A Systematic Review on the Efficacy of Intravenous Racemic Ketamine for Bipolar Depression

Background Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder. Methods Major databases were searched for open-label and randomized controlled trials (RCT). Two independent reviewers screened and selected the studies that met the inclusion criteria. Studies were selected following the standard Cochrane methodology, and the findings are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methodological quality of the included studies was assessed using standardized measures. Results A total of 1442 articles were screened. Five studies were included in the systematic review (3 RCTs and 2 open-label studies) enrolling 110 subjects (mean age, 45.54 ± 12.65 years; 68.18% female). All the RCTs and open-label studies showed improvement in depressions symptoms after receiving a single infusion of ketamine. Included studies also suggested improvement in suicidal ideation and anhedonia after ketamine infusion. Dissociation and transient increase in blood pressure were the most common reported adverse effects with ketamine. Ketamine infusions did not increase mania symptoms. Conclusions Limited data show efficacy and feasibility of intravenous racemic ketamine in treatment-resistant bipolar depression. Further studies with larger sample size are required to strengthen the evidence.