Adding psychotherapy to drug therapy works, but the FDA may not be able to handle it

Many people were stunned when an FDA advisory committee voted “no” on a new drug application for MDMA-assisted psychotherapy for post-traumatic stress disorder (PTSD) earlier this summer. I was not among them.

Several things were stacked against approval: The FDA greenlights only about 50 new drugs each year. Drug development is a high-risk business with an overall success rate between 10% and 20%. Most FDA applications for new drug approval are from massive global companies with decades of experience and deep pockets, while the application for MDMA-assisted psychotherapy was based on two philanthropy-funded trials of a Schedule I compound — insider speak for a drug with no currently accepted medical use and a high potential for abuse (MDMA’s street name is Ecstasy or Molly) — submitted by a small public-benefit corporation with no track record.

The odds tilted even further against the application because of an innovative approach that was ill-suited for FDA review but which might be a path to optimal care. The application proposed that MDMA facilitated a psychotherapeutic intervention by influencing the processing of trauma. In contrast to an antibiotic or a cardiovascular drug, which by themselves modify disease, the proposed effectiveness of MDMA was specifically linked to psychotherapy, which the application defined as a total of nine sessions divided across preparation, drug administration, and integration of the drug experience.

It’s worth reflecting for a moment on this radical notion to link a medication to psychotherapy. While considerable data demonstrate that the combination of medication and psychological treatment is better than either intervention alone, most people being treated in the U.S. for PTSD, as well as for other anxiety and mood disorders, are offered either medication from a primary care provider or psychotherapy from a behavioral health provider.

In contrast to most other medications, psychiatric medications confer change through experience. In his book, “Ordinarily Well,” psychiatrist Peter Kramer describes the mechanism of antidepressants like this: “When medication works, the world does its bit. Patients are freed to notice what’s precious in their lives. That’s why doctors prescribe.”

But for the FDA, psychotherapy is a bug, not a feature. As the FDA document submitted to the advisory committee noted, “FDA does not regulate the practice of psychotherapy, and the Agency is limited in our ability to describe the elements of psychotherapy in product labeling.”

Administration of MDMA within the context of psychotherapy might constitute best practice, and might confer effectiveness and safety that is profoundly different from taking the same drug at a rave or outside of a therapeutic environment. But the FDA approval process — optimized for drugs used in other areas of medicine — is not really adapted for psychiatric medications in which “the world does its bit.” Indeed, a regulatory approach that looks at psychiatric medications without attention to such powerful psychological interventions as exposure and cognitive therapy is not aligned with the research showing that the combination of medication and psychotherapy is preferable to either intervention alone.

One lesson from the “no” vote on MDMA-assisted psychotherapy for PTSD is that the U.S. regulatory system is not optimized for mental health care. A vast literature demonstrates the value of standardized psychological interventions such as cognitive behavior therapy for depression, or exposure and response prevention for obsessive-compulsive disorder. Yet no agency reviews the effectiveness and safety of specific psychological interventions, nor is there any form of enforcement for ensuring that these evidence-based interventions are delivered with fidelity.

From a regulatory perspective, psychotherapy is a procedure, like surgery, that is out of the FDA’s scope. But unlike surgery, which usually occurs in a hospital setting with intense scrutiny, psychotherapy is most often delivered in the black box of an outpatient solo practice or online therapy platform.

Yes, psychotherapy is a procedure. But it is a potentially powerful intervention that needs to be regulated. In the trial of MDMA for severe PTSD included in this new drug application, 47.6% of those receiving psychotherapy alone (versus 71.2% in the combined MDMA-assisted psychotherapy group) improved sufficiently so they no longer met criteria for PTSD at the end of the trial.

Just as the FDA was formed over more than a century ago to help the public distinguish medicine from snake oil, a regulatory process is needed today that defines the effectiveness and safety of psychological treatments.

The FDA usually, but doesn’t always, follow the recommendations of its advisory committees. So it’s possible the agency could approve the new drug application for MDMA-assisted psychotherapy for PTSD when it meets on August 11.

While this application has attracted attention mainly because of the possibility of approving a psychedelic drug as a medical treatment, I believe the key innovation here was the proposal to combine medication and psychotherapy as a bundled intervention. This combination was not convenient for the FDA or its advisory committee, but wasn’t it really a proposal for a best practice that needs to scale across mental health care? I believe this new drug application could serve as a wake-up call for new regulatory processes that would view psychological treatments as key facilitators rather than as confounders of behavioral change.

Medicines (and mushrooms) are not magic bullets for treating mental illnesses. But combined with evidence-based psychological treatments, they can help people with severe mood and anxiety disorders recover. The combination is the overlooked innovation of this new drug application. People with severe mental illnesses need a regulatory process that addresses this innovation as a feature, not a bug.

Thomas Insel, M.D., is a psychiatrist and neuroscientist who co-founded several mental health start-ups, was the director of the National Institute of Mental Health from 2002 to 2015, and is the author of “Healing: Our Path from Mental Illness to Mental Health” (Penguin Random House, 2022).