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Moreover, although change in severity of depressive symptoms was strongly correlated with change in suicidal ideation, after controlling for improvement in severity of depressive symptoms, ketamine’s effects on suicidal ideation remained significant. “This suggests that ketamine has a specific effect on suicidal ideation that depends only partly on change in overall severity of depressive symptoms,” Samuel T. Wilkinson, M.D., of the Department of Psychiatry and the Child Study Center at Yale School of Medicine and colleagues wrote.
Wilkinson and colleagues searched MEDLINE using the terms “ketamine,” “NMDA receptor antagonist,” “ketamine-like,” or “rapid antidepressant” and “suicide,” “suicidality,” or “suicidal ideation” for articles published between Jan. 1, 2000, and Nov. 15, 2016. Eleven eligible trials were identified from 153 citations, and corresponding authors provided individual subject data on 298 patients who participated in the 10 included ketamine trials; patients in the control arm of the trials received either saline or midazolam, which is used as a preoperative sedative.
A total of 167 patients met criteria for baseline suicidal ideation. Ketamine reduced suicidal ideation more rapidly than was observed with the control treatments on the Montgomery-Åsberg Depression Scale and the Hamilton Depression Scale, as well as on patient self-reports, with significant benefits appearing as early as day 1 after treatment and extending up to day 7.
After adjusting for change in severity of depressive symptoms over time, the time-by-treatment interaction remained significant regardless of whether clinician-administered or self-report outcome measures were used.
“The present analysis provides evidence drawn from the largest sample to date that ketamine reduces suicidal ideation partially independently of mood symptoms,” Wilkinson and colleagues wrote. “However, the specificity of this effect requires further exploration. … For ketamine to have a future as a potential anti-suicidal therapeutic in patients with a range of mood and anxiety disorders, studies specifically recruiting diverse populations must be conducted.”
For related information, see the Psychiatric News PsychoPharm article “Ketamine Clinics Attract Patients Despite Unknowns.”
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