What is Psychedelic Assisted Therapy?
From the underground
It seems fitting to start my practice and my blogs with the hottest topic in Psychiatry right now: psychedelic-assisted therapy.
Psychedelic-assisted therapy is undergoing a renaissance and I’m excited. Especially now that it is legal in Australia. But you can’t pop down to the local pharmacy to fill a prescription; psychedelic-assisted therapy is still very tightly controlled.
Psychedelic-assisted therapy is a novel form of therapy of psychotherapy that uses a psychedelic drug to enhance the experience of psychotherapy. Whilst the exact approach is evolving, psychedelic-assisted therapy typically involves a 12-week structured approach to weekly supportive psychotherapy combined with roughtly two dosing sessions.
In Australia, a psychiatrist can prescribe psilocybin (“magic mushrooms”) for the treatment of treatment-resistant depression or MDMA (“ecstasy”) for the treatment of Posttraumatic stress Disorder (PTSD). However, they need to obtain approval to do this and there are stringent controls over where psychedelic-assisted therapy can legally be performed.
This is exciting because it may offer a new form of therapy for patients. Freeing up the access to these forms of novel therapy allows more clinicians and researchers to test how psilocybin and MDMA compare with the current range of treatments that we have available. After all, the treatments that we have available don’t work for everyone, and so new and effective forms of therapy are always valuable.
Excitement can lead to hype. And this is where things can go wrong. So I want to spend a little time delving into psychedelic-assisted therapy.
Treatment-resistant depression
Let’s begin with a brief overview of what treatment-resistant depression is. Major Depressive Disorder (MDD) is more than a low mood. It is a low mood with negative thoughts, lack of motivation, difficulty thinking, poor sleep, changes in appetite (usually loss of appetite), slow movement (or alternatively restlessness) and low energy. These additional symptoms indicate the depression involves brain function. In very severe cases it can include a loss of connection with reality (psychosis).
Treatment of MDD typically involves either antidepressants or psychotherapy, or a combination of both. If a person has had limited change in their symptoms after an “adequate trial” of an “appropriate antidepressant” then their doctor may trial a change in antidepressant, or failing that they may add alternative medication such as mood stabilisers or antipsychotics. A trial of a physical treatment may be required, such as repetitive Transcranial Magnetic Stimulation (rTMS) or Electroconvulsive Therapy (ECT), if there are indications that the symptoms will be responsive.
Treatment-resistant depression isn’t really a diagnosis. Rather it describes the failure to achieve a clinical response to two or more adequate courses of antidepressants. However, this may require a critical examination of the diagnosis. Diagnosis guides treatment, and an alternative diagnosis or the emergence of concurrent psychiatric and medical illnesses may in fact underpin treatment-resistant depression.
Posttraumatic Stress Disorder
PTSD is a syndrome of stress reactions that can develop after either direct or indirect exposure to a traumatic event. These reactions are categorised within four symptom clusters: intrusive symptoms (nightmares and flashbacks), avoidance symptoms, negative changes in thoughts and mood, and heightened arousal. In addition, these symptoms must be present for at least one month and must cause psychological, social, or functional impairment. Despite the high prevalence of traumatic events, the outcome is widely variable, and depends upon genetic factors, history of prior exposure, and physical injuries sustained at the time of the trauma.
Treatment of PTSD is complex and also includes both psychological and pharmacological therapies, as well as social and complimentary interventions. Medication is used to reduce symptom severity so that patients can engage in psychological therapies. Eye movement desensitisation and reprocessing (EMDR) and trauma-focused cognitive behavioural therapy (CBT) are both widely used and equally effective, and both are superior to non-trauma focused therapies. However, there tend to be high drop-out rates with trauma-focused therapies due to the distress that they can cause.
Enter psychedelics
This is a rapidly evolving field of research but there are a few key landmarks along the way.
Robin Carhat-Harris and colleagues conducted an important trial of psilocybin in participants with long-standing MDD. They compared psilocybin with escitalopram (lexapro), which is a commonly prescribed antidepressant, and combined both interventions with psychotherapy. They also provided a “microdose” of psilocybin to the participants who were taking escitalopram so that they could be blinded.
Interestingly, they didn’t find any significant difference in depression scores between psilocybin and escitalopram. This is an important finding because it’s the only psilocybin study that compares a conventional treatment of MDD. All other psilocybin studies compare psilocybin either to a “microdose” or patients waiting to trial psilocybin.
In their landmark trial of MDMA-assisted therapy in participants with PTSD, Jennifer Mitchell and colleagues used randomised participants to supportive psychotherapy combined with either MDMA or a non-active placebo (effectively a “sugar pill”). They reported a significant reduction in PTSD symptoms that was sustained to two months.
To me, this isn’t particularly surprising as treatment of PTSD is considerably more complex than what can be worked with using supportive psychotherapy alone. In fact, no MDMA study compares MDMA-assisted therapy with conventional treatment of PTSD. What is important is that they found an effect and that there weren’t any significant adverse outcomes.
Using Dr Mitchell’s results, Elliot Marseille and colleagues studied how much MDMA-assisted therapy would cost in the United States. They found significant cost savings compared with standard care and estimated that twelve weeks of MDMA-assisted therapy costs $US11537 per patient. How this translates to the Australian system is not clear.
A silver bullet?
As excited as I am, I think that it’s important to keep in mind the limitations with the current body of evidence. Taking a critical lens helps us to really understand the strenghts and weaknesses of a particular therapy so that you can then build on them.
The studies are vulnerable to participants and researchers realising whether they’re in the psychedelic arm of the trial or not. After all, it’s not clear how a participant of a psychedelic trial remains blinded after they receive their first inactive placebo dose or microdose when the psychedelic session runs for about 8 hours.
The current body of evidence is within a highly restricted patient population that largely comprises white, middle-aged females who are either educated in the case of TRD or have a history of developmental trauma in the case of PTSD. This is important because it means that the current evidence cannot be generalised to a clinical population, especially since comorbid psychotic illnesses, personality disorders, and substance use disorders are all excluded from the studies. Whilst tight control of variables is an artefact of early clinical trials, the risks associated with psychedelics within clinical populations may limit their application and may indicate important contraindications.
Each of the studies utilizes supportive psychotherapy together with the psychedelic. This is the most basic form of psychotherapy and doesn’t include any of the deeper or more challenging aspects of more sophisticated forms of psychotherapy. There are no studies that explore the use of other more effective modalities of psychotherapy in the treatment of TRD or PTSD. It is not clear whether the psychedelic interaction with the psychotherapy depends upon the type of psychotherapy. This reflects the early phase of the evidence to identify the overall approach to PAT.
It is important to keep in mind that the use of inappropriate comparators reflects the general purpose of these studies, which is to demonstrate safety or identify a dose-response relationship. Drawing conclusions about the efficacy requires the use of an appropriate comparator, which occurred in only one study. Even in that study, the comparator (escitalopram) was initiated during the trial but was found to be as effective as psilocybin-assisted therapy. Moreover, conventional treatment for PTSD requires a complex biopsychosocial approach that is not adequately assessed in the MDMA-assisted therapy trials.
Finally, most of the studies were funded by organisations that have an interest in the success of these trials. Whilst research needs to be funded, this introduces a perceived (if not actual) conflict of interest.
Whilst the evidence shows safety, the efficacy data at best raises the hypothesis that psychedelic assisted therapy may be a useful treatment that could be offered alongside conventional therapies. It’s too premature for me to agree with the fierce advocates of psychedelic-assisted therapy, but this underscores the importance of continuing to carefully study these novel therapeutics while critical examining the findings.
Steps forward
That being said, altered-mental states are profound experiences that need to be gently integrated into our lives afterwards through careful psychotherapy. There are many ways to achieve altered states of consciousness, psychedelics is but one pathway.
