical Global Impression-Improvement Scales, the Patient Global Evaluation, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Major Depressive Episode Checklist. Tolerability and safety assessments were performed throughout the trial.

The safety population comprised 8 outpatients with a mean (SD) baseline MADRS score of 31.9 (4.45), indicative of severe depression. Seven subjects completed the study. All patients attained the target dose of 20 mg/d; 3 patients were titrated to 30 mg/d after week 8, and 2 patients were titrated to 40 mg/d after week 10. The mean dosage across all weeks was 18.1 mg. Patients improved on all efficacy measures within 1 week of treatment initiation. The mean improvement peaked at week 8 and was maintained through week 12 (MADRS, 18.5 [10.3]; last-observation-carried-forward). All memantine doses were well tolerated.

Memantine demonstrated early-onset efficacy in patients with MDD. The treatment was well tolerated. This study suggests that double-blind, placebo-controlled studies of memantine in depression are merited.