A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009-January 2019

Background: Sub-anaesthetic administration of ketamine is an emerging practice in patients presenting treat-ment resistant depression (TRD), however several outstanding questions have yet to be answered. Objective: To evaluate the effect of intravenous ketamine infusion for patients presenting TRD on depression scores, clinical remission and response rates, and to assess its efficacy over both time and frequency. Methods: Five databases were searched up to January 4th 2019 to include primary studies evaluating the use of sub-anaesthetic dose of ketamine in adults presenting TRD. Two reviewers independently performed the study selection, quality assessment and data extraction. Results were summarised in a narrative synthesis. A meta analysis using a random effects model was performed when possible to examine changes in standardized mean differences and odds ratios of outcome measures at 4 hours, 24 hours, or 7 days post-infusion. Results: Twenty-eight studies in 35 publications were included. A strong ketamine effect was observed within 4 hours following a single infusion, and peaked at 24 hours. Ketamine's effectiveness was still present, yet somewhat diminished, 7 days post-infusion. Multiple infusions resulted in an enhanced and prolonged ketamine effect. Limits: Due to insufficient data, long-term safety and efficacy of ketamine utilisation in patients presenting TRD are yet to be investigated. Conclusions: Results provide support for the use of ketamine in the rapid management of depressive symptoms. While ketamine appears promising in the short-term treatment of TRD, more clinical and experimental data is needed with regards to the efficacy, tolerance and security of long-term administration of ketamine.