A real-world study has revealed the long-term impact of Johnson & Johnson’s (J&J) Spravato (esketamine) in treatment-resistant depression (TRD), which analysts say could pave the way for the uptake of classical psychedelic medicines.
The Phase IV ECHO trial (54135419TRD4008) spanned sites across Europe and Israel, enrolling 570 patients with severe and chronic TRD characterised by a mean Montgomery-Åsberg Depression Rating Scale (MADRS) score of 33.3 and episodes of three years or longer. 301 of the patients enrolled in this study were evaluated in the six-month post-treatment follow-up period.
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In the study, patients treated with the nasal spray experienced a statistically significant 14-point improvement in MADRS scores from baseline after 12 weeks of treatment, with this impact deepening to a 17.6-point reduction after 48 weeks.
Spravato’s antidepressant effects were also maintained after patients discontinued treatment, as those who stopped taking the therapy saw a mean -1.4-point change from the post-treatment follow-up baseline to week 24. According to J&J, most patients evaluated in this portion of the study remained stable, with no indication of relapse.
Spravato’s safety and tolerability profile was also similar to prior studies, with no new signals identified amongst this patient population. However, 81.4% of those given the drug experienced a treatment-emergent adverse event (TEAE), with events of this nature causing 7.7% of patients to discontinue treatment.
These data were presented at the 2026 European Psychiatric Association Congress, which is taking place in Prague from 28 to 31 March.
Reframing thoughts around treating depression
The results of the ECHO study come as depression is set to become the leading cause of global disease burden by 2030, as per a prediction from the World Health Organization (WHO).
Despite the advances in the pharma industry’s understanding of depression and how to treat it, TRD remains an area of significant unmet need, Tamara Werner-Kiechle, J&J’s head of neuroscience, cardiopulmonary and early portfolio for EMEA, told Clinical Trials Arena.
“Around one-third of people with major depressive disorder (MDD) don’t adequately respond to available antidepressants,” Werner-Kiechle commented. “The burden of TRD is disproportionately higher among people who do not respond to antidepressant treatments and is likely underestimated as there is limited published research on the use of social services and the burden for caregivers,” she added.
Currently, there are few treatment options available to patients with TRD, with Spravato being the only monotherapy approved for use in this indication.
While steps have been made to advance the treatment landscape for TRD, Werner-Kiechle believes that there needs to be a wider reframing to reflect the increasing burden of depression. According to Werner-Kiechle, this should be achieved by the promotion of ongoing innovation, as well as the adoption of “value-based pricing approaches” to make sure treatments become available to patients in a timely manner.
“Reframing mental health as a long-term investment, rather than a short-term cost, is essential if innovation is to translate into meaningful access for patients,” Werner-Kiechle added.
According to an analyst consensus forecast by GlobalData, parent company of Clinical Trials Arena, Spravato will generate $4.9bn in 2032.
Paving the way for psychedelic uptake
While Spravato is not a traditional psychedelic, it can elicit psychoactive responses similar to those seen in patients given classic psychedelic medicines. This means that the drug has to be administered in a structured and monitored clinical setting to support safe use.
As Spravato’s uptake increases within the TRD setting, Philippa Salter, managing neurology analyst at GlobalData, notes that the drug will pave the way for other therapies with similar requirements – including AtaiBeckley’s mebufotenin benzoate nasal spray and Compass Therapeutics’ COMP360.
“Since Spravato is only available through a restricted programme, it is likely that future psychedelic therapies approved for TRD will also follow this pathway,” Salter says.
According to Salter, this means that Spravato’s launch and uptake procedure can be followed by other companies entering the TRD space. “Clinics that administer Spravato could be targeted by companies with new psychedelic drugs, as they are well placed to have some of the infrastructure and processes in place required for psychedelic drug administration,” Salter adds.
Overcoming hurdles to psychedelic therapy uptake
While psychedelic medicines edge closer to the market, Salter notes that developers will have to navigate several challenges – including the amount of healthcare provider time required to administer such drugs.
“Patients who are given Spravato have to be monitored for two hours post administration; the longer the length of monitoring required will increase the hurdles for new psychedelics entering the market,” Salter comments.
Salter adds that psychedelic drugs designed to be paired with psychotherapy could face hurdles associated with the coordination between different departments in a healthcare practice, as the drug and therapy sessions will have to be given concomitantly.
In a previous conversation with Clinical Trials Arena, Erela Dana, director for Neurology and Immunology Research and Analysis at GlobalData noted that COMP360, a pharmaceutical based on the classic psychedelic, psilocybin, could “materially reshape the top of the TRD pyramid”. The drug, Dana says, could achieve this by offering an alternative to Spravato that requires less frequent dosing – provided reimbursement is comparable.
