The Effectiveness of Repeated Intravenous Ketamine on Subjective and Objective Psychosocial Function in Patients with Treatment-Resistant Depression and Suicidal Ideation.

Background: Ketamine has rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD), while its effects on functional outcomes have not been sufficiently evaluated. The aim was to evaluate the efficacy of ketamine treatment on both subjective and objective functioning, and to explore whether improvements in depressive symptom and cognition mediated changes in functioning.

Methods: Adults (n=111) with TRD and/or suicidality received six infusions of ketamine (0.5mg/kg, thrice-weekly). Depression symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline, day 13 and day 26. Cognitive domains, including processing speed, working memory, visual learning and verbal learning were measured with the MATRICS Consensus Cognitive Battery, and subjective and objective functioning were measured with the Sheehan Disability Scale (SDS) and the Global Assessment of Functioning (GAF) at the same time-points.

Results: Significant improvement was observed in SDS total score (effect size [ES]=-1.563) and GAF score (ES=1.700) during the 26-day observation. Results from path analysis indicated that reductions of the total MADRS score and improvements in processing speed aggregately significantly mediated the reductions of SDS total score (total indirect effect coef=-3.993, 95%CI [-4.9, -3.2], direct effect coef=-1.374, 95%CI [-2.4, -0.4]) as well as the increases of GAF score (total indirect effect coef=6.022, 95%CI [4.5, 7.8], direct effect coef=3.987, 95%CI [2.1, 5.8]).

Conclusion: Six infusions of ketamine was associated with improvements in functional outcomes in adults with TRD and/or suicidality. Depressive symptoms severity and processing speed performance were significant partial mediators of objective and subjective functioning improvements.