Restarting the mental health pipeline

The scale and impact of mental illness in the UK – as in most countries across the world – is huge. The latest report by the mental health charity MQ estimates that each year, one in four adults experience a mental illness (such as anxiety, depression, bipolar disorder, schizophrenia or an eating disorder) and that suicide is the leading cause of death in young men and women.

The treatment options for mental illness are many and varied, but existing drugs still leave a lot to be desired, either in terms of their speed of action (antidepressants can take 1–2 months to take effect), lack of efficacy or because of their common and significant side effects. For some, such as eating disorders, there is a lack of any effective therapy.

Reactive, not proactive

There is little doubt about the importance and impact which drug therapy can have in this area – the introduction of chlorpromazine in the 1950s led to the closure of the asylum system of mental hospitals. However, the lack of UK investment in new drugs for mental health disorders is having an ever increasing consequence as sadly more people than ever before are now suffering from mental health illnesses.

Healthcare in this area remains largely reactive. Currently, people suffering with mental health disorders go to their GP or hospital and are treated with exactly the same drugs which they would have been treated with 20 or 30 years ago. As the independent Mental Health Taskforce to the NHS in England noted in a report in February 2016: ‘The NHS needs a far more proactive and preventative approach.’

This is a complex goal. For a drug to be recommended on the NHS, it must (quite rightly) receive a positive cost-benefit analysis from the National Institute for Health and Care Excellence (Nice). Such a favourable analysis is difficult for new drugs that only offer incremental improvements. And, unlike neurological disorders such as Alzheimer’s and Parkinson’s disease, where there are clear changes that occur in patients, there are no obvious pathological changes in the brains of people with mental illness that can provide clues as to the underlying disease process and therefore offer the hope of a cure rather than just treating the symptoms.

Many drug companies have therefore significantly reduced or stopped altogether their development of drugs for mental illness because of the difficulties in identifying new ‘breakthrough’ treatments. A decade ago there were ten or so companies within the UK conducting research into new treatments for mental illness – sadly none continue to do so.

Turning the tide

However, now more than ever there is a critical need for companies to invest in drug discovery in this area. We vitally need to help people who are suffering from these disorders, by producing new drugs which not only help to control symptoms but restore patients to a fully-functional, ‘normal’ life.

At the University of Sussex, we have chosen to swim against this tide of underinvestment by establishing the Sussex Drug Discovery Centre, which has a core mission to identify new treatments for mental illness. We are currently working on projects, funded by the Medical Research Council and the Wellcome Trust, to identify new drugs for anxiety disorders, cognitive deficit for schizophrenia and cognitive deficit associated with Huntington’s disease. These various projects are supported by a number of drug companies that clearly retain a strong interest in the area, although they do not fund their own internal research.

Encouragingly, recent large-scale genetic studies are also beginning to provide exciting new insights into disease mechanisms that offer the possibility of disease-modifying rather than simply symptomatic treatments. For example, a recent study by the Psychiatric Genome Consortium found there are 108 different genes associated with schizophrenia.

As with any drug research, developing medicines is a slow process, though there may be quicker ways to the market. One option is the MRC-Industry Asset Sharing Initiative, whereby seven Pharma companies (AstraZeneca, GSK, J&J, Lilly, Pfizer, Takeda and UCB) have placed deprioritised experimental drugs into a pot and are inviting researchers to experiment to see if they could have effects in a variety of therapeutic areas – including mental health.

With the obvious caveat that there remains a long way to go, it does appear that the tide may be turning for drug discovery research for mental illness. Those who are now investing in drug discovery in this area will hopefully be well placed to ride this wave of (cautious) optimism – to deliver new drugs which will improve the lives of millions of people.

John Atack is a professor of molecular pharmacology at the University of Sussex’s Drug Discovery Centre