A Systematic Review of Modafinil: Potential Clinical Uses and Mechanisms of Action
J Clin Psychiatry 2006;67(4):554-566
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and
shift work sleep disorder and as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has a novel mechanism and is theorized to work in a localized manner, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It is a well-tolerated medication with low propensity
for abuse and is frequently used for off-label
indications. The objective of this study was to
systematically review the available evidence
supporting the clinical use of modafinil.
Data Sources: The search term
modafinil OR Provigil was searched on PubMed. Selected
articles were mined for further potential sources
of data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturer
of modafinil in the United States was asked to provide all publications, abstracts, and
unpublished data regarding studies of modafinil.
Data Synthesis: There have been 33
double-blind, placebo-controlled trials of modafinil.
Additionally, numerous smaller studies have been performed, and case reports of modafinil's
use abound in the literature.
Conclusions: Modafinil is a promising
drug with a large potential for many uses in
psychiatry and general medicine. Treating daytime
sleepiness is complex, and determining the precise
nature of the sleep disorder is vital. Modafinil
may be an effective agent in many sleep conditions.
To date, the strongest evidence among off-label
uses exists for the use of modafinil in
attention-deficit disorder, postanesthetic sedation, and
cocaine dependence and withdrawal and as an adjunct
to antidepressants for depression.