Modafinil - Revision history

Maintenance script: Medicine page v3: citation-integrity correction, restore ref wisor-2001 PMID 11222668 (PM-approved deploy 2026-06-03)

2026-06-03T20:58:50Z

Medicine page v3: citation-integrity correction, restore ref wisor-2001 PMID 11222668 (PM-approved deploy 2026-06-03)

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	\| pregnancy = Not adequately studied in pregnant humans. Animal data (rats, rabbits) showed developmental toxicity at clinically relevant doses, including visceral and skeletal variations. The FDA label does not assign a letter category under the post-2015 labeling rule; the prior category was C (Australia: Category D).{{citation needed}} A pregnancy registry existed but enrollment data are limited. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Modafinil may reduce the effectiveness of hormonal contraceptives (see Interactions), which has indirect reproductive implications: women of childbearing potential should use alternative or additional contraception during modafinil therapy and for one month after discontinuation.<ref name="provigil-label" />		\| pregnancy = Not adequately studied in pregnant humans. Animal data (rats, rabbits) showed developmental toxicity at clinically relevant doses, including visceral and skeletal variations. The FDA label does not assign a letter category under the post-2015 labeling rule; the prior category was C (Australia: Category D).{{citation needed}} A pregnancy registry existed but enrollment data are limited. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Modafinil may reduce the effectiveness of hormonal contraceptives (see Interactions), which has indirect reproductive implications: women of childbearing potential should use alternative or additional contraception during modafinil therapy and for one month after discontinuation.<ref name="provigil-label" />
	\| legal = [[USLegal:Schedule IV\|Schedule IV controlled substance]] in the United States (DEA scheduling effective 1999). Prescription-only in the United Kingdom, European Union, Canada, and Australia. Not scheduled in Japan; available by prescription. In the European Union, the EMA restricted modafinil's approved indication to narcolepsy only in 2011, withdrawing the OSA and shift-work indications after a benefit-risk review.{{citation needed}} International status varies; in some jurisdictions modafinil is available without prescription. Modafinil was placed in Schedule IV based on evidence of lower abuse potential relative to Schedule II psychostimulants ([[amphetamines]], [[methylphenidate]]), though reinforcing effects have been demonstrated in laboratory settings.<ref name="jasinski2000">Jasinski DR. An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol. 2000;14(1):53-60. PMID 10757254.</ref>		\| legal = [[USLegal:Schedule IV\|Schedule IV controlled substance]] in the United States (DEA scheduling effective 1999). Prescription-only in the United Kingdom, European Union, Canada, and Australia. Not scheduled in Japan; available by prescription. In the European Union, the EMA restricted modafinil's approved indication to narcolepsy only in 2011, withdrawing the OSA and shift-work indications after a benefit-risk review.{{citation needed}} International status varies; in some jurisdictions modafinil is available without prescription. Modafinil was placed in Schedule IV based on evidence of lower abuse potential relative to Schedule II psychostimulants ([[amphetamines]], [[methylphenidate]]), though reinforcing effects have been demonstrated in laboratory settings.<ref name="jasinski2000">Jasinski DR. An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol. 2000;14(1):53-60. PMID 10757254.</ref>
	\| mechanism = Modafinil promotes wakefulness through mechanisms that remain incompletely understood. The best-established molecular target is the dopamine transporter (DAT): modafinil binds DAT and inhibits dopamine reuptake, increasing extracellular dopamine concentrations in wakefulness-relevant brain regions including the nucleus accumbens and prefrontal cortex.<ref name="volkow2009">Volkow ND, Fowler JS, Logan J, et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA. 2009;301(11):1148-1154. PMID 19293415.</ref> PET imaging in humans demonstrated that therapeutic doses (200-400 mg) occupy DAT and increase dopamine in the nucleus accumbens, establishing that modafinil is, at the molecular level, a dopamine reuptake inhibitor.		\| mechanism = Modafinil promotes wakefulness through mechanisms that remain incompletely understood. The best-established molecular target is the dopamine transporter (DAT): modafinil binds DAT and inhibits dopamine reuptake, increasing extracellular dopamine concentrations in wakefulness-relevant brain regions including the nucleus accumbens and prefrontal cortex.<ref name="volkow2009">Volkow ND, Fowler JS, Logan J, et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA. 2009;301(11):1148-1154. PMID 19293415.</ref> PET imaging in humans demonstrated that therapeutic doses (200-400 mg) occupy DAT and increase dopamine in the nucleus accumbens, establishing that modafinil is, at the molecular level, a dopamine reuptake inhibitor.<ref name="wisor-2001">Wisor JP, Nishino S, Sora I, Uhl GH. Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001;21(5):1787-1794. PMID 11222668.</ref>

	Despite sharing a DAT mechanism with [[amphetamines]] and [[methylphenidate]], modafinil's clinical and behavioral profile differs substantially. It produces wakefulness without the pronounced euphoria, sympathomimetic cardiovascular activation, or rebound hypersomnia characteristic of classical psychostimulants at therapeutic doses.<ref name="ballon2006">Ballon JS, Feifel D. A systematic review of modafinil: potential clinical uses and mechanisms of action. J Clin Psychiatry. 2006;67(4):554-566. PMID 16669720.</ref> The reasons for this divergence are not fully resolved. Proposed contributors include:		Despite sharing a DAT mechanism with [[amphetamines]] and [[methylphenidate]], modafinil's clinical and behavioral profile differs substantially. It produces wakefulness without the pronounced euphoria, sympathomimetic cardiovascular activation, or rebound hypersomnia characteristic of classical psychostimulants at therapeutic doses.<ref name="ballon2006">Ballon JS, Feifel D. A systematic review of modafinil: potential clinical uses and mechanisms of action. J Clin Psychiatry. 2006;67(4):554-566. PMID 16669720.</ref> The reasons for this divergence are not fully resolved. Proposed contributors include:

Maintenance script: Medicine page v2: full MedTemplate build (PM-approved deploy 2026-06-03)

2026-06-03T17:10:56Z

Medicine page v2: full MedTemplate build (PM-approved deploy 2026-06-03)

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Maintenance script: Create Modafinil medicine page (eugeroic for narcolepsy/OSA/shift-work)

2026-05-31T17:12:01Z

Create Modafinil medicine page (eugeroic for narcolepsy/OSA/shift-work)

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MDElliottMD: Retag from Category:Eugeroics (Wakefulness-Promoting Agents) to Category:Eugeroics: verbose category name simplified per the standing category-naming convention.

2026-05-19T03:42:16Z

Retag from Category:Eugeroics (Wakefulness-Promoting Agents) to Category:Eugeroics: verbose category name simplified per the standing category-naming convention.

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	[[Category:Psychostimulants]]		[[Category:Psychostimulants]]
	[[Category:Eugeroics ~~(Wakefulness-Promoting Agents)~~]]		[[Category:Eugeroics]]
	[[Category:Psychostimulants]]		[[Category:Psychostimulants]]

MDElliottMD: Recategorize: Stimulants -> Psychostimulants

2026-05-17T10:50:55Z

Recategorize: Stimulants -> Psychostimulants

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	[[Category:~~Stimulants~~]]		[[Category:Psychostimulants]]
	[[Category:Eugeroics (Wakefulness-Promoting Agents)]]		[[Category:Eugeroics (Wakefulness-Promoting Agents)]]
	[[Category:Psychostimulants]]		[[Category:Psychostimulants]]

MDElliottMD: Recategorize: Stimulants & Wake-Promoting Agents -> Stimulants

2026-05-17T10:45:10Z

Recategorize: Stimulants & Wake-Promoting Agents -> Stimulants

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	[[Category:Stimulants ~~& Wake-Promoting Agents~~]]		[[Category:Stimulants]]
	[[Category:Eugeroics (Wakefulness-Promoting Agents)]]		[[Category:Eugeroics (Wakefulness-Promoting Agents)]]
	[[Category:Psychostimulants]]		[[Category:Psychostimulants]]

MediaWiki default: Assign pharmacological categories from List_of_CNS-active_medicines

2026-05-14T15:06:56Z

Assign pharmacological categories from List_of_CNS-active_medicines

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	}}		}}


			[[Category:Stimulants & Wake-Promoting Agents]]
			[[Category:Eugeroics (Wakefulness-Promoting Agents)]]
	[[Category:Psychostimulants]]		[[Category:Psychostimulants]]

MDElliottMD: Pharmacopedia: add

2026-05-14T03:31:00Z

Pharmacopedia: add <pharmaInteractions/>

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	\| dosing =		\| dosing =
	\| effects =		\| effects =
	\| interactions =		\| interactions = <pharmaInteractions/>
	\| pregnancy_details =		\| pregnancy_details =
	\| monitoring =		\| monitoring =

MDElliottMD: Pharmacopedia: remove contraindications parameter

2026-05-14T02:40:42Z

Pharmacopedia: remove contraindications parameter

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	\| dosing =		\| dosing =
	\| effects =		\| effects =
	~~\| contraindications =~~
	\| interactions =		\| interactions =
	\| pregnancy_details =		\| pregnancy_details =

MDElliottMD: Added empty fda_max parameter to MedTemplate call

2026-05-13T02:32:44Z

Added empty fda_max parameter to MedTemplate call

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	\| starting_dose =		\| starting_dose =
	\| preparations =		\| preparations =
			\| fda_max =
	\| routes =		\| routes =
	\| onset =		\| onset =
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	[[Category:Psychostimulants]]		[[Category:Psychostimulants]]