A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response-related difference in mitochondrial networks.
A Villaseñor, A Ramamoorthy, M Silva Dos Santos, M P Lorenzo, G Laje, C Zarate, C Barbas, I W Wainer
British journal of pharmacology April 1, 2014 Peer reviewed DOI: 10.1111/bph.12494 via PubMed
Summary
(R,S)-ketamine has rapid antidepressant effects in about 65% of patients with treatment-resistant bipolar depression. A study analyzed plasma samples from 22 bipolar depression patients to identify metabolic patterns related to ketamine response. It found significant differences in metabolomic patterns based on whether patients were maintained on lithium or valproate, with specific biomarkers identified in responders. The findings suggest that differences in fatty acid metabolism may explain response variability to ketamine.
Study at a glance
| Design | placebo-controlled crossover study |
|---|---|
| Sample size | 22 |
| Population | patients with treatment-resistant bipolar depression |
| Key finding | Differences in mitochondrial β-oxidation of fatty acids explain the variability in response to ketamine among patients. |
Abstract
(R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non-targeted determination of endogenous metabolic patterns, to identify potential markers of ketamine response and non-response. Plasma samples from 22 BD patients were analyzed to produce metabolomic patterns. The patients had received ketamine in a placebo-controlled crossover study and the samples were obtained 230 min post-administration at which time the patients were categorized as responders or non-responders. Matching plasma samples from the placebo arm of the study were also analysed. During the study, the patients were maintained on either lithium or valproate. The metabolomic patterns were significantly different between the patients maintained on lithium and those maintained on valproate, irrespective of response to ketamine. In the patients maintained on lithium, 18 biomarkers were identified. In responders, lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased relative to non-responders. The results indicate that the differences between patients who respond to ketamine and those who do not are due to alterations in the mitochondrial β-oxidation of fatty acids. These differences were not produced by ketamine administration. The data indicate that pretreatment metabolomics screening may be a guide to the prediction of response and a potential approach to the individualization of ketamine therapy.