In this Opinions piece, Clerkenwell Health’s Arda Ozcubukcu discusses the potential value that could be derived from a greater focus on the use of evidence-based psychotherapies in psychedelic research and practice. Below, Arda shares how such an approach may support efforts to prove cost-effectiveness, enable psychedelics to be more easily integrated into existing systems, and more.
“I worry that we are wasting precious time simply using non-directive psychological support models in psychedelic-assisted therapy trials” says Dr Sarah Bateup, Head of Therapy at Clerkenwell Health and former Head of Therapy Research and Training at COMPASS Pathways. “We don’t have evidence showing if, and how, these models work. I have seen first-hand how therapists struggle to deliver something they just don’t understand, and how therapists who default to using an evidence-based model such as CBT are far more effective.”
Access to psychedelic-assisted therapy within the healthcare system requires more than market approval of the drug. Public and private healthcare payers must be convinced of the treatment’s cost-effectiveness and the quality of its evidence base. Integration into health systems also poses practical challenges that can hinder access, even when payers are willing to cover the treatment.
Psychedelic-assisted therapy presents unique challenges for demonstrating cost-effectiveness and integration into the health system. Some of these challenges could be overcome if the sector focuses on evidence-based psychotherapy models. Unfortunately, most clinical trials do not investigate the efficacy of psychedelics alongside evidence-based psychotherapy. This is typically due to cost considerations related to the therapists’ time and/or a desire to isolate the drug effect. In some instances, it may also reflect a drug developer’s nervousness around the placebo arm which would then also require the use of an evidence-based therapy model without drug.
“I worry that we are wasting precious time simply using non-directive psychological support models in psychedelic-assisted therapy trials.”
Best practice for psychedelic-assisted therapy includes integration sessions, as they are crucial for translating insights into long-lasting life changes. The format of these sessions can range from minimal non-directive psychological support to structured evidence-based psychotherapy. In any case, most agree that the drug doesn’t do the work alone and the therapeutic effect of the drug and psychological support is practically inseparable.
When psychedelics’ reliance on “set and setting” renders it impossible, why do we insist on trying to demonstrate the drug effect alone? As Guy Goodwin, Professor of Psychiatry at University of Oxford puts it “if patients experience lasting improvement because of insights or re-framing of their view of life […], the approach really does represent psychotherapy, albeit drug assisted”. In this case, combining psychedelics with evidence-based psychotherapy should lead to a more effective treatment as well as making it easier to scale it up within existing health system structures.
Psychedelic trials already suffer from limitations such as blinding, expectation bias and standardisation of treatment. To prove cost-effectiveness, we need clear evidence of high efficacy, particularly in the long-term since these treatments will be relatively expensive to deliver frequently when compared to currently available psychiatric drugs.
Commercial incentives and drug approval processes designed to evaluate drugs as stand-alone treatments push drug developers to foreground the drug and ignore the psychotherapeutic intervention during clinical trials. Although psychotherapies are outlined in treatment manuals, they remain black-boxed in the regulatory approval process reducing the quality of clinical trial evidence.
We need to demystify this “black box” by evidencing the therapy and not just the drug. Decades of evidence exist for the effectiveness of existing therapy models for different patient populations. Rather than designing new models for different clinical trials and attempting to evidence them for regulators and health payers, we should demonstrate how psychedelic drugs can amplify the efficacy of existing therapy models. This way, more patients are likely to get better for longer, improving the cost-effectiveness of psychedelic treatments in the long-term.
Using evidence-based therapies in psychedelic trials will also allow for more robust meta-analyses and comparative studies – the crux of cost-effectiveness analyses. This will then help generate the evidence for translating these therapies from a trial context to delivery at scale. For instance, proving the cost effectiveness of psilocybin against SSRIs will be very difficult, but comparing psychedelic-assisted therapy to other prescribed treatments such as Acceptance and Commitment Therapy (ACT) would be simpler, requiring mainly a head-to-head trial of ACT alone versus ACT plus psilocybin.
The therapist bottleneck is a commonly highlighted issue which will limit access, at least for some period of time. We need to train more therapists and we need to do it in a scalable and credible way. Delivering evidence-based therapy has the advantage of utilising established infrastructure for training,
Unlike psychological support models that are developed for specific clinical trials, evidence-based models can be more easily integrated into accredited traditional training pathways. Universities and healthcare organisations, which are responsible for training the workforce at scale, can readily adopt modules on psychedelic therapies into their existing courses.
If we want to provide access to any patient who might benefit from psychedelics, we must integrate psychedelic-assisted therapy into normal care delivery and referral pathways. For example, a patient with a cancer diagnosis receiving psychotherapy for adjustment disorder should be easily referred for a psychedelic dosing session to increase the effectiveness of their treatment. Developing such referral pathways would require more research demonstrating the synergies between psychedelics and evidence-based psychotherapy models.
What does this mean in practice?
Despite the lack of direct evidence supporting the effectiveness of evidence-based therapy over non-directive psychological support, inferences can be made by looking at how results differ across companies who take different approaches. Companies such as Beckley Psytech for example have relatively more intensive therapy models compared to the likes of GH Research. Although they are working with different trial protocols, it will be interesting to compare level and duration of effect with the differing models.
Obviously, the gold standard would be to compare the two modalities head-to-head in a randomised controlled trial. However, with the commercial sector tight for cash today, head-to-head trials between different therapy models are likely to fall to universities. No academic studies currently taking place are investigating this, but there is a pressing need to understand the effectiveness of different therapy models.
For drug developers, employing evidence-based therapy should not dramatically impact the cost of individual trials. Instead, it might reduce the overall cost of the drug development process. Many trials that use non-directive psychological support already involve multiple preparation and integration sessions, which can simply be replaced with evidence-based models. If required, a few remote sessions can be added without significantly increasing the cost. Using evidence-based models could instead reduce the chances of regulators requesting additional data by leading to better clinical outcomes and higher-quality evidence.
Designing trials with evidence-based models can therefore be more cost-effective in the long run for both drug developers and patients. With implications for better integration in health systems, using evidence-based therapy will ultimately lead to wider access. Wider access means more people benefiting from psychedelic-assisted therapy and higher revenues for drug developers. It is in a trial sponsor’s interest, both from ethical and commercial standpoints, to consider access early on in the development process and design clinical trials accordingly.
Arda Ozcubukcu is a Communications Associate at Clerkenwell Health.