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Attention Deficit Hyperactivity Disorder (ADHD) Medication

  • Author: Stephen Soreff, MD; Chief Editor: Glen L Xiong, MD  more...
 
Updated: Jul 19, 2016
 

Medication Summary

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.[31] 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.[32] Another benefit of the long-acting medications is time of effectiveness (ie, full-day coverage).[33]  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.[34]  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.[35]

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.[36] 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.[37]

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.[38]

Prescription practices

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.[39]

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.[40]

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Stimulants

Class Summary

These agents are known to treat ADHD effectively.

Methylphenidate (Ritalin, Metadate CD, Methylin ER, Ritalin SR)

 

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 (Focalin, Focalin XR)

 

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 (Adderall)

 

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 (Dexedrine)

 

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 (Vyvanse)

 

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.

Amphetamine (Dyanavel XR, Evekeo)

 

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.

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Psychiatry Agents, Other

Class Summary

Selective norepinephrine reuptake inhibitors have been shown to be effective in the treatment of ADHD.

Atomoxetine (Strattera)

 

Atomoxetine elicits selective inhibition of the presynaptic norepinephrine transporter. It is used to improve symptoms of ADHD.

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Atypical antidepressants

Class Summary

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 (Wellbutrin)

 

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 (Effexor)

 

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).

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Tricyclic antidepressants

Class Summary

See article entitled Depression. Patients may require lower doses for ADHD. They may have a quicker onset of action.

Imipramine (Tofranil)

 

Imipramine inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neurons. It may be useful in pediatric ADHD.

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Alpha2 agonists, central-acting

Class Summary

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 (Intuniv)

 

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 (Kapvay)

 

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.

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Contributor Information and Disclosures
Author

Stephen Soreff, MD President of Education Initiatives, Nottingham, NH; Faculty, Boston University, Boston, MA and Daniel Webster College, Nashua, NH

Stephen Soreff, MD is a member of the following medical societies: ACMHA: The College for Behavioral Health Leadership

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Glen L Xiong, MD Associate Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California, Davis, School of Medicine; Medical Director, Sacramento County Mental Health Treatment Center

Glen L Xiong, MD is a member of the following medical societies: AMDA - The Society for Post-Acute and Long-Term Care Medicine, American College of Physicians, American Psychiatric Association, Central California Psychiatric Society

Disclosure: Received royalty from Lippincott Williams & Wilkins for book editor; Received grant/research funds from National Alliance for Research in Schizophrenia and Depression for independent contractor; Received consulting fee from Blue Cross Blue Shield Association for consulting. for: Received book royalty from American Psychiatric Publishing Inc.

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