Journal of Affective Disorders
November 1, 2020
R. Mcintyre, Isabelle P. Carvalho, L. Lui et al.
186 citations
Ketamine is a rapid and effective treatment for adults with treatment-resistant depression, but different formulations and routes of delivery vary in effect size. A meta-analysis of studies found that intranasal ketamine or esketamine had a large effect on depression symptoms at 24 hours and again at 7-20 days. Intravenous ketamine or esketamine showed a large but not statistically significant effect at 2-6 days. Oral ketamine had a moderate effect at 21-28 days. No conclusions about which formulation or route is best could be drawn because direct comparisons are lacking. More studies with larger samples are needed, especially for oral ketamine.
Psychopharmacology
February 1, 2021
Richard J Zeifman, Nikhita Singhal, Rafael G Dos Santos et al.
79 citations
Suicidality is a major public health problem with few treatment options. In an open-label trial, 17 adults with recurrent major depressive disorder received a single dose of ayahuasca. Among the 15 who had suicidality at baseline, suicidality decreased acutely (within 40 to 180 minutes after administration) and remained lower at 1, 7, 14, and 21 days afterward. Post-acute effect sizes were large (Hedges' g = 1.31–1.75), with the largest effect at 21 days (g = 1.75). When administered in an appropriate context, ayahuasca may produce rapid and sustained reductions in suicidality. The authors call for randomized, double-blind studies with larger samples to confirm these early findings.
ACS Pharmacology & Translational Science
March 11, 2021
Richard J. Zeifman, Nikhita Singhal, Leah Breslow et al.
60 citations
Classic psychedelics such as psilocybin, ayahuasca, and LSD are being used more often and studied as a potential mental health treatment. Suicidality is a safety concern with these substances, yet they may also help reduce suicidal thoughts. A systematic review of 64 articles found mixed results for non-clinical use: some studies showed positive, negative, or no link between lifetime psychedelic use and suicidality. Early psychedelic therapy had some suicide cases, but it was unclear if therapy caused them. Recent clinical trials found no increased suicidality and preliminary evidence for acute and sustained decreases after treatment.
Psychedelic Med (New Rochelle)
March 12, 2024
Alexander Wen, Nikhita Singhal, Brett D.M. Jones et al.
36 citations
Blinding is especially difficult in randomized controlled trials of psychedelics because these drugs produce noticeable changes in consciousness. This systematic review of 50 papers from 48 clinical trials published between 1963 and January 2023 found that most studies were double-blinded, used within-subjects designs, and employed inert placebos. The majority did not report on whether blinding procedures were successful, and in those that did, blinding failed. To reduce unblinding and expectancy effects, the authors recommend using active placebos and dose-response or active comparator designs.
The Journal of Clinical Psychiatry
January 13, 2022
Richard J. Zeifman, Dengdeng Yu, Nikhita Singhal et al.
18 citations
A meta-analysis of 7 psychedelic therapy clinical trials found that, relative to baseline, psychedelic therapy was associated with large decreases in suicidality acutely (80–240 minutes) and at 1 day, 1–8 weeks, and 3–4 months (standardized mean differences ranging from −1.48 to −2.36). At 6 months, the effect was medium (SMD = −0.65). Reductions were significant at all time points except 7–8 weeks. Acute and post-acute elevations in suicidality were rare (6.5% and 3.0%, respectively). The authors note limitations including heterogeneous samples and interventions, and suggest that controlled trials specifically evaluating psychedelic therapy for suicidality may be warranted.
The Journal of Clinical Psychiatry
May 9, 2022
Richard J. Zeifman, Dengdeng Yu, Nikhita Singhal et al.
2 citations
correction
In a meta-analysis of patient-level data on psychedelics and suicidality, two serious adverse events occurred that the original study authors deemed unrelated to the drug. One participant in a very low-dose psilocybin condition (1 mg/70 kg) completed suicide 11 days after administration, having reported boredom and left the session early. Another participant attempted suicide about two months after an active psilocybin dose (21–25.2 mg/70 kg), following a partner's sudden death and subsequent methamphetamine and crack cocaine use, with a brief psychotic episode. These events highlight the need for close monitoring of all participants during and after psychedelic therapy trials.