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.
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.
Frontiers in Psychiatry
February 23, 2023
Rammohan Shukla, Mohamed Sherif, Mostafa Z. Khalil et al.
1 citation
Destroying synapses in a machine-learning model of the neocortex reduces the confidence of its predictions before reducing their number. The model, based on the temporal memory algorithm, was trained on random letter sequences representing affective states. Removing 50% of synapses only slightly lowered the number of predictions, but a 25% reduction distinctly dropped prediction confidence. This suggests that in major depressive disorder, synaptic loss in interoceptive cortices could trap the brain in limited affective states with high prediction error. The growth of new synapses, as proposed for ketamine and psilocybin, would allow more confident and futuristic predictions.
bioRxiv (Cold Spring Harbor Laboratory)
July 3, 2022
Mohamed Sherif, Mostafa Z. Khalil, Rammohan Shukla et al.
1 citation
preprint
Synaptic atrophy in major depressive disorder may impair the brain's ability to confidently predict future affective states, even when predictions remain accurate. Using a temporal memory algorithm that mimics a single neocortical layer with Hebbian learning, researchers simulated depression by progressively destroying synapses. Destroying 50% of synapses slightly reduced the number of predictions, but a 25% reduction distinctly lowered prediction confidence. This suggests that in depression, interoceptive cortices become stuck in limited affective states with high prediction error. Treatments like ketamine and psilocybin may help by growing new synapses, enabling more confident and futuristic predictions.
Frontiers in Psychology
August 17, 2021
Fiamma Cavallero, Michael C. Gold, Eric Tirrell et al.
Combining mindfulness-based cognitive therapy (MBCT) guided audio exercises with daily transcranial magnetic stimulation (TMS) sessions for major depressive disorder proved largely unfeasible. Of 29 depressed patients who started, 17 completed the 5-week protocol and 12 dropped out. Reasons for discontinuation included inability to meditate in the treatment setting and induction of negative mood states. TMS percussive sensations and clicking sounds hindered concentration on the audio narrator. Some patients felt overwhelmed, increased pressure, anxiety, or aggravation trying to meditate during TMS. The findings highlight numerous feasibility issues with delivering MBCT via guided audiotapes concurrently with TMS.