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William M. Mcdonald

5 papers in the library · 1,213 citations · publishing 2015-2025

Papers

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

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.

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders

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.

Psychedelics and Psychedelic-Assisted Psychotherapy

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.

Psilocybin: From Psychiatric Pariah to Perceived Panacea

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.

Novel Pharmacologic and Other Somatic Treatment Approaches for Posttraumatic Stress Disorder in Adults: State of the Evidence.

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.