Widge Alik S, Malone Donald A, Dougherty Darin D
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Department of Psychiatry, Cleveland Clinic, Cleveland, OH, United States.
Front Neurosci. 2018 Mar 21;12:175. doi: 10.3389/fnins.2018.00175. eCollection 2018.
Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.
重度抑郁发作是精神残疾的最大原因，且常常对药物治疗和心理治疗产生抵抗。对抑郁症神经回路基础认识的进展，再加上深部脑刺激（DBS）在运动障碍治疗中的成功，促使多个研究团队对DBS治疗难治性抑郁症进行试验。目前，在开放标签和双盲研究中已对多个脑区进行了刺激。最初的开放标签研究结果令人瞩目，但后续的对照/双盲临床试验结果却不一致，既有达到终点的成功案例，也有未达终点的失败案例。后续研究数据表明，这是因为这些试验中的DBS并非针对实现生理反应进行靶向治疗。我们在技术生命周期框架内审视这些结果，在该框架中，这些早期试验“失败”是对不成熟技术过度热衷的自然结果。该框架预测，从这个“幻灭低谷”来看，DBS可能正接近“启迪斜坡”。具体而言，通过结合近期的机制见解和脑机接口（BCI）技术的成熟，下一代试验将更有能力针对病理生理学进行靶向治疗。实现这一点的关键将是开发基于患者个体表型半自主改变刺激策略的闭环系统。这种下一代DBS方法有望极大地改善精神科护理。
