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J Affect Disord. 2018 Dec 1;241:86-93. doi: 10.1016/j.jad.2018.07.077. Epub 2018 Jul 30.

Characterizing the course of suicidal ideation response to ketamine.

Author information

1
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 10, CRC Room 7-5341, 10 Center Drive, MSC 1282, Bethesda, MD 20892, United States. Electronic address: Elizabeth.Ballard@nih.gov.
2
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 10, CRC Room 7-5341, 10 Center Drive, MSC 1282, Bethesda, MD 20892, United States.
3
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 10, CRC Room 7-5341, 10 Center Drive, MSC 1282, Bethesda, MD 20892, United States; Department of Psychiatry and Behavioral Health, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
4
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 10, CRC Room 7-5341, 10 Center Drive, MSC 1282, Bethesda, MD 20892, United States; Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Science Center, Houston, TX 77021, United States.

Abstract

BACKGROUND:

No pharmacological treatments exist for active suicidal ideation (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We developed data-driven subgroups of SI trajectories after ketamine administration, then evaluated clinical, demographic, and neurobiological factors that might predict SI response to ketamine.

METHODS:

Data were pooled from five clinical ketamine trials. Treatment-resistant inpatients (n = 128) with DSM-IV-TR-diagnosed major depressive disorder (MDD) or bipolar depression received one subanesthetic (0.5 mg/kg) ketamine infusion over 40 min. Composite SI variable scores were analyzed using growth mixture modeling to generate SI response classes, and class membership predictors were evaluated using multinomial logistic regressions. Putative predictors included demographic variables and various peripheral plasma markers.

RESULTS:

The best-fitting growth mixture model comprised three classes: Non-Responders (29%), Responders (44%), and Remitters (27%). For Responders and Remitters, maximal improvements were achieved by Day 1. Improvements in SI occurred independently of improvements in a composite Depressed Mood variable for Responders, and partially independently for Remitters. Indicators of chronic SI and self-injury were associated with belonging to the Non-Responder group. Higher levels of baseline plasma interleukin-5 (IL-5) were linked to Remitters rather than Responders.

LIMITATIONS:

Subjects were not selected for active suicidal thoughts; findings only extend to Day 3; and plasma, rather than CSF, markers were used.

CONCLUSION:

The results underscore the heterogeneity of SI response to ketamine and its potential independence from changes in Depressed Mood. Individuals reporting symptoms suggesting a longstanding history of chronic SI were less likely to respond or remit post-ketamine.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00088699.

KEYWORDS:

Depression; Growth mixture modeling; Ketamine; Suicidal ideation; Suicide

PMID:
30099268
PMCID:
PMC6193483
DOI:
10.1016/j.jad.2018.07.077
[Indexed for MEDLINE]
Free PMC Article

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