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 Richards, Jennifer L. Vande Voort, Elizabeth D. Ballard, Nancy E. Brutsche, Rodrigo Machado-Vieira, Carlos A. Zarate

Research output: Contribution to journalArticle

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 (F1,118 = 152.08, p<0.001, and d=2.27) and valproate (F1,128 = 20.12, p<0.001, and d=0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F1,28 = 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.

Original languageEnglish (US)
Article number858251
JournalNeural Plasticity
Volume2015
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Treatment-Resistant Depressive Disorder
Ketamine
Valproic Acid
Bipolar Disorder
Lithium
Antidepressive Agents
Depression
Glycogen Synthase Kinase 3
Serum
Cross-Over Studies
Rodentia
Placebos
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Lithium and valproate levels do not correlate with ketamine's antidepressant efficacy in treatment-resistant bipolar depression. / Xu, Annie J.; Niciu, Mark J.; Lundin, Nancy B.; Luckenbaugh, David A.; Ionescu, Dawn F.; Richards, Erica; Vande Voort, Jennifer L.; Ballard, Elizabeth D.; Brutsche, Nancy E.; Machado-Vieira, Rodrigo; Zarate, Carlos A.

In: Neural Plasticity, Vol. 2015, 858251, 01.01.2015.

Research output: Contribution to journalArticle

Xu, AJ, Niciu, MJ, Lundin, NB, Luckenbaugh, DA, Ionescu, DF, Richards, E, Vande Voort, JL, Ballard, ED, Brutsche, NE, Machado-Vieira, R & Zarate, CA 2015, 'Lithium and valproate levels do not correlate with ketamine's antidepressant efficacy in treatment-resistant bipolar depression', Neural Plasticity, vol. 2015, 858251. https://doi.org/10.1155/2015/858251
Xu, Annie J. ; Niciu, Mark J. ; Lundin, Nancy B. ; Luckenbaugh, David A. ; Ionescu, Dawn F. ; Richards, Erica ; Vande Voort, Jennifer L. ; Ballard, Elizabeth D. ; Brutsche, Nancy E. ; Machado-Vieira, Rodrigo ; Zarate, Carlos A. / Lithium and valproate levels do not correlate with ketamine's antidepressant efficacy in treatment-resistant bipolar depression. In: Neural Plasticity. 2015 ; Vol. 2015.
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