The Costs and Health Benefits of Expanded Access to MDMA-assisted Therapy for Chronic and Severe PTSD in the USA: A Modeling Study

This study (2022) uses a decision-analytic model to assess the cost and health benefits of expanded access to MDMA-assisted therapy (MDMA-AT) in the phase III clinical trials from MAPS. Expanding access to MDMA-AT to 25-75% of eligible patients was projected to avert 43,618-106,932 deaths and gain 3.3-8.2 million quality-adjusted life-years (QALYs).

Abstract

“Background and objective: Intensive psychotherapy assisted with 3,4-methylenedioxymethamphetamine (MDMA-AT) was shown in Phase 3 clinical trials to substantially reduce post-traumatic stress disorder (PTSD) symptoms compared to psychotherapy with placebo. This study estimates potential costs, health benefits, and net savings of expanding access to MDMA-AT to eligible US patients with chronic and severe PTSD.

Methods: Using a decision-analytic model, we compared the costs, deaths averted, and quality-adjusted life-years (QALYs) gained of three, 10-year MDMA-AT coverage targets (25%, 50%, and 75%) compared to providing a standard of care to the same number of eligible patients with chronic and severe PTSD. We used a payer perspective and discounted costs (in US$) and QALYs to 2020. We conducted one-way, scenario, and probabilistic sensitivity analyses and calculated the net monetary value of MDMA-AT using a cost-effectiveness threshold of $100,000 per QALY gained.

Results: Expanding access to MDMA-AT to 25-75% of eligible patients is projected to avert 43,618-106,932 deaths and gain 3.3-8.2 million QALYs. All three treatment targets are dominant or cost-saving compared to the standard of care. Our sensitivity analyses found that accounting for parameter uncertainty and changes in various assumptions did not alter the main finding-MDMA-AT is dominant compared to standard of care.

Conclusion: Expanding access to MDMA-AT to patients with chronic and severe PTSD will provide substantial health and financial benefits. The precise magnitude is uncertain and will depend on the number of eligible patients and other inputs.”

Authors: Anton L. V. Avancena, James G. Khan & Elliot Marseille

Summary

A study showed that intensive psychotherapy assisted with 3,4-methylenedioxymethamphetamine (MDMA-AT) reduced post-traumatic stress disorder symptoms compared to psychotherapy with placebo.

1 Introduction

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that adversely affects mood, cognition, physical and emotional health, and can lead to suicidal ideation and behavior.

About half of people with PTSD achieve recovery or remission spontaneously or following standard of care, but the remainder require long-term treatment. A new treatment for PTSD involving MDMA combined with psychotherapy has been shown to be significantly more effective than placebo.

MDMA-AT is dominant over SoC in terms of health benefits and net costs among US adult patients with chronic and severe PTSD.

2.1 Overview

We developed a decision-analytic model to evaluate the cost-effectiveness of MDMA-AT for patients with chronic and severe PTSD using annual cycles and a 3% yearly rate over a 30-year time horizon.

We modeled three hypothetical MDMA-AT treatment targets for chronic and severe PTSD. These targets were selected because they are within the Healthy People 2030 goal for the proportion of adults with serious mental illness who receive treatment.

2.2.1 Patients Eligible for MDMA‑AT

We estimated the number of adult patients with chronic and severe PTSD who are eligible for MDMA-AT using published sources and a state-transition model.

Our prior study produced Markov traces for 1000 simulated patients who received MDMA-AT and SoC. These traces showed that 71.4% of simulated patients who receive SoC start from the severe PTSD health state, while 28.6% begin from the extreme PTSD health state.

Previous studies estimate that 50% of people with PTSD experience a chronic and severe form. However, 21.9% of these patients would be ineligible for MDMA-AT due to psychiatric and medical comorbidities.

2.2.2 Transition Probabilities

We based our transition probabilities on a previous modeling study and used a Markov trace to determine the costs of treating PTSD, health state utilities, and annual mortality.

In the base-case analysis, we assume that patients with PTSD receive the same MDMA-AT protocol as in the Phase 3 trial, and that they experience the same level of efficacy.

2.2.3 Costs

MDMA-AT costs $11,537, including three 90-min preparatory psychotherapy sessions, three 8-h MDMA sessions, and nine 90-min integration sessions.

The costs of medical care incurred by patients with PTSD are positively associated with PTSD severity according to previous research.

2.2.4 Health Outcomes

In this study, the outcomes of interest were deaths averted and quality-adjusted life years (QALYs) gained. These outcomes were calculated using EQ-5D-5L scores of participants in the MDMA-AT Phase 3 trial.

2.3.1 Incremental Costs and Benefits

We calculated the incremental costs and health benefits of MDMA-AT versus SoC over 30 years, and used $100,000 per QALY gained as the threshold to determine the cost effectiveness of an intervention.

2.3.2 Sensitivity Analysis

We generated base-case results for each treatment target by using the base value of each input parameter in the model, and then conducted one-way, scenario, and probabilistic sensitivity analyses (PSA). The results are presented in tornado diagrams that show how extreme values affect the cost effectiveness of MDMA-AT.

We varied the effectiveness of MDMA-AT and SoC, and assumed that MDMA-AT’s effectiveness declines over time and that patients who receive MDMA-AT experience a 10% annual regression in their PTSD severity.

We varied selected inputs simultaneously over 10,000 independent Monte Carlo trials and plotted the results in cost-effectiveness acceptability curves.

3.1 Base‑case

Between 780,000 and 1.41 million patients with PTSD receive MDMA-AT. Achieving the 50% treatment target would save 78,768 lives and gain over 6 million discounted QALYs over 10 years.

3.2 One‑way Sensitivity Analysis

One-way sensitivity analysis found that MDMA-AT is dominant when compared to SoC, and the most influential parameters are the time horizon used and the number of eligible patients with chronic and severe PTSD.

3.4 Probabilistic Sensitivity Analysis

We conducted 10,000 independent simulations and found that MDMA-AT was dominant compared to SoC. MDMA-AT was found to provide greater NMV 100% of the time across various cost-effectiveness thresholds.

4 Discussion

This study estimated that expanding access to MDMA-AT for treating chronic and severe PTSD would save between $109 and $266 billion.

The findings from this study suggest that MDMA-AT is comparable to other widely used therapies in the USA, and that it can prevent more deaths and QALYs than antiretroviral therapy and smoking cessation programs.

Our study builds on two economic evaluations of MDMA-AT that demonstrated the value of this intervention. It is estimated that providing 1000 patients with PTSD access to MDMA-AT would save the healthcare system $132.9 million and generate 4856 QALYs over 30 years.

Our study finds that MDMA-AT is cost-saving under a range of assumptions, but it will require significant initial outlay to expand access to MDMA-AT.

MDMA-AT is being developed by MAPS, which obtained an FDA breakthrough therapy designation in 2017. MAPS expects to apply for full FDA approval by 2023.

Federal and state action is needed to fully legalize the production and prescription of MDMA-AT. Descheduling MDMA would enable it to be regulated as an approved therapeutic and provide access to federal research dollars.

To achieve the savings and health benefits we estimated, demand-side determinants must be addressed, such as financial barriers to care and high levels of care-seeking and treatment adherence among people with PTSD.

4.1 Limitations

This study has several limitations, including uncertainty around the true number of eligible patients with chronic and severe PTSD for MDMA-AT. Additionally, the prevalence of any current alcohol and substance use disorder was used to determine the proportion of cases that would be ineligible for MDMA-AT. We modeled a closed cohort of patients with chronic and severe PTSD, and we have likely underestimated the benefits of access to MDMA-AT over the time horizon of our study.

Our model relies on a previous cost-effectiveness analysis that assumed that patients with PTSD who receive SoC experience no improvements in their disease severity. We conducted scenario analyses to relax these assumptions, but the true long-term efficacy of MDMA-AT remains unknown.