PSYCHOACTIVES

Kabir Nath from Compass Pathways explores the need for new treatments in the mental health space, as well as assessing whether psychoactives could be the way forward

We are living in a mental health crisis. Depression affects 280 million people worldwide, and it is estimated for one in three, existing treatments do not work.1,2 Some of the most difficult-to-treat mental health conditions, including treatmentresistant depression (TRD), post-traumatic stress disorder (PTSD) and eating disorders, have very few treatment options.

Only 20-30% of patients with PTSD who are treated with currently approved interventions will make a full recovery.3 For conditions such as TRD, a subset of major depressive disorder, many find themselves in a trial-and-error cycle of available options that ultimately fail. Anorexia nervosa has the highest mortality rate of any mental illness, with no currently approved pharmacological treatment options.4 There is a clear and urgent need for innovation.

In recent years, we have seen growing evidence to support the use of psychedelic medicines to treat mental illnesses and in the last 12 months we saw critical milestones in this space. The US Food and Drug Administration (FDA) has demonstrated it is open to the use of psychedelics in medical settings, accepting a new drug application for MDMA treatment for PTSD. Some companies have also been researching the use of psilocybin in TRD, with various phase 2b and 3 programmes underway. Confidence in the potential of these and other drug candidates has increased, with investors supporting continued innovation. Treatment delivery frameworks have also been built to allow for future access, with the introduction of regulatory guidelines and a new CPT Code, a key element of commercial infrastructure in the US. Momentum is accelerating, and while there’s a desire to bring these new treatments to patients as quickly as possible, pharma companies must act deliberately and with appropriate rigour. The industry needs to focus both on the large-scale research required to generate evidence of safety and efficacy, as well as understanding how these potential medicines can be effectively integrated into existing and emerging care settings.

Innovation in mental health has fallen behind other areas of medicine, with few meaningful developments for almost forty years. People living with little or no hope of symptom relief have put hope in the potential for new psychedelic treatments and what they could offer.

While currently prescribed mental health medications are effective for some, challenges exist. They are not always effective for a significant number of people, particularly for conditions such as TRD, which is defined as the failure of two or more different treatments in a single depressive episode.5 Others also struggle with side effects, which can then cause issues with compliance.6

Psychedelic treatments could signal a new paradigm of care. However, with a novel, complex modality, it’s essential to build a robust evidence base that regulators such as the FDA, European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA) and others can use to better understand safety and efficacy. Clinical trials are a necessary element, designed to ensure they address the right questions for regulators, policymakers and payers. Early and open dialogue can help with this. In the US, the Reagan-Udall Foundation has held virtual public meetings on ‘Advancing Psychedelic Clinical Study Design’, which discussed the experience of researchers in the field, as well as approaches to addressing key issues in psychedelic drug development and research.

The FDA also recently issued draft guidance for clinical study of psychedelics. Psychedelic Drugs: Considerations for Clinical Investigations acknowledges the potential of psychedelics and provides key considerations for industry when it comes to how it designs and conducts trials, collect data and ensure patient safety.

European bodies are also considering regulatory frameworks for potential psychedelic treatments. They are bringing together stakeholders from across the healthcare spectrum in workshops to look at the safe and effective use of psychedelics and to evaluate where regulatory guidance is required.

The evidence base is building, but is far from complete. As we continue to innovate, it will be essential to ensure we collect the right type of evidence to confidently demonstrate safety and efficacy. This will ultimately drive change and, if approved by regulators, eventual adoption. It should also encourage those working in industry and academia to continue sharing and publishing data from trials and studies, so we can collectively understand how we can continue to address the urgent need for new mental health treatments. is especially true in the US, where commercial payers are dominant.

There are steps we can take now to make this process easier and lay the groundwork for the future. In the US, procedure codes are essential to getting a treatment prescribed, delivered and reimbursed, and to tracking its efficacy. In January, the American Medical Association approved a first-of-its-kind Current Procedural Terminology (CPT) III code for ‘Continuous In-Person Monitoring and Intervention During Psychedelic Medication Therapy’.

CPT codes are little known outside of the provider/payer world, but the accurate and effective use of them is essential for patient access to new treatments. When they don’t exist, adoption of new treatments can be disrupted, as we saw with the initial launch of other psychiatric medicines with in-person service delivery, such as brexanolone and esketamine.

More broadly within the mental healthcare industry, companies are conducting research with providers to better understand the existing care delivery infrastructure and the associated challenges and opportunities in various settings of care. For example, some companies have set up research collaborations with mental health service providers of different sizes and structures, to understand the real-world challenges and opportunities of delivering treatment to those living with depression. These will also help to inform how future clinical trials are designed and how treatments will be delivered to patients, if approved.

We must also consider how healthcare systems will need to be adapted to deliver psychedelic treatments, if they are approved. ‘Set and setting’ are important elements of the safe administration of these drugs, along with psychological support from a skilled and trained healthcare professional. It’s essential that payers and providers can facilitate billing and reimbursement, to ensure these treatments will be cost-effective and broadly accessible, as well as delivered seamlessly to patients. The easier they are to integrate, the easier they will be for healthcare professionals to prescribe and to be reimbursed through health insurance. This

When working with existing specialised interventional psychiatry treatment centres, companies must understand the mental healthcare pathways that currently exist and the infrastructure, capabilities and workforce required to deliver these treatments. Gaining provider perspectives on financially viable service delivery and their operational and administrative requirements following approval will also be essential.

Innovation in the field of mental health is long overdue. Now, research into psychedelic treatments offers a potential opportunity to make a meaningful change for patients with few good existing options. These are brand new types of drugs and will be delivered in a completely new way. If approved and integrated into health systems effectively, they could deliver transformational impact. By following the medical model – robust clinical trials, pursuing evidence-based medicine with rigour and working closely with health systems – we can achieve safe, broad and equitable access once approved.

Only through this can we create the paradigm shift needed to change the future of mental healthcare for the millions of people who urgently need new treatment options.

References

1. Visit: who.int/news-room/fact-sheets/detail/depression
2. Visit: apps.who.int/iris/handle/10665/254610
3. Visit: compasspathways.com/our-work/post-traumatic-stress-disorder-ptsd
4. Himmerich H, et al. Pharmacology & therapeutics. 2020;217:107667.
5. Al-Harbi KS. Patient Preference and Adherence. 2012;6:369-388
6. Visit: ncbi.nlm.nih.gov/pmc/articles/ PMC8100773/