World Psychiatry
September 15, 2023
Roger S. McIntyre, Mohammad Alsuwaidan, Bernhard T. Baune et al.
712 citations
At least 30% of people with depression meet the common definition of treatment-resistant depression (TRD): inadequate response to two or more antidepressants despite adequate trials and adherence. Many cases are actually pseudo-resistant due to insufficient treatment or non-adherence. No consensus definition with proven predictive utility for clinical decisions exists, leading to varied prevalence estimates and inconsistent care. Intravenous ketamine and intranasal esketamine are effective for TRD. Some second-generation antipsychotics (e.g., aripiprazole, quetiapine XR) help as adjuncts in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation and electroconvulsive therapy are established effective interventions. Evidence for extending trials, switching, or combining antidepressants is mixed, and manual-based psychotherapies are not effective alone but help when added to antidepressants.
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.
American Journal of Psychiatry
July 12, 2023
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
187 citations
Psilocybin, a hallucinogen derived from mushrooms, significantly improved psychological well-being in 70% of participants in a recent drug study. Involving 100 adults undergoing therapy, those receiving psilocybin experienced enhanced emotional processing and reduced anxiety. This effect is attributed to psilocybin's influence on neurotransmitter receptors, which alters behavior and mood. Psychotherapists reported that patients showed increased openness and decreased fear of death after treatment, highlighting the potential of psychedelics like psilocybin for therapeutic use in mental health care.
Neurotherapeutics
January 25, 2024
Bryan R. Barksdale, Manoj K. Doss, Gregory A. Fonzo et al.
22 citations
Psychedelics show promise as treatments for severe psychiatric disorders, especially those resistant to standard therapies. Their effects arise from receptor binding and downstream changes in cells and genes, altering brain structure and function from individual neurons to large-scale circuits. This perspective reviews evidence on how psychedelics produce acute and lasting changes in consciousness, linking molecular, cellular, circuit, and psychological levels. A key controversy is that theoretical models from different levels of inquiry often conflict. Bridging these explanations through innovative methods and collaboration is essential to fully harness psychedelics' therapeutic potential.
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.
American Journal of Psychiatry
January 1, 2024
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
12 citations
No Summary
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.
Neuropsychopharmacology
January 16, 2026
Philip D. Harvey, Charles B. Nemeroff
2 citations
Interest in psychedelic therapies is booming, yet no psychedelic treatment has been approved for any psychiatric condition. The one large-scale MDMA development program that reached the FDA was disapproved for reasons that could also apply to classical psychedelic trials. This review defines psychedelics, surveys current therapies, targeted conditions, compounds under investigation, and research strategies. Some interventions combine drugs with psychotherapy, bringing both benefits and challenges. Debate continues over whether the psychedelic experience itself is essential for therapeutic effect, complicating blinded trials. The review also addresses societal issues like deregulation of formerly illegal substances and regulatory hurdles, including alternatives to blinded trials and whether targets like adjustment disorder pose problems under current standards.
BJPsych Open
February 12, 2026
David A. Bender, Holly Dunn, Amanda Pekau et al.
1 citation
From 2000 to 2025, media coverage of psychedelic drugs increasingly focused on their therapeutic potential, rising from 13.3% of articles in 2000–2009 to 85.3% in 2020–2025. Overall sentiment was positive, with an average score of 78.5 out of 100. However, negative and neutral coverage has grown since 2020: the proportion of articles with sentiment scores of 65 or below rose from 3.6% in 2020 to 20.9% in 2024, and average sentiment dropped significantly in 2024 compared to 2020–2023. Artificial intelligence sentiment ratings closely matched human ratings.