Expert Opinion on Drug Safety
April 13, 2022
Sina Nikayin, Eva Murphy, John H. Krystal et al.
114 citations
Ketamine and its derivative esketamine (Spravato) can rapidly relieve depression, but their long-term safety is reviewed here. Common side effects are temporary and mild, including dissociation, nausea, headache, and changes in heart rate and blood pressure. Esketamine may increase lower urinary tract symptoms, but severe bladder problems have not occurred at prescribed depression doses. High-dose ketamine can impair cognition long-term, but esketamine trials show cognition remains stable or improves, indicating no increased cognitive risk with appropriate use.
Expert Opinion on Drug Safety
February 26, 2022
Jan Van Amsterdam, Wim van den Brink
74 citations
Psilocybin, when combined with psychotherapy or psychotherapeutic support, shows promise as a treatment for various mental disorders, including treatment-resistant conditions. However, larger double-blind randomized controlled trials with objective long-term outcomes are needed to confirm these findings before standard clinical use can be considered.
Expert Opinion on Drug Safety
March 9, 2022
Anees Bahji, Carlos A. Zarate, Gustavo H. Vazquez
71 citations
Ketamine and esketamine are effective, safe, and acceptable treatments for depression. A meta-analysis of 36 randomized controlled trials (2,903 participants, 57% female, average age 45 years) found that treatment with either form of ketamine improved response (2.14 times more likely), remission (1.64 times more likely), and depression severity compared to placebo. There was no difference in treatment retention, dropouts due to adverse events, or overall number of adverse events between ketamine and placebo.
Expert Opinion on Drug Safety
June 15, 2020
Nelson B Rodrigues, R. Mcintyre, Orly Lipsitz et al.
50 citations
Intravenous ketamine is safe and well-tolerated in community-based clinics for treatment-resistant depression. Among 203 patients, fewer than 5% withdrew due to tolerability concerns. Blood pressure increased significantly during infusion, with 44.3% meeting criteria for treatment-emergent hypertension (≥165/100 mmHg), and 12% of those with hypertension required medication. Common adverse events were drowsiness (56.4%), dizziness (45.2%), dissociation (35.6%), and nausea (13.3%). Dissociation severity lessened after the first infusion then plateaued. No patients developed psychosis, mania, or new onset suicidality.
Expert Opinion on Drug Safety
April 6, 2022
Muhammad Youshay Jawad, Joshua D. Di Vincenzo, Felicia Ceban et al.
29 citations
Intranasal esketamine, when added to an oral antidepressant, is safe and more effective than a placebo nasal spray at reducing depressive symptoms in people with treatment-resistant depression and depression with suicidal thoughts or behavior. Pooling data from seven randomized controlled trials showed a small but significant improvement in depressive symptoms, with higher rates of response and remission. Year-long studies found lower relapse rates and no major long-term side effects. The treatment appears well tolerated and rapidly effective for these difficult-to-treat populations.
Expert Opinion on Drug Safety
August 15, 2023
Roger S. McIntyre
26 citations
The text discusses concerns about psilocybin, lysergic acid diethylamide (LSD), and ecstasy in relation to valvular heart disease, focusing on 5HT2B receptor agonism and FDA guidance. It highlights the potential risk of these substances to cause heart valve damage through activation of the 5HT2B receptor, a mechanism linked to certain drugs. The abstract underscores regulatory considerations from the FDA regarding this safety issue, suggesting that agonism at this receptor may be a key factor in assessing the cardiac risks of psychedelic compounds.
Expert Opinion on Drug Safety
April 15, 2022
Marcus A. Doyle, Susan Ling, Leanna M.W. Lui et al.
24 citations
Hallucinogen persisting perception disorder (HPPD) is an uncommon but serious condition in which individuals repeatedly experience hallucinations and perceptual disturbances after prior hallucinogen use. As some hallucinogens are being developed to treat mental disorders, understanding HPPD becomes more important. A scoping review of the literature up to July 2021 covered treatments, prevalence, risk factors, and pathophysiology of HPPD. The renewed interest in psychedelics as potential treatments highlights the need to better characterize HPPD's frequency, risk and protective factors, key features, and clinical factors.
Expert Opinion on Drug Safety
April 15, 2022
Giordano Novak Rossi, Jaime E. C. Hallak, José Carlos Bouso Saiz et al.
24 citations
In the reviewed studies, no serious adverse events were linked to psilocybin or LSD administration. Most side effects were anticipated, manageable, and temporary. However, concerns persist about certain effects like dissociation, paranoia, and confusion. The authors conclude that larger randomized controlled trials are needed to confirm therapeutic benefits and further assess safety and tolerability.
Expert Opinion on Drug Safety
May 3, 2022
Danica Nogo, Hana Nazal, Yuetong Song et al.
17 citations
Ketamine is an established treatment for treatment-resistant depression, but long-term adverse effects from repeated doses are not well characterized. Animal models and studies of people with substance use disorder who use high daily doses of ketamine show clear neurotoxic effects, including potential brain lesions. No studies have specifically evaluated the effects of the lower, infrequent sub-anesthetic doses typically prescribed for depression. It is difficult to separate ketamine's direct effects from other factors like comorbidities and dose differences. It remains unknown whether repeated sub-anesthetic dosing in adults with depression causes brain lesions or other neuropathologies. Practitioners should remain vigilant, recognizing that depression itself is linked to neurodegenerative processes.
Expert Opinion on Drug Safety
March 18, 2022
Giordano Novak Rossi, Isabella Caroline Da Silva Dias, Glen B. Baker et al.
17 citations
In controlled settings, ayahuasca administration appears relatively safe, with no serious adverse events reported. Common side effects include nausea, vomiting, headaches, and temporary increases in heart rate and blood pressure. Research on ayahuasca's antidepressant effects is still early, lacking large, robust clinical trials. Major obstacles to its therapeutic use include dose standardization, legal prohibition of its alkaloids, and questions about compensating traditional communities if ayahuasca becomes an approved medicine.
Expert Opinion on Drug Safety
August 28, 2023
Roger S. McIntyre
16 citations
The article reviews the pharmacology and therapeutic potential of psychedelics such as psilocybin and lysergic acid diethylamide, focusing on their mechanisms of action and regulatory status. It discusses how these compounds influence neurotransmitter receptors and their possible applications in treating mood disorders, including depression. The authors highlight the growing interest in psychedelic-assisted therapy and note that the FDA has granted breakthrough therapy designation for some psychedelic treatments, suggesting a shift in the medical and regulatory landscape toward these substances as antidepressants.