Grand Challenges for Psychiatric Drug Discovery: A Perspective

Looking to the future of research in pediatric anxiety disorders

“…[5] As shown by increased funding for both developmental cellular and molecular and cognitive and affective neuroscience, a brief review of the NIHM portfolio, program announcements, and RFAs along with the strategic plan highlights the importance NIMH places on this undertaking. Since the NIH now funds the complete continuum for drug discovery through global health (for the NIMH view, see [8,18,46] ), including opportunities for collaboration between industry, academic, and the NIH, [18] it is clear that the interventions community in pediatric anxiety and mood disorders needs to move beyond current generation treatments to embrace this new vision if it is to remain scientifically productive and, more importantly, to bring new and better treatments to patients.…”

“…Understanding the fundamental biology of the illnesses we treat is clearly the key to developing new more effective treatments. [8,66,67] On the other hand, the identification and validation of biomarkers and/or biosignatures that reflect this underlying biology is a key component of interventions research since running a biomarker stratified trial (selected by using a companion diagnostic) is not only the best way to match a drug to a patient population that needs it but the best way to insure a positive clinical development program. To illustrate the point, biomarkers are routinely used in other therapeutic areas during intervention development.…”

“…[5] The simple fact that these are trajectory-based illnesses have enormous implications for the nature and organization of how we understand interventions for anxious youth. [5,6] Despite the fact that the fundamental biology will be difficult to disentangle and where it does it may not initially be clear how to translate, say, a newly discovered genetic deficit in a gene that determines neuronal migration into a drugable target, [7,8] efforts to preempt, prevent, and cure pediatric anxiety disorders across the lifespan will have to begin in childhood using interventions that directly target key neurodevelopmental processes that drive trajectories of atypical as contrasted to typical development. [9] Responding in part to the recent National Advisory Mental Health Council (NAMHC) workgroup report (co-chaired by Drs.…”

“…[14] While tools and technologies, such as the ability to define the patterns of gene expression and to manipulate the major pathways for signal transduction in brain subregions as they impact early development, now permit interrogation, the CNS in model organisms and human children, the translational payoff is years away. [8,15,16] Hence, driven by high costs, an empty pipeline, success rates that are lower for neuroscience trials that in any other therapeutic area, competition with generics, and the need to satisfy not only the FDA but payers regarding a treatments incremental value, [14] companies such as Glaxo-Smith-Kline and AstraZenica have pulled out of R&D for mood and anxiety disorders altogether. [17] With some exceptions notably with biotech and small pharma, many others are downsizing preferring to wait until improvements in our understanding of fundamental biology generates new drugable targets that can be moved through the preclinical drug development process and eventually into early phase clinical trial programs.…”

NIMH Initiatives to Facilitate Collaborations Among Industry, Academia, and Government for the Discovery and Clinical Testing of Novel Models and Drugs for Psychiatric Disorders

“…Despite tremendous advances in basic neuroscience and behavioral science that drive our understanding of the neural circuitry and neurobiological mechanisms underlying psychiatric disorders and significant increases in pharmaceutical research and development funding, there is a dearth of new mechanism of action therapeutics in the drug discovery pipeline (for recent reviews, see Brady et al , 2008; Carpenter and Koenig, 2008; Conn and Roth, 2008; Mathew et al , 2008). The significant challenges facing the pharmaceutical and biotechnology industry to produce new small molecule drugs for mental disorders, however, are not unique to psychiatric drug development.…”