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. Brutsché, Rodrigo Machado‐Vieira, Carlos A. Zarate
Neural Plasticity 2015 DOI: 10.1155/2015/858251 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Patients with treatment-resistant bipolar depression |
| Intervention | Ketamine infusion |
| Dose | 0.5 mg/kg |
| Topics | Ketamine Depression Esketamine |
| Keywords | Lithium medication Algorithm Pharmacology Anesthesia |
| Citations | 27 |
| Key findings | Lithium does not significantly potentiate ketamine's antidepressant effects compared with valproate in treatment-resistant bipolar depression. |
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.