Attention Deficit Hyperactivity Disorder (ADHD) Medication
- Author: Stephen Soreff, MD; Chief Editor: Glen L Xiong, MD more...
Although health care providers, parents, and teachers have hoped for effective therapies and methods that do not involve medications for children with attention deficit hyperactivity disorder (ADHD), evidence to date supports that the specific symptoms of ADHD are poorly treated without medication. Perhaps the mildest cases of ADHD can be treated with moderate success with environmental restructuring and behavioral therapy, but other than these limited situations, pharmacotherapy often is needed.
Compliance issues with medications for ADHD in children and adults is common. Therefore, the use of long-acting medications at once-a-day dosing to treat ADHD has been shown to have advances over the shorter acting drugs. They have led to higher rates of remission. Their use has been marked to better adherence and they have been demonstrated to be less stigmatizing. Another benefit of the long-acting medications is time of effectiveness (ie, full-day coverage). In 2015, the FDA approved a once-daily extended-release oral liquid for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children aged 6 years and older. In the same year, the FDA also approved a chewable tablet form of extended-release methylphenidate, to be sold as QuilliChew ER, for treatment of ADHD in patients aged 6 years or older. The tablet comes in strengths of 20, 30, and 40 mg and are scored so they can be split easily.The product is to be taken once daily in the morning.
ADHD has been associated with traffic accidents. Chang et al demonstrated that not only are persons with ADHD involved in more accidents but patients who adhere to their medication have reduced rates of such accidents. The association between ADHD and accidents was estimated with Cox proportional hazards regression. The authors conclude that this should lead to increased awareness about the association between serious traffic accidents and ADHD medication.
No link between current or new use of ADHD medications and an increased risk of serious cardiovascular events in young and middle-aged adults has been found.
The FDA has warned that methylphenidate may rarely cause prolonged and painful erections, known as priapism. Because priapism may cause permanent damage to the penis, patients taking methylphenidate who develop an erection lasting longer than 4 hours should seek immediate medical attention.
Webb JR et al report a high prevalence of stimulant use among medical students when compared with a larger, general population. More than 83% of students who took stimulants used them to stay awake, specifically for cognitive performance enhancement. The study suggests that this could impact attitudes towards prescribing such medications to patients with ADHD.
Numerous studies have shown a link between patients with ADHD and criminal activity. Lichtenstein and colleagues found that patients receiving ADHD medication had a significant decline in criminal activity. They found a significant reduction of 32% in the criminality rate for men (adjusted hazard ratio, 0.68; 95% confidence interval [CI], 0.63-0.73) and 41% for women (hazard ratio, 0.59; 95% CI, 0.50-0.70) during medicated periods compared with nonmedication periods.
These agents are known to treat ADHD effectively.
Methylphenidate is the drug of choice approved by FDA for ADHD in children aged 6 years or older. It is the most commonly used drug. Methylphenidate is available in sustained-release forms.
Dexmethylphenidate contains the more pharmacologically active d-enantiomer of racemic methylphenidate. It blocks norepinephrine and dopamine reuptake into presynaptic neurons and increases the release of these monamines into extraneuronal spaces. To allow once-daily dosing, each extended-release (XR) capsule contains half the dose as immediate-release capsules and half as enteric-coated, delayed-release capsules.
Dextroamphetamine and amphetamine mixtures produce CNS and respiratory stimulation. The CNS effect may occur in the cerebral cortex and reticular activating system. This combination may have direct effects on both alpha- and beta-receptor sites in the peripheral system, as well as release stores of norepinephrine in adrenergic nerve terminals.
The mixture contains various salts of amphetamine and dextroamphetamine. It is available as 5-, 7.5-, 10-, 12.5-, 15-, 20-, and 30-mg scored tablets.
Dextroamphetamine is commonly used first or in case of methylphenidate failure. It is approved by the FDA for use in children aged 3 years or older. It is available in sustained-release forms, which may allow for daily dosing.
Lisdexamfetamine is an inactive prodrug of dextroamphetamine. It elicits CNS stimulant activity. Lisdexamfetamine blocks norepinephrine and dopamine reuptake in presynaptic neurons and increases release of these monoamines in extraneuronal spaces. It is indicated for initial and maintenance treatment of ADHD for children aged 6-17 years and adults.
Noncatecholamine, sympathomimetic amine that elicits CNS stimulant activity. The precise mechanism by which amphetamines produce mental and behavioral effects are unclear. Available as short-acting tablets (Evekeo) that need 2-3 doses/day in children aged 3 years or older. It is also available as a long-acting, once daily oral suspension (Dyanavel XR) or extended release oral disintegrating tablets (Adzenys XR-ODT) for patients aged 6 years or older.
Psychiatry Agents, Other
Selective norepinephrine reuptake inhibitors have been shown to be effective in the treatment of ADHD.
Atomoxetine elicits selective inhibition of the presynaptic norepinephrine transporter. It is used to improve symptoms of ADHD.
Recent studies support efficacy of venlafaxine and bupropion in ADHD. They may have a slower onset of action than stimulants but potentially fewer adverse effects.
Bupropion inhibits neuronal dopamine reuptake in addition to being a weak blocker of serotonin and norepinephrine reuptake. It is also available in sustained-release preparations (Wellbutrin SR).
Venlafaxine may inhibit neuronal serotonin and norepinephrine reuptake. In addition, venlafaxine causes beta-receptor down-regulation. It is available in sustained-release preparations (Effexor XR).
See article entitled Depression. Patients may require lower doses for ADHD. They may have a quicker onset of action.
Imipramine inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neurons. It may be useful in pediatric ADHD.
Alpha2 agonists, central-acting
Centrally acting antihypertensives clonidine and guanfacine have been used to treat children with ADHD. Inhibition of norepinephrine release in the brain may be the mechanism of action.
Guanfacine has a similar mechanism of action to clonidine but has a longer half-life and may be less sedative. The extended-release formulation (Intuniv) is indicated for children with ADHD aged 6-17 years as monotherapy or as adjunctive therapy to stimulant medications.
Clonidine is a central alpha2 agonist. Its mechanism of action for ADHD is unknown. It is indicated for ADHD as adjunctive therapy to stimulants or as monotherapy. It is available as an extended-release tablet.
Moffitt TE, Houts R, Asherson P, Belsky DW, Corcoran DL, Hammerle M, et al. Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study. Am J Psychiatry. 2015 May 22. appiajp201514101266. [Medline].
Rosack J. PET Scans Reveal Action of Methylphenidate in Brain. Psychiatric News. Sept 21, 2001. 36, 18:
Kooistra L, van der Meere JJ, Edwards JD, Kaplan BJ, Crawford S, Goodyear BG. Preliminary fMRI findings on the effects of event rate in adults with ADHD. J Neural Transm. 2010 Feb 16. [Medline].
Cherkasova MV, Hechtman L. Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry. Can J Psychiatry. 2009 Oct. 54(10):651-64. [Medline].
Yang P, Wu MT, Dung SS, Ko CW. Short-TE proton magnetic resonance spectroscopy investigation in adolescents with attention-deficit hyperactivity disorder. Psychiatry Res. 2010 Feb 10. [Medline].
Sobel LJ, Bansal R, Maia TV, Sanchez J, Mazzone L, Durkin K, et al. Basal Ganglia surface morphology and the effects of stimulant medications in youth with attention deficit hyperactivity disorder. Am J Psychiatry. 2010 Aug. 167(8):977-86. [Medline].
Shaw P, Gilliam M, Liverpool M, et al. Cortical development in typically developing children with symptoms of hyperactivity and impulsivity: support for a dimensional view of attention deficit hyperactivity disorder. Am J Psychiatry. 2011 Feb. 168(2):143-51. [Medline].
Volkow ND, Wang GJ, Newcorn J, Telang F, Solanto MV, Fowler JS, et al. Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2007 Aug. 64(8):932-40. [Medline].
Morein-Zamir S, Hommersen P, Johnston C, Kingstone A. Novel Measures of Response Performance and Inhibition in Children with ADHD. J Abnorm Child Psychol. 2008 May 9. [Medline].
Akinbami LJ, Liu X, Pastor PN, Reuben CA. Attention deficit hyperactivity disorder among children aged 5-17 years in the United States, 1998-2009. NCHS Data Brief. 2011 Aug. 1-8. [Medline].
Goodman DW, Thase ME. Recognizing ADHD in adults with comorbid mood disorders: implications for identification and management. Postgrad Med. 2009 Sep. 121(5):20-30. [Medline].
Semiz UB, Basoglu C, Oner O, Munir KM, Ates A, Algul A, et al. Effects of diagnostic comorbidity and dimensional symptoms of attention-deficit-hyperactivity disorder in men with antisocial personality disorder. Aust N Z J Psychiatry. 2008 May. 42(5):405-13. [Medline].
Upadhyaya HP, Carpenter MJ. Is attention deficit hyperactivity disorder (ADHD) symptom severity associated with tobacco use?. Am J Addict. 2008 May-Jun. 17(3):195-8. [Medline].
Reiersen AM, Todd RD. Co-occurrence of ADHD and autism spectrum disorders: phenomenology and treatment. Expert Rev Neurother. 2008 Apr. 8(4):657-69. [Medline].
Halmoy A, Halleland H, Dramsdahl M, Bergsholm P, Fasmer OB, Haavik J. Bipolar symptoms in adult attention-deficit/hyperactivity disorder: a cross-sectional study of 510 clinically diagnosed patients and 417 population-based controls. J Clin Psychiatry. 2010 Jan. 71(1):48-57. [Medline].
Arcos-Burgos M, Jain M, Acosta MT, Shively S, Stanescu H, Wallis D, et al. A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol Psychiatry. 2010 Feb 16. [Medline].
Kopecková M, Paclt I, Petrásek J, Pacltová D, Malíková M, Zagatová V. Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case-control study of 100 subjects 6-10 age. Neuro Endocrinol Lett. 2008 Apr. 29(2):246-51. [Medline].
Faraone SV, Mick E. Molecular Genetics of Attention Deficit Hyperactivity Disorder. Psychiatr Clin North Am. 2010 Mar. 33(1):159-180. [Medline]. [Full Text].
Bellgrove MA, O'Connell RG, Vance A. Genetics of cognitive deficits in ADHD: clues for novel treatment methods. Expert Rev Neurother. 2008 Apr. 8(4):553-61. [Medline].
Padrón A, Galán I, García-Esquinas E, Fernández E, Ballbè M, Rodríguez-Artalejo F. Exposure to secondhand smoke in the home and mental health in children: a population-based study. Tob Control. 2015 Mar 25. [Medline].
Martel MM, Nikolas M, Jernigan K, Friderici K, Nigg JT. Personality Mediation of Genetic Effects on Attention-Deficit/Hyperactivity Disorder. J Abnorm Child Psychol. 2010 Feb 10. [Medline].
Tcheremissine OV, Salazar JO. Pharmacotherapy of adult attention deficit/hyperactivity disorder: review of evidence-based practices and future directions. Expert Opin Pharmacother. 2008 May. 9(8):1299-310. [Medline].
Volkow ND, Swanson JM. Does childhood treatment of ADHD with stimulant medication affect substance abuse in adulthood?. Am J Psychiatry. 2008 May. 165(5):553-5. [Medline].
Mannuzza S, Klein RG, Truong NL, Moulton JL 3rd, Roizen ER, Howell KH, et al. Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry. 2008 May. 165(5):604-9. [Medline].
Semrud-Clikeman M, Pliszka S, Liotti M. Executive functioning in children with attention-deficit/hyperactivity disorder: Combined type with and without a stimulant medication history. Neuropsychology. 2008 May. 22(3):329-40. [Medline].
Blader JC, Schooler NR, Jensen PS, Pliszka SR, Kafantaris V. Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. Am J Psychiatry. 2009 Dec. 166(12):1392-401. [Medline].
Solanto MV, Marks DJ, Wasserstein J, Mitchell K, Abikoff H, Alvir JM, et al. Efficacy of Meta-Cognitive Therapy for Adult ADHD. Am J Psychiatry. 2010 Aug. 167(8):958-968. [Medline].
Pelham WE Jr, Fabiano GA. Evidence-based psychosocial treatments for attention-deficit/hyperactivity disorder. J Clin Child Adolesc Psychol. 2008 Jan. 37(1):184-214. [Medline].
Young S, Myanthi Amarasinghe J. Practitioner Review: Non-pharmacological treatments for ADHD: A lifespan approach. J Child Psychol Psychiatry. 2009 Nov 4. [Medline].
Sonuga-Barke EJ, Brandeis D, Cortese S, et al. Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments. Am J Psychiatry. 2013 Mar 1. 170(3):275-89. [Medline].
Adler LD, Nierenberg AA. Review of medication adherence in children and adults with ADHD. Postgrad Med. 2010 Jan. 122(1):184-91. [Medline].
Hosenbocus S, Chahal R. A review of long-acting medications for ADHD in Canada. J Can Acad Child Adolesc Psychiatry. 2009 Nov. 18(4):331-9. [Medline]. [Full Text].
Buitelaar J, Medori R. Treating attention-deficit/hyperactivity disorder beyond symptom control alone in children and adolescents: a review of the potential benefits of long-acting stimulants. Eur Child Adolesc Psychiatry. 2009 Oct 13. [Medline]. [Full Text].
Cassels, C. FDA Okays Once-Daily Dyanavel XR for ADHD in Children. Medscape Medical News. Available at http://www.medscape.com/viewarticle/852988. October 21, 2015; Accessed: October 27, 2015.
Pfizer. Pfizer Receives U.S. FDA Approval of New QuilliChew ER™ (methylphenidate hydrochloride) extended-release chewable tablets CII. December 7, 2015. Available at http://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_u_s_fda_approval_of_new_quillichew_er_methylphenidate_hydrochloride_extended_release_chewable_tablets_cii?linkId=19384409.
Chang Z, Lichtenstein P, D'Onofrio BM, Sjölander A, Larsson H. Serious Transport Accidents in Adults With Attention-Deficit/Hyperactivity Disorder and the Effect of Medication: A Population-Based Study. JAMA Psychiatry. 2014 Jan 29. [Medline].
Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA. 2011 Dec 28. 306(24):2673-83. [Medline].
FDA. FDA warns of rare risk of long-lasting erections in males taking methylphenidate ADHD medications and has approved label changes. US Food and Drug Administration. Available at http://www.fda.gov/Drugs/DrugSafety/ucm375796.htm. Accessed: January 16, 2014.
Webb JR, Valasek MA, North CS. Prevalence of stimulant use in a sample of US medical students. Ann Clin Psychiatry. 2013 Feb. 25(1):27-32. [Medline].
Lichtenstein P, Halldner L, Zetterqvist J, et al. Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med. 2012 Nov 22. 367(21):2006-14. [Medline]. [Full Text].
Klein RG, Mannuzza S, Olazagasti MA, et al. Clinical and Functional Outcome of Childhood Attention-Deficit/Hyperactivity Disorder 33 Years Later. Arch Gen Psychiatry. 2012 Oct 15. 1-9. [Medline].
Chronis-Tuscano A, Molina BS, Pelham WE, Applegate B, Dahlke A, Overmyer M, et al. Very early predictors of adolescent depression and suicide attempts in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2010 Oct. 67(10):1044-51. [Medline].
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). 4th ed. Washington, DC: American Psychiatric Association; 2000. 78-85.
Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1. 57(11):1313-23. [Medline].
Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition?. World Psychiatry. 2003 Jun. 2(2):104-113. [Medline].
Kaplan HI, Sadock BJ, Grebb JA. Kaplan and Sadock's Synposis of Psychiatry. 7th ed. Baltimore, Md: Williams & Wilkins; 1994. 1063-8.
Rugino TA, Samsock TC. Modafinil in children with attention-deficit hyperactivity disorder. Pediatr Neurol. 2003 Aug. 29(2):136-42. [Medline].
Shillington AM, Reed MB, Lange JE, Clapp JD, Henry S. College undergraduate Ritalin abusers in Southwestern California: Protective and Risk Factors. J Drug Iss. 2006. 36:4:999-1014.
Spencer T, Biederman J, Wilens T. Nonstimulant treatment of adult attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2004 Jun. 27(2):373-83. [Medline].
White BP, Becker-Blease KA, Grace-Bishop K. Stimulant medication use, misuse, and abuse in an undergraduate and graduate student sample. J Am Coll Health. 2006 Mar-Apr. 54(5):261-8. [Medline].