What would it take to make drug repurposing work for mental health?

For many decades, most medicines used to treat schizophrenia worked in largely similar ways. Then, in 2024, the FDA approved Cobenfy, the first schizophrenia treatment based on an entirely new approach. But the story behind this medicine began much earlier. It was originally developed as a potential treatment for Alzheimer's disease, but researchers noticed that it also reduced delusions, agitation and hallucinations that occur in Alzheimer's. Development was halted due to adverse side effects until researchers returned much later with a novel approach to address them, ultimately creating Cobenfy. The story raises an interesting question: how many mental health treatments of the future are already out there, waiting to be noticed? 

Bringing a new medicine to patients is a long, complex and expensive process. Many promising medicines fail along the way for a variety of reasons. Repurposing can give researchers a head start, building on existing knowledge about how a medicine works, its safety profile and how it behaves in the body. 

Over many decades, pharmaceutical companies and research organisations have generated thousands of drug compounds. Some became licensed medicines. Others were shelved because they did not work well enough for their original purpose, development became too difficult or commercial priorities changed. 

These compounds represent a huge body of scientific knowledge. What has not always been explored is whether they could help treat a completely different condition. 

There are already examples of repurposing changing clinical practice. Ketamine, originally developed as an anaesthetic, is now used in some settings to treat severe depression. Cobenfy shows how an existing medicine can contribute to a genuinely new treatment when researchers look at it through a different lens. 

The challenge is finding the opportunities worth pursuing. A promising biological connection is only the starting point. We need to establish whether it translates into meaningful benefits for patients and if there is enough evidence to justify development. 

To make repurposing work, three things need to happen: researchers need a way to find promising candidates, a way to test them efficiently and a way to support opportunities that may not attract commercial investment.

Advances in computational biology and artificial intelligence are creating new opportunities to explore drug repurposing at scale. Researchers can increasingly analyse large datasets, scientific literature and drug libraries to identify unexpected connections between medicines, biological pathways and diseases. Instead of relying solely on chance observations, it may become possible to systematically search for and prioritise promising drug-disease combinations. 

At the same time, improvements in our understanding of mental health biology are helping researchers to identify and validate new drug targets that existing compounds can act on. 

Neither of these developments is a shortcut around scientific evidence. But together they could help researchers ask better questions and identify better candidates for testing.

Finding promising candidates is only the first step. The next challenge is generating the evidence needed to show whether a treatment genuinely benefits people. This is where new approaches to clinical trials could make a significant difference. 

Traditional clinical trials often test one treatment at a time. Platform trials work differently: they can evaluate several treatments within the same infrastructure, allowing researchers to add promising candidates and stop those that do not work. This can make clinical development faster and more efficient. For mental health, this could make a real difference and help us learn more quickly what works and what doesn’t.

That is why Wellcome invests in PUMA and EU-PEARLDIVER, which are the first dynamic trial platforms set up for psychosis and treatment-resistant depression, respectively in the UK and the EU. These programmes systematically identified the most promising generic medicines to repurpose and will deliver efficient testing of four medicines in the next few years.

A successful clinical trial is an important milestone, but it does not automatically mean a treatment will reach patients. Drug companies often rely on patents and high drug pricing to cover the cost of running extensive clinical trials. This is where the economic reality of repurposing can be difficult. A generic medicine may lack patent protection, so no single company has the financial incentive to fund its new uses.  

Within this context, charities and philanthropies can play an important role: supporting the science needed to identify promising candidates, building shared infrastructure and collaborations, funding rigorous clinical studies and generating the economic and real-world evidence needed to move successful treatments into practice. By funding evidence generation without requiring a financial return, charities and philanthropies can bridge this gap and unlock safe, existing treatments for patients in a fraction of the time and cost of standard drug development. It turns a market failure into a significant opportunity for donors. 

Repurposing will not solve every challenge in mental health drug development, and still, most potential candidates will not succeed. But there is an enormous body of scientific knowledge and pharmaceutical development to build on.

Some of tomorrow's breakthroughs may come from entirely new medicines. Others may come from medicines that have been sitting in laboratories or pharmacies for years. The opportunity is to get better at turning those possibilities into evidence, and then turn this evidence into treatments that reach the people who really need them.