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Clinical predictors of ketamine response in treatment-resistant major depression
Journal article   Open access   Peer reviewed

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 Brutsche, Neal M Nolan and Carlos A Zarate Jr
The journal of clinical psychiatry, Vol.75(5), pp.e417-e423
05/2014
DOI: 10.4088/JCP.13m08698
PMCID: PMC4310499
PMID: 24922494
url
http://doi.org/10.4088/JCP.13m08698View
Open Access

Abstract

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. 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). 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. 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.
 Body Mass Index Severity of Illness Index Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Follow-Up Studies Humans Middle Aged Excitatory Amino Acid Antagonists - administration & dosage Male Treatment Outcome Excitatory Amino Acid Antagonists - pharmacology Depressive Disorder, Treatment-Resistant - drug therapy Bipolar Disorder - drug therapy Ketamine - administration & dosage Psychiatric Status Rating Scales Time Factors Adult Female Infusions, Intravenous Ketamine - pharmacology Depressive Disorder, Major - drug therapy

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