Conducting clinical studies targeting cognition in psychiatry: guiding principles and design

CNS Spectr. 2019 Feb;24(1):16-21. doi: 10.1017/S1092852918001074. Epub 2018 Sep 24.


Cognitive dysfunction is common in many psychiatric disorders. While it has long been described as a core feature in schizophrenia, more recent data suggest qualitatively similar impairments in patients with bipolar disorder and major depressive disorder. There is compelling evidence to suggest that cognitive impairment contributes directly to functional disability and reduced quality of like across these disorders. As current treatments focus heavily on "primary" symptoms of mood and psychosis, the standard of care typically leaves cognitive deficits unmanaged. With this in mind, the field has recently begun to consider intervening directly on this important symptom domain, with several ongoing trials in schizophrenia. Fewer studies have targeted cognition in bipolar disorder and still fewer in MDD. With progress toward considering this domain as a target for treatment comes the need for consensus guidelines and methodological recommendations on cognitive trial design. In this manuscript, we first summarize the work conducted to date in this area for schizophrenia and for bipolar disorder. We then begin to address these same issues in MDD and emphasize the need for additional work in this area.

Keywords: Bipolar disorder; clinical trial; cognition; depression; schizophrenia; treatment.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / physiopathology
  • Clinical Trials as Topic / methods*
  • Clinical Trials as Topic / standards
  • Cognition*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Humans
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology


  • Antipsychotic Agents
  • Nootropic Agents