RETRACTED ARTICLE: Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials

Abstract

Rationale Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual's health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD. Objectives To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD. Methods Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire. Results There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = − 44.8 (2.82), p < .0001), with a Cohen's d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = − 5.2 (2.29), p < .05), with a Cohen's d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation. Conclusions PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

The Use of Classic Hallucinogens/Psychedelics in a Therapeutic Context: Healthcare Policy Opportunities and Challenges

“…For instance, in all current studies with these drugs only 1–3 doses are being used, and sometimes therapeutic effects are observed weeks to months afterwards. 7 , 10 , 59 This is perhaps one of the most important benefits associated with these drugs since it would be cheaper for individuals and society in the long term. Although in the short term it will be necessary to invest time and resources in the treatment sessions (which may or may not include psychotherapeutic processes), only one or few treatment sessions would be performed, and benefits would last longer than current pharmacotherapy and/or standard psychotherapy.…”

The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis

“…For Monson et al [ 21 ] , the effect size from before treatment to after was 2.1, while for pre-MDMA to long-term follow-up at six months, Cohen’s d was 2.25. Finally, for Jerome et al [ 29 ], from which Cohen’s d was calculated using the other six studies, the pre-treatment to post-treatment effect size was 1.58, while from pre-treatment to long-term follow-up, it was 0.23 at 12 months.…”

“…MDMA dosage varied from 25 mg to 187.5 mg (Table 2 ). At least three studies [ 3 , 10 , 29 ] allowed participants in the experimental groups to receive a supplemental dose of MDMA within 2-3 hours of the initial dose. These additional doses were given at half the original dose strength to boost the therapeutic effect.…”

“…In order to be classified as being in remission, these patients had to no longer meet the criteria for a PTSD diagnosis as noted in Table 2 . As seen in Table 2 , the mean baseline severity of PTSD per study was as follows: Bouso et al: 41.5 [ 18 ]; Jerome et al: 85.1 [ 29 ]; MP-16 (NCT03282123): 45.42 [ 22 ]; MP-17 (NCT03485287) : 45.25 [ 23 ]. Table 2 shows that the mean baseline severity of PTSD for the groups ranged between 41.42 and 92, yielding 3 out of 4 of the studies discussed in Table 5 at a lesser severity compared to some of the studies.…”

“…Table 4 shows that while all studies had a significant original pre-to-post treatment effect size, two studies, Bouso et al [ 18 ] and Monson et al [ 21 ], showed an increase in the pretreatment to long-term follow-up effect size. One study, Jerome et al [ 29 ], however, showed a decrease in their long-term follow-up effect size. This was due to the number of patients who no longer met the PTSD criteria according to CAPS-4 total scores had increased to 67.0% at the time of follow-up compared to 56.0% at the time of treatment exit.…”