Durability of antidepressant effects following ketamine based interventions in adults with treatment-resistant depression: A systematic review of randomized controlled trials

Aim: To assess the effectiveness of ketamine-based treatment for adults with treatment-resistant depression in terms of the persistence of antidepressant responses or remission after treatment discontinuation. Data Sources: PubMed/MEDLINE database search was performed to select randomized clinical trials that assessed the effect of ketamine interventions on TRD in adults. Study Selection: The inclusion criteria were based on the study population (adults with TRD), intervention (ketamine-based treatment), control (treatment with other interventions or placebo), and outcome (response/remission). Nineteen RCTs were included in the analysis.

Results: A single intravenous (IV), subcutaneous, or intramuscular (IM) ketamine dose had a significant antidepressant effect, which was limited to a short-term response. Maintenance strategies such as repeated ketamine doses or esketamine administration, including intranasal esketamine and repeated IV treatments, were more likely to contribute to longer-lasting treatment response or reduced risk of relapse/remission after treatment discontinuation. However, antidepressant effects of repeated ketamine treatments were limited to within six months of the last intervention. There was a significant between-group variability in the majority of the RCTs, including high risk of bias due to the nature of the interventions, insufficient sample sizes for certain treatment groups, and issues with blinding. Moreover, dissociation was reported as an adverse effect, contributing to the challenges with blinding.

Conclusion: Ketamine-based treatment interventions for TRD are associated with considerable antidepressant effects that are short-term in nature. Individual maintenance strategies may be required for each patient in order to ensure the long-term effectiveness of the treatment.