Ketamine may be effective modulator for suicide-related cognition in adults

Key takeaways:

• A study found that ketamine given to participants at high risk for suicide positively modulated suicide-related cognition.
• “More objective” measures of suicidal ideation are needed for future research.

MIAMI BEACH, Fla. — Treatment with ketamine may be an effective augmenter of risk mitigation for suicidality and effective modulator for suicide-related cognitive processing in adults, according to data presented here.

“Since 1999, the trajectory (of suicide) has been on the rise,” Steven J. Lamontagne, PhD, postdoctoral fellow in the Division of Intramural Research Program at the National Institute of Mental Health, said in his presentation at the American Society of Clinical Psychopharmacology annual meeting. “Despite the fact that suicide rates are increasing, we think there are clear advancements in the field in terms of mitigation and prevention.”

Given a need to identify neural correlates associated with varying levels of suicide risk, as well as to develop fast-acting therapeutics which modulate activity within neural networks, Lamontagne and colleagues sought to examine the role ketamine plays in moderating suicidality in a small cohort of adults.

They recruited 75 individuals via a suicide-focused research protocol and assigned them to four categories: those with a suicide attempt in the past 2 weeks and/or lifetime suicidal ideation with intent (high risk; n = 15); those with a history of attempt, but no suicidal behavior or ideation with intent in the past year (moderate risk; n = 18); those with anxiety or mood symptoms, but no suicide history (low risk n = 19) and those without psychiatric or suicide history (minimal risk; n = 23). Electrophysiological signs of suicide were measured by CTF 275-channel whole-head magnetoencephalography (MEG), during which participants completed a modified online Life-Death Implicit Association Task that measured associations to either life or death based on reaction times to words representing each category.

The primary outcome was D-score, the difference in mean reaction times between self-death and self-life trials, while MEG data were source-localized in the gamma (30-58 Hz) frequency.

Researchers also conducted an open-label pilot study, in which five high-risk individuals were given a subanesthetic-dose of ketamine, a N-methyl-D-aspartate receptor antagonist utilized for fast-acting anti-suicidal ideation properties.

According to results, D-scores in the high risk group did not differ from zero, but were significantly higher compared with the moderate, low, and minimal risk groups. D-scores for the latter three groups did not differ from each other and were significantly lower than zero, indicative of self-life bias.

Data additionally showed D-scores unaffected by ketamine administration, yet a session-by-condition interaction (P < 0.05) revealed enhanced gamma power for self-death trials in the left insula after ketamine administration compared to baseline (P < 0.001). Post-ketamine insular gamma power for self-death trials revealed an inverse correlation with D-score (r=-0.89), suggesting the insula may be a telltale biomarker for implicit thought process on death in high-risk individuals.

“We need more objective measures in suicidal states to complement the traditional self-reporting which might give us a fuller picture of risk and what it means to be at risk,” Lamontagne said. “And second, to be able to identify drug interventions that modulate (risk).”