Razmjou Sara, Litteljohn Darcy, Rudyk Chris, Syed Shuaib, Clarke Melanie, Pentz Rowan, Dwyer Zach, Hayley Shawn
Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Neuropsychiatr Dis Treat. 2016 Sep 8;12:2049-56. doi: 10.2147/NDT.S111131. eCollection 2016.
Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration. However, it is also a drug with an abusive potential and can have marked side effects. Hence, this study aimed at enhancing the antidepressant-like effects of ketamine (allowing for lower dosing regimens) by coadministering magnesium hydroaspartate (Mg(2+) normally affects the same receptors as ketamine) and also assessed whether an Mg(2+)-deficient diet would modify the impact of ketamine. It was found that a single 15 mg/kg dose of ketamine did indeed induce rapid antidepressant-like effects in the forced swim test but did not affect brain levels of the brain-derived neurotrophic factor. Contrary to our hypothesis, magnesium administration or deficiency did not influence the impact of ketamine on these outcomes. Thus, these data do not support the use of magnesium as an adjunct agent and instead suggest that further research involving other antidepressant and animal models is required to confirm the present findings.
大约三分之一的重度抑郁症（MDD）患者对当前的治疗方法有抗药性，并且大多数病例在治疗期间的某个时间点会复发。这导致了新的治疗方法被采用，包括亚麻醉剂量的氯胺酮，它会影响异常的神经可塑性回路、谷氨酸能信号传导以及脑源性神经营养因子的产生。氯胺酮能迅速缓解难治性重度抑郁症患者的抑郁症状，即使单次给药后，其效果也能持续长达2周。然而，它也是一种具有滥用潜力的药物，并且可能有明显的副作用。因此，本研究旨在通过联合给予天门冬氨酸镁（Mg²⁺通常与氯胺酮作用于相同的受体）来增强氯胺酮的抗抑郁样作用（允许采用更低的给药方案），并且还评估了缺镁饮食是否会改变氯胺酮的作用。研究发现，15 mg/kg剂量的氯胺酮单次给药确实在强迫游泳试验中诱导了快速的抗抑郁样作用，但并未影响脑源性神经营养因子的脑内水平。与我们的假设相反，给予镁或缺镁并未影响氯胺酮对这些结果的作用。因此，这些数据不支持将镁用作辅助药物，相反表明需要进一步开展涉及其他抗抑郁药和动物模型的研究来证实目前的发现。
