Management of attention deficit hyperactivity disorder

{{see also|Neurobiological effects of physical exercise#Cognitive control and memory}}

There are a variety of psychotherapeutic approaches employed by psychologists and psychiatrists; the one used depends on the patient and the patient's symptoms. The approaches include psychotherapy, cognitive-behavior therapy, support groups, parent training, meditation, and social skills training. In a 2019 review the effectiveness of social skills training was evaluated in children aged 5 to 18 years. At the time there was little evidence to support or refute this type of training for the treatment of ADHD in this age group.{{Cite journal|last1=Storebø|first1=Ole Jakob|last2=Elmose Andersen |first2=Mette |last3=Skoog|first3=Maria|last4=Joost Hansen|first4=Signe|last5=Simonsen |first5=Erik|last6=Pedersen|first6=Nadia |last7=Tendal |first7=Britta |last8=Callesen|first8=Henriette E.|last9=Faltinsen|first9=Erlend|last10=Gluud|first10=Christian|date=21 June 2019|title=Social skills training for attention deficit hyperactivity disorder (ADHD) in children aged 5 to 18 years|journal=The Cochrane Database of Systematic Reviews|volume=2019|issue=6 |pages=CD008223 |doi=10.1002/14651858.CD008223.pub3 |issn=1469-493X|pmc=6587063|pmid=31222721}}

Improving the surrounding home and school environment can improve the behavior of children with ADHD.{{cite journal |author1=American Academy of Pediatrics Subcommittee on Attention-Deficit/Hyperactivity Disorder |author2=American Academy of Pediatrics Committee on Quality Improvement |title=Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder |journal=Pediatrics |volume=108 |issue=4 |pages=1033–44 |date=October 2001 |pmid=11581465 |doi=10.1542/peds.108.4.1033 |doi-access=free }} Parents of children with ADHD often show similar deficits themselves, and thus may not be able to sufficiently help the child with his or her difficulties.Kazdin, Alan E. Parent management training: treatment for oppositional, aggressive, and antisocial behavior in children and adolescents. Oxford University Press, 2005 Improving the parents' understanding of the child's behavior and teaching them strategies to improve functioning and communication and discourage unwanted behavior has measurable effect on the children with ADHD. The different educational interventions for the parents are jointly called Parent Management Training. Techniques include operant conditioning: a consistent application of rewards for meeting goals and good behavior (positive reinforcement) and punishments such as time-outs or revocation of privileges for failing to meet goals or poor behavior. Classroom management is similar to parent management training; educators learn about ADHD and techniques to improve behavior applied to a classroom setting. Strategies utilized include increased structuring of classroom activities,{{cite web |url=https://www.helpseeker.net/AD/HD/13-tips-for-better-facilitation-in-school-for-students-with-adhd |title=Guidelines for better facilitation in school for students with ADHD |website=Helpseeker.net |access-date=2020-12-10 |archive-date=26 February 2021 |archive-url=https://web.archive.org/web/20210226035514/https://www.helpseeker.net/AD/HD/13-tips-for-better-facilitation-in-school-for-students-with-adhd |url-status=dead }} daily feedback, and token economy. In order for Token Economy to benefit students with ADHD, all staff must be consistent in rewarding the same behaviors. Additionally, establishing classroom routines will help to ensure that students with ADHD remain focused throughout the day.{{Cite journal |last=Landolfi |first=Anna-Maria |date=April 2014 |title=Inclusive Classroom Communities: Supporting Students with Characteristics of Attention Deficit Hyperactivity Disorder |url=https://tspace.library.utoronto.ca/bitstream/1807/67035/1/Landolfi_Anna-Maria_201406_MT_MTRP.pdf |journal=Ontario Institute for Studies in Education of the University of Toronto}}

Cognitive trainings can be delivered in a number of methods, including at home or hospital based programs.{{Cite report |url=https://effectivehealthcare.ahrq.gov/products/attention-deficit-hyperactivity-disorder/research |title=ADHD Diagnosis and Treatment in Children and Adolescents |last=Peterson |first=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 |date=2024-03-25 |publisher=Agency for Healthcare Research and Quality (AHRQ) |doi=10.23970/ahrqepccer267|url-access=subscription }} A 2013 paper published by two researchers from the University of Oslo concluded that working memory training provides short term improvements, but that there was limited evidence that these improvements were sustained or that they were generalized to improved verbal ability, mathematical skills, attention, or word decoding.{{cite journal |vauthors=Melby-Lervåg M, Hulme C |title=Is working memory training effective? A meta-analytic review |journal=Dev Psychol |volume=49 |issue=2 |pages=270–91 | date=February 2013 |pmid=22612437 |doi=10.1037/a0028228 |citeseerx=10.1.1.281.7759 |s2cid=12370312 }} A 2014 paper published by a group of researchers from the University of Southampton presented the result of meta analysis study of 14 recently published randomized controlled trials (RCTs). The authors concluded that "more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms".{{cite journal|last1=Sonuga-Barke|first1=E|last2=Brandeis|first2=D|last3=Holtmann|first3=M|last4=Cortese|first4=S|title=Computer-based Cognitive Training for ADHD: A Review of Current Evidence|journal=Child and Adolescent Psychiatric Clinics of North America|date=October 2014|volume=23|issue=4|pages=807–824|pmid=25220088|doi=10.1016/j.chc.2014.05.009}} A more recent 2023 meta-analysis of RCTs examined the efficacy of computerized cognitive training (CCT) in reducing ADHD symptoms through computer programs. In addition to finding short-term working memory improvements, they also found some evidence of long-term verbal working memory effects. However, the results were limited to the study’s settings, and the authors highlighted the need for more targeted intervention strategies.{{Cite journal |last=Westwood |first=Samuel J. |last2=Parlatini |first2=Valeria |last3=Rubia |first3=Katya |last4=Cortese |first4=Samuele |last5=Sonuga-Barke |first5=Edmund J. S. |date=April 2023 |title=Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes |url=https://www.nature.com/articles/s41380-023-02000-7 |journal=Molecular Psychiatry |language=en |volume=28 |issue=4 |pages=1402–1414 |doi=10.1038/s41380-023-02000-7 |issn=1476-5578|hdl=20.500.11850/615355 |hdl-access=free }}

=== Stimulants ===

Stimulants are the most commonly prescribed medications for ADHD. The stimulant medications indicated to treat ADHD are methylphenidate (Ritalin, Biphentin, Concerta), dexmethylphenidate (Focalin, Focalin XR), Serdexmethylphenidate/dexmethylphenidate (Azstarys), mixed amphetamine salts (Adderall, Mydayis),{{cite journal|vauthors=Sulzer D, Sonders MS, Poulsen NW, Galli A |title=Mechanisms of neurotransmitter release by amphetamines: a review |journal=Progress in Neurobiology |volume=75 |issue=6 |pages=406–33 |date=April 2005|pmid=15955613 |doi=10.1016/j.pneurobio.2005.04.003|s2cid=2359509 }} dextroamphetamine (Dexedrine), lisdexamfetamine (Vyvanse),{{cite journal|author=Howland RH|title=Lisdexamfetamine: a prodrug stimulant for ADHD |journal=Journal of Psychosocial Nursing and Mental Health Services |volume=46 |issue=8 |pages=19–22 |date=August 2008|pmid=18777964|doi=10.3928/02793695-20080801-05}} and in rare cases dextromethamphetamine (Desoxyn).{{cite journal |vauthors=Moszczynska A, Callan SP |date=September 2017 |title=Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=362 |issue=3 |pages=474–488 |doi=10.1124/jpet.116.238501 |pmc=11047030 |pmid=28630283 |quote=METH is a schedule II drug, which can only be prescribed for attention deficit hyperactivity disorder (ADHD), extreme obesity, or narcolepsy (as Desoxyn; Recordati Rare Diseases LLC, Lebanon, NJ), with amphetamine being prescribed more often for these conditions due to amphetamine having lower reinforcing potential than METH (Lile et al., 2013). ...
The initial strong central effect of Adderall comes from the d-enantiomer, whereas the prolonged effect is provided by l-enantiomer (Cody et al., 2003). This allows a patient to take the medication less frequently than a medication containing d-amphetamine only. ...
As a result, drugs that contain d-/l-mixture (e.g., Adderall) were reported to result in better clinical response in some children with ADHD (Patrick et al., 2009). ...
Desoxyn, which is d-METH, is rarely medically prescribed due to its strong reinforcing properties.}}{{cite journal|author=National Toxicology Program|title=NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines|journal=NTP Cerhr Mon|issue=16|pages=vii–III1|date=July 2005|pmid=16130031}} Controlled-release pharmaceuticals may allow once daily administration of medication in the morning. This is especially helpful for children who do not like taking their medication in the middle of the school day. Several controlled-release methods are used.{{Cite web |title=ADHD Medications: How They Work & Side Effects |url=https://my.clevelandclinic.org/health/treatments/11766-adhd-medication |access-date=2024-01-08 |website=Cleveland Clinic |language=en}}{{Cite journal |last1=Mechler |first1=Konstantin |last2=Banaschewski |first2=Tobias |last3=Hohmann |first3=Sarah |last4=Häge |first4=Alexander |date=2022-02-01 |title=Evidence-based pharmacological treatment options for ADHD in children and adolescents |journal=Pharmacology & Therapeutics |volume=230 |pages=107940 |doi=10.1016/j.pharmthera.2021.107940 |pmid=34174276 |issn=0163-7258|doi-access=free }}

Stimulants used to treat ADHD raise the extracellular concentrations of the neurotransmitters dopamine and norepinephrine, which increases cellular communication between neurons that utilize these compounds. Stimulants increase the availability of synaptic dopamine, reduce the overactivity, impulsivity, and inattention characteristics of patients with ADHD, and improve associated behaviors, including on-task behavior, academic performance, and social functioning.{{Cite journal |last1=Faraone |first1=Stephen V |last2=Biederman |first2=Joseph |last3=Spencer |first3=Thomas J |last4=Aleardi |first4=Megan |date=2006-10-05 |title=Comparing the Efficacy of Medications for ADHD Using Meta-analysis |journal=Medscape General Medicine |volume=8 |issue=4 |pages=4 |issn=1531-0132 |pmc=1868385 |pmid=17415287}}

The therapeutic benefits are due to noradrenergic effects at the locus coeruleus and the prefrontal cortex and dopaminergic effects at the ventral tegmental area, nucleus accumbens, and prefrontal cortex.{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 266, 318–323 | edition = 2nd | chapter = Chapters 10 and 13 }}{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 148, 154–157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin}}

Stimulant medications are considered safe when used under medical supervision. Nonetheless, there are concerns that the long term safety of these drugs has not been adequately documented,{{cite journal|last1=King |first1=S |last2=Griffin |first2=S |last3=Hodges |first3=Z |title=A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents |journal=Health Technology Assessment |volume=10 |issue=23 |pages=iii–iv, xiii–146 |date=July 2006 |pmid=16796929 |doi=10.3310/hta10230 |doi-access=free }}{{cite book |last1=Murphy |first1=Kevin R |url=https://books.google.com/books?id=EkyTTvjNRZAC&q=long+term+safety+of+stimulants&pg=PA626 |title=Attention-Deficit Hyperactivity Disorder: A Clinical Workbook |last2=Barkley |first2=Russell A |publisher=Guilford Press |year=2005 |isbn=978-1-59385-227-6 |edition=Third |location=New York}}{{cite journal |vauthors=Stern HP, Stern TP |date=September 2002 |title=When children with attention-deficit/hyperactivity disorder become adults |journal=South. Med. J. |volume=95 |issue=9 |pages=985–91 |doi=10.1097/00007611-200209000-00011 |pmid=12356139}}{{cite journal |vauthors=Lerner M, Wigal T |date=January 2008 |title=Long-term safety of stimulant medications used to treat children with ADHD |journal=Pediatric Annals |volume=37 |issue=1 |pages=37–45 |doi=10.3928/00904481-20080101-11 |pmid=18240852}} as well as social and ethical issues regarding their use and dispensation. The U.S. FDA has added black-box warnings to some ADHD medications, warning that abuse can lead to psychotic episodes, psychological dependence, and that severe depression may occur during withdrawal from abusive use.{{cite web |url=http://www.concerta.net/adult/prescribing-information.html |title=Full U.S. Concerta Prescribing Information |date=15 July 2014 |publisher=Janssen Pharmaceuticals, Inc. |access-date=6 September 2014 |archive-url=https://web.archive.org/web/20141126153726/http://www.concerta.net/adult/prescribing-information.html |archive-date=26 November 2014 |df=dmy-all }} Studies consistently show that most students report using stimulant medications, legally or illegally to improve academic performance, specifically to increase concentration, organization, and the ability to stay up longer and study.{{Cite journal |last=Advokat |first=Claire |date=2010-07-01 |title=What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD) |url=https://www.sciencedirect.com/science/article/pii/S0149763410000801 |journal=Neuroscience & Biobehavioral Reviews |language=en |volume=34 |issue=8 |pages=1256–1266 |doi=10.1016/j.neubiorev.2010.03.006 |pmid=20381522 |s2cid=20105233 |issn=0149-7634|url-access=subscription }} The abuse of this drug has made prescribing it much more meticulous.

Stimulants are some of the most effective medications available for the treatment of ADHD.{{cite journal|pmid=16135621|last1=Jensen|last2=Garcia|first2=JA|last3=Glied|first3=S|last4=Crowe|first4=M|last5=Foster|first5=M|last6=Schlander|first6=M|last7=Hinshaw|first7=S|last8=Vitiello|first8=B|last9=Arnold|first9=LE|title=Cost-Effectiveness of ADHD Treatments: Findings from the Multimodal Treatment Study of Children With ADHD|journal=American Journal of Psychiatry|volume=162|issue=9|pages=1628–1636|year=2005|doi=10.1176/appi.ajp.162.9.1628|hdl=1811/51178|s2cid=18620849 |hdl-access=free}} Seven different formulations of stimulants have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD: four amphetamine-based formulations, two methylphenidate-based formulations, and dextromethamphetamine hydrochloride. Atomoxetine, viloxazine, guanfacine, and clonidine are the only non-controlled, non-stimulant FDA approved drugs for the treatment of ADHD.{{Citation needed|date=January 2024}}

Short-term clinical trials have shown medications to be effective for treating ADHD, but the trials usually use exclusion criteria, meaning knowledge of medications for ADHD is based on a small subset of the typical patients seen in clinical practice.{{cite journal|vauthors=Weiss MD, Gadow K, Wasdell MB |title=Effectiveness outcomes in attention-deficit/hyperactivity disorder|journal=J Clin Psychiatry|volume=67 |issue=Suppl 8 |pages=38–45 |year=2006 |pmid=16961429}} They have not been found to improve school performance and data is lacking on long-term effectiveness and the severity of side effects. Stimulants, however, may reduce the risk of unintentional injuries in children with ADHD.{{cite journal|last1=Ruiz-Goikoetxea|first1=Maite|last2=Cortese|first2=Samuele|last3=Aznarez-Sanado|first3=Maite|last4=Magallón|first4=Sara|last5=Alvarez Zallo|first5=Noelia|last6=Luis|first6=Elkin O.|last7=de Castro-Manglano|first7=Pilar|last8=Soutullo|first8=Cesar|last9=Arrondo|first9=Gonzalo|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|year=2018|pages=63–71|issn=0149-7634|doi=10.1016/j.neubiorev.2017.11.007|pmid=29162520|doi-access=free|hdl=10171/45012|hdl-access=free}}{{Cite journal|last1=Dalsgaard|first1=Søren|last2=Leckman|first2=James F.|last3=Mortensen|first3=Preben Bo|last4=Nielsen|first4=Helena Skyt|last5=Simonsen|first5=Marianne|date=1 August 2015|title=Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study|journal=The Lancet. Psychiatry|volume=2|issue=8|pages=702–709|doi=10.1016/S2215-0366(15)00271-0|issn=2215-0374|pmid=26249301}}

This class of medicines is generally regarded as one unit; however, they affect the brain differently.{{cite journal|last=Arnold|first=LE|title=Methylphenidate vs Amphetamine: Comparative Review|journal=Journal of Attention Disorders|volume=3|issue=4|pages=200–211|year=2000|doi=10.1177/108705470000300403|doi-access=free|hdl=1811/51577|hdl-access=free}} Some investigations are dedicated to finding the similarities of children who respond to a specific medicine. The behavioral response to stimulants in children is similar regardless of whether they have ADHD or not.{{cite journal|vauthors=Rapoport JL, Inoff-Germain G |title=Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002|journal=J Atten Disord|volume=6 |issue=Suppl 1|pages=S57–60 |year=2002 |pmid=12685519 |doi=10.1177/070674370200601s07 |s2cid=24320882}}  

Stimulant medication is an effective treatment{{cite journal|author1=Dusan Kolar |author2=Amanda Keller |author3=Maria Golfinopoulos |author4=Lucy Cumyn |author5=Cassidy Syer |author6=Lily Hechtman |title=Treatment of adults with attention-deficit/hyperactivity disorder|journal=Neuropsychiatr Dis Treat|volume=4|issue=1|pages=107–121|date=February 2008|pmid=18728812|pmc=2515906|doi=10.2147/ndt.s1747 |doi-access=free }} for adult attention-deficit hyperactivity disorder{{cite journal|author=Spencer TJ |title=Pharmacology of adult ADHD with stimulants|journal=CNS Spectr|volume=12|issue=4 (Suppl 6)|pages=8–11|date=April 2007|pmid=17715564|doi=10.1017/S1092852900026018|s2cid=32723902 }}{{cite journal|author=Rostain, Anthony L.|title=ADHD in Adults: Attention-Deficit/Hyperactivity Disorder in Adults: Evidence-Based Recommendations for Management|journal=Postgraduate Medicine|volume=120|issue=3|pages=27–38|date=September 2008|pmid=18824823|doi=10.3810/pgm.2008.09.1905|s2cid=23171226|url=http://www.postgradmed.com/index.php?art=pgm_09_2008?article=1905|access-date=17 February 2022|archive-date=19 July 2009|archive-url=https://web.archive.org/web/20090719130508/http://www.postgradmed.com/index.php?art=pgm_09_2008%3Farticle%3D1905|url-access=subscription}} although the response rate may be lower for adults than children.{{cite journal|author=Spencer, Thomas |author2=Biederman, Joseph |author3=Wilens, Timothy|title=Stimulant treatment of adult attention-deficit/hyperactivity disorder|journal=Psychiatric Clinics of North America|volume=27|issue=2|pages=361–372|date=June 2004|doi=10.1016/j.psc.2003.12.002|pmid=15064002 |url=http://www.mdconsult.com/das/article/body/138353191-2/jorg=journal&source=&sp=14616830&sid=0/N/410882/1.html?issn=0193-953X|url-access=subscription}} A 2025 meta-analytic systematic review of 113 randomized controlled trials demonstrated that stimulant medications significantly improved core ADHD symptoms in adults over a three-month period, with good acceptability compared to other pharmacological and non-pharmacological treatments.{{Cite journal |vauthors=Ostinelli EG, Schulze M, Zangani C, Farhat LC, Tomlinson A, Del Giovane C, Chamberlain SR, Philipsen A, Young S, Cowen PJ, Bilbow A, Cipriani A, Cortese S |year=2025 |title=Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis |url=https://pubmed.ncbi.nlm.nih.gov/39701638 |journal=The Lancet. Psychiatry |volume=12 |issue=1 |pages=32–43 |doi=10.1016/S2215-0366(24)00360-2 |pmid=39701638 |quote=Our findings were based on 113 RCTs, including 14 887 participants, and indicated that stimulants were the only intervention that was supported by evidence of efficacy in the short term (ie, at timepoints closest to 12 weeks) for core symptoms of ADHD in adults (both self-reported and clinician-reported) and was associated with good acceptability (all-cause discontinuation). |doi-access=free|hdl=11380/1368079 |hdl-access=free }}

Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants{{cite journal|author=Higgins ES|title=A comparative analysis of antidepressants and stimulants for the treatment of adults with attention-deficit hyperactivity disorder|journal=J Fam Pract|volume=48|issue=1|pages=15–20|date=January 1999|pmid=9934377}} although antidepressants have much lower treatment effect sizes than stimulant medication.{{cite journal|vauthors=Verbeeck W, Tuinier S, Bekkering GE |title=Antidepressants in the treatment of adult attention-deficit hyperactivity disorder: a systematic review|journal=Adv Ther|volume=26|issue=2|pages=170–184|date=February 2009|pmid=19238340|doi=10.1007/s12325-009-0008-7|s2cid=5975939}}

{{further|Amphetamine}}

Amphetamine is a chiral compound which is composed of two isomers: levoamphetamine and dextroamphetamine. Levoamphetamine and dextroamphetamine have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to produce a small difference in their pharmacological properties; levoamphetamine has a slightly longer half-life and confers greater peripheral effects than dextroamphetamine, whereas dextroamphetamine is a more potent central nervous system stimulant.{{cite book |title=Goodman & Gilman's Pharmacological Basis of Therapeutics |vauthors=Tilley DG, Houser SR, Koch WJ |publisher=McGraw-Hill |year=2022 |isbn=9781264258079 |veditors=Brunton LL, Knollmann BC |edition=14th |location=New York, US |section=Chapter 14: Adrenergic Agonists and Antagonists |quote=Substitution on either α- or β-carbon yields optical isomers. Levorotatory substitution on the β-carbon confers the greater peripheral activity, so that the naturally occurring l-EPI and l-NE are at least 10 times more potent than their unnatural d-isomers. Dextrorotatory substitution on the α-carbon generally results in a more potent compound. d-Amphetamine is more potent than l-amphetamine in central but not peripheral activity.}}{{cite journal |vauthors=Mignot EJ |date=October 2012 |title=A practical guide to the therapy of narcolepsy and hypersomnia syndromes |journal=Neurotherapeutics |volume=9 |issue=4 |pages=739–752 |doi=10.1007/s13311-012-0150-9 |pmc=3480574 |pmid=23065655 |quote=The D-isomer is more specific for DA transmission and is a better stimulant compound.}} Although it is effective in reducing primary ADHD symptoms such as hyperactivity and inattention, multiple adverse side effects presented. Included in these were headaches, anxiety, nausea and insomnia.{{Cite journal|last=Punja|first=Salima|s2cid=39851826|date=February 2016|title=Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents|journal=Cochrane Database of Systematic Reviews |doi=10.1002/14651858.CD009996.pub2 |pmid=26844979 |volume=2016 |issue=2 |pages=CD009996|pmc=10329868}}

Five different amphetamine-based pharmaceuticals are currently used in ADHD treatment: racemic amphetamine, dextroamphetamine, lisdexamfetamine, and two mixed enantiomer products (Adderall and Dyanavel XR). Lisdexamfetamine is an inactive prodrug of dextroamphetamine (i.e., lisdexamfetamine itself does not do anything in the body, but it metabolizes into dextroamphetamine). Adderall is a proprietary mixture of (75%) dextroamphetamine and (25%) levoamphetamine salts, which results in very mild differences between their effects. Dyanavel XR contains a similar mixture. Levoamphetamine-containing mixtures may result in longer clinical effects, relative to enatiopure dextroamphetamine, due to levoamphetamine's longer half-life.{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE, Holtzman DM | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071827706 | edition = 3rd | chapter = Chapter 14:Higher Cognitive Function and Behavioral Control | quote= The most widely used treatments are sustained-release preparations of methylphenidate that compensate for its short half-life, or mixtures of amphetamine derivatives with different half-lives to provide both early and extended treatment during the day.}} Some children with ADHD have been reported to respond better to medications containing levoamphetamine. Amphetamines are modestly more effective than methylphenidate but report more side effects.{{cite journal |last1=Stuhec |first1=Matej |last2=Lukić |first2=Petar |last3=Locatelli |first3=Igor |date=February 2019 |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 |doi=10.1177/1060028018795703 |pmid=30117329 |s2cid=52019992}}{{cite journal |last1=Faraone |first1=Stephen V. |last2=Biederman |first2=Joseph |last3=Roe |first3=Christine |date=October 2002 |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 |doi=10.1097/00004714-200210000-00005 |pmid=12352269 |s2cid=19726926}}{{cite journal |last1=Faraone |first1=Stephen V. |last2=Buitelaar |first2=Jan |date=April 2010 |title=Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis |journal=European Child & Adolescent Psychiatry |volume=19 |issue=4 |pages=353–364 |doi=10.1007/s00787-009-0054-3 |pmid=19763664 |s2cid=9447892}}

{{further|Methamphetamine}}

Methamphetamine, prescribed as its dextrorotatory enantiomer dextromethamphetamine under the brand name Desoxyn, is a second-line psychostimulant for ADHD in the United States. Despite having a similar therapeutic mechanism of action as first-line medications containing amphetamine, the prescription of dextromethamphetamine for ADHD is rare due its relatively greater reinforcing potential, in addition to the comparable efficacy and presumably greater safety of methylphenidate and amphetamine.{{cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE, Holtzman DM |publisher=McGraw-Hill Medical |year=2015 |isbn=9780071827706 |edition=3rd |location=New York |chapter=Chapter 16: Reinforcement and Addictive Disorders |quote=Methamphetamine is an amphetamine derivative whose pharmacologic effects are very similar to those of amphetamine, but is longer acting due to pharmacokinetic considerations. Methamphetamine is easily synthesized from over-the-counter products (eg, the α-adrenergic agonist, pseudoephedrine), and this has led to its increasing use as an abused drug. Unlike cocaine and amphetamine, methamphetamine is directly toxic at higher doses to midbrain dopamine neurons.}} The body metabolizes methamphetamine into amphetamine (in addition to less active metabolites). A quarter of methamphetamine will ultimately become amphetamine.{{cite journal|last1=Schepers|first1=RJ|title=Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers|journal= Clinical Chemistry|volume=49|issue=1|pages=121–132 [121, 130] |year=2003 |pmid=12507968 |doi=10.1373/49.1.121 |doi-access=free}} After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant.{{cite journal|author=Shoblock|last2=Sullivan |first2=EB|last3=Maisonneuve|first3=IM|last4=Glick |first4=SD |title=Neurochemical and Behavioral Differences Between D-Methamphetamine and D-Amphetamine in Rats|journal=Psychopharmacology |volume=165 |issue=4 |pages=359–369 (Page:366) |year=2003 |pmid=12491026|doi=10.1007/s00213-002-1288-7|s2cid=1933979|display-authors=etal}}

{{further|Methylphenidate}}

Like amphetamine, methylphenidate (MPH) is a chiral compound which is composed of two isomers: d-threo-methylphenidate (also known as dexmethylphenidate, d-methylphenidate, or d-MPH) and l-threo-methylphenidate (also known as l-methylphenidate or l-MPH). Both isomers have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. Unlike amphetamine, the difference in pharmacological properties between d-MPH and l-MPH is significant, as l-MPH is markedly inferior to d-MPH in its effects, which is due to a number of major differences between the isomers.{{cite journal|last1=Markowitz|first1=JS |last2=Patrick |first2=KS |title=Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?|journal=Journal of Clinical Psychopharmacology |date=June 2008|volume=28|issue=3 Suppl 2|pages=S54–61 |doi=10.1097/JCP.0b013e3181733560 |pmid=18480678}}{{cite journal |vauthors=Heal DJ, Pierce DM |title=Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system|journal=CNS Drugs|volume=20|issue=9|pages=713–738 (Page:730) |year=2006|pmid=16953648 |doi=10.2165/00023210-200620090-00002 |s2cid=39535277}}

The effectiveness of methylphenidate is comparable to atomoxetine{{cite journal |last1=Bushe |first1=Chris |last2=Day |first2=Kathleen |last3=Reed |first3=Victoria |last4=Karlsdotter |first4=Kristina |last5=Berggren |first5=Lovisa |last6=Pitcher |first6=Ashley |last7=Televantou |first7=Foula |last8=Haynes |first8=Virginia |date=May 2016 |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 |doi=10.1177/0269881116636105 |pmid=27005307 |s2cid=104938}}{{cite journal |last1=Hazell |first1=Philip L. |last2=Kohn |first2=Michael R. |last3=Dickson |first3=Ruth |last4=Walton |first4=Richard J. |last5=Granger |first5=Renee E. |last6=van Wyk |first6=Gregory W. |date=November 2011 |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 |doi=10.1177/1087054710379737 |pmid=20837981 |s2cid=43503227}}{{cite journal |last1=Hanwella |first1=Raveen |last2=Senanayake |first2=Madhri |last3=de Silva |first3=Varuni |date=December 2011 |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 |doi=10.1186/1471-244X-11-176 |pmc=3229459 |pmid=22074258 |doi-access=free}}{{cite journal |vauthors=Rezaei G, Hosseini SA, Akbari Sari A, Olyaeemanesh A, Lotfi MH, Yassini M, Bidaki R, Nouri B |date=10 February 2016 |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 |pages=325 |pmc=4898838 |pmid=27390695}} but modestly lower than amphetamines.

There are two major medications derived from methylphenidate's isomers: a racemic mixture of half d-threo-methylphenidate and half l-threo-methylphenidate called methylphenidate (Ritalin, Concerta), and an enantiopure formulation containing just d-threo-methylphenidate called dexmethylphenidate (Focalin).{{Citation needed|date=January 2024}}

Atomoxetine,{{cite web|url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/atomoxetine-marketed-strattera-information|title=Atomoxetine (marketed as Strattera) Information |access-date=12 July 2009| archive-url= https://web.archive.org/web/20090709165227/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107912.htm| archive-date= 9 July 2009 | url-status= live |website=U.S. Food and Drug Administration}} viloxazine, guanfacine, and clonidine are drugs approved for the treatment of ADHD that have been classified as "non-stimulant".

Based on a recent systematic literature review of diverse ADHD treatment modalities, no differences were found between stimulants and non-stimulants in their effectiveness in treating ADHD symptoms.{{Cite web |title=ADHD Diagnosis and Treatment in Children and Adolescents |url=https://www.ncbi.nlm.nih.gov/books/NBK603001/ |access-date=2024-06-19 |publisher=National Library of Medicine |language=en |date=March 2024|doi=10.23970/ahrqepccer267 |pmid=38657097 | vauthors = Peterson BS, Trampush J, Maglione M, Bolshakova M, Brown M, Rozelle M, Motala A, Yagyu S, Miles J, Pakdaman S, Gastelum M, Nguyen BT, Tokutomi E, Lee E, Belay JZ, Schaefer C, Coughlin B, Celosse K, Molakalapalli S, Shaw B, Sazmin T, Onyekwuluje AN, Tolentino D, Hempel S }}{{source-attribution}}

; Atomoxetine

: Atomoxetine is a selective norepinephrine reuptake inhibitor.{{cite web |title=Atomoxetine: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a603013.html |website=medlineplus.gov |language=en}} It has comparable efficacy, tolerability and response rate to methylphenidate in children and adolescents; efficacy and discontinuation rate is equivalent in adults. It carries a U.S. FDA black box warning regarding suicidal ideation and is associated with rare cases of liver damage.{{cite web|url=https://www.fda.gov/CDER/drug/infopage/atomoxetine/default.htm|title=Atomoxetine (marketed as Strattera) Information|work=FDA Center for Drug Evaluation and Research|date=22 February 2007|archive-date=11 May 2009|archive-url=https://web.archive.org/web/20090511201239/https://www.fda.gov/cder/drug/infopage/atomoxetine/default.htm}}{{cite web |url=http://pi.lilly.com/us/strattera-pi.pdf|title=Strattera Prescribing Information|publisher=Eli Lilly and Company|date=February 2014|access-date=6 September 2014}}{{Rp|5}} Controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea.{{cite journal | pmid = 16380617 | last1 = Allen | first1 = AJ| doi=10.1212/01.wnl.0000188869.58300.a7 | last2 = Kurlan | first2 = RM | last3 = Gilbert | first3 = DL | last4 = Coffey | first4 = BJ | last5 = Linder | first5 = SL | last6 = Lewis | first6 = DW | last7 = Winner | first7 = PK | last8 = Dunn | first8 = DW | last9 = Dure | first9 = LS | title = Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders | journal = Neurology | volume=65 | issue=12 |date=December 2005 | pages=1941–9 | last10 = Sallee | first10 = F. R. | last11 = Milton | first11 = D. R. | last12 = Mintz | first12 = M. I. | last13 = Ricardi | first13 = R. K. | last14 = Erenberg | first14 = G. | last15 = Layton | first15 = L. L. | last16 = Feldman | first16 = P. D. | last17 = Kelsey | first17 = D. K. | last18 = Spencer | first18 = T. J.|s2cid=878719}}

; Viloxazine

: Acts as a selective norepinephrine reuptake inhibitor (NRI). However, it may also act as an antagonist of the serotonin 5-HT_2B receptor and as an agonist of the serotonin 5-HT_2C receptors, actions which may be involved in its therapeutic effects. It was marketed for more than two decades as an antidepressant in Europe before being repurposed as a treatment for ADHD and launched in the United States in April 2021.{{cite web | title=Qelbree: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211964 | access-date=2 April 2021}}{{cite press release | title=Supernus Announces FDA Approval of Qelbree (SPN-812) for the Treatment of ADHD | website=Supernus Pharmaceuticals | date=2 April 2021 | url=https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-qelbreetm-spn-812-treatment-adhd | access-date=3 April 2021}}

; Guanfacine

: The extended release form has been approved by the FDA for the treatment of attention-deficit hyperactivity disorder (ADHD) in children as an alternative to stimulant medications. Its beneficial actions are likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior.{{cite journal | author = Arnsten AF | year = 2010 | title = The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder | journal = Expert Rev Neurother | volume = 10 | issue = 10| pages = 1595–605 | doi=10.1586/ern.10.133 | pmid=20925474 | pmc=3143019}}

; Clonidine

: An α_2A adrenergic receptor agonist has also been approved in the US. Clonidine was initially developed as a treatment for high blood pressure. Low doses in evenings and/or afternoons are sometimes used in conjunction with stimulants to help with sleep and because clonidine sometimes helps moderate impulsive and oppositional behavior and may reduce tics.{{cite web|last=Frazin|first=Natalie|url=http://www.ninds.nih.gov/news_and_events/news_articles/news_article_adhd.htm|title=Methylphenidate and Clonidine Help Children With ADHD and Tics|date=2 April 2002|publisher=National Institute of Neurological Disorders and Stroke|access-date=15 April 2007 | archive-url=https://web.archive.org/web/20070427163336/http://www.ninds.nih.gov/news_and_events/news_articles/news_article_adhd.htm|archive-date= 27 April 2007 | url-status= live}} It may be more useful for comorbid Tourette syndrome.

Some medications used to treat ADHD are prescribed off-label, outside the scope of their US government approved indications for various reasons. The U.S. FDA requires two clinical trials to prove a potential drug's safety and efficacy in treating ADHD. The drugs below have not been through these tests, so the efficacy is unproven (however these drugs have been licensed for other indications, so have been proven to be safe in those populations) and proper dosage and usage instructions are not as well characterized.{{Citation needed|date=January 2024}}

; Bupropion

: Bupropion is classified as an atypical antidepressant. It is the most common off-label prescription for ADHD.{{Cite journal|date=March 2005|title=C-10. Educational course: ADHD through the life span|journal=European Psychiatry|volume=20|issue=S1|pages=S196–S197|doi=10.1016/s0924-9338(05)80114-2|s2cid=232176755 |issn=0924-9338}} It inhibits the reuptake of norepinephrine, and to a lesser extent dopamine, in neuronal synapses,{{cite web |url= http://us.gsk.com/products/assets/us_wellbutrin_tablets.pdf |title= Wellbutrin: Prescribing Information |access-date= 15 April 2007 |archive-date= 8 June 2013 |archive-url= https://web.archive.org/web/20130608113733/http://us.gsk.com/products/assets/us_wellbutrin_tablets.pdf |url-status= dead }} {{small|(170 KB)}}. GlaxoSmithKline (September 2006). Retrieved 15 April 2007. and has little or no effect on serotonergic reuptake.{{cite journal|vauthors=Stahl S, Pradko J, Haight B, Modell J, Rockett C, Learned-Coughlin S |title=A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor|journal=Prim Care Companion J Clin Psychiatry|volume=6|issue=4|pages=159–166|year=2004|pmid=15361919|pmc=514842|doi=10.4088/PCC.v06n0403}} Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects.{{Cite journal |last1=Verbeeck |first1=Wim |last2=Bekkering |first2=Geertruida E |last3=Van den Noortgate |first3=Wim |last4=Kramers |first4=Cornelis |date=2017-10-02 |editor-last=Cochrane Developmental, Psychosocial and Learning Problems Group |title=Bupropion for attention deficit hyperactivity disorder (ADHD) in adults |journal=Cochrane Database of Systematic Reviews |language=en |volume=2017 |issue=10 |pages=CD009504 |doi=10.1002/14651858.CD009504.pub2 |pmc=6485546 |pmid=28965364}}

; Modafinil

: A wakefulness-promoting agent that operates primarily as a selective, relatively weak, and atypical dopamine reuptake inhibitor. Double-blind randomized controlled trials have demonstrated the efficacy and tolerability of modafinil in pediatric ADHD.{{cite journal|vauthors=Biederman J, Swanson JM, Wigal SB, Boellner SW, Earl CQ, Lopez FA |title=A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study|journal=The Journal of Clinical Psychiatry |volume=67 |issue=5 |pages=727–35 |date=May 2006|pmid=16841622 |doi=10.4088/JCP.v67n0506}}{{cite journal|vauthors=Greenhill LL, Biederman J, Boellner SW |title=A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder |journal=Journal of the American Academy of Child and Adolescent Psychiatry |volume=45 |issue=5 |pages=503–11 |date=May 2006 |pmid=16601402 |doi=10.1097/01.chi.0000205709.63571.c9}} There are risks of serious side effects such as skin reactions, however these are rare and modafinil is not recommended for use in children.{{cite web|author=Cephalon, Inc.|date=21 December 2007|format=PDF|url=http://secure.healthlinks.net.au/content/csl/pi.cfm?product=cspmodav11207 |title=Modavigil Product Information |access-date=2 July 2008 |work=healthlinks.net|publisher=healthlinks.net Pty. Ltd. |url-status=usurped| archive-url= https://web.archive.org/web/20080721114706/http://secure.healthlinks.net.au/content/csl/pi.cfm?product=cspmodav11207| archive-date= 21 July 2008}}{{Rp|7}} In the United States, it was originally pending marketing on-label as Sparlon, but approval was denied by the FDA due to major concerns over the occurrence of Stevens–Johnson syndrome in clinical trials.

;Selegiline

: Selegiline acts as a monoamine oxidase inhibitor, and increases levels of monoamine neurotransmitters in the brain. At doses under 20 mg/day, selegiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B), increasing levels of dopamine in the brain. In clinical trials, Selegiline has been used in the treatment of attention deficit hyperactivity disorder (ADHD).{{cite book | vauthors = Moore JJ, Saadabadi A | chapter = Selegiline | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing | date = January 2020 | pmid = 30252350 }} Selegiline may target specific symptoms of ADHD including: sustained attention, the learning of novel information, hyperactivity, and peer interactions. Selegiline has shown to be relatively effective in treating the inattention subtype of ADHD.{{cite journal |title=Placebo-controlled study examining effects of selegiline in children with attention-deficit/hyperactivity disorder |journal=Journal of Child and Adolescent Psychopharmacology|year=2006 |pmid=16958566 |last1=Rubinstein |first1=S. |last2=Malone |first2=M. A. |last3=Roberts |first3=W. |last4=Logan |first4=W. J. |volume=16 |issue=4 |pages=404–415 |doi=10.1089/cap.2006.16.404 }}

Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants (TCAs), SNRIs, SSRIs, or MAOIs.

Atypical antipsychotic medications, which are approved for the treatment of certain behavioral disorders, are sometimes prescribed off-label as a combination therapy with stimulants for the treatment of comorbid (i.e., co-occurring diseases) ADHD and disruptive behavioral disorders.{{cite journal|last1=Linton|first1=D|last2=Barr|first2=AM|last3=Honer|first3=WG|last4=Procyshyn|first4=RM|title=Antipsychotic and psychostimulant drug combination therapy in attention deficit/hyperactivity and disruptive behavior disorders: a systematic review of efficacy and tolerability|journal=Current Psychiatry Reports|date=May 2013|volume=15|issue=5|pages=355|pmid=23539465|doi=10.1007/s11920-013-0355-6|s2cid=45484062}}{{Cite journal|last1=Loy|first1=Jik H.|last2=Merry|first2=Sally N.|last3=Hetrick|first3=Sarah E.|last4=Stasiak|first4=Karolina|date=9 August 2017|title=Atypical antipsychotics for disruptive behaviour disorders in children and youths|journal=The Cochrane Database of Systematic Reviews|volume=2017|issue=8 |pages=CD008559|doi=10.1002/14651858.CD008559.pub3|issn=1469-493X|pmc=6483473|pmid=28791693}} Canadian clinical practice guidelines only support the use of dopaminergic antipsychotics with selectivity for D2-type dopamine receptors, particularly risperidone, as a third-line treatment for both disorders following the failure of stimulant monotherapy and psychosocial interventions.{{cite journal|last1=Gorman|first1=DA|last2=Gardner|first2=DM|last3=Murphy|first3=AL|last4=Feldman|first4=M|last5=Bélanger|first5=SA|last6=Steele|first6=MM|last7=Boylan|first7=K|last8=Cochrane-Brink|first8=K|last9=Goldade|first9=R|last10=Soper|first10=PR|last11=Ustina|first11=J|last12=Pringsheim|first12=T|title=Canadian guidelines on pharmacotherapy for disruptive and aggressive behaviour in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, or conduct disorder |journal=Canadian Journal of Psychiatry|date=February 2015|volume=60|issue=2|pages=62–76|pmid=25886657|quote = Conclusion: When severe disruptive or aggressive behaviour occurs with ADHD, medications for ADHD should be used first. Other medications have major adverse effects and, with the exception of risperidone, very limited evidence to support their use.|pmc=4344948|doi=10.1177/070674371506000204}} Combined use of D2-type receptor antagonists and ADHD stimulants for the treatment of ADHD with comorbid behavioral disorders does not appear to have significantly worse adverse effects than ADHD stimulant or antipsychotic monotherapy.{{cite journal|last1=Elbe|first1=D|last2=Barr|first2=AM|last3=Honer|first3=WG|last4=Procyshyn|first4=RM|title=Managing ADHD and disruptive behaviour disorders with combination psychostimulant and antipsychotic treatment |journal=Journal of Psychiatry & Neuroscience|date=May 2014|volume=39|issue=3|pages=E32–3|pmid=24758945|doi=10.1503/jpn.130288|pmc=3997610}} Research suggests, but has not yet confirmed, the treatment efficacy of antipsychotic and stimulant combination treatment for both disorders; it is unclear if the combination therapy for both disorders is superior to stimulant or antipsychotic monotherapy. There is no evidence to support the use of any subclass of antipsychotics for the treatment of the core symptoms of ADHD (i.e., inattention and hyperactivity) without comorbid behavioral disorders.{{cite journal | vauthors = Birnbaum ML, Saito E, Gerhard T, Winterstein A, Olfson M, Kane JM, Correll CU | title = Pharmacoepidemiology of antipsychotic use in youth with ADHD: trends and clinical implications | journal = Curr Psychiatry Rep | volume = 15 | issue = 8 | pages = 382 | year = 2013 | pmid = 23881713 | pmc = 4010184 | doi = 10.1007/s11920-013-0382-3 | quote = Most importantly, antipsychotics are not approved for the treatment of symptoms of ADHD and limited, if any, evidence exists to suggest their utility for the core symptoms of inattention and hyperactivity. Although, aripiprazole and risperidone are approved for irritability and aggression associated with autistic disorder (age 5 or 6–17 years), and data exist for their utility in disruptive behavior disorders and aggression, antipsychotics should be the last resort for the treatment of impulsivity, oppositionality and aggression.}}

Dopaminergic antipsychotics affect dopamine neurons by binding to postsynaptic dopamine receptors, where they function as receptor antagonists. In contrast, ADHD stimulants are indirect agonists of postsynaptic dopamine receptors; in other words, these stimulants increase levels of synaptic dopamine, which then binds to postsynaptic receptors. Stimulants increase the concentration of synaptic dopamine by activating certain presynaptic receptors (i.e., TAAR1) or by blocking or altering the function of reuptake transporters (e.g., DAT, VMAT2) in the presynaptic neuron.{{Citation needed|date=January 2024}}

{{Main|Attention-deficit hyperactivity disorder controversies#Concerns about medication}}

Some parents and professionals have raised questions about the side effects of drugs and their long-term use.{{cite journal |last1=Lakhan|first1=SE|last2=Hagger-Johnson|first2=G|title=The impact of prescribed psychotropics on youth|journal=Clinical Practice and Epidemiology in Mental Health|date=20 October 2007|volume=3|page=21|doi=10.1186/1745-0179-3-21|pmid=17949504|pmc=2100041|issue=1 |doi-access=free }} {{open access}}

Outpatient treatment rates held steady in the U.S. from the late 1990s to early 2000s. Prior to this, outpatient treatment for ADHD in the U.S. grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997.{{cite journal | doi = 10.1176/appi.ajp.160.6.1071 | last1 = Name | first1 =LM| last2 = Gameroff | first2 = M | last3 = Marcus | first3 = MJ | last4 = Jensen | first4 = SC | last5 = Jensen | first5 = PS | s2cid = 17985245 | year = 2003 | title = National trends in the treatment of attention deficit hyperactivity disorder | journal = American Journal of Psychiatry | volume = 160 | issue = 6| pages = 1071–1077 | pmid = 12777264 }} A survey conducted by the Centers for Disease Control and Prevention in 2011–2012 found 11% of children between the ages of 4 and 17 were reported to have ever received a health care provider diagnosis of ADHD at some point (15% of boys and 7% of girls),{{Cite journal|last1=Danielson|first1=Melissa L.|last2=Bitsko|first2=Rebecca H.|last3=Ghandour|first3=Reem M.|last4=Holbrook|first4=Joseph R.|last5=Kogan |first5=Michael D.|last6=Blumberg|first6=Stephen J.|date=2018-03-04|title=Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016|journal=Journal of Clinical Child & Adolescent Psychology|volume=47|issue=2 |pages=199–212 |doi=10.1080/15374416.2017.1417860 |issn=1537-4416|pmc=5834391|pmid=29363986}} a 16% increase since 2007 and a 41% increase over the last decade.{{cite journal |last1=Visser|first1=SN|last2=Danielson |first2=ML|last3=Bitsko|first3=RH |last4=Holbrook |first4=JR|last5=Kogan|first5=MD|last6=Ghandour |first6=RM |last7=Perou |first7=R|last8=Blumberg|first8=SJ|title=Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003–2011 |journal=Journal of the American Academy of Child and Adolescent Psychiatry|date=January 2014 |volume=53|issue=1|pages=34–46.e2|doi=10.1016/j.jaac.2013.09.001|pmid=24342384|pmc=4473855}} The CDC notes that community samples suggest the incidence of ADHD in American children is higher than the five percent stated by the American Psychiatric Association in DSM-5, with 8.8% of U.S. children having a current diagnosis in the 2011 survey.{{cite web|title=Attention-Deficit / Hyperactivity Disorder: Data & Statistics|url=https://www.cdc.gov/ncbddd/adhd/data.html|publisher=Centers for Disease Control and Prevention|date=13 November 2013|access-date=6 September 2014}} However, only 6.1% of children in the 2011 survey were taking ADHD medication, suggesting as many as 17.5% of children with current ADHD were not receiving treatment.

Parents of children with ADHD note that they usually display their symptoms at an early age. There have been few longitudinal studies on the long-term effects of stimulant use in children.{{cite journal|last1=Singh|first1=Ilina|title=Beyond polemics: science and ethics of ADHD|journal=Nature Reviews Neuroscience|volume=9| issue=12|year=2008| pages=957–964| doi=10.1038/nrn2514| url=http://www.adhdvoices.com/documents/Singh2008__Beyond_polemics.pdf|pmid=19020513|s2cid=205504587}} The use of stimulant medication has not been approved by the FDA for children under the age of six.{{cite journal |last1=Greenhill |first1=L. |last2=Kollins |first2=S. |last3=Abikoff |first3=H. |last4=McCracken |first4=J. |last5=Riddle |first5=M. |last6=Swanson |first6=J. |last7=McGough |first7=J. |last8=Wigal |first8=S. |last9=Wigal |first9=T. |title=Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD |journal=J Am Acad Child Adolesc Psychiatry| volume=45 |issue=11 |pages=1284–93 |date=November 2006 |doi=10.1097/01.chi.0000235077.32661.61| pmid=17023867 |last10=Vitiello |first10=Benedetto |last11=Skrobala |first11=A |last12=Posner |first12=K |last13=Ghuman |first13=J |last14=Cunningham |first14=C |last15=Davies |first15=M |last16=Chuang |first16=S |last17=Cooper |first17=T|s2cid=25250719 }} A growing trend is the diagnosis of younger children with ADHD. Prescriptions for children under the age of 5 rose nearly 50 percent from 2000 to 2003.{{cite news| url=https://query.nytimes.com/gst/fullpage.html?res=9C0DEEDF143FF934A25756C0A9629C8B63 |work=The New York Times | title=Behavior Drugs Lead in Sales For Children |first=Milt |last=Freudenheim |date=17 May 2004 |access-date=25 April 2010}}{{cite web |title=Medco Settles Fraud, Kickback Charges for $155 Million |url=http://www.consumeraffairs.com/news04/2006/10/medco_settles.html |date=24 October 2006 |website=ConsumerAffairs |publisher=Consumers Unified LLC |access-date=26 October 2013}} Research on this issue has indicated that stimulant medication can help younger children with "severe ADHD symptoms" but typically at a lower dose than older children. It was also found that children at this age are more sensitive to side effects and should be closely monitored. Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills,{{cite journal |last1=Wolraich |first1=M. |last2=Brown |first2=L. |last3=Wolraich |first3=RT. |last4=Brown |first4=G. |last5=Brown |first5=M. |last6=Dupaul |first6=HM. |last7=Earls |first7=TG. |last8=Feldman |first8=B. |last9=Ganiats |first9=B. |others=Steering Committee on Quality Improvement Management |last11=Meyer |first11=B |last12=Perrin |first12=B |last13=Pierce |first13=J |last14=Reiff |first14=K |last15=Stein |first15=M |last16=Visser |first16=MT |last17=Visser |first17=S |title=ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents |journal=Pediatrics |volume=128 |issue=5 |pages=1007–22 |date=November 2011 |doi=10.1542/peds.2011-2654 |pmid=22003063 |last10=Kaplanek |first10=B |pmc=4500647}} while medication only treats the symptoms of the disorder. "One of the primary reasons cited for the growing use of psychotropic interventions was that many physicians realize that psychological interventions are costly and difficult to sustain."{{cite journal|last1=Manos|first1=Michael J|title=Treating Severe ADHD in Very Young Children|journal=Medscape Psychiatry|date=2006|volume=11|issue=1|url=http://www.medscape.org/viewarticle/523542}}

Central nervous system stimulants such as lisdexamfetamine may be associated with occurrences of constipation, diarrhea, nausea, and stomach pain.{{cite journal | pmc=8561853 | date=2021 | last1=Hameed | first1=U. | last2=Khan | first2=A. | last3=Gomaa | first3=H. | last4=Garman | first4=J. C. | last5=Hameed | first5=A. | title=A Case of Constipation and Gastrointestinal Retention of Lisdexamfetamine Dimesylate Capsules in an 11-Year-Old | journal=Journal of the Canadian Academy of Child and Adolescent Psychiatry | volume=30 | issue=4 | pages=292–296 | pmid=34777513 }}

There is some evidence of mild reductions in growth rate with prolonged stimulant treatment in children, but no causal relationship has been established and reductions do not appear to persist long-term.{{cite journal|last1=Cortese|first1=S|last2=Holtmann|first2=M|last3=Banaschewski|first3=T|last4=Buitelaar|first4=J|last5=Coghill|first5=D|last6=Danckaerts|first6=M|last7=Dittmann|first7=RW|last8=Graham|first8=J|last9=Taylor|first9=E|last10=Sergeant|first10=J|last11=European ADHD Guidelines|first11=Group|s2cid=20052221|title=Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents|journal=Journal of Child Psychology and Psychiatry, and Allied Disciplines|date=March 2013|volume=54|issue=3|pages=227–46|pmid=23294014|doi=10.1111/jcpp.12036}} Weight loss almost always corresponds with loss of appetite, which may result from the medication. Severe weight loss is very uncommon though. Loss of appetite is very temporary and typically comes back as daily effects of stimulants wear off. Nausea, dizziness, and headaches, other side effect, can also indirectly affect appetite and result in weight loss.{{cite web|last1=Bhandari|first1=Smitha|title=Tips to Ease ADHD Drug Side Effects in Adults|url=http://www.webmd.com/add-adhd/guide/tips-reduce-adult-adhd-medication-side-effects|website=WebMD|access-date=16 October 2015}}

There is concern that stimulants and atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems.{{cite web|url=https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_06_01_Gelperin.pdf|title=Studying Cardiovascular Risk with Drug Treatments of ADHD: Feasibility of Available Study Methods in Children and Adults|first=Kate|last=Gelperin|date=9 February 2006|publisher=Food and Drug Administration (US)}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}{{Cite journal|last1=The ADDUCE consortium|last2=Hennissen|first2=Leonie|last3=Bakker|first3=Mireille J.|last4=Banaschewski|first4=Tobias|last5=Carucci|first5=Sara|last6=Coghill|first6=David|last7=Danckaerts|first7=Marina|last8=Dittmann|first8=Ralf W.|last9=Hollis|first9=Chris|last10=Kovshoff|first10=Hanna|last11=McCarthy|first11=Suzanne|date=March 2017|title=Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine|journal=CNS Drugs|language=en|volume=31|issue=3|pages=199–215|doi=10.1007/s40263-017-0410-7|pmid=28236285 |pmc=5336546 |issn=1172-7047}} Recent extremely large-scale studies by the FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, myocardial infarction, and stroke) and the medical use of amphetamine, methylphenidate, or other ADHD stimulants.{{cite journal |vauthors=Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA |title=ADHD drugs and serious cardiovascular events in children and young adults |journal=N. Engl. J. Med. |volume=365 |issue=20 |pages=1896–1904 |date=November 2011 |pmid=22043968 |doi=10.1056/NEJMoa1110212 |pmc=4943074}}{{cite web |title=FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults |date=15 December 2011 |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-medications-used-treat-attention-0 |work=United States Food and Drug Administration |access-date=4 November 2013}}{{cite journal |vauthors=Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV |title=ADHD medications and risk of serious cardiovascular events in young and middle-aged adults |date=December 2011 |journal=JAMA |volume=306 |issue=24 |pages=2673–2683 |pmid=22161946 |pmc=3350308 |doi=10.1001/jama.2011.1830}}{{cite web |title=FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults |date=20 December 2011 |url=https://www.fda.gov/Drugs/DrugSafety/ucm277770.htm |work=United States Food and Drug Administration |access-date=4 November 2013}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}

Many of these drugs are associated with physical and psychological dependence.{{cite web |year=2006 |title=ADHD Drug Labels |url=https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_16_01_ADHD%20Drug%20Labels.pdf |archive-url=https://web.archive.org/web/20060630123819/http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_16_01_ADHD%20Drug%20Labels.pdf |url-status=dead |archive-date=30 June 2006 |url-access=limited |publisher=Food and Drug Administration (US)}}{{Page needed|date=September 2014}} Sleep problems may occur.{{cite web|last1=Silver|first1=Larry|title=ADHD Medications: Say No to Side Effects|url=http://www.additudemag.com/adhd/article/957.html|website=ADDitude magazine|publisher=New Hope Media LLC|date=February 2006}}

Methylphenidate can worsen psychosis in psychotic patients, and in very rare cases it has been associated with the emergence of new psychotic symptoms.{{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 = Clin Neuropharmacol | volume = 33 | issue = 4 | pages = 204–6 | date = July 2010 | pmid = 20571380 | doi = 10.1097/WNF.0b013e3181e29174 | s2cid = 34956456 }} It should be used with extreme caution in patients with bipolar disorder due to the potential induction of mania or hypomania.{{cite journal|last1=Wingo|first1=AP|last2=Ghaemi|first2=SN|title=Frequency of stimulant treatment and of stimulant-associated mania/hypomania in bipolar disorder patients|journal=Psychopharmacology Bulletin|date=2008|volume=41|issue=4|pages=37–47|pmid=19015628}} There have been very rare reports of suicidal ideation, but evidence does not support a link. The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown.{{cite journal|vauthors=Kimko HC, Cross JT, Abernethy DR |title=Pharmacokinetics and clinical effectiveness of methylphenidate|journal=Clin Pharmacokinet|volume=37|issue=6|pages=457–70|date=December 1999|pmid=10628897|doi=10.2165/00003088-199937060-00002|s2cid=397390}}

A 2009 FDA review of 49 clinical trials found that approximately 1.5% of children in clinical trials of medications for ADHD had experienced signs or symptoms of psychosis or mania. Postmarketing reports were also analyzed, with nearly half of them involving children under the age of eleven. Approximately 90% of cases had no reported previous history of similar psychiatric events. Hallucinations involving snakes, worms or insects were the most commonly reported symptoms.{{cite journal |last1= Mosholder |first1= Andrew D. |last2= Gelperin |first2= Kate |date=1 February 2009 |title=Hallucinations and Other Psychotic Symptoms Associated With the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children |url=http://pediatrics.aappublications.org/content/123/2/611 |journal=Pediatrics |volume=123 |issue=2 |pages=611–616 |access-date=23 October 2013 |pmid= 19171629 |doi=10.1542/peds.2008-0185|s2cid= 22391693 |url-access=subscription }}

Long-term methylphenidate or amphetamine exposure in some species is known to produce abnormal dopamine system development or nerve damage,{{cite journal |vauthors=Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L |title=Toxicity of amphetamines: an update |journal=Arch. Toxicol. |volume=86 |issue=8 |pages=1167–1231 |date=August 2012 |pmid=22392347 |doi=10.1007/s00204-012-0815-5 |s2cid=2873101 }}{{cite journal|vauthors=Berman S, O'Neill J, Fears S, Bartzokis G, London ED | title=Abuse of amphetamines and structural abnormalities in the brain | journal=Ann. N. Y. Acad. Sci. | year= 2008 | volume= 1141 | issue= 1| pages= 195–220 | pmid=18991959 | doi=10.1196/annals.1441.031 | pmc=2769923 | bibcode=2008NYASA1141..195B }} but humans experience normal development and nerve growth.{{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 }}{{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=J. Clin. Psychiatry |volume=74 |issue=9 |pages=902–917 |date=September 2013 |pmid=24107764 |doi=10.4088/JCP.12r08287 |pmc=3801446}}{{cite journal | title=Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects | journal=Acta Psychiatrica Scandinavica | date=February 2012 | volume=125 | issue=2 | pages=114–126 | pmid=22118249 |vauthors=Frodl T, Skokauskas N | 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 ACC 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. | doi=10.1111/j.1600-0447.2011.01786.x| s2cid=25954331 | doi-access=free }} 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, and improves function of the right caudate nucleus.

Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.{{cite book | author = Millichap JG | editor = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York | isbn = 978-1-4419-1396-8 | pages = 111–113 | edition = 2nd | chapter = Chapter 3: Medications for ADHD}}{{cite journal |vauthors=Huang YS, Tsai MH | title = Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge | journal = CNS Drugs | volume = 25 | issue = 7 | pages = 539–554 |date=July 2011 | pmid = 21699268 | doi = 10.2165/11589380-000000000-00000 | s2cid = 3449435 }} Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety. One review highlighted a nine-month randomized controlled trial of amphetamine in children that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity.{{cite book | author = Millichap JG | editor = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York | isbn = 978-1-4419-1396-8 | pages = 121–123 | edition = 2nd | chapter = Chapter 3: Medications for ADHD}}

There is some evidence that ADHD itself may protect the brain against the natural aging process later in life,{{cite journal |last1=Dutta |first1=Cintya |last2=Christov-Moore |first2=Leonardo |last3=Ombao |first3=Hernando |last4=Douglas |first4=PK |title=Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan |journal=Front Hum Neurosci |date=2022 |volume=16 |page=938501 |doi=10.3389/fnhum.2022.938501 |pmid=36226261|pmc=9548548 |hdl=10754/681712 |hdl-access=free |doi-access=free }} perhaps by exercising the brain, and helping maintain volume. It is unknown how long term medication treatment effects the trajectory of brain volume decline in the aging ADHD brain.

Tolerance to the therapeutic effects of stimulants can occur,{{cite journal |vauthors=Fusar-Poli P, Rubia K, Rossi G, Sartori G, Balottin U |title=Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis |journal=Am J Psychiatry |volume=169 |issue=3 |pages=264–72 |date=March 2012 |pmid=22294258 |doi=10.1176/appi.ajp.2011.11060940 |hdl=11577/2482784 |hdl-access=free }} and rebound of symptoms may occur when the dose wears off.{{cite journal |last1=Kooij |first1=SJ. |last2=Bejerot |first2=S. |last3=Blackwell |first3=A. |last4=Caci |first4=H. |last5=Casas-Brugué |first5=M. |last6=Carpentier |first6=PJ. |last7=Edvinsson |first7=D. |last8=Fayyad |first8=J. |last9=Foeken |first9=K. |title=European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD |journal=BMC Psychiatry |volume=10 |pages=67 |year=2010 |doi=10.1186/1471-244X-10-67 |pmid=20815868 |pmc = 2942810 |last10=Fitzgerald |first10=M |last11=Gaillac |first11=V |last12=Ginsberg |first12=Y |last13=Henry |first13=C |last14=Krause |first14=J |last15=Lensing |first15=MB |last16=Manor |first16=I |last17=Niederhofer |first17=H |last18=Nunes-Filipe |first18=C |last19=Ohlmeier |first19=MD |last20=Oswald |first20=P |last21=Pallanti |first21=S |last22=Pehlivanidis |first22=A |last23=Ramos-Quiroga |first23=JA |last24=Rastam |first24=M |last25=Ryffel-Rawak |first25=D |last26=Stes |first26=S |last27=Asherson |first27=P |doi-access=free }} Rebound effects are often the result of the stimulant dosage being too high or the individual not being able to tolerate stimulant medication. Signs that the stimulant dose is too high include irritability, feeling stimulated or blunting of affect and personality.{{cite journal | last1 = Brown | first1 = TE | title = ADD/ADHD and Impaired Executive Function in Clinical Practice | journal = Curr Psychiatry Rep | volume = 10 | issue = 5 | pages = 407–11 |date=October 2008 |doi=10.1007/s11920-008-0065-7 |pmid=18803914| s2cid = 146463279 }}

Stimulant withdrawal or rebound reactions can occur and can be minimised in intensity via a gradual tapering off of medication over a period of weeks or months.{{cite journal|author=Garland EJ|title=Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats|journal=J. Psychopharmacol. (Oxford)|volume=12|issue=4|pages=385–95|year=1998|pmid=10065914|doi=10.1177/026988119801200410|s2cid=38304694}} A small study of abrupt withdrawal of stimulants did suggest that withdrawal reactions are not typical, and may only occur in susceptible individuals.{{cite journal|vauthors=Nolan EE, Gadow KD, Sprafkin J |title=Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder|journal=Pediatrics|volume=103|issue=4 Pt 1|pages=730–7|date=April 1999|pmid=10103294|doi=10.1542/peds.103.4.730|s2cid=43176603}}

Concerns about chromosomal aberrations and possible cancer later in life was raised by a small-scale study on the use of methylphenidate, though a review by the Food and Drug Administration (FDA) found significant methodological problems with the study.{{cite news|last=Ackerman|first=Todd|title=Closer look for possible Ritalin, cancer link|url=http://www.chron.com/disp/story.mpl/front/3250025.html|access-date=10 July 2011|newspaper=Houston Chronicle|date=1 July 2005}} A follow-up study performed with improved methodology found no evidence that methylphenidate might cause cancer, stating "the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported."{{cite journal|title=Does Methylphenidate Cause a Cytogenetic Effect in Children with Attention Deficit Hyperactivity Disorder?|journal=Environmental Health Perspectives|date=June 2007 |volume=115|issue=6|pages=936–940|last=Walitza |first=Susanne |pmid=17589603 |pmc=1892117 |doi=10.1289/ehp.9866 |display-authors=etal}}

The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937.{{cite journal | last1= Lange| first1=KW.| last2=Reichl| first2=S.| last3=Lange| first3=KM.| last4=Tucha| first4=L.| last5=Tucha| first5=O.| title=The history of attention deficit hyperactivity disorder| journal=Atten Defic Hyperact Disord| volume=2| issue=4| pages=241–55|date=December 2010| doi=10.1007/s12402-010-0045-8| pmid=21258430| pmc=3000907}} Charles Bradley in Providence, Rhode Island, reported that a group of children with behavioral problems improved after being treated with the stimulant Benzedrine.{{cite journal|last1=Brown|first1=Walter A.|title=Charles Bradley, M.D., 1902–1979|journal=American Journal of Psychiatry|date=July 1998|volume=155|issue=7|page=968|doi=10.1176/ajp.155.7.968|doi-access=free}} In 1954, the stimulant methylphenidate (Ritalin, which was first produced in 1944) became available; it remains one of the most widely prescribed medications for ADHD. Initially the drug was used to treat narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications. The drug began to be used for ADHD in the 1960s and steadily rose in use.

In 1975, pemoline (Cylert) was approved by the U.S. FDA for use in the treatment of ADHD. While an effective agent for managing the symptoms, the development of liver failure in 14 cases over the next 27 years would result in the manufacturer withdrawing this medication from the market. New delivery systems for medications were invented in 1999 that eliminated the need for multiple doses across the day or taking medication at school. These new systems include pellets of medication coated with various time-release substances to permit medications to dissolve hourly across an 8–12 hour period (Metadate CD, Adderall XR, Focalin XR) and an osmotic pump that extrudes a liquid methylphenidate sludge across an 8–12 hour period after ingestion (Concerta).{{Citation needed|date=September 2008}}

In 2003, atomoxetine (Strattera) received the first FDA approval for a nonstimulant drug to be used specifically for ADHD.{{cite web|title=Straterra |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_Approv.pdf |publisher=FDA |access-date=May 22, 2019}} In 2007, lisdexamfetamine (Vyvanse) became the first prodrug{{cite web|title=Vyvance Approval |url= https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021977lbl.pdf|archive-url= https://web.archive.org/web/20130307020944/http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021977lbl.pdf|url-status= dead|archive-date= 7 March 2013|publisher=FDA |access-date=May 22, 2019}} for ADHD to receive FDA approval.{{cite journal |title=Vyvance |journal=Pharmacy Times |date= September 2007 |url= https://www.pharmacytimes.com/publications/issue/2007/2007-09/2007-09-6763 |publisher=FDA |access-date=May 22, 2019|last1=Domenici |first1=Caryn |last2=Patel |first2=Alka }} In March 2019, a Purdue Pharma subsidiary received approval from the FDA for Adhansia XR, a methylphenidate medication to treat ADHD.{{cite news|title=Sacklers quit Purdue Pharma board amid shifts for OxyContin maker |url=https://www.stamfordadvocate.com/business/article/Sacklers-quit-Purdue-Pharma-board-signaling-13742946.php |date=April 7, 2019 |work=Stamford Advocate |access-date=May 22, 2019 | vauthors = Schott BP }}

Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. In terms of cost-effectiveness, management with medication has been shown to be the most cost-effective, followed by behavioral treatment, and combined treatment. The individually most effective and cost-efficient way is with stimulant medication. Additionally, long-acting medications for ADHD, in comparison to short-acting varieties, generally seem to be cost-effective.{{cite journal |author=Schlander|title=Long-acting medications for the hyperkinetic disorders: a note on cost-effectiveness|journal=European Child & Adolescent Psychiatry|volume=16|issue=7|pages=421–429 (Page:421)|year=2007|doi=10.1007/s00787-007-0615-2|pmid=17401606|s2cid=142779320 |url=http://www.michaelschlander.com/pnp/publications_en/Schlander-CEAs-ADHD-Long-Acting-Meds-ECAP-2007.pdf |archive-url=https://web.archive.org/web/20071014131641/http://www.michaelschlander.com/pnp/publications_en/Schlander-CEAs-ADHD-Long-Acting-Meds-ECAP-2007.pdf |archive-date=14 October 2007 }} Comorbid (relating to two diseases that occur together, e.g. depression and ADHD) disorders makes finding the right treatment and diagnosis much more costly than when comorbid disorders are absent.{{Citation needed|date=January 2024}}

File:Koffein_-_Caffeine.svg is sometimes used to manage ADHD symptoms.]]

{{See also|Alternative therapies for developmental and learning disabilities}}

Most alternative therapies do not have enough supporting evidence to recommend them.{{cite journal|last1=Bader|first1=A|last2=Adesman|first2=A|title=Complementary and alternative therapies for children and adolescents with ADHD.|journal=Current Opinion in Pediatrics|date=December 2012|volume=24|issue=6|pages=760–9|pmid=23111680|doi=10.1097/mop.0b013e32835a1a5f|s2cid=41643161}}{{cite journal|last1=Sonuga-Barke|first1=EJ|last2=Brandeis|first2=D|last3=Cortese|first3=S|last4=Daley|first4=D|last5=Ferrin|first5=M|last6=Holtmann|first6=M|last7=Stevenson|first7=J|last8=Danckaerts|first8=M|last9=van der Oord|first9=S|last10=Döpfner|first10=M|last11=Dittmann|first11=RW|last12=Simonoff|first12=E|last13=Zuddas|first13=A|last14=Banaschewski|first14=T|last15=Buitelaar|first15=J|last16=Coghill|first16=D|last17=Hollis|first17=C|last18=Konofal|first18=E|last19=Lecendreux|first19=M|last20=Wong|first20=IC|last21=Sergeant|first21=J|last22=European ADHD Guidelines|first22=Group|s2cid=434310|title=Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments |journal=The American Journal of Psychiatry|date=1 March 2013|volume=170|issue=3|pages=275–89|pmid=23360949|doi=10.1176/appi.ajp.2012.12070991|url=https://biblio.ugent.be/publication/4088857/file/6800877 |url-access=subscription}} Moreover, when only the best conducted studies are taken into account results tend to be similar to placebo.

According to a study done by the National Institute of Mental Health, medication, either alone or combined with behavioral therapy was the most effective course of treatment in reducing ADHD symptoms. They also found that although medication had some long-term side effects, it was ultimately safer and more effective than routine community care. The researchers studies 600 7-9 year old children and found that the benefits lasted at least 14 months with great improvement in academic performance and social skills. The researchers also found that combining medication with behavioral therapy allowed for the same effectiveness with a lower dosage of medicine.{{Cite journal |last=Newcorn |first=Jeffrey H. |date=2000 |title=The multimodal treatment study of children with attention deficit hyperactivity disorder |url=http://link.springer.com/10.1007/s11920-000-0050-2 |journal=Current Psychiatry Reports |language=en |volume=2 |issue=2 |pages=85–89 |doi=10.1007/s11920-000-0050-2 |issn=1523-3812|url-access=subscription }}

Neurofeedback (NF) or EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD.{{cite journal|pmid=17386306|last1=Greydanus|first1=DE|last2=Pratt|first2=HD|last3=Patel|first3=DR|title=Attention deficit hyperactivity disorder across the lifespan: the child, adolescent, and adult|journal=Disease-a-Month|volume=53|issue=2|pages=70–131|date=February 2007|doi=10.1016/j.disamonth.2007.01.001}} The human brain emits electrical energy which is measured with electrodes. Neurofeedback alerts the patient when beta waves are present. This theory believes that those with ADHD can train themselves to decrease ADHD symptoms.{{citation needed|date=June 2013}}

No serious adverse side effects from neurofeedback have been reported.{{cite journal |vauthors=Moriyama TS, Polanczyk G, Caye A, Banaschewski T, Brandeis D, Rohde LA |title=Evidence-based information on the clinical use of neurofeedback for ADHD |journal=Neurotherapeutics |volume=9 |issue=3 |pages=588–98 |date=July 2012 |pmid=22930416 |doi=10.1007/s13311-012-0136-7 |pmc=3441929}} Research into neurofeedback has been mostly limited and of low quality. While there is some indication on the effectiveness of biofeedback it is not conclusive: several studies have yielded positive results, however the best designed ones have either shown reduced effects or non-existing ones.{{Failed verification|date=August 2016}}{{cite journal |vauthors=Lofthouse N, Arnold LE, Hurt E |title=Current status of neurofeedback for attention-deficit/hyperactivity disorder |journal=Curr Psychiatry Rep |volume=14 |issue=5 |pages=536–42 |date=October 2012 |pmid=22890816 |doi=10.1007/s11920-012-0301-z |s2cid=37075142 }} In general no effects have been found in the most blinded ADHD measures, which could be indicating that positive results are due to the placebo effect.{{cite journal|last1=Holtmann|first1=M|last2=Sonuga-Barke|first2=E|last3=Cortese|first3=S|last4=Brandeis|first4=D|title=Neurofeedback for ADHD: A Review of Current Evidence|journal=Child and Adolescent Psychiatric Clinics of North America|date=October 2014|volume=23|issue=4|pages=789–806|pmid=25220087|doi=10.1016/j.chc.2014.05.006|url=https://biblio.ugent.be/publication/5841198|hdl=1854/LU-5841198|hdl-access=free}}

Preliminary studies have supported the idea that playing video games is a form of neurofeedback, which helps those with ADHD self-regulate and improve learning.{{cite news| url=http://usatoday30.usatoday.com/tech/gaming/2006-03-09-game-therapy_x.htm | work=USA Today | first1=Susan | last1=Jenks | title=ADHD patients play video games as part of treatment | date=9 March 2006}}{{cite journal | author = Butnik S.M. | s2cid = 25108272 | year = 2005 | title = Neurofeedback in adolescents and adults with attention deficit hyperactivity disorder | journal = Journal of Clinical Psychology | volume = 61 | issue = 5 | pages = 621–625 | doi = 10.1002/jclp.20124 | pmid = 15723361 | doi-access = free }} Memory, multitasking, fluid intelligence, and other cognitive talents may be improved by certain computer programmes and video games.{{Cite journal |last1=Small |first1=Gary W. |last2=Lee |first2=Jooyeon |last3=Kaufman |first3=Aaron |last4=Jalil |first4=Jason |last5=Siddarth |first5=Prabha |last6=Gaddipati |first6=Himaja |last7=Moody |first7=Teena D. |last8=Bookheimer |first8=Susan Y. |date=June 2020 |title=Brain health consequences of digital technology use |journal=Dialogues in Clinical Neuroscience |volume=22 |issue=2 |pages=179–187 |doi=10.31887/DCNS.2020.22.2/gsmall |issn=1958-5969 |pmc=7366948 |pmid=32699518 }} On the other hand, ADHD may experience great difficulty disengaging from the game, which may in turn negate any benefits gained from these activities,{{cite journal |author1=Shaw R. |author2=Grayson A. |author3=Lewis V. | year = 2000 | title = Inhibition, ADHD, and computer games: The inhibitory performance of children and ADHD on computerized tasks and games | journal = Journal of Attention Disorders | volume = 8 | issue = 4 | pages = 160–168 | doi = 10.1177/1087054705278771 | pmid = 16110046 |s2cid=21265539 }} and time management skills may be negatively impacted as well.{{cite journal | author = Tolchinsky A. |author2=Jefferson, S.D. | year = 2011 | title = Problematic video game play in a college sample and its relationship to time management skills and Attention-Deficit/Hyperactivity disorder symptomology |journal = Cyberpsychology, Behavior, and Social Networking | volume = 14 | issue = 9| pages = 489–496 | doi = 10.1089/cyber.2010.0315 | pmid=21288135}}

Children who spend time outdoors in natural settings, such as parks, seem to display fewer symptoms of ADHD, which has been dubbed "Green Therapy".{{cite journal|last1=Rojas|first1=NL|last2=Chan|first2=E|title=Old and new controversies in the alternative treatment of attention-deficit hyperactivity disorder|journal=Mental Retardation and Developmental Disabilities Research Reviews|date=2005|volume=11|issue=2|pages=116–30|pmid=15977318|doi=10.1002/mrdd.20064}}

{{Main|Diet and attention deficit hyperactivity disorder}}

There is insufficient evidence to support dietary changes in ADHD and thus they are not recommended by the American Academy of Pediatrics as of 2019.{{cite journal |last1=Wolraich |first1=ML |last2=Hagan JF |first2=Jr |last3=Allan |first3=C |last4=Chan |first4=E |last5=Davison |first5=D |last6=Earls |first6=M |last7=Evans |first7=SW |last8=Flinn |first8=SK |last9=Froehlich |first9=T |last10=Frost |first10=J |last11=Holbrook |first11=JR |last12=Lehmann |first12=CU |last13=Lessin |first13=HR |last14=Okechukwu |first14=K |last15=Pierce |first15=KL |last16=Winner |first16=JD |last17=Zurhellen |first17=W |author18=Subcommittee on Children and Adolescents with attention-deficit/hyperactive disorder |title=Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents |journal=Pediatrics |date=October 2019 |volume=144 |issue=4 |pages=e20192528 |doi=10.1542/peds.2019-2528 |pmid=31570648|doi-access=free |pmc=7067282 }} Perhaps the best known of the dietary alternatives is the Feingold diet which involves removing salicylates, artificial colors and flavors, and certain synthetic preservatives from children's diets.{{cite journal | doi = 10.1023/A:1022321017467 | pmid = 12737097 | last1 = Schnoll | first1 = R | last2 = Burshteyn | first2 = D | last3 = Cea-Aravena | first3 = J | title = Nutrition in the treatment of attention-deficit hyperactivity disorder: a neglected but important aspect | journal = Applied Psychophysiology and Biofeedback| volume=28 | issue=1 |date=March 2003 | pages=63–75| s2cid = 7783422 }} However, studies have shown little if any effect of the Feingold diet on the behavior of children with ADHD.{{cite journal| doi=10.1080/10408399609527717| vauthors=Krummel DA, Seligson FH, Guthrie HA| s2cid=32631191| title=Hyperactivity: is candy causal?| journal=Critical Reviews in Food Science and Nutrition| volume=36| issue=1–2| pages=31–47| year=1996| pmid=8747098 }}

Results of studies regarding the effect of eliminating artificial food coloring from the diet of children with ADHD have been very varied. It has been found that it might be effective in some children but as the published studies have been of low quality results can be more related to research problems such as publication bias.{{cite journal |vauthors=Nigg JT, Lewis K, Edinger T, Falk M |title=Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives |journal=J Am Acad Child Adolesc Psychiatry |volume=51 |issue=1 |pages=86–97.e8 |date=January 2012 |pmid=22176942 |doi=10.1016/j.jaac.2011.10.015 |pmc=4321798}}

The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings{{cite web|url=http://www.biohealthbase.org/pages/food-coloring-ban-in-uk-but-usa-usage-continues/|title=Food coloring ban in the UK but usage continues for USA|work=BioHealthBase BRC Team |archive-url = https://web.archive.org/web/20141102230222/http://www.biohealthbase.org/pages/food-coloring-ban-in-uk-but-usa-usage-continues/ | archive-date = 2 November 2014 |date=23 October 2014}} and the European Union (EU) has ruled that some food dyes must be labeled with the relevant E number as well as this warning: "may have an adverse effect on activity and attention in children."{{cite web|url=http://www.flex-news-food.com/console/PageViewer.aspx?page=17642|title=Modernising the Rules on Food Additives and Labelling of Azo Dyes|work=FLEXNEWS: Business News for the Food Industry|publisher=Global Data Systems|archive-url = https://web.archive.org/web/20081202060545/http://www.flex-news-food.com/console/PageViewer.aspx?page=17642 | archive-date = 2 December 2008 |agency = European Parliament |date=9 July 2008}} Nevertheless, existing evidence neither refutes nor supports the association between ADHD and food colouring.{{cite journal |vauthors=Kleinman RE, Brown RT, Cutter GR, Dupaul GJ, Clydesdale FM |title=A research model for investigating the effects of artificial food colorings on children with ADHD |journal=Pediatrics |volume=127 |issue=6 |pages=e1575–84 |date=June 2011 |pmid=21576306 |doi=10.1542/peds.2009-2206 |doi-access=free }}

Dietary supplements, self-medication,{{cite journal |last1=Wilson |first1=JJ |last2=Levin |first2=FR |title=Attention deficit hyperactivity disorder (ADHD) and substance use disorders. |journal=Current Psychiatry Reports |date=December 2001 |volume=3 |issue=6 |pages=497–506 |doi=10.1007/s11920-001-0044-8 |pmid=11707164|s2cid=46121828 }} and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. However a 2009 article in the Harvard Mental Health Letter states, "Although vitamin or mineral supplements [micronutrients] may help children diagnosed with particular deficiencies, there is no evidence that they are helpful for all children with ADHD. Furthermore, megadoses of vitamins, which can be toxic, must be avoided."{{cite Q|Q28251071|volume=25|issue=12|pages=4–5|pmid=19582942|archive-url = https://web.archive.org/web/20091227105634/https://www.health.harvard.edu/newsletters/Harvard_Mental_Health_Letter/2009/June/Diet-and-attention-deficit-hyperactivity-disorder |archive-date = 27 December 2009 |issn = 1057-5022 |url=http://www.health.harvard.edu/newsletters/Harvard_Mental_Health_Letter/2009/June/Diet-and-attention-deficit-hyperactivity-disorder}} In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA.{{cite web |url=https://www.fda.gov/cder/drug/infopage/ADHD/default.htm|title=FDA Asks Attention-Deficit Hyperactivity Disorder (ADHD) Drug Manufacturers to Develop Patient Medication Guides |access-date=13 April 2009 |publisher=Food and Drug Administration|date=21 September 2007 |archive-url = https://web.archive.org/web/20080221173118/https://www.fda.gov/cder/drug/infopage/ADHD/default.htm |archive-date = 21 February 2008}}

Some popular supplements used to manage ADHD symptoms:

• Caffeine – ADHD is associated with increased caffeine consumption, and caffeine's stimulant effects on cognition may have some benefits for ADHD.{{cite journal|last1=Ioannidis|first1=K|last2=Chamberlain|first2=SR|last3=Müller|first3=U|s2cid=13465319|title=Ostracising caffeine from the pharmacological arsenal for attention-deficit hyperactivity disorder—was this a correct decision? A literature review|journal=Journal of Psychopharmacology|date=September 2014|volume=28|issue=9|pages=830–6|doi=10.1177/0269881114541014|pmid=24989644}} Limited evidence suggests a small therapeutic effect that is markedly inferior to standard treatments like methylphenidate and dextroamphetamine while still producing similar or greater side effects.{{cite journal|last1=Schechter|first1=MD|last2=Timmons|first2=GD|title=Objectively measured hyperactivity—II. Caffeine and amphetamine effects|journal=Journal of Clinical Pharmacology|date=1985|volume=25|issue=4|pages=276–80|pmid=4008672|doi=10.1002/j.1552-4604.1985.tb02838.x|s2cid=33184695}}
• Nicotine – The association between ADHD and nicotine intake is well known, and limited evidence suggests that nicotine may help improve some of the symptoms of ADHD, although the effect is generally small.{{cite journal |vauthors=Toledano A, Alvarez MI, Toledano-Díaz A |title=Diversity and variability of the effects of nicotine on different cortical regions of the brain – therapeutic and toxicological implications |journal= Central Nervous System Agents in Medicinal Chemistry|volume=10 |issue=3 |pages=180–206 |date=September 2010 |pmid=20528766 |doi=10.2174/1871524911006030180 |hdl=10261/61750 }}{{cite journal|last1=McClernon|first1=FJ|last2=Kollins|first2=SH|title=ADHD and smoking: from genes to brain to behavior|journal=Annals of the New York Academy of Sciences|date=October 2008|volume=1141|issue=1|pages=131–47|doi=10.1196/annals.1441.016|pmid=18991955|pmc=2758663|bibcode=2008NYASA1141..131M}}{{cite journal|last1=Potter|first1=AS|last2=Schaubhut|first2=G|last3=Shipman|first3=M|title=Targeting the nicotinic cholinergic system to treat attention-deficit/hyperactivity disorder: rationale and progress to date |journal=CNS Drugs|date=December 2014|volume=28|issue=12|pages=1103–13|doi=10.1007/s40263-014-0208-9|pmid=25349138|pmc=4487649}}
• Omega-3 fatty acids – There is no evidence that supplementation with omega-3 or other polyunsaturated fatty acids provides any improvement in the symptoms of ADHD in children or adolescents.{{cite journal |vauthors=Gillies D, Leach MJ, Perez Algorta G |date=April 2023 |title=Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents |journal=Cochrane Database Syst Rev |volume=2023 |issue=4 |pages=CD007986 |doi=10.1002/14651858.CD007986.pub3 |pmid=37058600|pmc=10103546 }} A 2011 meta analysis found a "small but significant benefit", with benefits being "modest compared to the efficacy of currently available pharmacological treatments for ADHD".{{cite journal |vauthors=Bloch MH, Qawasmi A |title=Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis |journal=J Am Acad Child Adolesc Psychiatry |volume=50 |issue=10 |pages=991–1000 | date=October 2011 |pmid=21961774 |pmc=3625948 |doi=10.1016/j.jaac.2011.06.008 }} The review concluded that supplementation may be worth consideration as an augmentative treatment in combination with medication due to its "relatively benign side-effect profile", but not as a primary treatment. Most research on omega-3 fatty acids is considered to be of very poor quality with widespread methodological weaknesses.
• Zinc – Although the role of zinc in ADHD has not been elucidated, there is a small amount of limited evidence that lower tissue zinc levels may be associated with ADHD.{{cite journal|vauthors=Arnold LE, DiSilvestro RA|title=Zinc in attention-deficit/hyperactivity disorder|journal=Journal of Child and Adolescent Psychopharmacology|volume=15|issue=4|pages=619–27|year=2005|pmid=16190793|doi=10.1089/cap.2005.15.619 |hdl=1811/51593|hdl-access=free}} In the absence of a demonstrated zinc deficiency (which is rare outside of developing countries), zinc supplementation is not recommended as a treatment option for ADHD.{{cite journal|last1=Bloch|first1=MH|last2=Mulqueen|first2=J|title=Nutritional supplements for the treatment of ADHD|journal=Child and Adolescent Psychiatric Clinics of North America|date=October 2014|volume=23|issue=4|pages=883–97|pmid=25220092|doi=10.1016/j.chc.2014.05.002|pmc=4170184}}
• In the 1980s vitamin B₆ was promoted as a helpful remedy for children with learning difficulties including inattentiveness; however, a study of large doses of vitamins with ADHD children showed that they were ineffective in changing behavior.{{cite journal|vauthors=Haslam RH, Dalby JT, Rademaker AW |title=Effects of megavitamin therapy on children with attention deficit disorders|journal=Pediatrics|year=1984|volume=74|pages=103–111 | pmid= 6234505|issue=1|doi=10.1542/peds.74.1.103 |s2cid=24645872 }}

Regular physical exercise, particularly aerobic exercise, is an effective add-on treatment for ADHD in children and adults, particularly when combined with stimulant medication (although the best intensity and type of aerobic exercise for improving symptoms are not currently known).{{cite journal |vauthors=Den Heijer AE, Groen Y, Tucha L, Fuermaier AB, Koerts J, Lange KW, Thome J, Tucha O |title=Sweat it out? The effects of physical exercise on cognition and behavior in children and adults with ADHD: a systematic literature review |journal=Journal of Neural Transmission |volume=124 |issue=Suppl 1 |pages=3–26 |date=February 2017 |pmid=27400928 |pmc=5281644 |doi=10.1007/s00702-016-1593-7 |quote=Beneficial chronic effects of cardio exercise were found on various functions as well, including executive functions, attention and behavior. }}{{cite journal |vauthors=Kamp CF, Sperlich B, Holmberg HC |title=Exercise reduces the symptoms of attention-deficit/hyperactivity disorder and improves social behaviour, motor skills, strength and neuropsychological parameters |journal=Acta Paediatrica |volume=103 |issue=7 |pages=709–714 |date=July 2014 |pmid=24612421 |doi=10.1111/apa.12628 |quote=We may conclude that all different types of exercise ... attenuate the characteristic symptoms of ADHD and improve social behaviour, motor skills, strength and neuropsychological parameters without any undesirable side effects. Available reports do not reveal which type, intensity, duration and frequency of exercise is most effective |s2cid=45881887 |url=http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-22594|doi-access=free }}{{cite journal |vauthors=Rommel AS, Halperin JM, Mill J, Asherson P, Kuntsi J |title=Protection from genetic diathesis in attention-deficit/hyperactivity disorder: possible complementary roles of exercise |journal=Journal of the American Academy of Child and Adolescent Psychiatry |volume=52 |issue=9 |pages=900–910 |date=September 2013 |pmid=23972692 |pmc=4257065 |doi=10.1016/j.jaac.2013.05.018 |quote=The findings from these studies provide some support for the notion that exercise has the potential to act as a protective factor for ADHD. }} The long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved executive functions (including attention, inhibitory control, and planning, among other cognitive domains), faster information processing speed, and better memory. Parent-teacher ratings of behavioral and socio-emotional outcomes in response to regular aerobic exercise include: better overall function, reduced ADHD symptoms, better self-esteem, reduced levels of anxiety and depression, fewer somatic complaints, better academic and classroom behavior, and improved social behavior. Exercising while on stimulant medication augments the effect of stimulant medication on executive function. It is believed that these short-term effects of exercise are mediated by an increased abundance of synaptic dopamine and norepinephrine in the brain.

Based on a 2024 systematic literature review and meta analysis commissioned by the Patient-Centered Outcomes Research Institute (PCORI), seven randomized control trials were identified that report on the effectiveness of physical exercise for treating ADHD symptoms. The type and amount of exercise varied widely across studies from martial arts interventions to treadmill training, to table tennis or aerobic exercise. Because any effects reported were not replicated, the authors concluded that there is currently insufficient evidence that exercise intervention is an effective form of treatment for ADHD symptoms for children and adolescents.

Because ADHD comorbidities are diverse and the rate of comorbidity is high, special care must dedicated to certain comorbidities. The FDA is not set up to address this issue, and does not approve medications for comorbidities, nonetheless certain such topics have been extensively researched.

Patients with Tourette syndrome who are referred to specialty clinics have a high rate of comorbid ADHD. Patients who have ADHD along with tics or tic disorders may also have problems with disruptive behaviors, overall functioning, and cognitive function, accounted for by the comorbid ADHD.{{cite journal |vauthors=Sukhodolsky DG, Scahill L, Zhang H, etal | date = January 2003 | title = Disruptive behavior in children with Tourette's syndrome: association with ADHD comorbidity, tic severity, and functional impairment | journal = J Am Acad Child Adolesc Psychiatry | volume = 42 | issue = 1| pages = 98–105 | pmid = 12500082 | doi=10.1097/00004583-200301000-00016| s2cid = 24550481 }}

{{cite journal |vauthors=Hoekstra PJ, Steenhuis MP, Troost PW, etal | date = August 2004 | title = Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems in tic disorders | journal = J Dev Behav Pediatr | volume = 25 | issue = 4| pages = 272–9 | pmid = 15308928 | doi=10.1097/00004703-200408000-00007| s2cid = 22578353 }}

{{cite journal |vauthors=Carter AS, O'Donnell DA, Schultz RT, etal | date = February 2000 | title = Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome: associations with ADHD and family functioning. Attention Deficit Hyperactivity Disorder | journal = J Child Psychol Psychiatry | volume = 41 | issue = 2| pages = 215–23 | pmid = 10750547 | doi=10.1111/1469-7610.00602}}

{{cite journal | doi = 10.1111/1469-7610.00406 | last1 = Spencer | first1 = T | last2 = Biederman | first2 = J | last3 = Harding | first3 = M | last4 = O'Donnell | first4 = D | last5 = Wilens | first5 = T | last6 = Faraone | first6 = S | last7 = Coffey | first7 = B | last8 = Geller | first8 = D | title = Disentangling the overlap between Tourette's disorder and ADHD | journal = J Child Psychol Psychiatry | volume = 39 | issue = 7| pages = 1037–44 | pmid = 9804036 |date=October 1998}}

The treatment of ADHD in the presence of tic disorders has long been a controversial topic. Past medical practice held that stimulants could not be used in the presence of tics, due to concern that their use might worsen tics;{{cite web |last=Freeman |first=Roger D. |url=http://www.tourette-confusion.blogspot.com/ |title=Tourette's Syndrome: minimizing confusion |access-date=8 February 2006 |archive-date=11 April 2006 |archive-url=https://web.archive.org/web/20060411182519/http://www.tourette-confusion.blogspot.com/ |url-status=live }} RD Freeman, MD, is Clinic Head of Neuropsychiatry Clinic at British Columbia Children's Hospital, Vancouver, professional advisory board member of Tourette Syndrome Foundation of Canada, and former member of the Tourette Syndrome Association Medical Advisory Board. Freeman has over 180 journal-published articles on [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi PubMed.] however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders.{{cite journal |last1=Palumbo |first1=D |last2=Spencer |first2=T |last3=Lynch |first3=J |last4=Co-Chien |first4=H |last5=Faraone |first5=SV |title=Emergence of tics in children with ADHD: impact of once-daily OROS methylphenidate therapy |journal=Journal of Child and Adolescent Psychopharmacology |date=Summer 2004 |volume=14 |issue=2 |pages=185–94 |pmid=15319016 |doi=10.1089/1044546041649138 }}

{{cite journal |last1=Kurlan |first1=Roger |title=Tourette's syndrome: are stimulants safe? |journal=Current Neurology and Neuroscience Reports |date=July 2003 |volume=3 |issue=4 |pages=285–8 |pmid=12930697 |doi=10.1007/s11910-003-0004-2 |s2cid=35508887 }}

{{cite journal |last1=Law |first1=SF |last2=Schachar |first2=RJ |title=Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? |journal=Journal of the American Academy of Child and Adolescent Psychiatry |date=August 1999 |volume=38 |issue=8 |pages=944–51 |pmid=10434485 |doi=10.1097/00004583-199908000-00009 }} Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity.{{cite journal | pmid = 11865128 | author = Tourette's Syndrome Study Group | title = Treatment of ADHD in children with tics: a randomized controlled trial | journal = Neurology| volume=58 | issue=4 |date=February 2002 | pages=527–36 | doi = 10.1212/WNL.58.4.527| s2cid = 224482 }} A 2011 Cochrane Collaboration review concluded that most major ADHD medications were effective in children with tics, and that stimulants did not generally worsen tics outside of individual cases.{{Cite journal|last1=Osland|first1=Sydney T.|last2=Steeves|first2=Thomas Dl|last3=Pringsheim|first3=Tamara|date=26 June 2018|title=Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders|journal=The Cochrane Database of Systematic Reviews|volume=2018|issue=6 |pages=CD007990|doi=10.1002/14651858.CD007990.pub3|issn=1469-493X|pmc=6513283|pmid=29944175}} Methylphenidate, guanfacine, clonidine, and desipramine were associated with improvement of tic symptoms. Controversy remains, and the PDR continues to carry a warning that stimulants should not be used in the presence of tic disorders, so physicians may be reluctant to use them. Others are comfortable using them and even advocate for a stimulant trial when ADHD co-occurs with tics, because the symptoms of ADHD can be more impairing than tics.{{cite journal | pmid = 11077021 | last1 = Zinner |first1 = Samuel H. | title = Tourette disorder | journal = Pediatrics in Review | volume=21 | issue=11 |date=November 2000 | pages=372–83 |doi=10.1542/pir.21-11-372 | s2cid = 7774922 }}

The stimulants are the first line of treatment for ADHD, with proven efficacy, but they do fail in up to 20% of cases, even in patients without tic disorders.{{cite journal | pmid = 16554257 | last1 = Scahill | first1 = L| doi=10.1016/j.nurx.2006.01.009 | last2 = Erenberg | first2 = G | last3 = Berlin | first3 = CM | last4 = Budman | first4 = C | last5 = Coffey | first5 = BJ | last6 = Jankovic | first6 = J | last7 = Kiessling | first7 = L | last8 = King | first8 = RA | last9 = Kurlan | first9 = R | title = Contemporary assessment and pharmacotherapy of Tourette syndrome | journal = NeuroRx | volume=3 | issue=2 |date=April 2006 | pages=192–206 | last10 = Lang | first10 = Anthony | last11 = Mink | first11 = Jonathan | last12 = Murphy | first12 = Tanya | last13 = Zinner | first13 = Samual | last14 = Walkup | first14 = John | others = Tourette Syndrome Association Medical Advisory Board: Practice Committee | pmc = 3593444}} Current prescribed stimulant medications include: methylphenidate, dextroamphetamine, and mixed amphetamine salts (Adderall). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists (clonidine and guanfacine), tricyclic antidepressants (desipramine and nortriptyline), and newer antidepressants (bupropion and venlafaxine). There have been case reports of tics worsening with bupropion. There is good empirical evidence for short-term safety and efficacy for the use of desipramine, bupropion and atomoxetine.

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• List of investigational attention deficit hyperactivity disorder drugs

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de:Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung#Behandlung

fr:Trouble déficitaire de l'attention avec hyperactivité#Traitement