EClinicalMedicine
May 7, 2022
Hewa Artin, Sean Bentley, Eamonn Mehaffey et al.
35 citations
In an open-label retrospective analysis of 35 Veterans with co-occurring depression and PTSD, repeated intranasal (S)-ketamine treatments over four weeks were associated with reductions in both depression and PTSD symptoms. Depression scores on the PHQ-9 fell by an average of 5.1 points, from 19.8 to 14.7, with 14% of patients showing a clinically meaningful response. PTSD scores on the PCL-5 dropped by an average of 15.5 points, from 54.8 to 39.3, with 46% showing a clinically meaningful response. Changes in depression and PTSD symptoms were only moderately correlated, and some individuals experienced PTSD improvement without antidepressant response, suggesting distinct mechanisms of action for the two conditions.
Frontiers in Psychiatry
January 1, 2025
Dimitri Perivoliotis, Kayla Knopp, Shannon Remick et al.
2 citations
Set and setting—the mindset a person brings to therapy and the environment in which it occurs—are foundational to MDMA-assisted therapy for PTSD and critically influence its efficacy. Drawing on experience conducting clinical trials in the Veterans Health Administration, this article describes advantages and challenges of implementing this intervention in large healthcare systems. Specific, practical suggestions are offered for optimizing set and setting from both participant and clinician perspectives, aiming to leverage opportunities and adapt to challenges. These recommendations are intended to inform future research and potential clinical implementation efforts in traditional healthcare settings.
Psychedelic medicine (New Rochelle, N.Y.)
August 1, 2025
Kush V. Bhatt, Jason Compton, Em Ellerman et al.
1 citation
Mystical experiences, which may have therapeutic value, occurred in about 17-18% of ketamine treatments among 60 veterans with treatment-resistant depression. In those receiving esketamine, more treatment sessions were linked to higher mystical experience scores; in those receiving racemic ketamine, higher doses were linked to higher scores. The findings suggest that ketamine can occasion mystical experiences in this population.
CNS Drugs
June 1, 2025
Sijia Zhang, Houtan Afshar, Peter J Colvonen et al.
1 citation
Repeated ketamine or esketamine sessions significantly reduced depression and PTSD symptoms in veterans. However, those who also had traumatic brain injury (TBI) and severe obstructive sleep apnea (OSA) did not show improvement in depression, suggesting that these comorbidities may require alternative or pre-treatment before starting ketamine or esketamine therapy.
Psychiatric Research and Clinical Practice
July 2, 2026
Kush V. Bhatt, Tara Austin, Danny Alam et al.
Intramuscular (IM) ketamine is as effective as intranasal (IN) esketamine for treatment-resistant depression, with comparable safety and a dramatically lower cost. In a retrospective cohort of 179 Veterans, the difference in depression symptom improvement was only 0.04 points on the PHQ-9, well within the non-inferiority margin. PTSD symptom reductions were also similar, and rates of emergency department visits or hospitalizations did not differ significantly. The cost per eight-treatment course was $6069 for IN esketamine versus $647 for IM ketamine, driven primarily by the cost of the nasal spray. These results indicate that IM ketamine could be a high-value alternative that expands access to care.
September 7, 2025
Mathew Herbert, Brian H. Blanco, Dimitri Perivoliotis et al.
preprint
MDMA-assisted psychotherapy shows promise for treating PTSD, but the FDA rejected its current form due to concerns about standardization and empirical grounding of the psychotherapy methods. Acceptance and Commitment Therapy (ACT), an evidence-based cognitive behavioral therapy, is proposed as a well-suited alternative to pair with MDMA. The subjective effects of MDMA directly support key ACT processes; ACT methods could prepare patients for MDMA administration, guide therapists during sessions, and help integrate MDMA experiences to improve functioning and quality of life. ACT offers a scalable, structured yet flexible framework for a new PTSD treatment approach.