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Progress has been made in developing new approaches for patients with serious mental health conditions.
Approximately one in 25 adults in the U.S. experience serious mental illness; and globally around 450 million people live with mental health disorders, which are among the leading causes of ill-health and disability worldwide. The World Health Organization (WHO) has focused international attention on this major societal problem through its Mental Health Action Plan 2013 - 2020 and set a goal of accelerated implementation of the WHO Special Initiative for Mental Health through 2023. We will continue to see an ever-increasing need for the advancement of policies, advocacy, and integrated services for people living with mental health conditions. Coupled with significant progress in science and medicine, including in the diagnosis and treatment of mental illnesses, we hope to see meaningful alleviation of the global burden of disease over the next decade.
Our industry is starting to find ways to provide more accurate diagnoses for people with mental health conditions through new technical advances that could improve quality of life and change the course of illness. This includes digital health and related wearable and smart phone technologies that can help monitor patients’ behavior and provide feedback in almost real time. At the same time, advances in the biology and genetics of serious mental illnesses are occurring at a rapid pace and will also lead to major improvements in diagnostic understanding and therapeutic outcomes.
Yet, mental illnesses are qualitatively different from other diseases. Psychiatrists cannot generally use biochemical tests or MRIs to diagnosis mental illnesses, and must also continue to observe how patients behave, and ask questions about thoughts and feelings. Psychiatric medications are commonly developed, approved, and prescribed without a precise knowledge of how they may work in individual cases. We simply don’t understand the underlying pathophysiology of mental illness in the same way as some other medical conditions or even other brain disorders, such as multiple sclerosis or Parkinson’s disease, for example.
Increased emphasis on the validation of novel therapeutic mechanisms by the industry, as well as NIH and academia, is helping to move the drug discovery and development ecosystem forward. We can use what we do know about the genetics, neurobiology and behavioral science of mental illness to improve diagnosis and treatment. In 2013 the National Institute of Mental Health (NIMH), under then-director Tom Insel, launched its Research Domain Criteria (RDoC) project which attempted to broaden our understanding of the underlying neurobehavioral dimensions of mental illness. The idea is to move away from using the lists of symptoms describing specific mental disorders, as noted in the Diagnostic and Statistical Manual of Mental Disorders (DSM), and toward an approach that better reflects the fundamental neuropsychiatric impairments associated with mental illness. This new diagnostic paradigm is aimed at facilitating the development of novel therapeutics that may address a wider array of abnormal mood, cognitive, and behavioral impairments than is currently possible. Ultimately, we would like to see personalized treatments targeted at aspects of psychiatric illness that are most likely to lead to symptomatic and functional improvement.
For example, schizophrenia is an incredibly diverse disease, with a broad spectrum of symptoms that vary from one person to the next. One patient may hear voices and harbor delusions, while another may show disorganized behavior and have difficulty learning or comprehending tasks. Yet another may become extremely isolative and close him or herself off from the world. But the reality is that antipsychotic drugs are only indicated for the overall treatment of schizophrenia, not for specific types of symptoms. As a result, psychiatrists and other mental health practitioners rely on past experience and professional expertise when needing to treat specific types of symptoms. This may work well in many cases, but it’s not exactly precision medicine.
This problem is also encountered in developing new medicines to treat patients with schizophrenia. The most widely used assessment of schizophrenia severity, called the PANSS (Positive and Negative Syndrome Scale), is used in most schizophrenia clinical trials. However, the scale broadly encompasses many areas affected by the illness and, 30 years after its introduction, lags behind our growing understanding of the nature of schizophrenia symptoms. Because the PANSS total score is a composite-like the often-criticized IQ measure of intelligence-it is difficult to understand which specific symptoms a treatment may target. For researchers, this limitation makes it nearly impossible to assert that any improvements are in the areas of current unmet need we hope to address.
We must take up the challenge to build and improve upon diagnostic standards to isolate different clusters of schizophrenia symptoms. This is just one example of how improving psychiatric assessments could pave the way toward more precise evaluations of new treatments with more specific clinical endpoints. Also, it potentially allows regulatory bodies to include these updated scales and their results in treatment labels, so physicians have more information to guide prescribing.
Unlocking the full potential of precision medicine in mental illness will require not only refining our psychiatric assessment tools, but a better understanding of the myriad of factors that influence how these disorders emerge and develop. For example, researchers at Massachusetts General Hospital and Harvard Medical School have developed a method to extract symptom information from electronic health records that predicts length of hospital stays or readmission risk in neuropsychiatric illnesses. Researchers at Stanford University are using brain imaging, along with other clinical and social information, to identify “biotypes” of depression and anxiety that can be studied with different treatments in clinical trials.
Ultimately, these efforts will enhance the efficiency of clinical development and empower physicians, researchers, and patients with more reliable and comprehensive information about the nature of serious mental illness. Through better diagnostic tools and deeper insights into the biological, psychological, and social variables contributing to each person’s mental health, we can begin to bring precision medicine approaches to this area of great unmet need. The end goal is really to improve quality of life for patients with various mental health conditions by diagnosing more accurately, utilizing new technical advances, and finding novel therapeutics that actually change the course of illness over time.
As an industry we face great, but not insurmountable, challenges in finding these new therapeutics. Over the past 10 years, neuropsychiatric drug development has waxed and waned. Many companies have exited this development space due to perceived high risks and a discouraging rate of failed programs. As a result, there remains high demand for new and innovative medicines and a persistent need for investment to advance the field.
Despite such concerns, I’m optimistic about the future of neuropsychiatric drug development and commercialization, and the direction of the biopharmaceutical industry and health care generally. Much progress has been made in developing new approaches on behalf of people living with the serious health conditions that we aim to treat. There is significant complexity in balancing the needs of the various stakeholders involved, but the patient’s voice must always come first as we consider how to collectively move forward. Overall, this is an exciting time to be at the forefront of science and medicine, and to enable better outcomes for patients, families, and clinicians.
Antony Loebel, MD, President and Chief Executive Officer, Sunovion Pharmaceuticals Inc.