Cognitive changes in patients with unipolar TRD treated with IV ketamine: A systematic review

Unipolar treatment-resistant depression (MDD-TRD) is associated with neurocognitive impairment. Ketamine, an emerging treatment for MDD-TRD, may have neurocognitive benefits, but evidence remains limited.

We conducted a systematic search on EMBASE, Google Scholar, PsycINFO, and PubMed and included studies exploring the cognitive effects of intravenous (IV) ketamine treatment in the management of MDD-TRD following the PRISMA guidelines. We analyzed cognitive scale score changes pre- and post-IV ketamine treatment and the quality of the evidence using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).

Out of 1171 identified studies, fourteen studies were included in this study. Most studies reported positive cognitive outcomes post-ketamine treatment, including improvements in processing speed, working memory, verbal and visual memory, executive function, attention, emotional processing, and auditory verbal episodic memory. Variability existed, with one study reporting negative effects on verbal memory. Overall, studies exhibited a low risk of bias.

Several limitations impacted the results observed, including confining our scope to articles in English, heterogeneity of the included studies, small sample sizes, and the predominance of a female, Western, and Caucasian population, constraining the generalizability of the findings.

IV ketamine treatment shows promise in improving neurocognitive function in MDD-TRD patients. However, further research is warranted to elucidate long-term effects, control for confounders such as concomitant medications, and explore neurocognitive subgroups within the TRD population. These findings underscore the need for comprehensive assessment and management of cognitive symptoms in TRD, informing future clinical practice.