11.5) ( n = 37) in the placebo with therapy group. 11.6) ( n = 42) in the MDMA-assisted therapy group compared with −13.9 (s.d. The mean change in CAPS-5 scores from baseline to 18 weeks after baseline in the completers (per protocol set) was −24.4 (s.d. MDMA-assisted therapy for PTSD was granted an FDA Breakthrough Therapy designation, and the protocol and statistical analysis plan (SAP) were developed in conjunction with the FDA 16. Primary and secondary outcome measures (CAPS-5 and SDS, respectively) were assessed by a centralized pool of blinded, independent diagnostic assessors. Participants were given three doses of MDMA or placebo in a controlled clinical environment and in the presence of a trained therapy team. Here, we assess the efficacy and safety of MDMA-assisted therapy in individuals with severe PTSD. Pooled analysis of six phase 2 trials of MDMA-assisted therapy for PTSD have now shown promising safety and efficacy findings 15. MDMA has been shown to enhance fear memory extinction, modulate fear memory reconsolidation (possibly through an oxytocin-dependent mechanism), and bolster social behavior in animal models 13, 14. The substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) induces serotonin release by binding primarily to presynaptic serotonin transporters 12. Novel cost-effective therapeutics are therefore desperately needed 11. Likewise, although evidenced-based trauma-focused psychotherapies such as prolonged exposure and cognitive behavioral therapy are considered to be the gold standard treatments for PTSD 8, many participants fail to respond or continue to have significant symptoms, and dropout rates are high 9, 10. However, an estimated 40–60% of patients do not respond to these compounds 7. The selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine are Food and Drug Administration (FDA)-approved first-line therapeutics for the treatment of PTSD. It is therefore imperative to identify a therapeutic that is beneficial in those individuals with the comorbidities that typically confer treatment resistance. There are a number of environmental and biological risk factors that contribute to the development and maintenance of PTSD 1, and poor PTSD treatment outcomes are associated with several comorbid conditions that include childhood trauma 2, alcohol and substance use disorders 3, depression 4, suicidal ideation 5 and dissociation 6. PTSD is a common and debilitating condition with immeasurable social and economic costs that affects the lives of hundreds of millions of people annually. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo ( P < 0.0001, d = 0.91) and to significantly decrease the SDS total score ( P = 0.0116, d = 0.43). Adverse events and suicidality were tracked throughout the study. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. After psychiatric medication washout, participants ( n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. Nature Medicine volume 27, pages 1025–1033 ( 2021) Cite this article MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |