Ketamine benefits neurocognition in depression with suicidal ideation

Ketamine improved neurocognitive outcomes at 24 hours among patients with depression and suicidal ideation, according to study results published in Journal of Clinical Psychiatry.

“Intravenous ketamine, an N-methyl-d-aspartate receptor antagonist, has robust therapeutic effects on both depression and suicidal ideation within hours to days in some depressed patients,” John G. Keilp, PhD, of the department of molecular imaging and neuropathology at New York State Psychiatric Institute, and colleagues wrote. “However, its impact on neurocognition, particularly aspects of neurocognition associated with suicidal behavior, is not well understood.”

The investigators reported neurocognitive results from a randomized trial that compared ketamine with midazolam among 78 patients with depression who had clinically significant suicidal ideation. Their primary goal was to examine neurocognitive changes between baseline and 24 hours after treatment and to assess correlations between these changes in neurocognitive performance and changes in depressive symptoms and suicidal thinking. Patients completed neuropsychological testing before and 1 day after double blind treatment with IV ketamine (n = 39) or midazolam (n = 39). A subgroup randomly assigned to midazolam who did not experience ideation remittance after initial infusion received open ketamine and other neurocognitive testing 1 day after treatment. Change in performance on this neurocognitive battery served as the primary outcome.

Results showed rapid improvement in suicidal ideation and mood associated with blinded ketamine vs. midazolam. Compared with midazolam, ketamine correlated with specific improvement in reaction time and interference processing/cognitive control, the latter measure having previously been shown to be linked to past suicide attempt in depression. Those who received midazolam but did not remit who later received open ketamine and retested exhibited improved reaction time and interference processing/cognitive control compared with both of their prior assessments. The researchers did not observe an association between neurocognitive improvement and changes in depression, suicidal thinking or general mood.

“Overall, in this sample of depressed adults with suicidal ideation, neurocognitive improvement at 24 hours after a single, subanesthetic ketamine infusion appeared specific to response time and interference processing/attention control tasks,” Keilp and colleagues wrote. “These improvements were independent of reductions in depression severity or suicidal ideation, suggesting that ketamine-related therapeutic effects on neurocognition may be orthogonal to ketamine’s effects on mood symptoms.

“Neuropsychological risks of long-term, repeated therapeutic ketamine treatment are unknown but warrant further study given that heavy, chronic use, as in addiction, is associated with neurocognitive impairment, with some impairment persisting even when use is discontinued,” they added.