Braxia Health, Mississauga, ON, Canada.
Department of Psychology, Neuropsychology Track, University of Windsor, Windsor, ON, Canada.
J Psychopharmacol. 2024 Apr;38(4):375-381. doi: 10.1177/02698811241238284. Epub 2024 Mar 13.
Converging lines of evidence indicate that ketamine is a rapid antidepressant for individuals with treatment-resistant depression. Hitherto, no reliable a priori predictors of ketamine response have been reported. Pharmacogenetic biomarkers have yielded mixed results regarding potential candidate genes associated with ketamine's biochemistry as reliable predictors of response.
No studies have examined the effects of Val66Met and CYP2B6 genotypes on patients receiving repeated infusions of intravenous ketamine.
In all, 85 participants with major depressive disorder who had previously received four infusions of intravenous ketamine were recruited to the foregoing study. Buccal swabs were collected and genotype variants across the Val66Met and CYP2B6 genes were analyzed. A repeated measures mixed linear model was used to assess change in depressive symptoms, suicidality, and anxiety, correcting for sex and age. Multiple regression was run to determine whether these genetic markers were associated with treatment efficacy for depressive severity, suicidal ideation, anxiolytic response, and degree of dissociation to intravenous ketamine.
Participants experienced significant overall reductions in depression, suicide, and anxiety. Overall, 25% met the response criteria and 15% met the remission criteria. However, Val66Met and CYP2B6 did not significantly predict changes in symptoms of depression, suicide, anxiety, or average dissociation.
This study contributes to the growing literature that ketamine efficacy is unlikely to be predicted by single genes, and a pleiotropic approach may likely be necessary for developing reliable predictors of clinical benefits.
越来越多的证据表明，氯胺酮是一种治疗难治性抑郁症患者的快速抗抑郁药。迄今为止，尚未报道氯胺酮反应的可靠先验预测因子。关于与氯胺酮的生物化学相关的潜在候选基因作为反应的可靠预测因子的药物遗传学生物标志物，结果喜忧参半。
尚无研究检查 Val66Met 和 CYP2B6 基因型对接受重复静脉注射氯胺酮的患者的影响。
共有 85 名患有重度抑郁症的患者被招募到这项研究中，这些患者之前已经接受了四次静脉注射氯胺酮。收集口腔拭子并分析 Val66Met 和 CYP2B6 基因的基因型变体。使用重复测量混合线性模型来评估抑郁症状、自杀意念和焦虑的变化，同时校正性别和年龄。进行多元回归以确定这些遗传标记是否与治疗重度抑郁、自杀意念、抗焦虑反应和对静脉注射氯胺酮的分离程度的疗效相关。
参与者的抑郁、自杀和焦虑症状总体显著减轻。总体而言，25%的患者符合反应标准，15%的患者符合缓解标准。然而，Val66Met 和 CYP2B6 并没有显著预测抑郁、自杀、焦虑或平均分离症状的变化。
这项研究为越来越多的文献做出了贡献，即氯胺酮的疗效不太可能由单个基因预测，可能需要采用多效性方法来开发临床获益的可靠预测因子。
