Editing Attention deficit hyperactivity disorder (section)

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

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

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

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

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

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

'''Alpha-2a agonists'''

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