Editing Modafinil (section)

==Research==
===Psychiatric conditions===
====Major depressive disorder====
Modafinil has been studied in the treatment of [[major depressive disorder]].<ref name="pmid28318897">{{cite journal | vauthors = Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S | title = Efficacy of off-label augmentation in unipolar depression: A systematic review of the evidence | journal = European Neuropsychopharmacology | volume = 27 | issue = 5 | pages = 423–441 | date = May 2017 | pmid = 28318897 | doi = 10.1016/j.euroneuro.2017.03.003 | s2cid = 3740987 }}</ref><ref name="pmid28590365">{{cite journal | vauthors = McIntyre RS, Lee Y, Zhou AJ, Rosenblat JD, Peters EM, Lam RW, Kennedy SH, Rong C, Jerrell JM | title = The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis | journal = Journal of Clinical Psychopharmacology | volume = 37 | issue = 4 | pages = 412–418 | date = August 2017 | pmid = 28590365 | doi = 10.1097/JCP.0000000000000723 | s2cid = 27622964 }}</ref><ref name="pmid34144366">{{cite journal | vauthors = Bahji A, Mesbah-Oskui L | title = Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis | journal = Journal of Affective Disorders | volume = 292 | pages = 416–423 | date = September 2021 | pmid = 34144366 | doi = 10.1016/j.jad.2021.05.119 }}</ref> In a 2021 [[systematic review]] and meta-analysis of [[randomized controlled trial]]s of [[psychostimulant]]s for depression, modafinil and other stimulants such as [[methylphenidate]] and amphetamines improved depression in traditional meta-analysis.<ref name="pmid34144366" /> However, when subjected to [[network meta-analysis]], modafinil and most other stimulants did not significantly improve depression, with only methylphenidate remaining effective.<ref name="pmid34144366" /> Modafinil and other stimulants likewise did not improve [[quality of life]] in the meta-analysis, although there was evidence for reduced fatigue and sleepiness with modafinil and other stimulants.<ref name="pmid34144366" /> While significant effectiveness of modafinil for depression has been reported by particular trials,<ref name="pmid25295426">{{cite journal | vauthors = Corp SA, Gitlin MJ, Altshuler LL | title = A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder | journal = The Journal of Clinical Psychiatry | volume = 75 | issue = 9 | pages = 1010–1018 | date = September 2014 | pmid = 25295426 | doi = 10.4088/JCP.13r08851 }}</ref><ref name="pmid28590365" /><ref name="pmid24330897">{{cite journal | vauthors = Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH | title = Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials | journal = The Journal of Clinical Psychiatry | volume = 74 | issue = 11 | pages = 1101–1107 | date = November 2013 | pmid = 24330897 | doi = 10.4088/JCP.13r08560 }}</ref> reviews and meta-analyses note that the effectiveness of modafinil for depression is limited, the quality of available evidence is low, and the results are inconclusive.<ref name="pmid34144366" /><ref name="pmid26906078">{{cite journal | vauthors = Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G | title = Stimulants for depression: On the up and up? | journal = The Australian and New Zealand Journal of Psychiatry | volume = 50 | issue = 3 | pages = 203–207 | date = March 2016 | pmid = 26906078 | doi = 10.1177/0004867416634208 | s2cid = 45341424 }}</ref><ref name="pmid35174594">{{cite journal | vauthors = Miskowiak KW, Seeberg I, Jensen MB, Balanzá-Martínez V, Del Mar Bonnin C, Bowie CR, Carvalho AF, Dols A, Douglas K, Gallagher P, Hasler G, Lafer B, Lewandowski KE, López-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes P, Sumiyoshi T, Torres IJ, Van Rheenen TE, Yatham LN, Young AH, Kessing LV, Burdick KE, Vieta E | title = Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force | journal = Bipolar Disorders | volume = 24 | issue = 4 | pages = 354–374 | date = June 2022 | pmid = 35174594 | pmc = 9541874 | doi = 10.1111/bdi.13193 }}</ref>

====Attention deficit hyperactivity disorder (research)==== <!-- This "(research)" in the heading is not redundant, it is used to distinguish between the same topic in the uses section, and is used as a wikilink target. -->
Modafinil was considered for the treatment of ADHD because of its lower [[abuse potential]] than conventional psychostimulants<ref name="pmid38725665"/> like methylphenidate and amphetamines.<ref name="pmid16623645" /><ref name="pmid27810669">{{cite journal | vauthors = Wang SM, Han C, Lee SJ, Jun TY, Patkar AA, Masand PS, Pae CU | title = Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis | journal = Journal of Psychiatric Research | volume = 84 | pages = 292–300 | date = January 2017 | pmid = 27810669 | doi = 10.1016/j.jpsychires.2016.09.034 }}</ref> In 2008, an application to market modafinil for pediatric ADHD was submitted to the [[Food and Drug Administration]] in the US.<ref name="pmid18729534">{{cite journal | vauthors = Kumar R | title = Approved and Investigational Uses of Modafinil | journal = Drugs | volume = 68 | issue = 13 | pages = 1803–1839 | year = 2008 | pmid = 18729534 | doi = 10.2165/00003495-200868130-00003 | s2cid = 38542387 }}</ref><ref name="pmid38433530"/>

However, evidence of modafinil for treatment of adult ADHD is mixed, and a 2016 systematic review of alternative drug therapies for adult ADHD did not recommend its use in this context.<ref name="pmid26693882">{{cite journal | vauthors = Buoli M, Serati M, Cahn W | title = Alternative pharmacological strategies for adult ADHD treatment: a systematic review | journal = Expert Review of Neurotherapeutics | volume = 16 | issue = 2 | pages = 131–144 | date = 2016 | pmid = 26693882 | doi = 10.1586/14737175.2016.1135735 | s2cid = 33004517 }}</ref> In a later large [[Phase III trial|phase&nbsp;3]] clinical trial of modafinil for adult ADHD, modafinil was not effective in improving symptoms, there was also a high rate of side effects (86%) and discontinuation (47%).<ref name="pmid30453134">{{cite journal | vauthors = Kooij JJ, Bijlenga D, Salerno L, Jaeschke R, Bitter I, Balázs J, Thome J, Dom G, Kasper S, Nunes Filipe C, Stes S, Mohr P, Leppämäki S, Casas M, Bobes J, Mccarthy JM, Richarte V, Kjems Philipsen A, Pehlivanidis A, Niemela A, Styr B, Semerci B, Bolea-Alamanac B, Edvinsson D, Baeyens D, Wynchank D, Sobanski E, Philipsen A, McNicholas F, Caci H, Mihailescu I, Manor I, Dobrescu I, Saito T, Krause J, Fayyad J, Ramos-Quiroga JA, Foeken K, Rad F, Adamou M, Ohlmeier M, Fitzgerald M, Gill M, Lensing M, Motavalli Mukaddes N, Brudkiewicz P, Gustafsson P, Tani P, Oswald P, Carpentier PJ, De Rossi P, Delorme R, Markovska Simoska S, Pallanti S, Young S, Bejerot S, Lehtonen T, Kustow J, Müller-Sedgwick U, Hirvikoski T, Pironti V, Ginsberg Y, Félegyházy Z, Garcia-Portilla MP, Asherson P | title = Updated European Consensus Statement on diagnosis and treatment of adult ADHD | journal = European Psychiatry | volume = 56 | pages = 14–34 | date = February 2019 | pmid = 30453134 | doi = 10.1016/j.eurpsy.2018.11.001 | s2cid = 53714228 | doi-access = free | title-link = doi | hdl = 10651/51910 | hdl-access = free }}</ref> The poor [[tolerability]] of modafinil in this study was possibly due to the use of high doses ({{Val|210|-|510|u=mg/day}}).<ref name="pmid30453134" /> Another reason for the denial of the approval was due to concerns about rare but serious dermatological toxicity in [[Stevens–Johnson syndrome]].<ref name="pmid18729534" />

The research on the use of modafinil for treating individuals with Autism Spectrum Disorder (ASD) who also exhibit ADHD symptoms is currently in its early stages with no results delivered.<ref name="pmid39004333">{{cite journal |vauthors=Martins PL, Torquato GC, Dias GA, Leite IB, Gaspar TM, Pinto JP, Macedo DS |title=Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis |journal=Prog Neuropsychopharmacol Biol Psychiatry |volume=134 |issue= |pages=111089 |date=August 2024 |pmid=39004333 |doi=10.1016/j.pnpbp.2024.111089 |url=}}</ref>

====Substance dependence====
Modafinil was studied for the treatment of [[stimulant dependence]], but the results are mixed and inconclusive.<ref name="pmid32927246"/><ref name="pmid34121988">{{cite journal | vauthors = Hersey M, Bacon AK, Bailey LG, Coggiano MA, Newman AH, Leggio L, Tanda G | title = Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap? | journal = Frontiers in Neuroscience | volume = 15 | pages = 656475 | date = 2021 | pmid = 34121988 | pmc = 8187604 | doi = 10.3389/fnins.2021.656475 | doi-access = free | title-link = doi }}</ref> Modafinil is not a [[controlled substance]] in some countries, unlike other medications, such as [[bupropion]], which is also used to treat [[Major depressive disorder|depression]] and [[nicotine dependence]].<ref name="pmid32601988">{{cite journal | vauthors = Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM | title = Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis | journal = Psychopharmacology | location = Berlin | volume = 237 | issue = 8 | pages = 2233–2255 | date = August 2020 | pmid = 32601988 | doi = 10.1007/s00213-020-05563-3 | s2cid = 220150476 }}</ref> The clinical trials that have tested modafinil as a treatment for stimulant abuse have failed to demonstrate its efficacy and the optimal dose and duration of modafinil treatment remain unclear, and modafinil is not a recommended treatment for stimulant abuse.<ref name="pmid32601988"/> 2024 reviews found that modafinil was ineffective for treating individuals with [[amphetamine dependence|amphetamine-type stimulant use disorder]]<ref name="ElkriefSharafiBakouni2024"/> or [[methamphetamine use disorder]]<ref name="pmid39228432">{{cite journal |vauthors=Yates JR |title=Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets |journal=Subst Abuse Rehabil |volume=15 |issue= |pages=125–161 |date=2024 |pmid=39228432 |pmc=11370775 |doi=10.2147/SAR.S431273|doi-access=free }}</ref> from these dependencies.<ref name="pmid39228432"/><ref name="ElkriefSharafiBakouni2024">{{cite journal | vauthors = Elkrief L, Sharafi H, Bakouni H, McAnulty C, Bastien G, Dubreucq S, Garel N, Trépanier A, Ziegler D, Jutras-Aswad D | title = Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials | journal = The Canadian Journal of Psychiatry | date = July 2024 | volume = 69 | issue = 11 | pages = 793–805 | pmid = 39033427 | doi = 10.1177/07067437241262967 | pmc = 11572177 }}</ref>

====Schizophrenia====
Modafinil and armodafinil were studied as a complement to [[antipsychotic]] medications in the treatment of [[schizophrenia]]. They showed no effect on positive symptoms or cognitive performance.<ref name="pmid20816042">{{cite journal | vauthors = Kane JM, D'Souza DC, Patkar AA, Youakim JM, Tiller JM, Yang R, Keefe RS | title = Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 11 | pages = 1475–1481 | date = November 2010 | pmid = 20816042 | doi = 10.4088/jcp.09m05950gry }}</ref><ref name="pmid25306261" /> A 2015 [[meta-analysis]] found that modafinil and armodafinil may slightly reduce negative symptoms in people with acute schizophrenia, though they do not appear useful for people with the condition who are stable, with high negative symptom scores.<ref name="pmid25306261">{{cite journal | vauthors = Andrade C, Kisely S, Monteiro I, Rao S | title = Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials | journal = Journal of Psychiatric Research | volume = 60 | pages = 14–21 | date = January 2015 | pmid = 25306261 | doi = 10.1016/j.jpsychires.2014.09.013 | url = https://espace.library.uq.edu.au/view/UQ:345290/UQ345290_OA.pdf }}</ref> Among medications demonstrated to be effective for reducing negative symptoms in combination with antipsychotics, modafinil, and armodafinil are among the smallest [[effect size]]s.<ref name="pmid28514486">{{cite journal | vauthors = Correll CU, Rubio JM, Inczedy-Farkas G, Birnbaum ML, Kane JM, Leucht S | title = Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the Meta-analytic Evidence | journal = JAMA Psychiatry | volume = 74 | issue = 7 | pages = 675–684 | date = July 2017 | pmid = 28514486 | pmc = 6584320 | doi = 10.1001/jamapsychiatry.2017.0624 }}</ref>

====Abstinence in cocaine addiction====
Modafinil is researched to determine whether it might improve abstinence in people with [[cocaine addiction]].<ref name="pmid28350194">{{cite journal | vauthors = Sangroula D, Motiwala F, Wagle B, Shah VC, Hagi K, Lippmann S | title = Modafinil Treatment of Cocaine Dependence: A Systematic Review and Meta-Analysis | journal = Substance Use & Misuse | volume = 52 | issue = 10 | pages = 1292–1306 | date = August 2017 | pmid = 28350194 | doi = 10.1080/10826084.2016.1276597 | s2cid = 4775658 }}</ref>

====Motivational disorders====
Modafinil has been found to reverse [[tetrabenazine]]-induced [[motivational disorder|motivational deficit]]s in animals and hence can produce [[pro-motivational agent|pro-motivational]] effects.<ref name="SalamoneCorrea2024">{{cite journal | vauthors = Salamone JD, Correa M | title = The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine | journal = Annu Rev Psychol | volume = 75 | issue = | pages = 1–32 | date = January 2024 | pmid = 37788571 | doi = 10.1146/annurev-psych-020223-012208 | url = | hdl = 10234/207207 | hdl-access = free }}</ref><ref name="SalamoneYohnLópez-Cruz2016">{{cite journal | vauthors = Salamone JD, Yohn SE, López-Cruz L, San Miguel N, Correa M | title = Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology | journal = Brain | volume = 139 | issue = Pt 5 | pages = 1325–1347 | date = May 2016 | pmid = 27189581 | pmc = 5839596 | doi = 10.1093/brain/aww050 | url = }}</ref><ref name="YohnGogojHaque2016">{{cite journal | vauthors = Yohn SE, Gogoj A, Haque A, Lopez-Cruz L, Haley A, Huxley P, Baskin P, Correa M, Salamone JD | title = Evaluation of the effort-related motivational effects of the novel dopamine uptake inhibitor PRX-14040 | journal = Pharmacol Biochem Behav | volume = 148 | issue = | pages = 84–91 | date = September 2016 | pmid = 27296079 | doi = 10.1016/j.pbb.2016.06.004 | url = }}</ref> Novel modafinil [[structural analog|analog]]s with greater [[potency (pharmacology)|potency]], including [[CE-123]], [[CE-158]], [[JJC8-088]], [[(S)-MK-26|MK-26]], and [[RDS03-94]], have also been developed and have shown pro-motivational effects in animals.<ref name="SalamoneCorrea2024" /><ref name="EcevitogluMekaRotolo2024">{{cite journal | vauthors = Ecevitoglu A, Meka N, Rotolo RA, Edelstein GA, Srinath S, Beard KR, Carratala-Ros C, Presby RE, Cao J, Okorom A, Newman AH, Correa M, Salamone JD | title = Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors | journal = Neuropsychopharmacology | volume = 49 | issue = 8 | pages = 1309–1317 | date = July 2024 | pmid = 38429498 | doi = 10.1038/s41386-024-01826-1 | pmc = 11224370 | pmc-embargo-date = July 1, 2025 | url = }}</ref> These agents are of potential interest in the treatment of [[motivational disorder]]s in humans.<ref name="SalamoneCorrea2024" /><ref name="EcevitogluMekaRotolo2024" />

===Cognitive enhancement===
A 2019 review conducted on the potential nootropic effects of modafinil in healthy, non-sleep-deprived individuals revealed the following:<ref name="pmid31433334">{{cite journal | vauthors = Kredlow MA, Keshishian A, Oppenheimer S, Otto MW | title = The Efficacy of Modafinil as a Cognitive Enhancer: A Systematic Review and Meta-Analysis | journal = Journal of Clinical Psychopharmacology | volume = 39 | issue = 5 | pages = 455–461 | date = 2019 | pmid = 31433334 | doi = 10.1097/JCP.0000000000001085 | s2cid = 201119084 }}</ref> a) while studies using basic testing paradigms demonstrated that modafinil enhances [[executive function]], only half of these studies showed improvements in attention, learning, and memory, with a few studies even reporting impairments in divergent creative thinking; b) modafinil displayed small levels of enhancement in attention, executive functions, and learning abilities; c) no substantial side effects or mood changes were observed; d) the available evidence showed limited evidence for modafinil as a cognitive enhancer outside of its use for sleep-deprived populations.

A 2020 review reported that modafinil has a modest effect on memory updating, but the effect is small and may not accurately reflect the perception that it is useful as a cognitive enhancer, as there is insufficient evidence to support such a claim.<ref name="pmid32709551">{{cite journal | vauthors = Roberts CA, Jones A, Sumnall H, Gage SH, Montgomery C | title = How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine | journal = European Neuropsychopharmacology | volume = 38 | pages = 40–62 | date = September 2020 | pmid = 32709551 | doi = 10.1016/j.euroneuro.2020.07.002 | url = https://researchonline.ljmu.ac.uk/id/eprint/13268/8/How%20effective%20are%20pharmaceuticals%20for%20cognitive%20enhancement%20in%20healthy%20adults%20A%20series%20of%20meta-analyses%20of%20cognitive%20performance%20during%20acute%20administration%20of%20modafinil%2C%20methylphenidate%20and%20d-amphetamine..pdf | url-status = live | s2cid = 220651670 | archive-url = https://web.archive.org/web/20220220101717/https://researchonline.ljmu.ac.uk/id/eprint/13268/8/How%20effective%20are%20pharmaceuticals%20for%20cognitive%20enhancement%20in%20healthy%20adults%20A%20series%20of%20meta-analyses%20of%20cognitive%20performance%20during%20acute%20administration%20of%20modafinil%2C%20methylphenidate%20and%20d-amphetamine..pdf | archive-date = February 20, 2022 }}</ref>

===Post-anesthesia sedation===
[[General anesthesia]] is required for many [[surgery|surgeries]], but may cause lingering fatigue, sedation, and/or drowsiness after surgery that lasts for hours to days.<ref name="Behar-2007">{{cite journal| doi=10.1136/sbmj.070256 | title=Anaesthesia: Induction and maintenance of general anesthesia | date=2007 | journal=BMJ | volume=334 | vauthors = Behar JM, Gogalniceanu P, Bromley L }}</ref><ref name="pmid34338712">{{cite journal |vauthors=Vacas S, Cole DJ, Cannesson M |title=Cognitive Decline Associated With Anesthesia and Surgery in Older Patients |journal=JAMA |date=August 2021 |volume=326 |issue=9 |page=863 |pmid=34338712 |pmc=8807795 |doi=10.1001/jama.2021.4773}}</ref> In [[outpatient surgery]] the [[sedation]], [[fatigue]], and occasional [[dizziness]] is problematic.<ref name="pmid12411816">{{cite journal|doi=10.1097/00000542-200211000-00035 |title=Fatigue in Anesthesia |date=2002 |journal=Anesthesiology |volume=97 |issue=5 |pages=1281–1294 |pmid=12411816 | vauthors = Warltier DC, Howard SK, Rosekind MR, Katz JD, Berry AJ }}</ref><ref name="pmid11964610">{{cite journal|doi=10.1097/00000542-200204000-00030 |title=Systematic Review and Analysis of Postdischarge Symptoms after Outpatient Surgery |date=2002 |journal=Anesthesiology |volume=96 |issue=4 |pages=994–1003 |pmid=11964610 | vauthors = Wu CL, Berenholtz SM, Pronovost PJ, Fleisher LA }}</ref> Modafinil was tested as a potential remedy to alleviate these symptoms.<ref name="pmid16669720"/> For example, it was expected that modafinil would help people recover quicker from general anesthesia after a short surgery,<ref name="pmid18729534"/> but the results were uncertain and the inconclusive studies could not reliably verify the expectation.<ref name="pmid16669720">{{cite journal | vauthors = Ballon JS, Feifel D | title = A systematic review of modafinil: Potential clinical uses and mechanisms of action | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = 4 | pages = 554–566 | date = April 2006 | pmid = 16669720 | doi = 10.4088/jcp.v67n0406 }}</ref> The use of modafinil to relieve post-anesthesia sedation is investigational.<ref name="pmid18729534"/>

===Postural orthostatic tachycardia syndrome===
Caution should be exercised in people who have narcolepsy in [[comorbidity]] with [[postural orthostatic tachycardia syndrome]] (POTS).<ref name="pmid16943900">{{cite journal |vauthors=Raj SR |title=The Postural Tachycardia Syndrome (POTS): pathophysiology, diagnosis & management |journal=Indian Pacing Electrophysiol J |volume=6 |issue=2 |pages=84–99 |date=April 2006 |pmid=16943900 |pmc=1501099}}</ref>

===Myotonic dystrophy===
Modafinil is being researched as a potential remedy for excessive daytime sleepiness in [[myotonic dystrophy]] (DM), an inherited condition characterized by progressive muscle loss, weakness, and [[myotonia.]] Myotonia is a condition where muscles cannot relax after they contract.<ref name="pmid39011358">{{cite journal |vauthors=Hoxhaj D, Pascazio A, Maestri M, Ricci G, Fabbrini M, Torresi FB, Siciliano G, Bonanni E |title=Excessive daytime sleepiness in myotonic dystrophy: a narrative review |journal=Front Neurol |volume=15 |issue= |pages=1389949 |date=2024 |pmid=39011358 |pmc=11248093 |doi=10.3389/fneur.2024.1389949|doi-access=free }}</ref> Myotonic dystrophy has two main types: DM1 (Steinert disease) and DM2 (proximal myotonic myopathy). Both types can cause excessive daytime sleepiness. Studies suggest that modafinil may be a promising drug that can reduce both daytime sleepiness and myotonia itself, without significant cardiac conduction effects. These presumed property of modafinil is of particular interest for eventual treatment of people with myotonic dystrophy who often have underlying cardiac issues.<ref name="pmid39011358"/> Still, modafinil is not approved by the FDA for use in myotonic dystrophy, and the value and role of modafinil in DM remain the subject of debate.<ref name="pmid39011358"/>

===Disorders of consciousness===
Modafinil has been studied for its potential therapeutic effects in patients with [[Disorder of consciousness|disorders of consciousness]].<ref name="pmid39019729"/> Researchers are investigating whether modafinil can stimulate [[neurotransmitter]]s such as [[histamine]], [[norepinephrine]], [[serotonin]], [[dopamine]], and [[orexin]], and whether modafinil has potential [[Anti-oxidative|anti-oxidative effects]].<ref name="pmid39019729">{{cite journal |vauthors=Barra ME, Solt K, Yu X, Edlow BL |title=Restoring consciousness with pharmacologic therapy: Mechanisms, targets, and future directions |journal=Neurotherapeutics |volume=21 |issue=4 |pages=e00374 |date=July 2024 |pmid=39019729 |pmc=11452330 |doi=10.1016/j.neurot.2024.e00374}}</ref>

Disorders of consciousness are states characterized by impaired arousal and awareness.<ref name="pmid39019729"/> These states include [[coma]], [[vegetative state]]/[[unresponsive wakefulness syndrome]] (VS/UWS), [[minimally conscious state]] (MCS), [[cognitive motor dissociation]], and [[covert cortical processing]].<ref name="pmid39019729"/> Brain injuries can impair consciousness through [[neuroanatomic lesions]] involving the [[bilateral cerebral hemispheres]], [[rostral brainstem]], [[diencephalon]], or [[basal forebrain]].<ref name="pmid39019729"/>

[[Neuroimaging]] studies have shown that modafinil increases [[cerebral blood flow]] in several brain regions, such as the [[thalamus]], [[locus coeruleus]], [[limbic system]], and [[insular cortex]];<ref name="pmid39019729"/> still, observational reports on the use of modafinil in patients with disorders of consciousness have produced mixed results, indicating that its effectiveness may vary among individuals.<ref name="pmid39019729"/>

===Inflammation===
A possible link between [[inflammation|inflammatory processes]] and depressive disorders<ref name="pmid27640518">{{cite journal | vauthors = Kohler O, Krogh J, Mors O, Benros ME | title = Inflammation in Depression and the Potential for Anti-Inflammatory Treatment | journal = Current Neuropharmacology | volume = 14 | issue = 7 | pages = 732–742 | date = 2016 | pmid = 27640518 | pmc = 5050394 | doi = 10.2174/1570159x14666151208113700 }}</ref> has stimulated preliminary research on modafinil for its potential anti-inflammatory effects.<ref name="pmid32311496">{{cite journal | vauthors = Zager A | title = Modulating the immune response with the wake-promoting drug modafinil: A potential therapeutic approach for inflammatory disorders | journal = Brain, Behavior, and Immunity | volume = 88 | pages = 878–886 | date = August 2020 | pmid = 32311496 | doi = 10.1016/j.bbi.2020.04.038 | s2cid = 215807973 }}</ref>