Department of Psychiatry, 7938University of Toronto, Toronto, Ontario, Canada.
7978Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Can J Psychiatry. 2023 Jan;68(1):5-21. doi: 10.1177/07067437221111371. Epub 2022 Aug 17.
Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.
A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.
Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.
There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
血清素能致幻剂作为几种精神疾病（包括重度抑郁症）的潜在新型治疗方法重新出现。加拿大情绪和焦虑治疗网络（CANMAT）召集了一个工作组，审查证据并提供使用致幻剂治疗重度抑郁症的临床建议。
系统检索了 1990 年 1 月至 2021 年 7 月期间发表的关于血清素能致幻剂治疗重度抑郁症和与癌症相关的抑郁症的当代临床试验。通过搜索词组合、参考文献检查以及其他致幻剂审查和共识声明的审查，确定了研究。根据加拿大情绪和焦虑治疗网络的标准，对疗效的证据水平进行分级。
只有裸盖菇素和死藤水有评估抗抑郁作用的当代临床试验。两项初步研究显示，单剂量死藤水对治疗抵抗性抑郁症有初步的积极影响（3 级证据）。与安慰剂对照相比，小样本随机对照试验显示，与活性对照（伴支持性心理治疗的依他普仑）相比，接受裸盖菇素联合心理治疗的重度抑郁症患者具有优越性，并且在癌症相关抑郁症中显示出了有效性（3 级证据）。在治疗抵抗性单相抑郁症中，只有一项关于裸盖菇素的开放标签试验（4 级证据）。所有研究的主要局限性是样本量小和功能性未设盲。与致幻剂相关的不良事件包括心理（如，拟精神病作用）和身体（如，恶心、呕吐和头痛）作用，通常是短暂的。
目前只有低水平的证据支持致幻剂治疗重度抑郁症的疗效和安全性。在加拿大，截至 2022 年，裸盖菇素仍然是一种实验性选择，只能通过临床试验或特殊准入计划获得。因此，加拿大情绪和焦虑治疗网络认为裸盖菇素是一种实验性治疗方法，建议主要在临床试验中使用，或者在罕见的特殊情况下，通过特殊准入计划使用。
