Appendix E | 14.5
Spravato Case Study
Appendix E - Audio Recording
Spravato (esketamine) is a rapid‑acting nasal spray developed for treatment‑resistant depression (TRD) that received European Medicines Agency approval in 2019. As an NMDA receptor antagonist, it modulates glutamatergic pathways, offering an innovative mechanism of action distinct from traditional monoamine therapies.
14.5.1 Reimbursement Landscape
Its reimbursement journey in Europe has been mixed, reflecting the challenges of funding novel psychiatric treatments within strict health technology assessment (HTA) frameworks. As one of the first therapies derived from a psychedelic substance to navigate these pathways, Spravato’s experience provides important lessons for emerging psychedelic treatments such as psilocybin and MDMA‑assisted therapies.
In several European countries, Spravato has been approved with conditions or restrictions. For example, in the Netherlands, the therapy is reimbursed only for patients who have not responded to at least two other treatments, while in Ireland, approval was granted in 2022 following confidential price negotiations after initial cost‑effectiveness concerns.
In contrast, the United Kingdom’s National Institute for Health and Care Excellence (NICE) rejected Spravato twice, primarily citing unclear long‑term benefits, uncertainties in trial data, and its high cost relative to existing alternatives.
United Kingdom
The National Institute for Health and Care Excellence (NICE) has consistently rejected Spravato for NHS coverage. Their main concerns were value for money and proving that the treatment works better than existing options. NICE worried about the drug's high cost and the expense of setting up proper treatment facilities. They also questioned whether the clinical trials showed enough benefit to justify these costs. Spravato was however approved for reimbursement in Scotland by the Scottish Medicines Consortium (SMC).
Germany
The Federal Joint Committee (G-BA) takes a different approach. While it approved Spravato for reimbursement—rating it as having a high clinical benefit—it set strict conditions for its use. Some psychiatric centres now offer the treatment under public insurance, but uptake remains limited, and concentrated in specialist psychiatric hospitals. The need for supervised administration and high upfront costs have made many clinics hesitant to offer it, as well as conservatism as a new type of treatment.
Netherlands
The Dutch Healthcare Authority (NZa) and Zorginstituut Nederland (ZiN) have shown more flexibility in handling Spravato. Insurance companies already pay for both esketamine and the therapy sessions needed to deliver it.
Czech Republic
The State Institute for Drug Control (SÚKL) has approved Spravato for use and established standard reimbursement.
14.5.2 Clinical Trial Evidence
The clinical trials supporting Spravato’s approval have been subject to criticism. Many trials relied on short‑term endpoints, such as changes in Montgomery‑Åsberg Depression Rating Scale (MADRS) scores over four weeks or less. Furthermore, patient populations in these studies were often narrowly defined, excluding individuals with complex comorbidities and thereby limiting the applicability of the results to real‑world settings.
Although the therapy’s rapid onset of action has been viewed favourably for acute depressive episodes and suicidal ideation, HTA agencies have been reluctant to overlook the lack of longer‑term safety and effectiveness data. In addition, early trials frequently compared Spravato to placebo rather than to established active treatments, further complicating cost‑effectiveness assessments.
14.5.3 Reimbursement Strategies
These challenges have led to the development of various reimbursement strategies, including risk‑sharing agreements and outcomes‑based contracts. For instance, in the Netherlands, pay‑for‑performance models have been used to tie reimbursement to real‑world outcomes, thereby addressing some of the concerns over long‑term cost‑effectiveness. Such strategies, along with structured treatment algorithms that position Spravato as a last‑resort option, have helped mitigate budget impact concerns by limiting the potential number of patients eligible for treatment.
14.5.4 Implications for Psychedelic Therapies
The experience with Spravato yields several key lessons for psychedelic therapies. First, there is a clear need for robust, long‑term clinical evidence that demonstrates both short‑term efficacy and durable benefits such as sustained remission and relapse prevention. Clinical trials should incorporate extended follow‑up periods—ideally of two years or more—and include functional outcomes like return‑to‑work rates to better capture societal benefits.
Second, future studies must employ broader inclusion criteria and active comparators to ensure trial populations better reflect real‑world clinical practice. Finally, economic models for psychedelic therapies should address direct healthcare cost savings, such as reduced hospitalisations, and indirect societal benefits, thereby strengthening the overall cost‑effectiveness narrative.
14.5.5 Comparative Analysis
A comparison with other innovative therapies highlights valuable strategies. While Spravato faces challenges related to high per‑patient costs and short‑term data, therapies like CAR‑T and gene treatments have successfully employed outcomes‑based pricing and staggered payment models. Similarly, hepatitis C treatments have benefitted from volume‑based pricing and tiered cost structures. These examples underscore the importance of adaptive reimbursement frameworks and risk‑sharing agreements in addressing the economic challenges of high‑cost, novel treatments.
| Therapy | Reimbursement Challenges | Successful Strategies | Applicability to Psychedelics |
|---|---|---|---|
| Spravato (Esketamine) | High per‑patient cost; short‑term data; narrow trial populations | Risk‑sharing agreements; structured treatment algorithms | Emphasises the need for robust, long‑term data and adaptive payment models |
| CAR‑T and Gene Therapies | Extremely high upfront costs; evidence gaps on durability | Outcomes‑based pricing; staggered or installment payments | Encourages adaptive reimbursement frameworks linked to real‑world outcomes |
| Hepatitis C Treatments | Budget impact concerns; dependence on volume‑based pricing | Generic licensing; tiered pricing models | Suggests the benefits of tiered or volume‑based pricing in high‑income markets |
14.5.6 Conclusion
Overall, Spravato’s reimbursement journey highlights the tension between the drive for innovation and the necessity for economic prudence within healthcare systems. For developers of psychedelic therapies, the key to success will be to design clinical programmes that pre‑empt HTA requirements by generating high‑quality, long‑term evidence; to develop economic models that demonstrate value through both direct and indirect cost savings; and to engage in strategic negotiations that may include risk‑sharing and outcomes‑based agreements.
By adopting these approaches, emerging psychedelic therapies can navigate the complex European reimbursement landscape more effectively and ultimately improve patient access to transformative treatments.