Modafinil promotes wakefulness by acting as a dopamine reuptake inhibitor and modulating orexin pathways
the verdict
INSUFFICIENT LEANING
refutedsupported
the weight of evidence
2 sources for · 0 against
The available evidence partially supports modafinil's wake-promoting actions through dopaminergic systems and hypocretin/orexin theorization, but individual items only cover parts of the claim without fully establishing both specific mechanisms together.
<h4>Background</h4>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.<h4>Data sources</h4>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 Lastly, the manufacturer of modafinil in the United States was asked to provide all publications, abstracts, and unpublished data regarding studies of modafinil.<h4>Data synthesis</h4>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.<h4>Conclusions</h4>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.
A Systematic Review of Modafinil: Potential Clinical Uses and Mechanisms of Action Skip to content Back to top Open menu Purchase PDF Save Share Cite Reprints Sections No sections available PDF Save Share Cite Reprints Sections ··· The Journal of Clinical Psychiatry Depression (MDD) The Journal of Clinical Psychiatry Original Research April 15, 2006 A Systematic Review of Modafinil: Potential Clinical Uses and Mechanisms of Action David Feifel, MD, PhD ; Jacob S. Ballon, MD J Clin Psychiatry 2006;67(4):554-566 Related Articles When Do Physical Symptoms After Antidepressant Cessation Reflect Pharmacodynamic versus Non-pharmacodynamic Clinical Phenomena?
ASCP Corner Turning Stigma Into Stories of Hope with Aderonke Pederson, MD Podcast Impact of VNS on Suicidal Ideation in Markedly Treatment-Resistant Major Depression: A RECOVER Study Report Original Research Article Abstract Background: Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy andshift 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 sourcesof data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturerof 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 adjunctto antidepressants for depression.
Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances -60MOD + 2ATX and 60MOD + 4ATX- or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixtur
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