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Do the dissociative side effects of ketamine mediate its antidepressant effects?
Luckenbaugh, David A; Niciu, Mark J; Ionescu, Dawn F; Nolan, Neal M; Richards, Erica M; Brutsche, Nancy E; Guevara, Sara; Zarate, Carlos A.
Afiliación
  • Luckenbaugh DA; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Niciu MJ; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Ionescu DF; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Nolan NM; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Richards EM; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Brutsche NE; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Guevara S; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA.
  • Zarate CA; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA. Electronic address: zaratec@mail.nih.gov.
J Affect Disord ; 159: 56-61, 2014 Apr.
Article en En | MEDLINE | ID: mdl-24679390
BACKGROUND: The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression. Psychotomimetic symptoms, dissociation and hemodynamic changes are known side effects of ketamine, but it is unclear if these side effects relate to its antidepressant efficacy. METHODS: Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. 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 230min and Days 1 and 7. RESULTS: Pearson correlations showed 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. LIMITATIONS: Secondary data analysis, combined diagnostic groups, potential unblinding. CONCLUSIONS: 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Trastorno Depresivo Mayor / Trastornos Disociativos / Ketamina / Antidepresivos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Affect Disord Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Trastorno Depresivo Mayor / Trastornos Disociativos / Ketamina / Antidepresivos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Affect Disord Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos