Keep the Psychotherapy in Psychedelic-Assisted Psychotherapy

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Walking away from May’s American Psychiatric Association annual meeting in New York City, I was stunned by how many sessions focused on psychedelics. Though an advisory committee to the FDA voted 9-2 against recommending the use of 3,4-methylenedioxymethamphetamine (MDMA) for the treatment of post-traumatic stress disorder (PTSD) earlier this month, there continues to be a sense of optimism bubbling around this class of drugs. My experience at the annual meeting was a strong indication that it’s not just patients who believe that psychedelics could be highly effective tools within the field of psychiatry, but that researchers and clinicians also believe psychedelic-assisted psychotherapy may bring relief to patients who have long struggled with difficult to treat conditions.

Why All the Optimism?

The psychedelic renaissance that began 20 years ago was inspired by anecdotal evidence and promising results from a few observational studies. Since that time, the evidence has been buttressed by preclinical and phase I and II trials, with study results showing that psychedelic-assisted psychotherapy with MDMA, psilocybin (the compound found in “magic mushrooms”), and lysergic acid diethylamide (LSD) can help patients with not only PTSD, but also mood, anxiety, substance use, and even eating disorders, just to name a few.

Just how much better the treatment appears to be when compared to conventional treatment modalities is hard to believe. The use of MDMA-assisted psychotherapy for PTSD will serve as a good example.

PTSD is a condition that represents a dysfunction in trauma response, resulting in the symptoms that characterize the disorder: intrusive thoughts, memories, or dreams about the traumatic event; “flashbacks”; difficulty remembering the event; exaggerated startle responses; and avoidance of stimuli associated with the event. The lifetime prevalence of PTSD in the U.S. is estimated to be 6.9 percent (1), while the estimated annual cost of PTSD treatment in just the U.S. is $232.2 billion.

Standard treatments for PTSD include cognitive processing therapy, cognitive therapy, eye movement desensitization and reprocessing therapy, individual cognitive behavioral therapy with trauma focus, and prolonged exposure (2). Standard pharmacological treatments to manage symptoms include selective serotonin-reuptake inhibitors, which are oftentimes coupled with benzodiazepines. The serotonin-norepinephrine reuptake inhibitor venlafaxine and second-generation antipsychotic quetiapine are also frequently used off-label (2).

Even with treatment, the course of PTSD is varied, with approximately 17 to 33 percent of all individuals diagnosed with the condition experiencing chronic symptoms (3). Veterans have found symptom relief especially elusive, with one review reporting that approximately two-thirds of veterans continue to exhibit symptoms even after receiving treatment (4). Another issue in research is that participants cannot cope with challenging treatments. Dropout rates for all patients with PTSD have been estimated to be close to 20 percent (5). For veterans who are engaged in prolonged exposure and cognitive processing therapies, the dropout rates are reported to be 55.8 percent and 46.6 percent, respectively (6).

A randomized, placebo-controlled phase 3 trial with MDMA-assisted psychotherapy published last year by Mitchell and colleagues in Nature Medicine reported that the average Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores had fallen by 14.8 from baseline within the placebo group (n = 51), while the mean score for the MDMA group (n = 53) had decreased by 23.7 points at the end of the 18-week trial. Forty-five of the 52 participants (86.5 percent) in the MDMA group reported a clinically meaningful improvement in symptoms (defined as a 10-point decline in CAPS-5 score), while 37 participants (71.2 percent) no longer met DMS-5 criteria for PTSD, and 24 (46.2 percent) met remission criteria. Treatment-emergent adverse events were widely reported (102/104 participants), though most were minor (e.g., muscle tightness, nausea, decreased appetite, and hyperhidrosis). Seven severe treatment-emergent adverse events were reported—five in the MDMA group (including dissociation, flashback, grief reaction) and two in the control group (agitation and anxiety). There was one dropout in the MDMA group and eight in the placebo group, making the total dropout rate 11.56 percent (7).

There are concerns about the size of the trial, as well as “functional unblinding” with psychedelics like MDMA (i.e., it’s difficult not to recognize such pronounced effects of the active drug compared to placebo), and the frequent rate of treatment-emergent adverse events. Despite these concerns, one cannot ignore that these patients have struggled with symptoms for years and are finally finding relief—oftentimes with no more than a few sessions where the psychedelics are administered with a dyad of therapists in conjunction with a combination of preparatory and integrative sessions.

Psychedelics and the Public

Though trials with psychedelic drugs have only been administered in conjunction with talk therapy, the “psychedelic revolution” in psychiatry is often presented as being more about the substances than the work of the therapist. Many people believe that therapeutic response is primarily due to drug effects, and the therapists in the room are simply there to keep the proverbial guardrails in place.

This could not be further from the truth. Talk therapy is integral to any treatment involving psychedelic drugs, and an interesting analogy was presented during the APA at a session with Jennifer Mitchell, Aaron Wolfgang, and Bryan Barksdale. As they noted during their presentation, psychedelics should be considered akin to anesthesia and talk therapy to a surgical procedure. Anesthesia without the procedure provides temporary analgesia without treating any underlying issue. Meanwhile, trying to conduct a procedure without anesthesia is only appropriate in some cases because it may be too painful for the patient. When anesthesia is administered before the procedure, surgeons can more effectively address the underlying issue without causing the patient unnecessary pain and ultimately provide the best care.

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While there are risks associated with these drugs, the benefits are hard to ignore, and psychedelic-assisted psychotherapy is proving to be effective in the treatment of several conditions for which even first-line treatments often prove woefully ineffective. We owe it to our patients to develop protocols that prioritize safety while making use of psychedelic-assisted psychotherapy, lest we risk throwing the baby out with the bathwater.