Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression

Annie J Xu; Mark J Niciu; Nancy B Lundin; David A Luckenbaugh; Dawn F Ionescu; Erica M Richards; Jennifer L Vande Voort; Elizabeth D Ballard; Nancy E Brutsche; Rodrigo Machado-Vieira; Carlos A Zarate Jr

doi:10.1155/2015/858251

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Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression

Journal article

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Peer reviewed

Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression

Annie J Xu, Mark J Niciu, Nancy B Lundin, David A Luckenbaugh, Dawn F Ionescu, Erica M Richards, Jennifer L Vande Voort, Elizabeth D Ballard, Nancy E Brutsche, Rodrigo Machado-Vieira, …

Neural plasticity, Vol.2015, 858251

2015

DOI: 10.1155/2015/858251

PMCID: PMC4475570

PMID: 26137324

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Abstract

Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine's antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine's antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n = 23, 0.79 ± 0.15 mEq/L) or valproate (n = 13, 79.6 ± 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure-the Montgomery-Åsberg Depression Rating Scale (MADRS)-was assessed before infusion and at numerous postinfusion time points. Both lithium (F 1,118 = 152.08, p < 0.001, and d = 2.27) and valproate (F 1,128 = 20.12, p < 0.001, and d = 0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F 1,28 = 2.51, p = 0.12, and d = 0.60). Serum lithium and valproate levels did not correlate with ketamine's antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine's antidepressant efficacy in treatment-resistant bipolar depression.

Lithium - blood

Double-Blind Method

Depressive Disorder, Treatment-Resistant - blood

Humans

Middle Aged

Male

Treatment Outcome

Depressive Disorder, Treatment-Resistant - drug therapy

Bipolar Disorder - drug therapy

Bipolar Disorder - blood

Antidepressive Agents - therapeutic use

Cross-Over Studies

Psychiatric Status Rating Scales

Valproic Acid - blood

Adult

Female

Ketamine - therapeutic use

Drug Therapy, Combination

Details

Title: Subtitle: Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression
Creators: Annie J Xu - New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY 10595, USA
Mark J Niciu - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Nancy B Lundin - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
David A Luckenbaugh - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Dawn F Ionescu - Massachusetts General Hospital, Depression Clinical & Research Program, 1 Bowdoin Square, 6th Floor, Boston, MA 02114, USA
Erica M Richards - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Jennifer L Vande Voort - Department of Psychiatry & Psychological Services, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Elizabeth D Ballard - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Nancy E Brutsche - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Rodrigo Machado-Vieira - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Carlos A Zarate Jr - National Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USA
Resource Type: Journal article
Publication Details: Neural plasticity, Vol.2015, 858251
DOI: 10.1155/2015/858251
PMID: 26137324
PMCID: PMC4475570
NLM abbreviation: Neural Plast
ISSN: 2090-5904
eISSN: 1687-5443
Publisher: United States
Grant note: Intramural NIH HHS
Language: English
Date published: 2015
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003998002771

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