Characterizing the course of suicidal ideation response to ketamine

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

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Diagnostic and Statistical Manual of Mental Disorders
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Humans
  • Ketamine / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Suicidal Ideation*
  • Suicide / prevention & control

Substances

  • Excitatory Amino Acid Antagonists
  • Ketamine

Associated data

  • ClinicalTrials.gov/NCT00088699