Contract grant sponsor: Evotec, Janssen Pharmaceuticals, and Avanir, by NIMH Career Development Award 1K23 MH-094707, and by grant UL1 TR000067 from the NIH National Center for Advancing Translational Sciences (to J.W.M.); Contract grant sponsor: Icahn School of Medicine at Mount Sinai from AstraZeneca, Brainsway, Euthymics, Neosync, and Roche and CNS Response, Otsuka, Servier, and Sunovion (to D.V.I.); Contract grant sponsor: NIH, NIH/NIMH, NARSAD, and USAMRAA (to D.S.C.); Contract grant sponsor: AstraZeneca, Bristol-Myers Squibb, Naurex, Roche, Genentech, and NIMH grant RO1 MH-081870, by the Department of Veterans Affairs (VA), by a NARSAD Independent Investigator Award and funding from the Brown Foundation, Inc. (to S.J.M.); Contract grant sponsor: Career Development Award from NIMH (1K23MH100259) (to R.B.P.).
EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION
Article first published online: 25 MAR 2014
© 2014 Wiley Periodicals, Inc.
Depression and Anxiety
Volume 31, Issue 4, pages 335–343, April 2014
How to Cite
Price, R. B., Iosifescu, D. V., Murrough, J. W., Chang, L. C., Al Jurdi, R. K., Iqbal, S. Z., Soleimani, L., Charney, D. S., Foulkes, A. L. and Mathew, S. J. (2014), EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION. Depress. Anxiety, 31: 335–343. doi: 10.1002/da.22253
- Issue published online: 10 APR 2014
- Article first published online: 25 MAR 2014
- Manuscript Accepted: 18 JAN 2014
- Manuscript Revised: 14 JAN 2014
- Manuscript Received: 16 DEC 2013
- NIMH Career Development Award. Grant Numbers: 1K23 MH-094707, UL1 TR000067
- NIH National Center for Advancing Translational Sciences
- Icahn School of Medicine at Mount Sinai
- NIH, NIH/NIMH, NARSAD, and USAMRAA
- AstraZeneca, Bristol-Myers Squibb, Naurex, Roche, Genentech
- NIMH. Grant Number: RO1 MH-081870
- Brown Foundation, Inc.
- NIMH. Grant Number: 1K23MH100259
- clinical trials;
- biological markers;
- mood disorders;
Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior.
Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group.
Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ2 = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms.
Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher-risk samples.