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

Sub-anaesthetic administration of ketamine is an emerging practice in patients presenting treatment resistant depression (TRD), however several outstanding questions have yet to be answered. 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. 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. 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. Due to insufficient data, long-term safety and efficacy of ketamine utilisation in patients presenting TRD are yet to be investigated. 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.