Editing Modafinil (section)

===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" />