FAST: Fast-Fail Trials
Accelerating the Pace of Psychiatric Drug Discovery
There is an urgent need for new medications to treat mental disorders. Existing medications can be helpful but have significant limitations: for example, antidepressants now available require weeks to take effect and they fail to relieve symptoms in about a third of people who try them. Currently approved medications also do not target some of the core symptoms of CNS disorders, for example, cognitive difficulties in schizophrenia and the repetitive behaviors, social function, and communication deficits associated with autism. Side effects of the marketed drugs can also be a significant issue for patients.
Developing new medications is a lengthy and expensive process. Many promising compounds fail to prove effective in clinical testing after years of preliminary research. Many of the psychiatric medications available now are variations on a theme, interacting in similar ways on the same targets in the brain, yet the exact mechanisms by which these medications have their beneficial effects are incompletely understood.
A necessary first step towards developing a wider array of medications that offer alternatives to those available now is to identify targets in the brain at which intervention, like a pharmaceutical, could be directed to correct a dysfunction contributing to illness. The lack of such targets is one of the most important factors underlying the slow pace of medication development for mental illnesses and autism.
NIMH is supporting the Fast-Fail Trials (FAST) initiative through three (3) NIMH Contracts awarded in September 2012 (period of performance from September 24, 2012 through September 23, 2015), to provide a rapid way to test new or repurposed compounds for their potential as psychiatric medications. There are three FAST teams of researchers, focused on different mental disorders, led by:
- Andrew Krystal, M.D., Duke University – Mood and Anxiety Spectrum Disorders (FAST-MAS); Contract #: HHSN271201200006I
- Jeffrey Lieberman, M.D., Research Foundation for Mental Hygiene –Psychotic Spectrum Disorders (FAST-PS); Contract #: HHSN271201200007I
- James McCracken, M.D., University of California, Los Angeles – Autism Spectrum Disorders (FAST-AS); Contract #: HHSN271201200005I
The aim is not only to quickly identify compounds that merit more extensive testing, but to identify targets in the brain for the development of additional candidate compounds. FAST will aim at answering the following questions:
- Does the compound engage a target in the brain, for example, does it interact with a specific receptor in brain cells or alter signaling in the brain by a specific neurotransmitter?
- Does it measurably alter a feature of brain function; for example change the results of a test of memory, cognition, or attention?
Unlike standard clinical drug-testing trials, clinical trials in FAST will be small (about 10 to 30 subjects), and will be in human patients. Years of experience in drug testing suggests that positive results in animals do not necessarily translate to humans. With this type of testing, compounds that are found to engage a target in the brain, and alter an indicator (or biomarker) of brain function can quickly go forward to further testing. Negative results will avoid costly and time-consuming testing, and also provide information that will be helpful in designing future trials. The identification of new targets in the brain identified through this approach will broaden the avenues available for development and screening of new candidate compounds.