Modafinil (2-[(Diphenylmethyl) sulfinyl] acetamide, Provigil) is an FDA-approved 
medication with wake-promoting properties. Pre-clinical studies of modafinil 
suggest a complex profile of neurochemical and behavioral effects, distinct from 
those of amphetamine. In addition, modafinil shows initial promise for a variety 
of off-label indications in psychiatry, including treatment-resistant 
depression, attention-deficit/hyperactivity disorder, and schizophrenia. 
Cognitive dysfunction may be a particularly important emerging treatment target 
for modafinil, across these and other neuropsychiatric disorders. We aimed to 
comprehensively review the empirical literature on neurochemical actions of 
modafinil, and effects on cognition in animal models, healthy adult humans, and 
clinical populations. We searched PubMed with the search term 'modafinil' and 
reviewed all English-language articles for neurochemical, neurophysiological, 
cognitive, or information-processing experimental measures. We additionally 
summarized the pharmacokinetic profile of modafinil and clinical efficacy in 
psychiatric patients. Modafinil exhibits robust effects on catecholamines, 
serotonin, glutamate, gamma amino-butyric acid, orexin, and histamine systems in 
the brain. Many of these effects may be secondary to catecholamine effects, with 
some selectivity for cortical over subcortical sites of action. In addition, 
modafinil (at well-tolerated doses) improves function in several cognitive 
domains, including working memory and episodic memory, and other processes 
dependent on prefrontal cortex and cognitive control. These effects are observed 
in rodents, healthy adults, and across several psychiatric disorders. 
Furthermore, modafinil appears to be well-tolerated, with a low rate of adverse 
events and a low liability to abuse. Modafinil has a number of neurochemical 
actions in the brain, which may be related to primary effects on 
catecholaminergic systems. These effects are in general advantageous for 
cognitive processes. Overall, modafinil is an excellent candidate agent for 
remediation of cognitive dysfunction in neuropsychiatric disorders.