Predictors of Response to MDMA-Assisted and Ketamine-Based Treatments for Post-Traumatic Stress Disorder: A Systematic Review

Abstract

This systematic review examines nine randomized controlled trials investigating MDMA- and ketamine-assisted therapy for post-traumatic stress disorder (PTSD), with a focus on identifying clinical, neurobiological, and psychological predictors of treatment response. Findings suggest that certain neurobiological markers, such as reduced ventromedial prefrontal cortex–amygdala connectivity and D-serine plasma levels, may predict response to ketamine therapy. Psychological factors, including the strength of the therapeutic alliance, appear to influence the effectiveness of MDMA-assisted treatment. However, results across studies remain inconsistent, particularly regarding the predictive role of PTSD subtypes and prior SSRI use. There is insufficient evidence to determine the impact of demographic variables such as age or gender. Due to the limited number of available studies and variability in methodology, further research is needed to clarify which individual characteristics reliably predict treatment outcomes. Improving our understanding of these predictors may contribute to the development of more personalized and effective psychedelic therapies for PTSD.