Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression
Mark J. Niciu, David A. Luckenbaugh, Dawn F. Ionescu, Sara Guevara, Rodrigo Machado‐Vieira, Erica M. Richards, Nancy E. Brutsché, Neal M. Nolan, Carlos A. Zarate
The Journal of Clinical Psychiatry May 15, 2014 DOI: 10.4088/jcp.13m08698 via OpenAlex
Summary
Higher body mass index and a family history of alcohol use disorder in a first-degree relative were associated with greater improvement in depression symptoms after a single ketamine infusion. Patients with no prior suicide attempts also showed greater improvement, but only at day 7. The analysis combined data from four studies of treatment-resistant inpatients with major depressive disorder or bipolar depression who received a single 0.5 mg/kg ketamine infusion over 40 minutes. The findings suggest that certain clinical characteristics may help predict who benefits most from ketamine's rapid antidepressant effects, though the analysis was post hoc and the models explained only 13% to 36% of the variation in symptom improvement.
Study at a glance
| Characteristics | Post hoc analysis of pooled data from four studies Peer reviewed |
|---|---|
| Sample size | 108 |
| Population | Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or bipolar I or II depression experiencing a moderate-to-severe major depressive episode |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Single 40-minute infusion; assessed at 230 minutes, day 1, and day 7 |
| Topics | Depression Ketamine |
| Keywords | Depression economics Internal medicine Rating scale Body mass index |
| Citations | 167 |
| Key finding | Higher body mass index and family history of alcohol use disorder were associated with greater antidepressant improvement after a single ketamine infusion, while no prior suicide attempt was associated with greater improvement only at day 7. |
Abstract
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.