Cognitive dysfunction in bipolar disorder: future place of pharmacotherapy.

Bipolar disorder is an episodic affective illness, once believed to involve complete inter-episode remission. More recent data have highlighted the presence of persistent symptoms during purported periods of wellness, including subsyndromal affective symptoms and neurocognitive impairment. These unremitting symptoms are of extreme clinical importance, as they are directly related to a worsening of clinical course, functional impairments and psychosocial difficulties in patients with bipolar disorder. Although there is now substantial evidence demonstrating the prevalence of neurocognitive impairment during euthymia, there have been few studies, to date, targeting this disabling aspect of the illness using pharmacological strategies. While treatment approaches have previously focused on primary affective and psychotic symptoms of the disease, it is important to consider the debilitating impact that impaired cognition has on patients with bipolar disorder. A recent focus has been placed on the significant need for large-scale clinical trials designed to specifically target cognitive impairment in patients with schizophrenia, with a parallel need existing in the field of bipolar research. There is now early evidence for the presence of neurocognitive deficits in patients with bipolar disorder and a relationship between these impairments and functional disability, making this a symptom domain that requires immediate clinical attention. Convergent data indicate a compelling need for formal assessment of cognition in patients with bipolar disorder, and for researchers and clinicans alike to consider the necessity for treatment specific to cognition in this population. Although limited data exist from cognitive enhancement trials in this population, there are a number of potential pharmacotherapy targets based on evidence from neuroimaging, molecular genetic, pharmacological and animal studies related to the pathophysiology of bipolar disorder. Future directions for potential cognitive enhancement strategies in bipolar disorder may include medications that influence dopaminergic or glutamatergic neurotransmission; however, further work is needed to adequately assess the safety and effectiveness of these agents in bipolar patients. Finally, psychosocial intervention and/or cognitive remediation should be considered as alternatives to medications, although these techniques will also require additional systematic study.