Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression

Objective: The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically heterogeneous populations.

Method: Data were analyzed from 4 studies of treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I or II depression. Patients who were currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5 mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute postinfusion time point (n = 108), at day 1 (n = 82), and at day 7 (n = 71). Univariate Pearson correlations were performed for each variable with percent change from baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (P ≤ .05, 2-tailed).

Results: Higher body mass index correlated with greater HDRS improvement at 230 minutes (standardized β = −0.30, P = .004) and at day 1 (standardized β = −0.37, P = .001), but not at day 7 (standardized β = −0.18, P = .10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at day 1 (standardized β = −0.27, P = .014) and day 7 (standardized β = −0.41, P < .001). No prior history of suicide attempt(s) was associated with greater improvement only at day 7 (standardized β = 0.28, P = .01). The overall statistical model explained 13%, 23%, and 36% of HDRS percent change variance at 230 minutes, day 1, and day 7, respectively.

Conclusions: Despite its post hoc nature, this study identified several clinical correlates of ketamine’s rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression.