A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response‐related difference in mitochondrial networks

Abstract

BACKGROUND AND PURPOSE(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. EXPERIMENTAL APPROACHPlasma 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. KEY RESULTSThe 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. CONCLUSIONS AND IMPLICATIONSThe 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.

Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions

“…Several factors may have played a role in this, including ADEs resulting from simultaneous administration of opioids and benzodiazepines, as well as variable patient sensitivity to ketamine, some of which may be related to individual changes at the cellular level. 17 There may be other unidentified factors as well. Because 35 of the 37 patients had resolution of symptoms once the infusions were stopped, this suggests that the adverse effects were at least partially due to ketamine.…”

Application of fatty acid and lipid measurements in neuropsychiatry

“…Recent evidence has suggested an important role of lipids in the aetiology and treatment of depression [48,49]. Modern analytical platforms have also been applied in depression biomarker research [50][51][52][53].…”

Unsupervised analysis of combined lipid and coagulation data reveals coagulopathy subtypes among dialysis patients

“…With respect to the limitation regarding small sample size, it should be noted that, especially in human studies, this is not uncommon. In fact, there are many instances where such studies have led to the identification of valuable and informative candidate biomarkers bearing high significance to the relevant disease state (29)(30)(31)(32)(33)(34). In our study, this limitation of relatively small sample size is addressed via an established validation design geared toward minimizing the bias and risk of overfitting.…”