Psychopharmacology
April 1, 2023
David S Mathai, Sandeep M Nayak, David B Yaden et al.
36 citations
For esketamine, a form of ketamine used for treatment-resistant depression, there is no clinically meaningful link between how dissociated a person feels during the drug experience and how much their depression improves. Analyzing data from 576 participants across two clinical trials, researchers measured dissociation with the Clinician-Administered Dissociative States Scale (CADSS) and depression with the Montgomery-Åsberg Depression Rating Scale (MADRS). A statistical model found no significant interaction between dissociation and antidepressant effect over four weeks. A separate analysis showed that each additional point on the dissociation scale on day 1 was associated with a very small 0.
Journal of affective disorders
September 15, 2024
David S Mathai, Thomas D Hull, Leonardo Vando et al.
22 citations
In a large longitudinal study of 11,441 moderately-to-severely depressed patients who received four doses of sublingual ketamine at home over four weeks within a supportive digital health context, treatment was associated with improvement in depression symptoms. A modal antidepressant response occurred in both non-severe (55.8%) and severe (18.1%) baseline depression levels. Adverse events were detected in 3.0-4.8% of participants, predominantly neurologic or psychiatric. A second course of treatment extended improvements in those who responded favorably. Improvement was most strongly predicted by lower baseline depression scores and younger age. Symptoms of depressed mood and anhedonia persisted despite treatment. The study lacked a control group and fixed-dose procedure. At-home, telehealth-supported ketamine administration was largely safe, well-tolerated, and associated with improvement.
Scientific reports
November 14, 2024
Erin Wang, David S Mathai, Natalie Gukasyan et al.
18 citations
Among 879 U.S. healthcare professionals surveyed online, most endorsed strong belief in the therapeutic promise of psychedelic-assisted therapy with psilocybin and MDMA, and showed moderate openness to clinical use and support for legal access, with higher ratings for psilocybin than MDMA. However, objective knowledge of therapeutic uses, risks, and pharmacology was low. Primary concerns included lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted greater openness, while physicians reported lower openness. Results indicate a pressing need for formal training to provide balanced, evidence-based information.
Journal of affective disorders
September 1, 2022
David S Mathai, Scott M Lee, Victoria Mora et al.
16 citations
Informed consent documents from 23 American ketamine clinics for psychiatric treatment cover most required elements but vary greatly in detail. Key gaps include poor communication about long-term side effects, alternative treatments, pre-treatment evaluations, support during treatment, psychological interventions, and dissociative effects. All forms are written at a readability level too high for many patients. The findings suggest that both patients and providers would benefit from more deliberate, evidence-informed consent processes to support shared decision-making as off-label ketamine use expands.
Translational Behavioral Medicine
January 1, 2026
Joshua Mitchell, Logan Neitzke-Spruill, David S Mathai et al.
1 citation
Clinical investigators anticipate that psychedelic medicine, including MDMA and psilocybin, could eventually fit into routine clinical care and may even improve it, despite distinct challenges. These treatments differ from existing ones in drug effects, treatment models, and broader goals. Key translational challenges include uncertainty about the role of psychotherapy, high treatment costs and scalability issues, and the effects of hype and stigma on clinical uptake. The findings are based on interviews with 21 investigators at major academic psychedelic research centers across the United States.