Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
Journal of psychopharmacology (Oxford, England)
October 1, 2024
Jessica L Ables, Leah Israel, Olivia Wood et al.
17 citations
Harmine, a component of the hallucinogenic brew ayahuasca, was tested in a phase 1 clinical trial to determine its safety, tolerability, and psychoactive effects when taken alone. Twenty-five healthy adults received single oral doses of 100 to 500 mg of pharmaceutical-grade harmine hydrochloride. The maximum tolerated dose was between 100 and 200 mg, and doses above 2.7 mg/kg caused vomiting, drowsiness, and limited psychoactive effects in 90% of participants. No serious adverse events occurred. Harmine alone can be safely administered at low doses, but higher doses produce dose-limiting side effects and only mild psychoactivity.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
June 17, 2025
Clio E Franklin, Murat Altinay, Kala Bailey et al.
2 citations
For treatment-resistant mood disorders, intensive interventions such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine, and esketamine are commonly used, but how genetics influences response to these therapies remains unclear. A review of the current literature finds that most studies have examined single variants in candidate genes, particularly COMT and BDNF, yet none have been consistently reproducible. Genome-wide association studies are few and mostly underpowered, with only one exceeding 1000 participants, yielding few statistically significant single nucleotide polymorphisms outside COMT and BDNF. Large-scale data collection is needed to establish genetic predictors and differentiate responses among treatments, a goal being pursued by the worldwide Gen-ECT-ic consortium.
Psychiatry research
May 1, 2025
Gerard Sanacora, Brian S Barnett, Bo Hu et al.
2 citations
Patients with treatment-resistant depression who preferred ketamine over electroconvulsive therapy (ECT) were more likely to respond to treatment, regardless of which treatment they actually received. Matching patients to their preferred treatment improved response rates for ketamine but not for ECT, and reduced adverse events for ECT-treated patients. Ketamine was the more popular choice overall. The findings suggest that aligning treatment with patient preference can influence effectiveness, safety, and possibly adherence, but these effects vary by treatment modality and context.
Translational psychiatry
May 12, 2026
Linda Bryant, Laith Alexander, Sergio Mena et al.
A machine-learning model using structural brain scans predicted which adults with treatment-resistant depression would respond to a single ketamine infusion. The model, trained on 99 participants, achieved 72% balanced accuracy in the discovery sample and 60% in two independent groups, with performance dropping to chance in a saline-treated control group. Greater gray matter volume in frontal regions predicted response, while greater cerebellar volume predicted non-response. The findings suggest that pre-treatment brain structure may help guide personalized treatment decisions for ketamine therapy.
The Journal of clinical psychiatry
April 2, 2025
Adriana Feder, Oneysha Brown, Sarah B Rutter et al.
Combining six ketamine infusions with a brief exposure-based psychotherapy, written exposure therapy (WET), produced large and durable reductions in PTSD symptoms for patients with chronic, severe PTSD. In an open-label trial, 13 of 14 patients completed treatment. PTSD symptom severity, measured by the CAPS-5, dropped from an average of 41.6 before treatment to 20.8 at 12 weeks, a large-magnitude improvement. Nine patients (69%) were treatment responders, and eight (61.5%) maintained improvement up to six months. The authors suggest the combined treatment may be effective but call for larger randomized controlled trials to confirm efficacy and synergy.
International Journal of Neuropsychopharmacology
June 1, 2024
Mina M Rizk, James W Murrough
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