Perceived benefits of MDMA-assisted psychotherapy beyond symptom reduction: qualitative follow-up study of a clinical trial for individuals with treatment-resistant PTSD

This long-term follow-up study (n=19) applied qualitative interviews, an interpretative phenomenological analysis, and quantitative questionnaires to assess the perceived benefits of MDMA-assisted psychotherapy, following a two-year period after the completion of a Phase II clinical trial. Participant depictions of their experience before, during, and in the year after the treatment provide a rich context that demonstrates how MDMA-assisted psychotherapy can impact important areas of functioning as well as the overall quality of life, regardless of changes to PTSD symptoms.

Abstract of Perceived benefits of MDMA-assisted psychotherapy beyond symptom reduction

“Introduction: We present select findings from a long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD.

Methods: Semi-structured qualitative interviews were conducted at participants’ one-year follow-up after a recently completed phase 2 clinical trial. Available interviews from 19 of 24 participants were analyzed. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the Clinician Administered PTSD Scale (CAPS-IV) and supported by the Long-Term Follow-Up (LTFU) Questionnaire. Pertinent data from interview transcripts were coded and analyzed using an interpretative phenomenological analysis (IPA) methodological framework. We explore prominent thematic elements from participant accounts to better understand the outcomes experienced in this trial.

Results: All participants reported experiencing lasting personal benefits and enhanced quality of life that extend beyond quantifiable symptom reduction.

Discussion: We explore a range of treatment benefits beyond symptom reduction to highlight the utility of qualitative investigations of the process and effects of MDMA-assisted psychotherapy. Limitations and challenges encountered in conducting this study are discussed along with recommendations for improved qualitative research protocols in future clinical trials.”

Authors: William Barone, Jerome Beck, Michiko Mitsunaga-Whitten & Phillip Perl

Summary of Perceived benefits of MDMA-assisted psychotherapy beyond symptom reduction

A long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD was conducted. The results suggest that this treatment has lasting personal benefits and enhanced quality of life.

Introduction

Post-traumatic stress disorder (PTSD) is a growing public health concern, especially among military veterans and first responders. There are several pharmacotherapies and psychotherapies available, but many people with chronic PTSD have gained little benefit from them.

The Multidisciplinary Association for Psychedelic Studies (MAPS) has sponsored multiple FDA-regulated phase 2 clinical trials in evaluating the therapeutic potential of MDMA-assisted psychotherapy for individuals suffering from treatment-resistant PTSD.

MDMA-assisted psychotherapy trials have focused on collecting data from the Clinician Administered PTSD Scale (CAPS-IV), but the CAPS-IV does not fully capture the potential benefits of this treatment.

Qualitative research provides a means for evaluating the nuances of psychedelic-assisted therapies, and has focused on studies investigating the therapeutic potential of LSD and psilocybin for anxiety related to life-threatening illness, depression, and smoking cessation.

This study examines the long-term outcomes of MDMA-assisted psychotherapy using a long-term follow-up questionnaire. The study identifies key themes in participant experiences from before, during, and after the trial.

Methods

This study was approved by the John F. Kennedy University Institutional Review Board and Western-Copernicus Group Institutional Review Board. It included 19 individuals who participated in a phase 2 clinical trial investigating MDMA-assisted psychotherapy for treatment-resistant PTSD.

The phase 2 clinical trial involved randomized, double-blind, crossover, six- to eight-hour sessions of manualized MDMA-assisted psychotherapy with a male and female co-therapy team using a relatively non-directive or client-directed therapeutic approach.

A member of our research team helped revise the LTFU Questionnaire, and then designed the LTFU Qualitative Interview instrument. These interviews were conducted by one or both of the trial therapists at the time of each participant’s one-year site visit.

Coding and analysis

Nineteen interviews were recorded, transcribed, and made available to the research team via encrypted software. The themes that emerged from the interviews were discussed at weekly research meetings and any alterations to the codes were then applied to previous interviews.

We employed an Interpretative Phenomenological Analysis (IPA) methodological approach to analyze participants’ personal experiences and perceptions of the treatment process. This approach is particularly relevant for evaluating novel treatments such as MDMA-assisted psychotherapy.

A computer-assisted qualitative data analysis software package was used to analyze the interview transcripts. It helped identify emerging themes and develop tables of co-occurring codes.

Participants

Eligible participants were military veterans, police officers, and firefighters who had a confirmed diagnosis of PTSD and had failed to respond to more than one treatment.

Of the 26 original phase 2 study participants, 24 completed the study and were interviewed. Of these 19 participants, 16 were military veterans, two firefighters, and one police officer.

Results

In the phase 2 trial, 15 participants showed clinically significant decreases in PTSD symptoms at one year follow-up.

Benefits of MDMA-assisted psychotherapy beyond symptom reduction

Phase 2 clinical trials of MDMA have found significant and durable reductions in PTSD symptoms that persist more than one year following the treatment. Participants also reported qualitative improvement in their self-awareness, relationships and social skills, problem substance use, and openness to continued therapy.

Participants’ experiences with various qualitative themes are shown in Figure 2. Some quotes have been edited to remove filler words.

Improved self-awareness

Many participants expressed how their experiences with trauma and PTSD limited their ability to understand themselves or their issues. However, they gained valuable insights into their personal experiences during their LTFU interviews.

Improved relationships and social skills

All participants described how their PTSD symptoms had impacted their social functioning. The majority of participants reported improved relationships and social functioning after the treatment.

Engagement in new activities

Many participants expressed how their PTSD symptoms led to isolation and limited participation in activities, but all reported being able to take more healthy and rewarding action after the study.

Reduced medication and problem substance use

Medications have shown limited efficacy in treating certain symptoms and comorbid presentations associated with PTSD. Thirteen of 19 participants reported a decrease in medication and problematic substance use.

Nine of the participants recalled extensive substance use in attempting to cope with their PTSD symptoms. One participant said that his former reliance on alcohol had changed significantly.

Openness to future therapies

Participants had failed multiple pharmacological and psychotherapeutic PTSD treatments, but their experience with MDMA-assisted psychotherapy helped them feel more open to exploring other treatment modalities.

Perceived therapeutic factors of the treatment

In our study, participants described the therapeutic factors of MDMA-assisted psychotherapy in the treatment of PTSD. These factors included the effects of MDMA on the therapy process.

Discussion

MDMA-assisted psychotherapy can reduce symptoms of treatment-resistant PTSD on the CAPS-IV and other clinical measures, but also impacts other areas of functioning and overall quality of life.

MDMA-assisted psychotherapy for PTSD has been shown to improve CAPS-IV total scores, but does not necessarily improve quality of life, relationships, or self-awareness. These findings warrant further qualitative exploration to more thoroughly understand the full impetus of MDMA-assisted psychotherapy for PTSD.

We conducted a qualitative study after the clinical trial was underway, and our protocol was necessarily tailored to fit within existing study parameters. Although the relationship between the therapists and participants appears to be very strong, the nature of the interviews may have been altered.

Lessons from this study provide opportunities to improve future qualitative protocols of MDMA-assisted psychotherapy. These include performing qualitative interviews prior to the study, at the end of the treatment period, and at long-term follow-up intervals.

In future studies, it is important to assess outcomes with other therapy teams to understand the impact of the therapeutic relationship aside from the medication. Also, it is important to network with MAPS and clinical trial teams from the outset to help ensure success.

The reemergence of psychedelic-assisted psychotherapy has allowed for more research to present evidence of safety and efficacy for these treatments. This article explores the nuance of experience often missed by quantitative measures, and highlights the value of qualitative research.

Notes

This study is a qualitative investigation with the participants from an earlier study by Mithoefer and colleagues (2018). The specific group studied here is military veterans, firefighters, and police officers.