Sarah Brand

Sarah Brand

Do the dissociative side effects of ketamine mediate its antidepressant effects?

Luckenbaugh DA, Niciu MJ, Ionescu DF, Nolan NM, Richards EM, Brutsche NE, Guevara S, Zarate CA. Do the dissociative side effects of ketamine mediate its antidepressant effects? J Affect Disord. 2014 Apr;159:56-61. doi: 10.1016/j.jad.2014.02.017. Epub 2014 Feb 18. PMID: 24679390; PMCID: PMC4065787.


  • Dissociative effects predicted a better and longer antidepressant effect.
  • 108 treatment-resistant inpatient participants with major depressive disorder and bipolar disorder were analyzed using a single subanesthetic dose of ketamine infusion.
  • Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item Hamilton Depression Rating scale (HDRS) at 40 and 230 min and Days 1 and 7.


Pearson correlations showed a significant association between increased CADSS score at 40min and percent improvement with ketamine in HDRS at 230min (r=-0.35, p=0.007) and Day 7 (r=-0.41, p=0.01). Changes in YMRS or BPRS Positive Symptom score at 40min were not significantly correlated with percent HDRS improvement at any time point with ketamine. Changes in systolic blood pressure, diastolic blood pressure, and pulse were also not significantly related to HDRS change.


Among the examined mediators of ketamine’s antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant. Prospective, mechanistic investigations are critically needed to understand why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine.

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