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 January 1, 2015 DOI: 10.1155/2015/858251 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractKetamine and lithium both inhibit an enzyme called glycogen synthase kinase 3, and in rodents they show synergistic antidepressant-like effects at low doses. In a randomized, double-blind, placebo-controlled crossover trial, 36 patients with treatment-resistant bipolar depression maintained on either lithium or valproate received a single 0.5 mg/kg ketamine infusion. Both groups showed significant improvement in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale, but there was no statistically significant difference between the mood stabilizer groups. Serum levels of lithium or valproate did not correlate with ketamine's antidepressant effects. The results suggest that lithium may not enhance ketamine's antidepressant efficacy in this population.
Study at a glance
| 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 |
| Keywords | Lithium medication Algorithm Chemistry Pharmacology |
| Citations | 27 |
| Key finding | 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.