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DRUGS FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER

This discussion is about medications for attention received a black box warning in 2005 because of deficit hyperactivity disorder (ADHD). The focus is an increased risk of suicidal thinking in children and on new forms of and new information about the adolescents, but not in adults.3 medications. The information in this column is not is the only nonstimulant indicated adequate to guide the treatment of ADHD, which for treatment of ADHD. It is thought to act through should be initiated by a provider who has expertise selective inhibition of the presynaptic norepineph- in the field. Behavior therapy can be effective rine transporter, thus providing increased levels of either by itself or used with medications.1 The in the synaptic cleft. Atomoxetine American Academy of Pediatrics develops clinical can increase blood pressure and heart rate, like the practice guidelines for ADHD. See the National . Urinary hesitancy and retention are Guideline Clearinghouse for the latest guideline important risks. Somnolence and upset stomach (www.guideline.gov). are common.4 was briefly removed from the Canadian market in 2005 as a result of concerns about sudden deaths in children. Five of 12 cases were in patients with structural heart defects; others had concomitant conditions.5 Currently, the FDA is considering a black PRESCRIPTION PAD box warning for all stimulants regarding the risk of cardiac death. The cardiac effects of stimulants are not well understood. Maren Mayhew Daytrana, the transdermal patch, was released in June 2006.6 It is probably as effective as oral long-acting forms of the drug. The Food and Drug Administration (FDA) has However, the delay (2-6 hours) in onset of action issued a number of alerts and warnings about may cause difficulty. The advantage is that the some of the drugs used for ADHD in the past few patch can be removed in time to avoid insomnia. years. Pemoline (Cyclert) (sold from 1975 to 1999) Absorption increases after chronic use. Plasma was removed from the market as a result of life- concentrations were similar to Concerta at first, threatening hepatic failure. Pemoline is a central but later the concentrations were almost double. nervous system (CNS) with a different Skin reactions may be a problem.7 chemical structure from and The effect of stimulants on normal growth in methylphenidate. children is unknown and is much debated. Inci- Atomoxetine (Strattera), introduced in 2002, dents have been found of children with received a warning for severe injury in 2004.2 decreased growth rate on stimulants and on ato- There were reports of two patients, a teenager and moxetine, but a causal effect has not been an adult, both of whom recovered. Atomoxetine established.

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Table 1. ADHD Drugs

Trade Name Drug Name Supplied As Duration of Action Cost, $* Ritalin Methylphenidate (MPH) 5, 10, 20 mg IR 30 Ritalin LA Methylphenidate 20 mg 50% IR; then 50% 4 h later90 Ritalin SR Methylphenidate 20 mg Variable release over 5-8 h 110 Daytrana Methylphenidate patch 12.5 = 10 mg/9 h Apply to hip for 9 h. Onset 150 18.75 = 15 mg/9 h 1-6 h (average 3); half-life 25 = 20 mg/9 h after patch removed 3-4 h 37.5 = 30 mg/9 h Concerta Methylphenidate 18 mg 4 mg IR; then 14 mg over 8 100 h; total 12 h at 5 mg tid Metadate CD Methylphenidate 20 mg 30% IR then 70% XR = 10 105 mg in AM + 10 mg 4 h later Focalin 2.5, 5, 10 mg IR 70 (d-MPH) Focalin XR Dexmethylphenidate 5, 10, 20 mg 50% IR, second delayed 100 release of 50% Adderall 4, 7.5, 10, 12.5, 75 compounds 15, 20, 30 mg

Adderall XR Amphetamine 10, 15, 20, 25, Equivalent to two IR 75 compounds 30 mg doses 4 h apart

Dexedrine 5 mg Peak at 2 h; half-life 30 sulfate 10-25 h Dex Spansule Dextroamphetamine 5, 10, 15 mg Peak 8 to 10 h 65 sulfate Strattera Atomoxetine 10, 18, 25, 40, 60, Half-life 5 h 90 80, 100 mg

IR indicates immediate release; XR, extended release. *Cost is approximate, from Medical and Drug Letter. Most information in chart comes from product information.

Stimulants have abuse potential. Also, many chil- ligrams of methylphenidate is roughly equivalent to dren and adolescents with ADHD also have comor- 5 mg of dexmethylphenidate, and each has imme- bidity such as substance abuse disorder, opposi- diate release and extended release forms (Table 1). tional defiant disorder, enuresis, depressive disor- The mechanism of action of stimulants is through ders, and anxiety disorders. Use can lead to toler- two neurotransmitter systems, the monoamines ance and psychological dependence with abnormal and norepinephrine, making more behavior. Psychotic episodes can occur. Careful dopamine available in the synaptic cleft.8 supervision is required during withdrawal. The most common effects are anorexia and There are three types of stimulants— insomnia, headaches, and stomachaches. Other methylphenidate, dextroamphetamine, and adverse effects are nausea, rebound phenomena, amphetamine compounds. Dexmethylphenidate is anxiety, nightmares, dizziness, irritability, dysphoria, the right isomer of methylphenidate. Ten mil- and weight loss.9

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References

1. Chatfield J. AAP guideline of treatment of children with ADHD. Am Fam Physician. 2002;65(4). Available at:www.aafp.org/afp/20020215/ practice.html.Accessed June 28, 2006. 2. DA. Talk Paper: new warning for Strattera. 2004 Dec 17. Available at: www.fda.gov. Accessed June 28, 2006. 3. FDA Public Health Advisory: suicidal thinking in children and adolescents being treated with Strattera (atomoxetine). 2005 Sep 29.Available at:www.fda.gov.Accessed June 28, 2006. Official Journal 4. Mosby Drug Consult, Mosby, St. Louis, 2007. of the American 5. Food and Drug Administration. Public health advisory for Adderall College of Nurse and Adderall XR. 2005 Feb 9. Available at:www.fda.gov.Accessed June 28, 2006. Practitioners 6. FDA News. FDA approves methylphenidate patch to treat attention deficit hyperactivity disorder in children. 2006 Apr 10. Available at: Editor-in-Chief: www.fda.gov.Accessed June 28, 2006. Marilyn W. Edmunds, PhD, NP 7. Transdermal methylphenidate (Daytrana) for ADHD. Med Lett Drugs Ther. 2006;48(1237):49-51. ou are invited to 8. Parker S. Pediatric and adolescent ADHD: pharmacotherapy Ycontribute to The highlights. 2006 Mar 27. Available at:www.medscape.com/ viewprogram/5065.Last accessed June 28, 2006. Journal for Nurse 9. Mosby’s Drug Consult, Mosby, St. Louis, 2007. Practitioners (JNP). JNP provides a highly visible Maren Mayhew, MS, ANP, GNP, is the author and editor resource to help nurse of Pharmacology for Primary Care Providers, a textbook practitioners stay current for NPs published by Mosby. She can be reached at with the clinical and policy [email protected]. This is a monthly column Visit the Author on medication news and controversies. Suggestions for concerns affecting their topics are welcome. Guidelines section at day-to-day practice. www.npjournal.org 1555-4155/07/$ see front matte Be a part of JNP! © 2007 American College of Nurse Practitioners Submit your original doi:10.1016/j.nurpra.2007.11.008 articles today.

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