American Journal of Psychiatry
October 1, 2015
D. Jeffrey Newport, Linda L. Carpenter, William M. Mcdonald et al.
594 citations
A systematic review and meta-analysis of placebo-controlled, double-blind, randomized trials found that ketamine produces a rapid but short-lived antidepressant effect. In seven trials with 147 participants, ketamine greatly increased the odds of treatment response and transient remission of symptoms at 24 hours, though it also caused brief psychotomimetic and dissociative effects. When ketamine was added to electroconvulsive therapy (ECT) in five trials with 89 participants, depressive symptoms were reduced after the first treatment but not by the end of the ECT course. Other NMDA receptor antagonists generally did not show consistent efficacy, but two partial agonists, d-cycloserine and rapastinel, reduced depressive symptoms without psychotomimetic or dissociative effects. The fleeting benefit of ketamine, along with its abuse potential and neurotoxicity, warrant caution in clinical use.
JAMA Psychiatry
March 1, 2017
Gerard Sanacora, Mark A Frye, William M. Mcdonald et al.
577 citations
Ketamine can produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. However, existing studies have relatively small sample sizes, lack longer-term data on efficacy, and provide limited data on safety. Despite these limitations, ketamine is increasingly used off-label for mood and other psychiatric disorders. This review and consensus statement provides an overview of the data, highlights limitations, and offers suggestions to facilitate evidence-based clinical decision-making and patient safety.
The American journal of psychiatry
January 1, 2025
Aaron Wolfgang, Gregory A. Fonzo, Joshua C. Gray et al.
47 citations
MDMA-assisted therapy (MDMA-AT) using pharmaceutical-grade MDMA in controlled clinical settings is a safe and efficacious treatment for PTSD. After three MDMA administrations supported by psychotherapy, 67%–71% of individuals with PTSD no longer meet diagnostic criteria, compared with 32%–48% for placebo-assisted therapy, and effects persist at long-term follow-up. Unlike recreational use, which is confounded by adulterants and lack of precautions, MDMA-AT uniquely induces prosocial effects of trust and self-compassion while maintaining cognitive clarity. The review distinguishes evidence from recreational and therapeutic settings, describes neurobiological mechanisms, clinical evidence, public health and policy considerations, and future research directions.
FOCUS The Journal of Lifelong Learning in Psychiatry
January 1, 2021
Collin Reiff, Elon E. Richman, Charles B. Nemeroff et al.
17 citations
A review of clinical trials on psychedelic drugs for psychiatric disorders found the strongest evidence for MDMA and psilocybin, both designated by the FDA as breakthrough therapies for PTSD and treatment-resistant depression, respectively. Evidence for LSD and ayahuasca is observational but suggests potential therapeutic effects for mood, anxiety, trauma, and substance use disorders, as well as end-of-life care. Of 1,603 articles screened, 14 well-designed trials were identified. The database remains insufficient for FDA approval of any psychedelic for routine clinical use, but continued research is warranted.
American Journal of Psychiatry
January 1, 2025
Adrienne Grzenda, Gregory A. Fonzo, Aaron Wolfgang et al.
14 citations
Current evidence does not support recommending psilocybin combined with psychological support (PST) as a psychiatric treatment. More rigorous clinical trials are needed to confirm its effectiveness in larger and more diverse patient groups, determine appropriate dosing, improve blinding methods, and understand how it works and for whom it works best. Comparing it directly with other proven treatments will clarify its potential future role in treating major psychiatric disorders.
The American journal of psychiatry
December 1, 2024
Lauren M. Sippel, Jessica L. Hamblen, Benjamin Kelmendi et al.
11 citations
PTSD is common and can become chronic without treatment. First-line treatments are individual trauma-focused psychotherapies, with antidepressants and non-trauma-focused psychotherapies also evidence-based. Many patients do not fully recover, prompting a search for novel treatments. This review critically evaluates emerging pharmacological and somatic interventions, including medication-assisted psychotherapy (e.g., MDMA), novel monotherapies (e.g., ketamine, cannabidiol), and neuromodulation (e.g., transcranial magnetic stimulation), as well as treatments of increasing interest (hyperbaric oxygen, stellate ganglion block, neurofeedback). Evidence for most novel treatments is preliminary and highly variable, though data for transcranial magnetic stimulation are encouraging.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
June 17, 2025
Clio E Franklin, Murat Altinay, Kala Bailey et al.
2 citations
For treatment-resistant mood disorders, intensive interventions such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine, and esketamine are commonly used, but how genetics influences response to these therapies remains unclear. A review of the current literature finds that most studies have examined single variants in candidate genes, particularly COMT and BDNF, yet none have been consistently reproducible. Genome-wide association studies are few and mostly underpowered, with only one exceeding 1000 participants, yielding few statistically significant single nucleotide polymorphisms outside COMT and BDNF. Large-scale data collection is needed to establish genetic predictors and differentiate responses among treatments, a goal being pursued by the worldwide Gen-ECT-ic consortium.