Efficacy and safety of ketamine maintenance therapy in treatment-resistant depression: A systematic review of treatment protocols and clinical outcomes.

Introduction: Treatment-resistant depression (TRD) represents a significant therapeutic challenge, as conventional treatments demonstrate limited efficacy. Although ketamine's acute antidepressant effects are well-documented, the role of maintenance therapy remains understudied. We conducted a systematic review to assess the efficacy, safety, and optimal implementation strategies of ketamine maintenance therapy in TRD.

Methods: Following PRISMA guidelines, we searched major databases for studies published between January 2020 and November 2024 that examined ketamine maintenance therapy in TRD. Studies were assessed using the Cochrane Risk of Bias 2 tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies.

Results: Eleven studies met inclusion criteria. Regular maintenance dosing showed superior outcomes compared to variable protocols (relapse rates: 27.3 % vs 45.6 %). Younger age (<45 years) and shorter duration of depression (<2 years) predicted better response rates. Concurrent psychotherapy improved treatment maintenance (HR: 0.72 for relapse). Adverse events were generally mild to moderate, resulting in a 7.2 % discontinuation rate.

Conclusions: Ketamine maintenance therapy shows promise as a treatment option for TRD, with regular dosing schedules and early intervention associated with optimal outcomes. While safety profiles are reassuring, standardized protocols and careful patient selection remain essential. Future research should focus on determining the optimal maintenance duration and identifying reliable biomarkers for treatment response.