Does pre-treatment functioning influence response to intravenous ketamine in adults with treatment-resistant depression?

Background: The efficacy of monoamine-based antidepressants in adults with major depressive disorder (MDD) is attenuated in persons with greater pre-treatment functional impairment. Herein, we investigated whether pre-treatment functioning in outpatients with treatment-resistant depression (TRD) moderates response to intravenous (IV) ketamine. Methods: Adults (N= 326; M_age = 45) with DSM-5-defined MDD or bipolar disorder and TRD received repeat-dose IV ketamine at a community-based clinic. Function was evaluated with the Sheehan Disability Scale (SDS), using total scores as well as scores on the subdomains of workplace/school, social life, and family life/home responsibilities. The primary dependent measure was change in depressive symptoms from pre-treatment to post-infusion 4, as measured by the Quick Inventory for Depressive Symptomatology-Self Report-16. Results: Total functional disability, as well as the subdomains of social life and family life/home responsibilities, significantly moderated response to IV ketamine (p =.003; p =.008; p =.008). Follow-up simple slopes analyses indicated a significant improvement in depressive symptoms across the functional domain spectrum (ps <.001). Above average functional disability (i.e., 1 SD > mean functional impairment within the sample) was associated with a greater change in depressive symptoms. Workplace function did not significantly moderate response to IV ketamine (p =.307), suggesting that individuals with significantly impaired workplace functioning may expect a similar response to ketamine as those with less workplace impairment. Conclusions: Symptomatic benefit with IV ketamine was observed in patients with TRD and significant pre-treatment functional impairment. The foregoing result has implications for mechanism of action, cost-effectiveness, and patient selection in adults with TRD receiving IV ketamine.