Editing Modafinil (section)

==Uses==
===Medical===
====Sleep disorders====
{{See also|Sleep disorder}}
Modafinil, a [[eugeroic]] or [[wakefulness-promoting drug]], is primarily used for treating narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks.<ref name="pmid34743789">{{cite journal | vauthors = Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, Watson NF | title = Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline | journal = Journal of Clinical Sleep Medicine | volume = 17 | issue = 9 | pages = 1881–1893 | date = September 2021 | pmid = 34743789 | pmc = 8636351 | doi = 10.5664/jcsm.9328 }}</ref> Being a [[central nervous system]] (CNS) [[stimulant]] itself,<ref name="pmid38725665">{{cite journal |vauthors=Cid-Jofré V, Bahamondes T, Zúñiga Correa A, Ahumada Arias I, Reyes-Parada M, Renard GM |title=Psychostimulants and social behaviors |journal=Front Pharmacol |volume=15 |pages=1364630 |date=2024 |pmid=38725665 |pmc=11079219 |doi=10.3389/fphar.2024.1364630|doi-access=free }}</ref> modafinil has lower addictive potential than classical stimulants such as [[amphetamine]], [[cocaine]], or [[methylphenidate]],<ref name="pmid22375280">{{cite journal | vauthors = Kim D | title = Practical use and risk of modafinil, a novel waking drug | journal = Environmental Health and Toxicology | volume = 27 | pages = e2012007 | date = 2012 | pmid = 22375280 | pmc = 3286657 | doi = 10.5620/eht.2012.27.e2012007 }}</ref><ref name="pmid32927246">{{cite journal | vauthors = Tanda G, Hersey M, Hempel B, Xi ZX, Newman AH | title = Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder | journal = Current Opinion in Pharmacology | volume = 56 | pages = 13–21 | date = February 2021 | pmid = 32927246 | pmc = 8247144 | doi = 10.1016/j.coph.2020.07.007 }}</ref><ref name="pmid33435717">{{cite journal |vauthors= Kakehi S, Tompkins DM |title=A Review of Pharmacologic Neurostimulant Use During Rehabilitation and Recovery After Brain Injury |journal=Ann Pharmacother |volume=55 |issue=10 |pages=1254–1266 |date=October 2021 |pmid=33435717 |doi=10.1177/1060028020983607 |s2cid=231593912 }}</ref> but still produces [[Psychoactive drug|psychoactive]] and subjective effects typical of classical stimulants.<ref name="Drugs.com-Monograph-2023" /><ref name="Provigil FDA label"/><ref name="pmid30285371"/>

Narcolepsy causes a strong urge to sleep during the day and can include symptoms like [[cataplexy]] (sudden muscle weakness), [[sleep paralysis]] (inability to move or speak while falling asleep or waking up), and [[hallucination]]s. Narcolepsy is linked to a lack of the brain chemical [[hypocretin]] ([[orexin]]), primarily produced in the [[hypothalamus]].<ref name="pmid35624073">{{cite journal | vauthors = Barateau L, Pizza F, Plazzi G, Dauvilliers Y | title = Narcolepsy | journal = Journal of Sleep Research | volume = 31 | issue = 4 | pages = e13631 | date = August 2022 | pmid = 35624073 | doi = 10.1111/jsr.13631 | s2cid = 251107306 }}</ref><ref name="pmid34031309">{{cite journal | vauthors = Anderson D | title = Narcolepsy: A clinical review | journal = JAAPA | volume = 34 | issue = 6 | pages = 20–25 | date = June 2021 | pmid = 34031309 | doi = 10.1097/01.JAA.0000750944.46705.36 | s2cid = 241205299 | doi-access = free | title-link = doi }}</ref> Modafinil is not a cure for narcolepsy, but it can help manage the symptoms. While modafinil is primarily used to treat excessive sleepiness, it may also help reduce the frequency and severity of cataplexy attacks in some people. Modafinil is approved for management of narcolepsy with or without cataplexy. However, it is not specifically approved for the treatment of cataplexy.<ref name="govuk-Modafinil Now restricted to narcolepsy"/><ref name="pmid28443381">{{cite journal |vauthors=Kallweit U, Bassetti CL |title=Pharmacological management of narcolepsy with and without cataplexy |journal=Expert Opin Pharmacother |volume=18 |issue=8 |pages=809–817 |date=June 2017 |pmid=28443381 |doi=10.1080/14656566.2017.1323877 |s2cid=1906751 }}</ref>

Modafinil is also prescribed for [[shift work sleep disorder]].<ref name="Provigil FDA label" />

Modafinil performs moderately (but better than [[armodafinil]] or [[solriamfetol]])<ref name="pmid39243682">{{cite journal |vauthors=Wang Y, Zhang W, Ye H, Xiao Y |title=Excessive daytime sleepiness in obstructive sleep apnea: Indirect treatment comparison of wake-promoting agents in patients adherent/nonadherent to primary OSA therapy |journal=Sleep Med Rev |volume=78 |issue= |pages=101997 |date=August 2024 |pmid=39243682 |doi=10.1016/j.smrv.2024.101997 |url=|doi-access=free }}</ref> as a drug to overcome [[excessive daytime sleepiness]] caused by [[obstructive sleep apnea]],<ref name="pmid38754208">{{cite journal |vauthors=Neshat SS, Heidari A, Henriquez-Beltran M, Patel K, Colaco B, Arunthari V, Lee Mateus AY, Cheung J, Labarca G |title=Evaluating pharmacological treatments for excessive daytime sleepiness in obstructive sleep apnea: A comprehensive network meta-analysis and systematic review |journal=Sleep Med Rev |volume=76 |issue= |pages=101934 |date=August 2024 |pmid=38754208 |doi=10.1016/j.smrv.2024.101934}}</ref> though it is recommended that people with apnea use [[continuous positive airway pressure]] (CPAP) therapy, that is a sleep breathing apparatus to prevent apnea, before starting modafinil.<ref name="Provigil FDA label" /><ref name="pmid32341841">{{cite journal | vauthors = Hashemian SM, Farhadi T | title = A review on modafinil: the characteristics, function, and use in critical care | journal = Journal of Drug Assessment | volume = 9 | issue = 1 | pages = 82–86 | date = 2020 | pmid = 32341841 | pmc = 7170336 | doi = 10.1080/21556660.2020.1745209 }}</ref><ref name="pmid18041479">{{cite journal | vauthors = Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, Brown T, Chesson AL, Kapur V, Maganti R, Owens J, Pancer J, Swick TJ, Zak R | title = Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report | journal = Sleep | volume = 30 | issue = 11 | pages = 1445–1459 | date = November 2007 | pmid = 18041479 | pmc = 2082098 | doi = 10.1093/sleep/30.11.1445 }}</ref> When obstructive sleep apnea is comorbid with narcolepsy, modafinil is an effective drug to reduce the associated excessive daytime sleepiness.<ref name="pmid39386319">{{cite journal |vauthors=Miano S, Kheirandish-Gozal L, De Pieri M |title=Comorbidity of obstructive sleep apnea and narcolepsy: A challenging diagnosis and complex management |journal=Sleep Med X |volume=8 |issue= |pages=100126 |date=December 2024 |pmid=39386319 |doi=10.1016/j.sleepx.2024.100126|pmc=11462365 }}</ref>

Modafinil's use varies by region. In the US, it is approved for adult narcolepsy, shift work sleep disorder, and obstructive sleep apnea, but not for children.<ref name="pmid30285371"/> In the UK and the EU, since 2014, it is approved solely for narcolepsy, including in children ([[pediatric narcolepsy]]), with its use for other conditions restricted by the European Medicines Agency.<ref name="govuk-Modafinil Now restricted to narcolepsy">{{cite web | url=https://www.gov.uk/drug-safety-update/modafinil-provigil-now-restricted-to-narcolepsy | title=Modafinil (Provigil): Now restricted to narcolepsy | work=[[Medicines and Healthcare products Regulatory Agency]] | access-date=December 2, 2023 | archive-date=December 15, 2023 | archive-url=https://web.archive.org/web/20231215212604/https://www.gov.uk/drug-safety-update/modafinil-provigil-now-restricted-to-narcolepsy | url-status=live }}</ref><ref name="Modafinil: Restricted use recommended">{{cite web | url=https://www.gov.uk/drug-safety-update/modafinil-restricted-use-recommended | title=Modafinil: Restricted use recommended | publisher=[[Medicines and Healthcare products Regulatory Agency]] | access-date=December 2, 2023 | archive-date=December 2, 2023 | archive-url=https://web.archive.org/web/20231202141511/https://www.gov.uk/drug-safety-update/modafinil-restricted-use-recommended | url-status=live }}</ref>

{{As of|2024|post=,}} both the French and the American Academy of Sleep Medicine strongly recommend modafinil as the first-choice treatment for narcolepsy.<ref name="pmid36921459">{{cite journal | vauthors = Arnulf I, Thomas R, Roy A, Dauvilliers Y | title = Update on the treatment of idiopathic hypersomnia: Progress, challenges, and expert opinion | journal = Sleep Medicine Reviews | volume = 69 | pages = 101766 | date = June 2023 | pmid = 36921459 | doi = 10.1016/j.smrv.2023.101766 | s2cid = 257214950 | doi-access = free | title-link = doi | url = https://hal.science/hal-04588723/document | access-date = July 13, 2024 | archive-date = August 6, 2024 | archive-url = https://web.archive.org/web/20240806000406/https://hal.science/hal-04588723/document | url-status = live }}</ref> In Europe, modafinil is considered one of the primary drugs recommended for treating narcolepsy according to the guidelines.<ref name="pmid37839272">{{cite journal |vauthors=Winter Y, Lang C, Kallweit U, Apel D, Fleischer V, Ellwardt E, Groppa S |title=Pitolisant-supported bridging during drug holidays to deal with tolerance to modafinil in patients with narcolepsy |journal=Sleep Med |volume=112 |pages=116–121 |date=December 2023 |pmid=37839272 |doi=10.1016/j.sleep.2023.10.005 |doi-access=free }}</ref>

====Multiple sclerosis-related fatigue====
The UK's [[National Institute for Health and Care Excellence]] (NICE), and the US's [[National Multiple Sclerosis Society]], endorsed the off-label use of modafinil to alleviate fatigue associated with MS in 2022.<ref name="The National Institute for Health and Care Excellence (NICE)-2022">{{cite web | url=https://www.nice.org.uk/guidance/ng220 | title=Multiple sclerosis in adults: Management, Guidance | publisher=The National Institute for Health and Care Excellence (NICE) | date=June 22, 2022 | access-date=September 5, 2022 | archive-date=September 5, 2022 | archive-url=https://web.archive.org/web/20220905191147/https://www.nice.org.uk/guidance/ng220 | url-status=live }}</ref><ref name="National Multiple Sclerosis Society">{{cite web |url=https://www.nationalmssociety.org/Treating-MS/Medications/Provigil |title=Provigil |publisher=National Multiple Sclerosis Society |access-date=September 6, 2022 |archive-date=September 5, 2022 |archive-url=https://web.archive.org/web/20220905191147/https://www.nationalmssociety.org/Treating-MS/Medications/Provigil |url-status=live }}</ref>

MS-related fatigue is a common and often debilitating symptom experienced by people with multiple sclerosis.<ref name="pmid35572947">{{cite journal |vauthors=Ayache SS, Serratrice N, Abi Lahoud GN, Chalah MA |title=Fatigue in Multiple Sclerosis: A Review of the Exploratory and Therapeutic Potential of Non-Invasive Brain Stimulation |journal=Front Neurol |volume=13 |pages=813965 |date=2022 |pmid=35572947 |pmc=9101483 |doi=10.3389/fneur.2022.813965 |doi-access=free }}</ref><ref name="pmid34856949">{{cite journal |vauthors=Oliva Ramirez A, Keenan A, Kalau O, Worthington E, Cohen L, Singh S |title=Prevalence and burden of multiple sclerosis-related fatigue: a systematic literature review |journal=BMC Neurol |volume=21 |issue=1 |pages=468 |date=December 2021 |pmid=34856949 |pmc=8638268 |doi=10.1186/s12883-021-02396-1 |doi-access=free }}</ref> It can significantly impact their daily functioning, [[quality of life]], and ability to perform everyday activities. When prescribed for MS-related fatigue management, modafinil works by promoting wakefulness and increasing [[alertness]] without causing drowsiness or disrupting nighttime sleep. People with multiple sclerosis often report increased energy levels, reduced feelings of tiredness, improved cognitive function, and an overall improvement in their quality of life when taking modafinil.<ref name="pmid38988104">{{cite journal |vauthors=Ghazanfar S, Farooq M, Qazi SU, Chaurasia B, Kaunzner U |title=The use of modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta-analysis of controlled clinical trials |journal=Brain Behav |volume=14 |issue=7 |pages=e3623 |date=July 2024 |pmid=38988104 |pmc=11237168 |doi=10.1002/brb3.3623 }}</ref> While modafinil can provide relief from MS-related fatigue symptoms,<ref name="pmid38988104"/> it does not treat the underlying cause or cure MS itself.

====Attention deficit hyperactivity disorder====
{{See also|Attention deficit hyperactivity disorder}}
Modafinil is occasionally prescribed [[off-label]] for individuals with attention deficit hyperactivity disorder (ADHD).<ref name="pmid31200137">{{cite journal | vauthors = Wilms W, Woźniak-Karczewska M, Corvini PF, Chrzanowski Ł | title = Nootropic drugs: Methylphenidate, modafinil and piracetam - Population use trends, occurrence in the environment, ecotoxicity and removal methods - A review | journal = Chemosphere | volume = 233 | pages = 771–785 | date = October 2019 | pmid = 31200137 | doi = 10.1016/j.chemosphere.2019.06.016 | s2cid = 189861826 | bibcode = 2019Chmsp.233..771W }}</ref><ref name="pmid33516734">{{cite journal | vauthors = Kittel-Schneider S, Quednow BB, Leutritz AL, McNeill RV, Reif A | title = Parental ADHD in pregnancy and the postpartum period - A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 124 | pages = 63–77 | date = May 2021 | pmid = 33516734 | doi = 10.1016/j.neubiorev.2021.01.002 | s2cid = 231723198 | url = https://www.zora.uzh.ch/id/eprint/198979/1/Kittel-Schneider_et_al_2021.pdf | access-date = October 19, 2023 | archive-date = October 21, 2023 | archive-url = https://web.archive.org/web/20231021234946/https://www.zora.uzh.ch/id/eprint/198979/1/Kittel-Schneider_et_al_2021.pdf | url-status = live }}</ref><ref name="pmid29952165">{{cite journal | vauthors = Weiergräber M, Ehninger D, Broich K | title = Neuroenhancement and mood enhancement – Physiological and pharmacodynamical background | journal = Medizinische Monatsschrift für Pharmazeuten | volume = 40 | issue = 4 | pages = 154–164 | date = April 2017 | pmid = 29952165 }}</ref> It has not consistently shown efficacy in treating adult ADHD,<ref name="pmid38433530">{{cite journal |vauthors=Miskowiak KW, Obel ZK, Guglielmo R, Bonnin CD, Bowie CR, Balanzá-Martínez V, Burdick KE, Carvalho AF, Dols A, Douglas K, Gallagher P, Kessing LV, Lafer B, Lewandowski KE, López-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes PR, Sumiyoshi T, Torres IJ, Van Rheenen TE, Yatham LN, Young AH, Vieta E, Hasler G |title=Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force |journal=Bipolar Disord |volume=26 |issue=3 |pages=216–239 |date=May 2024 |pmid=38433530 |doi=10.1111/bdi.13414|url=https://eprints.ncl.ac.uk/file_store/production/297410/28FECDCD-DACE-49B2-8260-46BED7B5094C.pdf }}</ref> especially when compared to other treatments such as [[lisdexamfetamine]].<ref name="pmid30117329">{{cite journal | vauthors = Stuhec M, Lukić P, Locatelli I | title = Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis | journal = The Annals of Pharmacotherapy | volume = 53 | issue = 2 | pages = 121–133 | date = February 2019 | pmid = 30117329 | doi = 10.1177/1060028018795703 | s2cid = 52019992 }}</ref><ref name="pmid26693882" /> In children, modafinil is more effective than placebo for treating ADHD symptoms.<ref name="pmid30097390">{{cite journal | vauthors = Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, Atkinson LZ, Tessari L, Banaschewski T, Coghill D, Hollis C, Simonoff E, Zuddas A, Barbui C, Purgato M, Steinhausen HC, Shokraneh F, Xia J, Cipriani A | title = Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis | journal = The Lancet. Psychiatry | volume = 5 | issue = 9 | pages = 727–738 | date = September 2018 | pmid = 30097390 | pmc = 6109107 | doi = 10.1016/S2215-0366(18)30269-4 }}</ref><ref name="pmid32845025">{{cite journal | vauthors = Rodrigues R, Lai MC, Beswick A, Gorman DA, Anagnostou E, Szatmari P, Anderson KK, Ameis SH | title = Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis | journal = Journal of Child Psychology and Psychiatry, and Allied Disciplines | volume = 62 | issue = 6 | pages = 680–700 | date = June 2021 | pmid = 32845025 | doi = 10.1111/jcpp.13305 | s2cid = 221329069 }}</ref>

Given its approved status in the US to treat narcolepsy, physicians can also prescribe modafinil for off-label uses, such as treating ADHD in both children and adults.<ref name="pmid16669720" /><ref name="pmid16623645">{{cite journal | vauthors = Turner D | title = A review of the use of modafinil for attention-deficit hyperactivity disorder | journal = Expert Review of Neurotherapeutics | volume = 6 | issue = 4 | pages = 455–468 | date = April 2006 | pmid = 16623645 | doi = 10.1586/14737175.6.4.455 | s2cid = 24293088 }}</ref><ref name="pmid16954326">{{cite journal | vauthors = Lindsay SE, Gudelsky GA, Heaton PC | title = Use of modafinil for the treatment of attention deficit/hyperactivity disorder | journal = The Annals of Pharmacotherapy | volume = 40 | issue = 10 | pages = 1829–1833 | date = October 2006 | pmid = 16954326 | doi = 10.1345/aph.1H024 | s2cid = 37368284 }}</ref>

The Canadian Network for Mood and Anxiety Treatments (CANMAT) suggests modafinil as a second-line treament for comorbid ADHD and [[bipolar disorder]], after first-line [[Management of attention deficit hyperactivity disorder#Stimulants|psychostimulants]] and the antidepressant [[bupropion]].<ref name="pmid22303520">{{cite journal | vauthors = Bond DJ, Hadjipavlou G, Lam RW, McIntyre RS, Beaulieu S, Schaffer A, Weiss M | title = The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder | journal = Annals of Clinical Psychiatry | volume = 24 | issue = 1 | pages = 23–37 | date = February 2012 | pmid = 22303520 }}</ref>

====Bipolar disorder====
{{See also|Bipolar disorder}}
Modafinil is used off-label as an [[adjunctive treatment]] (i.e., in combination therapy) for the acute depressive phase in bipolar disorder.<ref name=retz-2022>{{cite book|chapter=Efficacy of Amphetamines, Methylphenidate, and Modafinil in the Treatment of Mental Disorders|doi=10.1007/978-3-030-62059-2_319|vauthors=Retz W|title=NeuroPsychopharmacotherapy |date=2022 |pages=2465–2486 |isbn=978-3-030-62058-5 }}</ref><ref name="pmid22717304">{{cite journal |vauthors=Dell'Osso B, Ketter TA |title=Use of adjunctive stimulants in adult bipolar depression |journal=Int J Neuropsychopharmacol |volume=16 |issue=1 |pages=55–68 |date=February 2013 |pmid=22717304 |doi=10.1017/S1461145712000326 |hdl=2434/265768 |hdl-access=free }}</ref><ref name="pmid28144880"/><ref name="pmid30069121">{{cite journal |vauthors=Shen YC |title=Treatment of acute bipolar depression |journal=Ci Ji Yi Xue Za Zhi |volume=30 |issue=3 |pages=141–147 |date=2018 |pmid=30069121 |pmc=6047324 |doi=10.4103/tcmj.tcmj_71_18 |doi-access=free }}</ref> The depressive phase of [[bipolar disorder]] may feature excessive sleepiness and fatigue. Adjunctive treatment with modafinil can be used as an augmentation for the main treatment to increase its effect and is safe and effective, especially for people who do not respond well to standard antidepressants.<ref name="pmid31643130">{{cite journal | vauthors = Nunez NA, Singh B, Romo-Nava F, Joseph B, Veldic M, Cuellar-Barboza A, Cabello Arreola A, Vande Voort JL, Croarkin P, Moore KM, Biernacka J, McElroy SL, Frye MA | title = Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta-analysis of randomized controlled trials | journal = Bipolar Disorders | volume = 22 | issue = 2 | pages = 109–120 | date = March 2020 | pmid = 31643130 | doi = 10.1111/bdi.12859 | doi-access = free | title-link = doi }}</ref><ref name="pmid36561896">{{cite journal | vauthors = Elsayed OH, Ercis M, Pahwa M, Singh B | title = Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions | journal = Neuropsychiatric Disease and Treatment | volume = 18 | pages = 2927–2943 | date = 2022 | pmid = 36561896 | pmc = 9767030 | doi = 10.2147/NDT.S273503 | doi-access = free | title-link = doi }}</ref><ref name="pmid38433530"/> Modafinil does not significantly increase the risk of mood switch to mania or suicide attempts in people with bipolar disorder.<ref name="r2">{{cite web | url=https://www.proquest.com/openview/017f800499b0259521ea4ef8ccf503a8/1?pq-origsite=gscholar&cbl=5540454 | title=Modafinil in the treatment of selected mental disorders | website=[[ProQuest]] | access-date=February 14, 2024 | archive-date=February 14, 2024 | archive-url=https://web.archive.org/web/20240214153327/https://www.proquest.com/openview/017f800499b0259521ea4ef8ccf503a8/1?pq-origsite=gscholar&cbl=5540454 | url-status=live }}</ref><ref name="pmid31643130"/> Modafinil may also have cognitive benefits in people with bipolar disorder who are in a remission state.<ref name="pmid31951804">{{cite journal |vauthors=Sousa A, Dinis-Oliveira RJ |date=2020 |title=Article commentary: Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects |journal=Substance Abuse |volume=41 |issue=2 |pages=155–173 |doi=10.1080/08897077.2019.1700584 |pmid=31951804 |bibcode=2020JPkR...41..155S |s2cid=210709160}}</ref><ref name="r4">{{cite journal | doi=10.4088/JCP.19r12767 | title=The Potential Procognitive Effects of Modafinil in Major Depressive Disorder | date=2019 | journal=The Journal of Clinical Psychiatry | volume=80 | issue=6 | pmid=31599501 | s2cid=204028869 | vauthors=Vaccarino SR, McInerney SJ, Kennedy SH, Bhat V }}</ref><ref name="pmid38433530"/>

Whereas modafinil and armodafinil are approved for narcolepsy, they have been repurposed as [[adjunct therapy|adjunctive treatments]] to alleviate symptoms of acute depressive phase in people with bipolar disorder.<ref name="pmid34509090">{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | volume = 143 | pages = 230–238 | date = November 2021 | pmid = 34509090 | doi = 10.1016/j.jpsychires.2021.09.018 | s2cid = 237485915 }}</ref> Drug repurposing in psychiatry is a strategy for discovering new uses for drugs that have already been approved or tested in clinical trials for other illnesses. As such, drug repurposing is a rapid, cost-effective, and reduced-risk strategy for the development of new treatment options for psychiatric disorders.<ref name="pmid34509090"/> 2021 [[meta-analysis]] concluded that add-on modafinil and armodafinil were more effective than placebo on response to treatment, clinical remission, and reduction in depressive symptoms, with only minor side effects, but the effect sizes are small and the quality of evidence is therefore low, limiting the clinical relevance of the evidence.<ref name="pmid34509090"/><ref name="r6">{{cite journal | doi=10.1080/14656566.2023.2194488 | title=An update on potential pharmacotherapies for cognitive impairment in bipolar disorder | date=2023 | journal=Expert Opinion on Pharmacotherapy | volume=24 | issue=5 | pages=641–654 | pmid=36946229 | s2cid=257665446 | vauthors=Johnson DE, McIntyre RS, Mansur RB, Rosenblat JD }}</ref> Very low rates of mood swing (a change in mood from one extreme to another)<ref name="r2"/><ref name="pmid20492846">{{cite journal | vauthors = Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, Zarate CA | title = The neurobiology of the switch process in bipolar disorder: a review | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 11 | pages = 1488–1501 | date = November 2010 | pmid = 20492846 | pmc = 3000635 | doi = 10.4088/JCP.09r05259gre }}</ref> have been observed with modafinil and armodafinil in depressive phase of bipolar disorder.<ref name="pmid28144880">{{cite journal | vauthors = Perugi G, Vannucchi G, Bedani F, Favaretto E | title = Use of Stimulants in Bipolar Disorder | journal = Current Psychiatry Reports | volume = 19 | issue = 1 | pages = 7 | date = January 2017 | pmid = 28144880 | doi = 10.1007/s11920-017-0758-x | s2cid = 2932701 }}</ref><ref name="pmid25295426" />

===Occupational===
{{See also|List of psychoactive drugs used by militaries}}

Modafinil was used during the [[Gulf War]] by the [[French Foreign Legion]],<ref name="pmid30174215" /> the [[United States Air Force|US Air Force]],<ref name="pmid34632515">{{cite journal | vauthors = Van Puyvelde M, Van Cutsem J, Lacroix E, Pattyn N | title = A State-of-the-Art Review on the Use of Modafinil as a Performance-enhancing Drug in the Context of Military Operationality | journal = Military Medicine | volume = 187 | issue = 1–2 | pages = 52–64 | date = January 2022 | pmid = 34632515 | doi = 10.1093/milmed/usab398 | doi-access = free | title-link = doi }}</ref><ref name="Brunye-2020">{{cite journal|vauthors=Brunyé TT, Brou R, Doty TJ|title=A Review of US Army Research Contributing to Cognitive Enhancement in Military Contexts|journal=J Cogn Enhanc|volume=4 |issue= 4|pages=453–468|year=2020|doi=10.1007/s41465-020-00167-3|s2cid=256621326 }}</ref> and [[United States Marine Corps|US Marine]]<ref name="Go Pills for Black Shoes?">{{cite journal | vauthors = Gonzalez J | url = https://www.usni.org/magazines/proceedings/2017/july/go-pills-black-shoes | title = Go Pills for Black Shoes? | journal = U.S. Naval Institute Proceedings | date = July 2017 | volume = 143 | issue = 7/1,373 | access-date = December 3, 2023 | archive-date = December 3, 2023 | archive-url = https://web.archive.org/web/20231203140637/https://www.usni.org/magazines/proceedings/2017/july/go-pills-black-shoes | url-status = live }}</ref> infantry to enhance "operational tempo" (a term that denotes the speed and intensity at which military operations or activities are executed), aiming to optimize the overall performance and efficiency of the units.<ref name="Brunye-2020" /><ref name="pmid16018329">{{cite journal | vauthors = Caldwell JA, Caldwell JL | title = Fatigue in military aviation: an overview of US military-approved pharmacological countermeasures | journal = Aviation, Space, and Environmental Medicine | volume = 76 | issue = 7 Suppl | pages = C39–C51 | date = July 2005 | pmid = 16018329 }}</ref><ref name="guardian2004">{{cite news | url=https://www.theguardian.com/society/2004/jul/29/health.sciencenews | title=MoD bought thousands of stay awake pills in advance of war in Iraq | newspaper=[[The Guardian]] | date=July 29, 2004 | vauthors=Sample I, Evans R | access-date=December 2, 2023 | archive-date=December 2, 2023 | archive-url=https://web.archive.org/web/20231202042216/https://www.theguardian.com/society/2004/jul/29/health.sciencenews | url-status=live }}</ref>

Armed forces in various countries, including the United States, the United Kingdom, India, and France, have considered modafinil as an alternative to traditional [[Substituted amphetamine|amphetamines]] for managing sleep deprivation in combat or extended missions.<ref name="Martin-2003">{{cite magazine|url=https://www.wired.com/2003/11/sleep/|title=It's Wake-Up Time|vauthors=Martin R|date=November 1, 2003|magazine=Wired|access-date=May 23, 2019|issn=1059-1028|archive-date=October 17, 2020|archive-url=https://web.archive.org/web/20201017212750/https://www.wired.com/2003/11/sleep/|url-status=live}}</ref> The US military approved modafinil for specific Air Force missions, replacing amphetamines for fatigue management.<ref name="Air Force Special Operations Command Instruction 48–101-2012">{{cite web | title = Air Force Special Operations Command Instruction 48–101 | archive-url = https://web.archive.org/web/20180410202141/http://static.e-publishing.af.mil/production/1/afsoc/publication/afi11-202v3_afsocsup/afi11-202v3_afsocsup.pdf | archive-date= April 10, 2018 | quote = (sects. 1.7.4), U.S. Air Force Special Operations Command | date = November 30, 2012 | url = http://static.e-publishing.af.mil/production/1/afsoc/publication/afi11-202v3_afsocsup/afi11-202v3_afsocsup.pdf }}</ref> The use of modafinil in military contexts without sleep deprivation is not recommended due to inconclusive evidence on its cognitive enhancement benefits and potential risks of adverse effects.<ref name="pmid34632515" />

Modafinil is also available to astronauts aboard the International Space Station for the management of fatigue caused by circadian dyssynchrony in orbit.<ref name="pmid19487390">{{cite journal | vauthors = Thirsk R, Kuipers A, Mukai C, Williams D | title = The space-flight environment: the International Space Station and beyond | journal = CMAJ | volume = 180 | issue = 12 | pages = 1216–1220 | date = June 2009 | pmid = 19487390 | pmc = 2691437 | doi = 10.1503/cmaj.081125 }}</ref>

===Non-medical===

Modafinil has been used non-medically as a "smart drug"<ref name="economist-2008-05-22">{{cite news |vauthors=Slotnik DE |title=Smart drugs |newspaper=[[The Economist]] |url=https://www.economist.com/leaders/2008/05/22/smart-drugs |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203141554/https://www.economist.com/leaders/2008/05/22/smart-drugs |url-status=live }}</ref><ref name="Slotnik-2017">{{cite news |vauthors=Slotnik DE |date=October 11, 2017 |title=Michel Jouvet, Who Unlocked REM Sleep's Secrets, Dies at 91 |work=[[The New York Times]] |url=https://www.nytimes.com/2017/10/11/obituaries/michel-jouvet-who-unlocked-rem-sleeps-secrets-dies-at-91.html |access-date=December 3, 2023 |issn=0362-4331 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203143118/https://www.nytimes.com/2017/10/11/obituaries/michel-jouvet-who-unlocked-rem-sleeps-secrets-dies-at-91.html |url-status=live }}</ref> by various groups, including students,<ref name="Cadwalladr-2015">{{cite news|vauthors=Cadwalladr C|title=Students used to take drugs to get high. Now they take them to get higher grades|url=https://www.theguardian.com/society/2015/feb/15/students-smart-drugs-higher-grades-adderall-modafinil|newspaper=[[The Guardian]]|date=February 14, 2015|access-date=January 7, 2017|archive-date=August 3, 2020|archive-url=https://web.archive.org/web/20200803132607/https://www.theguardian.com/society/2015/feb/15/students-smart-drugs-higher-grades-adderall-modafinil|url-status=live}}</ref><ref name="The Economist - The Drug Does Work">{{cite news |vauthors=Cumming E |date=November 3, 2009 |title=The drug does work |newspaper=[[The Economist]] |url=https://www.economist.com/1843/2009/11/03/the-drug-does-work |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203141443/https://www.economist.com/1843/2009/11/03/the-drug-does-work |url-status=live }}</ref><ref name="The Independent-2017">{{cite news|date=May 30, 2017 |title=Professors are taking the same 'smart drugs' as students to keep up with workloads |url=https://www.independent.co.uk/news/education/education-news/professor-smart-drugs-modafinil-noopept-students-workloads-university-research-teaching-academic-cambridge-a7763041.html |access-date=January 17, 2023 |website=The Independent |archive-date=December 7, 2022 |archive-url=https://web.archive.org/web/20221207055128/http://www.independent.co.uk/news/education/education-news/professor-smart-drugs-modafinil-noopept-students-workloads-university-research-teaching-academic-cambridge-a7763041.html |url-status=live }}</ref> office workers, [[transhumanist]]s,<ref name="Talbot - Brain Gain">{{cite magazine|vauthors=Talbot M|title=Brain Gain|url=http://www.newyorker.com/magazine/2009/04/27/brain-gain|magazine=[[The New Yorker]]|access-date=April 9, 2017|archive-date=August 19, 2020|archive-url=https://web.archive.org/web/20200819222934/https://www.newyorker.com/magazine/2009/04/27/brain-gain|url-status=live}}</ref><ref name="The Economist - Toward Immortality">{{cite news |title=Towards immortality |date=November 16, 2006 |newspaper=[[The Economist]] |url=https://www.economist.com/news/2006/11/16/towards-immortality |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203142303/https://www.economist.com/news/2006/11/16/towards-immortality |url-status=live }}</ref> and professionals in various sectors. Its use is attributed by these individuals to its potential for enhancing attention, cognitive capabilities, and [[alertness]].<ref name="pmid34382572">{{cite journal | vauthors = Van Rooyen LR, Gihwala R, Laher AE | title = Stimulant use among prehospital emergency care personnel in Gauteng Province, South Africa | journal = South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde | volume = 111 | issue = 6 | pages = 587–590 | date = May 2021 | pmid = 34382572 | doi = 10.7196/SAMJ.2021.v111i6.15465 | s2cid = 236402826 | doi-access = free | title-link = doi | doi-broken-date = November 1, 2024 }}</ref><ref name="The Economist - Supercharging the brain">{{cite news |title=Supercharging the brain |newspaper=[[The Economist]] |date=September 18, 2004 |url=https://www.economist.com/technology-quarterly/2004/09/18/supercharging-the-brain |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203143124/https://www.economist.com/technology-quarterly/2004/09/18/supercharging-the-brain |url-status=live }}</ref>

The effectiveness of modafinil as a cognitive enhancer is still debated. Some studies suggest significant increases in cognitive abilities, while others indicate mild to nonexistent cognitive improvements.<ref name="pmid17712350"/><ref name="pmid12417966">{{cite journal | vauthors = Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ | title = Cognitive enhancing effects of modafinil in healthy volunteers | journal = Psychopharmacology | volume = 165 | issue = 3 | pages = 260–269 | date = January 2003 | pmid = 12417966 | doi = 10.1007/s00213-002-1250-8 }}</ref><ref name=retz-2022/><ref name="pmid16142993">{{cite journal |vauthors=Keating GM, Raffin MJ | title=Modafinil: a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder | journal=CNS Drugs | volume=19 |issue=9 |pages=785–803 |date=2005 |pmid=16142993 |doi=10.2165/00023210-200519090-00005 |s2cid=43733424 }}</ref> In some cases, it has even been associated with impairments in certain cognitive functions.<ref name="pmid36056861">{{cite journal | vauthors = Zamanian MY, Karimvandi MN, Nikbakhtzadeh M, Zahedi E, Bokov DO, Kujawska M, Heidari M, Rahmani MR | title = Effects of Modafinil (Provigil) on Memory and Learning in Experimental and Clinical Studies: From Molecular Mechanisms to Behaviour Molecular Mechanisms and Behavioural Effects | journal = Current Molecular Pharmacology | volume = 16 | issue = 4 | pages = 507–516 | date = 2023 | pmid = 36056861 | doi = 10.2174/1874467215666220901122824 | s2cid = 252046371 }}</ref><ref name="pmid32341841" /><ref name="Meulen-2017">{{cite book | vauthors = Meulen R, Hall W, Mohammed A |title=Rethinking Cognitive Enhancement |date=2017 |publisher=Oxford University Press |isbn=978-0-19-872739-2 |page=116 |url=https://books.google.com/books?id=aAIXDgAAQBAJ&pg=PA116 }}</ref> It has been shown that modafinil's positive impact on cognitive abilities is more noticeable on sleep-deprived individuals.<ref name="pmid26381811">{{cite journal | vauthors = Battleday RM, Brem AK | title = Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review | journal = European Neuropsychopharmacology | volume = 25 | issue = 11 | pages = 1865–1881 | date = November 2015 | pmid = 26381811 | doi = 10.1016/j.euroneuro.2015.07.028 | s2cid = 23319688 }}</ref> Therefore, in people who are not sleep-deprived, the potential of modafinil as a cognitive enhancer may be limited.<ref name="pmid35366192">{{cite journal |vauthors=Schifano F, Catalani V, Sharif S, Napoletano F, Corkery JM, Arillotta D, Fergus S, Vento A, Guirguis A |title=Benefits and Harms of 'Smart Drugs' (Nootropics) in Healthy Individuals |journal=Drugs |volume=82 |issue=6 |pages=633–647 |date=April 2022 |pmid=35366192 |doi=10.1007/s40265-022-01701-7 |hdl=2299/25614 |s2cid=247860331 |hdl-access=free }}</ref>