Central nervous system (CNS) disorders, such as depression, epilepsy, and schizophrenia, account for 12 of the top 20 global causes of years lived with disability. In addition to the human costs, the economic burden of CNS disorders weighs heavily on national health expenditures. Of the estimated $157-215 billion total cost of dementia in the US, approximately $11 billion was paid by Medicare. Despite the social, clinical, and economic need for therapeutics treating CNS conditions, the pipeline of new medications may be declining, highlighting the exit of several large pharmaceutical companies from the field.

In our study, we examined the past two decades of experimental CNS drugs and assessed how they fared during pre-FDA approval clinical phases. We also determined the reasons for failures of these drugs in late-stage clinical trials. Our data support perceptions among policymakers that there has been a slowdown in CNS drug development since 1990, particularly as compared to oncology drugs. We also found that CNS drugs were significantly more likely than non-CNS drugs to fail at the final Phase 3 testing stage. Among discontinued CNS drugs, the most common reason was failure to demonstrate efficacy, which appeared to occur at a rate consistent with new drug failures overall.

(cite: Kesselheim AS, Hwang TJ, Franklin JM. Two decades of new drug development for central nervous system disorders. Nature Rev Drug Discovery 2015; 14(12): 815-816.)