Depression – discovering faster which treatment will work best for which individual

(Press-News.org) Depression can affect anyone. It is common, and in many cases severe. These days, there are good treatments available, typically involving a combination of psychotherapy and medication. However, finding the right treatment can take some time. Not everyone responds equally well to every medication. Researchers at six European university medical centers, led by Charité – Universitätsmedizin Berlin, teamed up to accelerate the process of arriving at solid findings relating to both new and known treatments. The key will be a joint study design, supported over the coming four years with more than 13 million euros (£11.7m) in funding from Wellcome.

According to the World Health Organization (WHO), severe depression is among the main drivers of the global burden of disease. Although there are many medications available to treat depression – some 30 antidepressants are approved in Germany alone – sustained improvement remains out of reach for some patients, in spite of multiple attempts using different treatment approaches. Why is that, and how can clinicians find out faster what really helps specific patients? Researchers at six member institutions of the European University Hospital Alliance (EUHA) are working together systematically in the PEARLDIVER project to find answers.

“Pearls” of depression research

Clinical trials are the basis of evidence-based medicine. However, many of the studies performed are not meaningful enough to yield sound conclusions for clinical practice. In many cases, the available treatments are only effective for some patients, and approval of new drugs for mental health conditions lags behind that of medications for other medical fields, such as oncology, infectious disease, and neurology.

“For patients with depression who do not respond to the first treatment, there is a huge need for evidence-based, safe and effective new therapies,” explains Prof. Christian Otte, Director of the Department of Psychiatry and Neurosciences on the Charité Campus Benjamin Franklin and medical director of the large-scale European project. He has high hopes for the structured new approach: “Our platform study will significantly accelerate the development and testing of  treatments for depression. At the same time, we will be able to clarify faster which of the therapies that are already available is most promising for a specific individual.”

One structure – many studies

To find the “pearls” of depression research and make new treatments available swiftly, the researchers have turned to the highly efficient platform study method. While new or existing treatment approaches have previously been evaluated in individual studies, in which patients are assigned at random to either the intervention group or a control group, a platform study relies on a shared infrastructure and shared control group to evaluate many different treatment approaches while still retaining the principle of random group assignment.

“Clinical trials are very resource-intensive. They are time-consuming and require a lot of effort. The previous practice has been to set up the entire infrastructure and all the logistics for each study fresh from the start. You could think of it as building a new stadium for every soccer game. In PEARLDIVER, we’re taking a different route. Metaphorically speaking, we’re building a big stadium together as the first step, and then all of the partners can use that infrastructure for an almost unlimited number of games – or, in our case, studies,” explains Prof. Stefan Gold, professor of clinical neuroscience at Charité and the project’s scientific director. “In addition to speeding up the process, this also makes the individual studies more meaningful and comparable.”

The goal is to build a Europe-wide research infrastructure over the next four years to allow researchers to arrive at solid findings aligned with the highest possible scientific standards in comparisons of treatment and control groups to study new and known treatment approaches. The first year will primarily focus on building the platform. Subsequently, the platform will assess the safety and efficacy of the first two new medications for depression to demonstrate the trial’s suitability and efficiency, with plans to add more treatments over time. Enrolment of participants is expected to start in 2026.

Patients have a voice

Platform studies are already successfully in use in other fields of medicine, such as oncological research. This approach is new to mental health. Another new aspect is that patients themselves played a role in designing the study as cooperation partners. The patient representative, Fanni-Laura Mäntylä, explains: “Our goal is to work together to find better solutions for how clinical trials in mental health are designed and run; how mental health treatment evolves; how to better help people with mental health challenges.” The European Patients’ Forum (EPF) is supporting the project.

Since multiple treatments can be reviewed at one and the same time, having a reusable infrastructure is extremely efficient. It represents less of a burden for study participants. Regulatory and ethical approval processes also take less time. Interim analyses permit rapid conclusions as to whether a treatment will be promising, and obviously ineffective study arms can also be discontinued quickly.

“This innovative platform study approach is very exciting because it will make testing new treatments for depression far more efficient and streamlined. It will help researchers collaborate to find answers about whether treatments are effective and for whom they would work best,” says Dr. Kim Donoghue, Senior Research Manager at Wellcome. This project to study depression, the largest Europe-wide, may also serve as a model for other mental health issues.


About Wellcome
Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health.

Links Department of Psychiatry and Neurosciences at CBF
Predecessor project: EU-PEARL supported by the IHI
About Wellcome

Contact Prof. Christian Otte
Director of the Department of Psychiatry and Neurosciences
Campus Benjamin Franklin
Charité – Universitätsmedizin Berlin
T: +49 30 450 517 501

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