Investigational New Drugs for The Treatment of Cognitive Impairments of Schizophrenia: A Review of Trials

Introduction: Cognitive impairments (CI) significantly burden over half of patients with schizophrenia in the United States. Given the extensive research on treating CI, we provide a review of trials for recent investigational new drugs (INDs).
Methods: We searched clinical trial databases, including clinicaltrials.gov and citeline.com, supplemented with information from PubMed, Google Scholar, and trial sponsor websites. The search focused on the most recent Phase I, II, and III trials of investigational drugs for CI in schizophrenia. The search cutoff date was 11, July 2024. Studies of repurposed drugs and open-label trials were excluded.
Results: Over the past two decades, 52 new drugs have been explored for treating CI, with the earliest trial starting in 2002. Of these, 40 continued to phase II, and only 2 advanced to phase III. One Phase III IND failed due to lack of efficacy. Currently, there are 7 drugs in active development: 1 in Phase I, 5 in Phase II, and 1 in Phase III. No INDs have received FDA approval for CI in schizophrenia. The included drugs target 22 distinct receptor groups. Cognition was primarily assessed using the MATRICS Consensus Cognitive Battery and the Brief Assessment of Cognition in schizophrenia.
Conclusion: Despite extensive research efforts, developing effective treatments for CI remains challenging. Continued research and innovation are crucial to address this unmet need. Ongoing trials may offer new hope for patients, pending successful outcomes.