Editing Attention deficit hyperactivity disorder (section)

===Medication===
The medications for ADHD appear to alleviate symptoms via their effects on the pre-frontal executive, striatal and related regions and networks in the brain; usually by increasing neurotransmission of [[norepinephrine]] and [[dopamine]].<ref>{{cite journal |vauthors=Devilbiss DM, Berridge CW |title=Cognition-enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness |journal=[[Biological Psychiatry (journal)|Biological Psychiatry]] |volume=64 |issue=7 |pages=626–635 |date=October 2008 |pmid=18585681 |pmc=2603602 |doi=10.1016/j.biopsych.2008.04.037}}</ref><ref name="Schulz_2012">{{cite journal |vauthors=Schulz KP, Fan J, Bédard AC, Clerkin SM, Ivanov I, Tang CY, Halperin JM, Newcorn JH |title=Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder |journal=Archives of General Psychiatry |volume=69 |issue=9 |pages=952–961 |date=September 2012 |pmid=22945622 |doi=10.1001/archgenpsychiatry.2011.2053}}</ref><ref name="Koda_2010">{{cite journal |vauthors=Koda K, Ago Y, Cong Y, Kita Y, Takuma K, Matsuda T |title=Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice |journal=[[Journal of Neurochemistry]] |volume=114 |issue=1 |pages=259–270 |date=July 2010 |pmid=20403082 |doi=10.1111/j.1471-4159.2010.06750.x}}</ref>

====Stimulants====
[[Methylphenidate]] and [[amphetamine]] or its derivatives are often first-line treatments for ADHD.<ref name="Dodson_2005" /><ref>{{cite journal |vauthors=Storebø OJ, Storm MR, Pereira Ribeiro J, Skoog M, Groth C, Callesen HE, Schaug JP, Darling Rasmussen P, Huus CL, Zwi M, Kirubakaran R, Simonsen E, Gluud C |title=Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD) |journal=[[The Cochrane Database of Systematic Reviews]] |volume=2023 |issue=3 |pages=CD009885 |date=March 2023 |pmid=36971690 |pmc=10042435 |doi=10.1002/14651858.CD009885.pub3}}</ref> About 70 per cent respond to the first stimulant tried and as few as 10 per cent respond to neither amphetamines nor methylphenidate.<ref name="CNS09" /> Stimulants may also reduce the risk of unintentional injuries in children with ADHD.<ref name="Ruiz-Goikoetxea_2017">{{cite journal |vauthors=Ruiz-Goikoetxea M, Cortese S, Aznarez-Sanado M, Magallón S, Alvarez Zallo N, Luis EO, de Castro-Manglano P, Soutullo C, Arrondo G |title=Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: A systematic review and meta-analysis |journal=[[Neuroscience & Biobehavioral Reviews]] |volume=84 |pages=63–71 |date=January 2018 |pmid=29162520 |doi=10.1016/j.neubiorev.2017.11.007 |hdl-access=free |doi-access=free |hdl=10171/45012}}</ref> [[Magnetic resonance imaging]] studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD.<ref name="Neuroplasticity 1">{{cite journal |vauthors=Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K |title=Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects |journal=[[JAMA Psychiatry]] |volume=70 |issue=2 |pages=185–198 |date=February 2013 |pmid=23247506 |doi=10.1001/jamapsychiatry.2013.277 |doi-access=free}}</ref><ref name="Neuroplasticity 2">{{cite journal |vauthors=Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J |title=Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies |journal=[[The Journal of Clinical Psychiatry]] |volume=74 |issue=9 |pages=902–917 |date=September 2013 |pmid=24107764 |pmc=3801446 |doi=10.4088/JCP.12r08287}}</ref><ref name="Neuroplasticity 3">{{cite journal |vauthors=Frodl T, Skokauskas N |title=Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects |journal=[[Acta Psychiatrica Scandinavica]] |volume=125 |issue=2 |pages=114–126 |date=February 2012 |pmid=22118249 |doi=10.1111/j.1600-0447.2011.01786.x |quote=Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like {{abbr|ACC|anterior cingulate cortex}} and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. |s2cid=25954331 |doi-access=free}}</ref> A 2018 review found the greatest short-term benefit with methylphenidate in children, and amphetamines in adults.<ref name="Comparative efficacy and tolerabili">{{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> Studies and meta-analyses show that amphetamine is slightly-to-modestly more effective than methylphenidate at reducing symptoms,<ref>{{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=[[Annals of Pharmacotherapy]] |volume=53 |issue=2 |pages=121–133 |date=February 2019 |pmid=30117329 |doi=10.1177/1060028018795703 |s2cid=52019992}}</ref><ref>{{cite journal |vauthors=Faraone SV, Biederman J, Roe C |title=Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis |journal=[[Journal of Clinical Psychopharmacology]] |volume=22 |issue=5 |pages=468–473 |date=October 2002 |pmid=12352269 |doi=10.1097/00004714-200210000-00005 |s2cid=19726926}}</ref> and they are more effective pharmacotherapy for ADHD than [[Alpha-adrenergic agonist#α2 agonist|α2-agonists]]<ref>{{cite journal |vauthors=Nam SH, Lim MH, Park TW |title=Stimulant Induced Movement Disorders in Attention Deficit Hyperactivity Disorder | journal = Soa--Ch'ongsonyon Chongsin Uihak = Journal of Child & Adolescent Psychiatry |volume=33 |issue=2 |pages=27–34 |date=April 2022 |pmid=35418800 |pmc=8984208 |doi=10.5765/jkacap.210034}}</ref> but methylphenidate has comparable efficacy to non-stimulants such as atomoxetine.
In a [[Cochrane (organisation)|Cochrane]] clinical synopsis, Dr Storebø and colleagues summarised their meta-review<ref>{{cite journal |vauthors=Storebø OJ, Krogh HB, Ramstad E, Moreira-Maia CR, Holmskov M, Skoog M, Nilausen TD, Magnusson FL, Zwi M, Gillies D, Rosendal S, Groth C, Rasmussen KB, Gauci D, Kirubakaran R, Forsbøl B, Simonsen E, Gluud C |title=Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials |journal=[[The BMJ]] |volume=351 |pages=h5203 |date=November 2015 |pmid=26608309 |pmc=4659414 |doi=10.1136/bmj.h5203}}</ref> on methylphenidate for ADHD in children and adolescents. The meta-analysis raised substantial doubts about the drug's efficacy relative to a placebo. This led to a strong critical reaction from the European ADHD Guidelines Group and individuals in the scientific community, who identified a number of flaws in the review.<ref>{{cite journal |vauthors=Banaschewski T, Buitelaar J, Chui CS, Coghill D, Cortese S, Simonoff E, Wong IC |title=Methylphenidate for ADHD in children and adolescents: throwing the baby out with the bathwater |journal=Evidence-Based Mental Health |volume=19 |issue=4 |pages=97–99 |date=November 2016 |pmid=27935807 |pmc=10699535 |doi=10.1136/eb-2016-102461}}</ref><ref>{{cite journal |vauthors=Hoekstra PJ, Buitelaar JK |title=Is the evidence base of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder flawed? |journal=[[European Child & Adolescent Psychiatry]] |volume=25 |issue=4 |pages=339–340 |date=April 2016 |pmid=27021055 |doi=10.1007/s00787-016-0845-2}}</ref><ref>{{cite journal |vauthors=Banaschewski T, Gerlach M, Becker K, Holtmann M, Döpfner M, Romanos M |title=Trust, but verify. The errors and misinterpretations in the Cochrane analysis by O. J. Storebo and colleagues on the efficacy and safety of methylphenidate for the treatment of children and adolescents with ADHD | journal = Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie |volume=44 |issue=4 |pages=307–314 |date=July 2016 |pmid=27270192 |doi=10.1024/1422-4917/a000433}}</ref><ref>{{cite journal |vauthors=Romanos M, Reif A, Banaschewski T |title=Methylphenidate for Attention-Deficit/Hyperactivity Disorder |journal=[[JAMA]] |volume=316 |issue=9 |pages=994–995 |date=September 2016 |pmid=27599342 |doi=10.1001/jama.2016.10279}}</ref><ref>{{cite journal |vauthors=Shaw P |title=Quantifying the Benefits and Risks of Methylphenidate as Treatment for Childhood Attention-Deficit/Hyperactivity Disorder |journal=[[JAMA]] |volume=315 |issue=18 |pages=1953–1955 |date=May 2016 |pmid=27163984 |doi=10.1001/jama.2016.3427}}</ref><ref>{{cite journal |vauthors=Gerlach M, Banaschewski T, Coghill D, Rohde LA, Romanos M |title=What are the benefits of methylphenidate as a treatment for children and adolescents with attention-deficit/hyperactivity disorder? |journal=Attention Deficit and Hyperactivity Disorders |volume=9 |issue=1 |pages=1–3 |date=March 2017 |pmid=28168407 |doi=10.1007/s12402-017-0220-2}}</ref> Since at least September 2021, there is a unanimous and global [[scientific consensus]] that methylphenidate is safe and highly effective for treating ADHD.<ref name="Faraone_2021" /><ref name="epa_consensus_2019" >{{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 |issue=1 |pages=14–34 |date=February 2019 |pmid=30453134 |doi=10.1016/j.eurpsy.2018.11.001 |hdl-access=free |hdl=10651/51910}}</ref> The same journal released a subsequent systematic review (2022) of extended-release methylphenidate for adults, concluding similar doubts about the certainty of evidence.<ref name="y943">{{cite journal |vauthors=Boesen K, Paludan-Müller AS, Gøtzsche PC, Jørgensen KJ |title=Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults |journal=[[The Cochrane Database of Systematic Reviews]] |volume=2022 |issue=2 |pages=CD012857 |date=February 2022 |pmid=35201607 |pmc=8869321 |doi=10.1002/14651858.CD012857.pub2 }}</ref> Other recent systematic reviews and meta-analyses, however, find certainty in the safety and high efficacy of methylphenidate for reducing ADHD symptoms,<ref name="Comparative efficacy and tolerabili"/><ref>{{cite journal |vauthors=Jaeschke RR, Sujkowska E, Sowa-Kućma M |title=Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review |journal=Psychopharmacology |volume=238 |issue=10 |pages=2667–2691 |date=October 2021 |pmid=34436651 |pmc=8455398 |doi=10.1007/s00213-021-05946-0}}</ref><ref>{{cite journal |vauthors=Carucci S, Balia C, Gagliano A, Lampis A, Buitelaar JK, Danckaerts M, Dittmann RW, Garas P, Hollis C, Inglis S, Konrad K, Kovshoff H, Liddle EB, McCarthy S, Nagy P, Panei P, Romaniello R, Usala T, Wong IC, Banaschewski T, Sonuga-Barke E, Coghill D, Zuddas A |title=Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis |journal=[[Neuroscience & Biobehavioral Reviews]] |volume=120 |pages=509–525 |date=January 2021 |pmid=33080250 |doi=10.1016/j.neubiorev.2020.09.031 |url=https://discovery.dundee.ac.uk/en/publications/fe01a9b8-95ee-46bf-bd2c-e88a9d6ead38 |hdl=11584/301387 |hdl-access=free}}</ref> for alleviating the underlying executive functioning deficits,<ref>{{cite journal |vauthors=Isfandnia F, El Masri S, Radua J, Rubia K |title=The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis |journal=[[Neuroscience & Biobehavioral Reviews]] |volume=162 |issue=105703 |page=105703 |date=July 2024 |pmid=38718988 |doi=10.1016/j.neubiorev.2024.105703 |url=https://kclpure.kcl.ac.uk/portal/en/publications/69dc26fe-1517-438e-9cd7-6788fc396dc9}}</ref> and for substantially reducing the adverse consequences of untreated ADHD with continuous treatment.<ref name="Faraone_2021" /> Clinical guidelines internationally are also consistent in approving the safety and efficacy of methylphenidate and recommending it as a first-line treatment for the disorder.<ref name="Faraone_2021" />

Safety and efficacy data have been reviewed extensively by medical regulators (e.g., the US Food and Drug Administration and the European Medicines Agency), the developers of evidence-based international guidelines (e.g., the UK National Institute for Health and Care Excellence and the American Academy of Pediatrics), and government agencies who have endorsed these guidelines (e.g., the Australian National Health and Medical Research Council). These professional groups unanimously conclude, based on the scientific evidence, that methylphenidate is safe and effective and should be considered as a first-line treatment for ADHD.<ref name="Faraone_2021" />
The likelihood of developing [[insomnia]] for ADHD patients taking stimulants has been measured at between 11 and 45 per cent for different medications,<ref name="Wynchank_2017">{{cite journal |vauthors=Wynchank D, Bijlenga D, Beekman AT, Kooij JJ, Penninx BW |title=Adult Attention-Deficit/Hyperactivity Disorder (ADHD) and Insomnia: an Update of the Literature |journal=[[Current Psychiatry Reports]] |volume=19 |issue=12 |page=98 |date=October 2017 |pmid=29086065 |doi=10.1007/s11920-017-0860-0 |publisher=Springer Science and Business Media LLC |quote=In varying percentages of trial participants, insomnia is a treatment-emergent adverse effect in triple-bead mixed amphetamine salts (40–45%), dasotraline (35–45%), lisdexamfetamine (10–19%), and extended-release methylphenidate (11%). |s2cid=38064951}}</ref> and may be a main reason for discontinuation. Other side effects, such as [[tic]]s, decreased appetite and weight loss, or [[emotional lability]], may also lead to discontinuation.<ref name="CNS09" /> [[Stimulant psychosis]] and [[mania]] are rare at therapeutic doses, appearing to occur in approximately 0.1% of individuals, within the first several weeks after starting amphetamine therapy.<ref name="Cochrane recreational amph psychosis">{{cite journal |vauthors=Shoptaw SJ, Kao U, Ling W |title=Treatment for amphetamine psychosis |journal=[[The Cochrane Database of Systematic Reviews]] |volume=2009 |issue=1 |pages=CD003026 |date=January 2009 |pmid=19160215 |pmc=7004251 |doi=10.1002/14651858.CD003026.pub3 |veditors=Shoptaw SJ, Ali R |quote=A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the presence of extreme agitation. More common (about 18%) is for frequent amphetamine users to report psychotic symptoms that are sub-clinical and that do not require high-intensity intervention&nbsp;...<br />About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983)&nbsp;...<br />Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis. }}</ref><ref>{{cite web |date=December 2013 |title=Adderall XR Prescribing Information |work=United States Food and Drug Administration |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf |url-status=live |archive-url=https://web.archive.org/web/20131230233702/http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf |archive-date=30 December 2013 |access-date=30 December 2013 |publisher=Shire US Inc |quote=Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without prior history of psychotic illness or mania can be caused by stimulants at usual doses.&nbsp;... In a pooled analysis of multiple short-term, placebo controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.}}</ref><ref name="pmid19171629">{{cite journal |vauthors=Mosholder AD, Gelperin K, Hammad TA, Phelan K, Johann-Liang R |title=Hallucinations and other psychotic symptoms associated with the use of attention-deficit/hyperactivity disorder drugs in children |journal=[[Pediatrics (journal)|Pediatrics]] |volume=123 |issue=2 |pages=611–616 |date=February 2009 |pmid=19171629 |doi=10.1542/peds.2008-0185 |s2cid=22391693}}</ref> The safety of these medications in pregnancy is unclear.<ref>{{cite journal |vauthors=Ashton H, Gallagher P, Moore B |title=The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder |journal=[[Journal of Psychopharmacology]] |volume=20 |issue=5 |pages=602–610 |date=September 2006 |pmid=16478756 |doi=10.1177/0269881106061710 |s2cid=32073083}}</ref> Symptom improvement is not sustained if medication is ceased.<ref name="PRBM.S49114">{{cite journal |vauthors=Parker J, Wales G, Chalhoub N, Harpin V |title=The long-term outcomes of interventions for the management of attention-deficit hyperactivity disorder in children and adolescents: a systematic review of randomized controlled trials |journal=Psychology Research and Behavior Management |volume=6 |pages=87–99 |date=September 2013 |pmid=24082796 |pmc=3785407 |doi=10.2147/PRBM.S49114 |quote=Results suggest there is moderate-to-high-level evidence that combined pharmacological and behavioral interventions, and pharmacological interventions alone can be effective in managing the core ADHD symptoms and academic performance at 14 months. However, the effect size may decrease beyond this period.&nbsp;... Only one paper examining outcomes beyond 36 months met the review criteria.&nbsp;... There is high level evidence suggesting that pharmacological treatment can have a major beneficial effect on the core symptoms of ADHD (hyperactivity, inattention, and impulsivity) in approximately 80% of cases compared with placebo controls, in the short term. |doi-access=free}}</ref><ref name="May_2008"/><ref name="Castells_2018">{{cite journal |vauthors=Castells X, Blanco-Silvente L, Cunill R |title=Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults |journal=[[The Cochrane Database of Systematic Reviews]] |volume=2018 |issue=8 |pages=CD007813 |date=August 2018 |pmid=30091808 |pmc=6513464 |doi=10.1002/14651858.CD007813.pub3 |collaboration=Cochrane Developmental, Psychosocial and Learning Problems Group}}</ref>

The long-term effects of ADHD medication have yet to be fully determined,<ref name="ADHD 2015 review">{{cite journal |vauthors=Kiely B, Adesman A |title=What we do not know about ADHD… yet |journal=Current Opinion in Pediatrics |volume=27 |issue=3 |pages=395–404 |date=June 2015 |pmid=25888152 |doi=10.1097/MOP.0000000000000229 |quote=In addition, a consensus has not been reached on the optimal diagnostic criteria for ADHD. Moreover, the benefits and long-term effects of medical and complementary therapies for this disorder continue to be debated. These gaps in knowledge hinder the ability of clinicians to effectively recognise and treat ADHD. |s2cid=39004402}}</ref><ref name="pmid21519262">{{cite journal |vauthors=Hazell P |title=The challenges to demonstrating long-term effects of psychostimulant treatment for attention-deficit/hyperactivity disorder |journal=Current Opinion in Psychiatry |volume=24 |issue=4 |pages=286–290 |date=July 2011 |pmid=21519262 |doi=10.1097/YCO.0b013e32834742db |url=https://zenodo.org/record/1230054 |access-date=19 July 2019 |url-status=live |s2cid=21998152 |archive-url=https://web.archive.org/web/20200726114012/https://zenodo.org/record/1230054 |archive-date=26 July 2020 }}</ref> although stimulants are generally beneficial and safe for up to two years for children and adolescents.<ref>{{cite journal |title=Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents |journal=Comparative Effectiveness Reviews |issue=203 |date=January 2018 |pmid=29558081 |url=http://www.ncbi.nlm.nih.gov/books/NBK487761/ |access-date=7 November 2021 |publisher=Agency for Healthcare Research and Quality (US) |url-status=live |place=Rockville (MD) |archive-url=https://web.archive.org/web/20220517212254/https://www.ncbi.nlm.nih.gov/books/NBK487761/ |archive-date=17 May 2022 |vauthors=Kemper AR, Maslow GR, Hill S, Namdari B, Allen Lapointe NM, Goode AP, Coeytaux RR, Befus D, Kosinski AS, Bowen SE, McBroom AJ, Lallinger KR, Sanders GD }}</ref> A 2022 meta-analysis found no statistically significant association between ADHD medications and the risk of [[cardiovascular disease]] (CVD) across age groups, although the study suggests further investigation is warranted for patients with preexisting CVD as well as long-term medication use.<ref>{{cite journal |vauthors=Zhang L, Yao H, Li L, Du Rietz E, Andell P, Garcia-Argibay M, D'Onofrio BM, Cortese S, Larsson H, Chang Z |title=Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis |journal=[[JAMA Network Open]] |volume=5 |issue=11 |pages=e2243597 |date=November 2022 |pmid=36416824 |pmc=9685490 |doi=10.1001/jamanetworkopen.2022.43597 |doi-access=free}}</ref> Regular monitoring has been recommended in those on long-term treatment.<ref name="pmid20571380">{{cite journal |vauthors=Kraemer M, Uekermann J, Wiltfang J, Kis B |title=Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature |journal=Clinical Neuropharmacology |volume=33 |issue=4 |pages=204–206 |date=July 2010 |pmid=20571380 |doi=10.1097/WNF.0b013e3181e29174 |s2cid=34956456}}</ref> There are indications suggesting that stimulant therapy for children and adolescents should be stopped periodically to assess continuing need for medication, decrease possible growth delay, and reduce tolerance.<ref name="pmid21530185">{{cite journal |vauthors=van de Loo-Neus GH, Rommelse N, Buitelaar JK |title=To stop or not to stop? How long should medication treatment of attention-deficit hyperactivity disorder be extended? |journal=European Neuropsychopharmacology |volume=21 |issue=8 |pages=584–599 |date=August 2011 |pmid=21530185 |doi=10.1016/j.euroneuro.2011.03.008 |s2cid=30068561}}</ref><ref>{{cite journal |vauthors=Ibrahim K, Donyai P |title=Drug Holidays From ADHD Medication: International Experience Over the Past Four Decades |journal=[[Journal of Attention Disorders]] |volume=19 |issue=7 |pages=551–568 |date=July 2015 |pmid=25253684 |doi=10.1177/1087054714548035 |url=https://www.researchgate.net/publication/266151922 |url-status=live |s2cid=19949563 |archive-url=https://web.archive.org/web/20160630122316/https://www.researchgate.net/profile/Kinda_Ibrahim2/publication/266151922_Drug_Holidays_From_ADHD_Medication_International_Experience_Over_the_Past_Four_Decades/links/56a5ec7408ae1b651134629a.pdf |archive-date=30 June 2016}}</ref> Although potentially addictive at high doses,<ref name="NHM therapeutic stim addiction liability">{{cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE |publisher=McGraw-Hill Medical |year=2009 |isbn=978-0-07-148127-4 |veditors=Sydor A, Brown RY |edition=2nd |location=New York |pages=323, 368|quote=supervised use of stimulants at therapeutic doses may decrease risk of experimentation with drugs to self-medicate symptoms. Second, untreated ADHD may lead to school failure, peer rejection, and subsequent association with deviant peer groups that encourage drug misuse.&nbsp;... amphetamines and methylphenidate are used in low doses to treat attention deficit hyperactivity disorder and in higher doses to treat narcolepsy (Chapter 12). Despite their clinical uses, these drugs are strongly reinforcing, and their long-term use at high doses is linked with potential addiction}}</ref><ref>{{Cite book |vauthors=McDonagh MS, Christensen V, Peterson K, Thakurta S |publisher=Oregon Health & Science University |title=Drug Class Review: Pharmacologic Treatments for Attention Deficit Hyperactivity Disorder: Final Report Update 3 [Internet] |chapter=Black box warnings of ADHD drugs approved by the US Food and Drug Administration |at=Appendix G: Black box warnings of ADHD drugs approved by the US Food and Drug Administration |via=United States National Library of Medicine |date=Oct 2009 |location=Portland, Oregon |url=https://www.ncbi.nlm.nih.gov/books/NBK47127/ |access-date=17 January 2014 |archive-date=8 September 2017 |archive-url=https://web.archive.org/web/20170908135126/https://www.ncbi.nlm.nih.gov/books/NBK47127/ |url-status=live}}</ref> stimulants used to treat ADHD have low potential for abuse.<ref name="Dodson_2005"/> Treatment with stimulants is either protective against substance abuse or has no effect.<ref name="Kooij_2010" />{{rp|12|quote=... the literature supports the view that stimulant treatment for ADHD either has no impact in risk for substance abuse, or may even lower the risk of substance abuse by reducing the early onset of substance abuse in adolescents.}}<ref name="ADHD 2015 review" /><ref name="NHM therapeutic stim addiction liability" />

The majority of studies on [[nicotine]] and other [[nicotinic agonist]]s as treatments for ADHD have shown favorable results; however, no nicotinic drug has been approved for ADHD treatment.<ref>{{cite journal |vauthors=Potter AS, Schaubhut G, Shipman M |title=Targeting the nicotinic cholinergic system to treat attention-deficit/hyperactivity disorder: rationale and progress to date |journal=[[CNS Drugs]] |volume=28 |issue=12 |pages=1103–1113 |date=December 2014 |pmid=25349138 |pmc=4487649 |doi=10.1007/s40263-014-0208-9}}</ref> [[Caffeine]] was formerly used as a second-line treatment for ADHD but research indicates it has no significant effects in reducing ADHD symptoms. Caffeine appears to help with alertness, arousal and reaction time but not the type of inattention implicated in ADHD (sustained attention/persistence).<ref>{{cite journal |vauthors=Perrotte G, Moreira MM, de Vargas Junior A, Teixeira Filho A, Castaldelli-Maia JM |title=Effects of Caffeine on Main Symptoms in Children with ADHD: A Systematic Review and Meta-Analysis of Randomized Trials |journal=Brain Sciences |volume=13 |issue=9 |page=1304 |date=September 2023 |pmid=37759905 |pmc=10526204 |doi=10.3390/brainsci13091304 |doi-access=free}}</ref> [[Pseudoephedrine]] and [[ephedrine]] do not affect ADHD symptoms.<ref name="Dodson_2005">{{cite journal |vauthors=Dodson WW |title=Pharmacotherapy of adult ADHD |journal=[[Journal of Clinical Psychology]] |volume=61 |issue=5 |pages=589–606 |date=May 2005 |pmid=15723384 |doi=10.1002/jclp.20122 |quote=For example, pseudoephedrine and ephedrine ... have no detectable effects on the symptoms of ADHD.}}</ref>

[[Modafinil]] has shown some efficacy in reducing the severity of ADHD in children and adolescents.<ref>{{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> It may be prescribed off-label to treat ADHD.<ref>{{Cite journal |last=Flavell |first=Joshua |date=July 26, 2020 |title=Modafinil-induced psychosis in a patient with attention deficit hyperactivity disorder |url=https://journals.sagepub.com/doi/10.1177/1039856220936630 |journal=Australasian Psychiatry |language=en |volume=29 |issue=3 |pages=366–367 |doi=10.1177/1039856220936630 |issn=1039-8562}}</ref>

====Non-stimulants====
Two non-stimulant medications, [[atomoxetine]] and [[viloxazine]], are approved by the FDA and in other countries for the treatment of ADHD.

[[Atomoxetine]], due to its lack of addiction liability, may be preferred in those who are at risk of recreational or compulsive stimulant use, although evidence is lacking to support its use over stimulants for this reason.<ref name="Kooij_2010"/>{{rp|13|The non stimulant atomoxetine may be an alternative to treatment with stimulants in substance abuse patients with ADHD, although studies showing superiority over stimulants in this difficult patient population are still lacking.}} Atomoxetine alleviates ADHD symptoms through norepinephrine reuptake and by indirectly increasing dopamine in the pre-frontal cortex,<ref name="Koda_2010"/> sharing 70-80% of the brain regions with stimulants in their produced effects.<ref name="Schulz_2012"/> Atomoxetine has been shown to significantly improve academic performance.<ref>{{cite journal |vauthors=Weiss M, Tannock R, Kratochvil C, Dunn D, Velez-Borras J, Thomason C, Tamura R, Kelsey D, Stevens L, Allen AJ |title=A randomized, placebo-controlled study of once-daily atomoxetine in the school setting in children with ADHD |journal=[[Journal of the American Academy of Child and Adolescent Psychiatry]] |volume=44 |issue=7 |pages=647–655 |date=July 2005 |pmid=15968233 |doi=10.1097/01.chi.0000163280.47221.c9}}</ref><ref>{{cite journal |vauthors=Biederman J, Wigal SB, Spencer TJ, McGough JJ, Mays DA |title=A post hoc subgroup analysis of an 18-day randomized controlled trial comparing the tolerability and efficacy of mixed amphetamine salts extended release and atomoxetine in school-age girls with attention-deficit/hyperactivity disorder |journal=[[Clinical Therapeutics]] |volume=28 |issue=2 |pages=280–293 |date=February 2006 |pmid=16678649 |doi=10.1016/j.clinthera.2006.02.008}}</ref> [[Meta-analysis|Meta-analyses]] and [[systematic review]]s have found that atomoxetine has comparable efficacy, equal tolerability and response rate (75%) to [[methylphenidate]] in children and adolescents. In adults, efficacy and discontinuation rates are equivalent.<ref name="Bushe_2016">{{cite journal |vauthors=Bushe C, Day K, Reed V, Karlsdotter K, Berggren L, Pitcher A, Televantou F, Haynes V |title=A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients |journal=[[Journal of Psychopharmacology]] |volume=30 |issue=5 |pages=444–458 |date=May 2016 |pmid=27005307 |doi=10.1177/0269881116636105 |s2cid=104938}}</ref><ref name="Hazell_2011">{{cite journal |vauthors=Hazell PL, Kohn MR, Dickson R, Walton RJ, Granger RE, Wyk GW |title=Core ADHD symptom improvement with atomoxetine versus methylphenidate: a direct comparison meta-analysis |journal=[[Journal of Attention Disorders]] |volume=15 |issue=8 |pages=674–683 |date=November 2011 |pmid=20837981 |doi=10.1177/1087054710379737 |s2cid=43503227}}</ref><ref name="Hanwella_2011">{{cite journal |vauthors=Hanwella R, Senanayake M, de Silva V |title=Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis |journal=[[BMC Psychiatry]] |volume=11 |issue=1 |page=176 |date=November 2011 |pmid=22074258 |pmc=3229459 |doi=10.1186/1471-244X-11-176 |doi-access=free}}</ref><ref name="Rezaei_2016">{{cite journal |vauthors=Rezaei G, Hosseini SA, Akbari Sari A, Olyaeemanesh A, Lotfi MH, Yassini M, Bidaki R, Nouri B |title=Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review and meta-analysis |journal=[[Medical Journal of the Islamic Republic of Iran]] |volume=30 |page=325 |date=10 February 2016 |pmid=27390695 |pmc=4898838}}</ref><ref>{{cite report |last1=Peterson |first1=Bradley S. |last2=Trampush |first2=Joey |last3=Maglione |first3=Margaret |last4=Bolshakova |first4=Maria |last5=Brown |first5=Morah |last6=Rozelle |first6=Mary |last7=Motala |first7=Aneesa |last8=Yagyu |first8=Sachi |last9=Miles |first9=Jeremy |last10=Pakdaman |first10=Sheila |last11=Gastelum |first11=Mario |last12=Nguyen |first12=Bich Thuy (Becky) |last13=Tokutomi |first13=Erin |last14=Lee |first14=Esther |last15=Belay |first15=Jerusalem Z. |last16=Schaefer |first16=Coleman |last17=Coughlin |first17=Benjamin |last18=Celosse |first18=Karin |last19=Molakalapalli |first19=Sreya |last20=Shaw |first20=Brittany |last21=Sazmin |first21=Tanzina |last22=Onyekwuluje |first22=Anne N. |last23=Tolentino |first23=Danica |last24=Hempel |first24=Susanne |title=ADHD Diagnosis and Treatment in Children and Adolescents |publisher=[[Agency for Healthcare Research and Quality]] |id=24-EHC003 |date=25 March 2024 |doi=10.23970/AHRQEPCCER267}}</ref>

Analyses of clinical trial data suggests that [[viloxazine]] is about as effective as atomoxetine and methylphenidate but with fewer side effects.<ref>{{cite journal |vauthors=Faraone SV, Gomeni R, Hull JT, Busse GD, Melyan Z, O'Neal W, Rubin J, Nasser A |title=Early response to SPN-812 (viloxazine extended-release) can predict efficacy outcome in pediatric subjects with ADHD: a machine learning post-hoc analysis of four randomized clinical trials |journal=[[Psychiatry Research]] |volume=296 |page=113664 |date=February 2021 |pmid=33418457 |doi=10.1016/j.psychres.2020.113664 |s2cid=230716405 |doi-access=free}}</ref>

[[Amantadine#Attention deficit hyperactivity disorder|Amantadine]] was shown to induce similar improvements in children treated with [[methylphenidate]], with less frequent side effects.<ref>{{cite journal |vauthors=Mohammadi MR, Kazemi MR, Zia E, Rezazadeh SA, Tabrizi M, Akhondzadeh S |date=November 2010 |title=Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial |journal=Human Psychopharmacology |volume=25 |issue=7–8 |pages=560–565 |doi=10.1002/hup.1154 |pmid=21312290 |s2cid=30677758}}</ref> A 2021 retrospective study showed that amantadine may serve as an effective adjunct to stimulants for ADHD–related symptoms and appears to be a safer alternative to second- or third-generation antipsychotics.<ref>{{cite journal |vauthors=Morrow K, Choi S, Young K, Haidar M, Boduch C, Bourgeois JA |date=September 2021 |title=Amantadine for the treatment of childhood and adolescent psychiatric symptoms |journal=Proceedings |volume=34 |issue=5 |pages=566–570 |doi=10.1080/08998280.2021.1925827 |pmc=8366930 |pmid=34456474}}</ref>

[[Bupropion]] is also used off-label by some clinicians due to research findings. It is effective, but modestly less than atomoxetine and methylphenidate.<ref>{{cite journal |vauthors=Stuhec M, Munda B, Svab V, Locatelli I |title=Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis with focus on bupropion |journal=[[Journal of Affective Disorders]] |volume=178 |pages=149–159 |date=June 2015 |pmid=25813457 |doi=10.1016/j.jad.2015.03.006}}</ref>

There is little evidence on the effects of medication on social behaviours.<ref name="McDonagh_20112">{{cite report |url=https://www.ncbi.nlm.nih.gov/books/NBK84419 |title=Drug Class Review: Pharmacologic Treatments for Attention Deficit Hyperactivity Disorder |date=December 2011 |publisher=United States Library of Medicine |pmid=22420008 |archive-url=https://web.archive.org/web/20160831152630/http://www.ncbi.nlm.nih.gov/books/NBK84419/ |archive-date=31 August 2016 |url-status=live |vauthors=McDonagh MS, Peterson K, Thakurta S, Low A |series=Drug Class Reviews}}</ref> Antipsychotics may also be used to treat aggression in ADHD.<ref>{{cite journal |vauthors=Gurnani T, Ivanov I, Newcorn JH |date=February 2016 |title=Pharmacotherapy of Aggression in Child and Adolescent Psychiatric Disorders |journal=Journal of Child and Adolescent Psychopharmacology |volume=26 |issue=1 |pages=65–73 |doi=10.1089/cap.2015.0167 |pmid=26881859 |quote=Several studies (e.g., Findling et al. 2000; Armenteros et al. 2007) have shown that antipsychotics, especially second generation agents, can be effective when used together with stimulants for aggression in ADHD}}</ref>

'''Alpha-2a agonists'''

Two [[Alpha-2 agonists|alpha-2a agonists]], extended-release formulations of [[guanfacine]] and [[clonidine]], are approved by the FDA and in other countries for the treatment of ADHD (effective in children and adolescents but effectiveness has still not been shown for adults).<ref>{{cite journal |vauthors=Childress AC, Sallee FR |title=Revisiting clonidine: an innovative add-on option for attention-deficit/hyperactivity disorder |journal=Drugs of Today |volume=48 |issue=3 |pages=207–217 |date=March 2012 |pmid=22462040 |doi=10.1358/dot.2012.48.3.1750904}}</ref><ref name="Huss Chen Ludolph 2016 pp. 1–252">{{cite journal |vauthors=Huss M, Chen W, Ludolph AG |title=Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe |journal=Clinical Drug Investigation |volume=36 |issue=1 |pages=1–25 |date=January 2016 |pmid=26585576 |pmc=4706844 |doi=10.1007/s40261-015-0336-0 |publisher=Springer Science and Business Media LLC}}</ref> They appear to be modestly less effective than the stimulants (amphetamine and methylphenidate) and non-stimulants (atomoxetine and viloxazine) at reducing symptoms,<ref>{{cite journal |vauthors = Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, Scherer N |title=A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder |journal=[[Pediatrics (journal)|Pediatrics]] |volume=121 |issue=1 |pages=e73–e84 |date=January 2008 |pmid=18166547 |doi=10.1542/peds.2006-3695 |s2cid=25551406 |collaboration=SPD503 Study Group}}</ref><ref>{{cite journal |vauthors=Palumbo DR, Sallee FR, Pelham WE, Bukstein OG, Daviss WB, McDERMOTT MP |title=Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes |journal=[[Journal of the American Academy of Child and Adolescent Psychiatry]] |volume=47 |issue=2 |pages=180–188 |date=February 2008 |pmid=18182963 |doi=10.1097/chi.0b013e31815d9af7}}</ref> but can be useful alternatives or used in conjunction with a stimulant. These medications act by adjusting the alpha-2a ports on the outside of noradrenergic nerve cells in the pre-frontal executive networks, so the information (electrical signal) is less confounded by noise.<ref>{{Cite journal |title=Focus: Translational Medicine: Guanfacine for the Treatment of Cognitive Disorders: A Century of Discoveries at Yale |date=2012 |pmc=3313539 |journal=The Yale Journal of Biology and Medicine |volume=85 |issue=1 |pages=45–58 |pmid=22461743 |vauthors=Arnsten AF, Jin LE}}</ref>

====Guidelines====
[[Medical guideline|Guidelines]] on when to use medications vary by country. The United Kingdom's [[National Institute for Health and Care Excellence]] recommends use for children only in severe cases, though for adults medication is a first-line treatment.<ref name="NICE_2019">{{Cite book |author=National Institute for Health and Care Excellence |url=https://www.nice.org.uk/guidance/ng87/ |title=Attention deficit hyperactivity disorder: diagnosis and management |publisher=National Guideline Centre (UK) |year=2019 |isbn=978-1-4731-2830-9 |series=NICE Guideline, No. 87 |location=London |pages= |oclc=1126668845 |access-date=9 January 2021 |archive-url=https://web.archive.org/web/20210112035209/https://www.nice.org.uk/guidance/ng87/ |archive-date=12 January 2021 |url-status=live}}</ref> Conversely, most United States guidelines recommend medications in most age groups.<ref name="CADDRA">{{cite web |title=Canadian ADHD Practice Guidelines |url=http://www.caddra.ca/cms4/pdfs/caddraGuidelines2011Introduction.pdf |url-status=live |archive-url=https://web.archive.org/web/20210121222344/https://www.caddra.ca/cms4/pdfs/caddraGuidelines2011Introduction.pdf |archive-date=21 January 2021 |access-date=4 February 2011 |work=Canadian ADHD Resource Alliance}}</ref> Medications are especially not recommended for preschool children.<ref name="NICE_2019" /><ref name="NICE 2009" /> Underdosing of stimulants can occur, and can result in a lack of response or later loss of effectiveness.<ref>{{cite journal |vauthors=Stevens JR, Wilens TE, Stern TA |title=Using stimulants for attention-deficit/hyperactivity disorder: clinical approaches and challenges |journal=The Primary Care Companion for CNS Disorders |volume=15 |issue=2 |date=2013 |pmid=23930227 |pmc=3733520 |doi=10.4088/PCC.12f01472}}</ref> This is particularly common in adolescents and adults as approved dosing is based on school-aged children, causing some practitioners to use weight-based or benefit-based off-label dosing instead.<ref>{{cite web |vauthors=Young JL |url=http://www.medscape.org/viewarticle/734449_print |title=Individualizing Treatment for Adult ADHD: An Evidence-Based Guideline |date=20 December 2010 |website=Medscape |archive-url=https://web.archive.org/web/20220508225446/https://www.medscape.org/viewarticle/734449_print |archive-date=8 May 2022 |url-status=live |access-date=8 May 2022}}</ref><ref>{{cite web |vauthors=Biederman J |url=http://www.medscape.com/viewarticle/464377_print |title=New-Generation Long-Acting Stimulants for the Treatment of Attention-Deficit/Hyperactivity Disorder |date=21 November 2003 |website=Medscape |archive-url=https://web.archive.org/web/20220508225829/https://www.medscape.com/viewarticle/464377_print |archive-date=8 May 2022 |url-status=live |access-date=8 May 2022 |quote=As most treatment guidelines and prescribing information for stimulant medications relate to experience in school-aged children, prescribed doses for older patients are lacking. Emerging evidence for both methylphenidate and Adderall indicate that when weight-corrected daily doses, equipotent with those used in the treatment of younger patients, are used to treat adults with ADHD, these patients show a very robust clinical response consistent with that observed in pediatric studies. These data suggest that older patients may require a more aggressive approach in terms of dosing, based on the same target dosage ranges that have already been established&nbsp;– for methylphenidate, 1–1.5–2 mg/kg/day, and for D,L-amphetamine, 0.5–0.75–1 mg/kg/day.... <br />In particular, adolescents and adults are vulnerable to underdosing, and are thus at potential risk of failing to receive adequate dosage levels. As with all therapeutic agents, the efficacy and safety of stimulant medications should always guide prescribing behavior: careful dosage titration of the selected stimulant product should help to ensure that each patient with ADHD receives an adequate dose, so that the clinical benefits of therapy can be fully attained.}}</ref><ref>{{cite journal |vauthors=Kessler S |title=Drug therapy in attention-deficit hyperactivity disorder |journal=[[Southern Medical Journal]] |volume=89 |issue=1 |pages=33–38 |date=January 1996 |pmid=8545689 |doi=10.1097/00007611-199601000-00005 |s2cid=12798818}}</ref>