Professor Matthew Hotopf, Director of NIHR Maudsley Biomedical Research Centre, and Professor John R Geddes, Director of NIHR Oxford Health Biomedical Research Centre, discuss the impact of the NIHR Translational Research Collaboration for Mental Health, and how it can fight back against dwindling investment in the discovery and development of mental health interventions
Drug discovery and development for mental disorders has stalled over the past two decades due to the lack of clear biological targets and the related absence of the reliable biomarkers required for efficient drug development programmes. Together, this has led to few genuinely innovative new drugs being developed with high failure rates in costly later phase trials. As identified by Kola and Landis in their important article in 2004, this situation was widespread across several therapeutic areas. Kola and Landis proposed several approaches to reducing the failure rate – the most important of which was to use experimental medicine and early phase trials to ensure that if failure (which is inevitable) does occur, it happens earlier, before expensive late phase drug development programmes. This is understandably considered to be more feasible in disease areas where more is known about basic disease mechanisms, and where better targets and biomarkers exist than in mental disorders. This has been a major reason for the large scale withdrawal of pharmaceutical companies from drug development in mental disorders.
It is perhaps worth noting that the situation in psychological treatment development is similar, although it has never stalled to such a dramatic extent as in drug therapy. The history of psychological treatment development can be seen as an initial phase of innovation (e.g. cognitive behaviour therapy) and research into effectiveness, followed by modest further innovation and extension (repurposing) into other disorders. Psychological treatments urgently need to be made both more precise and targeted on understanding of disease mechanism, and more efficient, for example by using new technology to enhance scalability to meet the population need.
There are now grounds for considerable optimism. As Directors of the UK’s two mental health-focussed NIHR Biomedical Research Centres at Kings/Maudsley and Oxford, we are in the highly privileged position of witnessing first-hand the emergence of new avenues for drug discovery-based on a combination of advances in basic biology and better technology. In drug therapy, we now have targets from genome-wide association studies (GWAS), from advances of knowledge into biological systems such as immunology, from deeper understanding of mechanisms of action of existing psychoactive drugs (cannabinoids, psychedelics, ketamine etc). Induced pluripotential stem cells are promising human cellular models – critically important given the known inadequacy of animal models – and advances in neuroimaging and digital phenotyping are leading to the development of efficient experimental medicine models and early phase clinical trials. In psychological therapies, we now have growing understanding into the cognitive mechanisms underlying disorder, with better information technology for delivering treatments at scale combined in the UK with the highly innovative Improving Access to Psychological Treatments service which includes routine outcome assessment.
Our optimism is shared by others. Husseini Manji, Head of Neuroscience at Janssen – one of the few large pharmaceutical companies with current large scale psychiatric development programmes – is reported as being optimistic. Manji believes that one or two successes would lead to widespread re-entry into the field.
UK National Institute for Health Research – infrastructure
The UK Life Sciences Industrial Strategy makes a number of recommendations to increase the potential for growing life sciences industry which is one of the UK’s dominant economic sectors. Several of these focus on how to build the UK’s health and academic environment to facilitate partnership with the life sciences industry in the broadest sense. The National Institute for Health Research (NIHR) was created in 2006 with the purpose of funding health and care re...
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