Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline
Allison A. Feduccia, Lisa Jerome, Berra Yazar‐Klosinski, Amy Emerson, Michael C. Mithoefer, Rick Doblin · 2019 · 173 citationsRead the paper
Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly eight-hour sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610
What the full text shows
Working prototype- MDMA-assisted psychotherapy showed a significantly larger effect size on PTSD symptom reduction compared to SSRIs. — 0.9 Cohen's d vs. 0.45–0.56 (paroxetine) and 0.31–0.37 (sertraline) (Pooled data from six Phase 2 trials)
- Active MDMA dose group showed a significantly greater drop in CAPS-IV total scores than the control group. — -37.8 vs. -11.6 (Pooled Phase 2 trials (n=72 active, n=31 control))
- High response rate in patients who previously failed to respond to or tolerate SSRIs. — 52.6% no longer met PTSD criteria (Subset of 38 participants who previously took paroxetine or sertraline)
- MDMA-assisted psychotherapy demonstrated durable improvement in PTSD symptoms. — 67.8% did not meet diagnostic criteria at 12-month follow-up (n=90 participants)
- Lower dropout rates for MDMA-assisted psychotherapy compared to SSRI trials. — 6.8% vs. 11.7% (paroxetine) and 28% (sertraline) (Phase 2 MDMA trials vs. SSRI trials)
- Rapid clinical response observed after a single dose of MDMA. — Significant difference (p=0.013) 3–5 days after first session (MP-1 study)
- Setup
- Phase 2 MDMA trials included participants with CAPS-IV total severity score ≥ 50 who failed at least one prior treatment; SSRI comparisons used Phase 3 trial data from Pfizer and GlaxoSmithKline.
- How
- The paper reviews pooled data from six randomized, double-blind, placebo-controlled Phase 2 trials of MDMA-assisted psychotherapy (3 preparatory sessions, 2-3 MDMA sessions, and integrative follow-up) and compares them to Phase 3 trial data for paroxetine and sertraline.
- Limitations
- MDMA has not yet been compared to trauma-focused therapies in a randomized trial · Phase 2 trials had relatively small sample sizes (e.g., n=103 pooled) · Long-term efficacy of SSRIs was not assessed in their original drug labels
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