Clinical predictors of ketamine response in treatment-resistant major depression.

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.

• Authors: Mark J Niciu, David A Luckenbaugh, Dawn F Ionescu, Sara Guevara, Rodrigo Machado-Vieira, Erica M Richards, Nancy E Brutsche, Neal M Nolan, Carlos A Zarate Jr
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 75 Issue 5 Pg. e417-23 (May 2014) ISSN: 1555-2101 [Electronic] United States
• PMID: 24922494 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2014 Physicians Postgraduate Press, Inc.

Chemical References

• Excitatory Amino Acid Antagonists
• Receptors, N-Methyl-D-Aspartate
• Ketamine

Topics

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