Short-term effects of oral ketamine for the treatment of depression: A systematic review and meta-analysis of randomized controlled trials

Oral ketamine is a novel treatment for management of depression. However, evidence related to its effectiveness and safety is unavailable. This systematic review aimed to assess the short-term efficacy and safety of oral ketamine compared to placebo or other modes of ketamine in randomized controlled trials (RCT) in unipolar depression, bipolar depression, and treatment-resistant depression. A comprehensive search was done for RCTs in multiple databases including PubMed, EMBASE, Scopus, Cochrane Central, Web of Science and ProQuest. The primary outcome was change in depression scores measured by validated scales. Meta-analysis was carried out using random-effects model. Eight studies (n=414) were included. The depression scores showed a significant decrease after oral ketamine treatment versus placebo, with a SMD of - 0.62 [95% CI= -0.39, -0.85, Z = 5.24, p < 0.00001] with moderate certainty of the evidence. A significant difference in remission outcome favouring ketamine was observed with a pooled RR of 2.38 [95% CI= 1.19, 4.77, p =0.01] with no heterogeneity [I 2 =0%, p=0.49].Compared to other forms of ketamine, depression scores showed no significant difference between oral ketamine treatment versus other forms of ketamine, with a MD of 0.28 [95% CI= -4.58, 5.14, p =0.91]. Oral ketamine was well-tolerated with no serious adverse events. The findings of our study suggest that oral ketamine can be safely applied and may be effective in reducing depressive symptoms in patients with depression. Further RCTs are needed to strengthen our results and identify the optimal treatment duration parameters. • Oral ketamine is effective in reducing depressive symptoms in MDD and TRD. • Oral ketamine is as effective as other forms of ketamine. • Oral ketamine is well tolerated with no serious adverse effects.