Pharmacology Update

Adderall XR—A New Long-Acting Drug for ADHD

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

Shire US Inc. has received FDA approval to market a once-daily extended-release form of mixed amphetamines (Adderall) for the treatment of attention deficit hyperactivity disorder (ADHD). Mixed amphetamines combine the neutral salts of dextroamphetamine and amphetamine, with the dextro isomers of amphetamine saccharate and d,l-amphetamine aspartate monohydrate at a 75:25% dextro to levoamphetamine. The mixture was first introduced 20 years ago as a diet drug, and has since been used extensively for ADHD. The extended-release capsules contain 50% of mixed amphetamines as immediate-release beads and 50% as extended-release beads. The product is marketed as Adderall XR.

Indications

Adderall XR is indicated for the treatment of ADHD.1

Dosage

The recommended starting dose for those being treated for the first time or those being switched to Adderall is 10 mg once daily in the morning. Those switching from Adderall should be started at the same daily dose administered once daily. The dose may be titrated in 5 mg or 10 mg increments weekly guided by efficacy and tolerability. The maximum dose is 30 mg daily.1 Dosage should be individualized. The capsules should be taken whole but the contents may be sprinkled on applesauce. High-fat meals delay the rate of absorption by about 2.5 hours compared to Adderall XR but does not affect extent of absorption.1

Adderall XR is available as 5-mg, 10-mg, 15-mg, 20-mg, 25-mg, and 30-mg capsules. Adderall XR is schedule C-II.

Potential Advantages

A single dose of Adderall XR provides plasma levels comparable to Adderall administered twice daily 4 hours apart.1 This provides a more convenient regimen avoiding the need for dosing at school or work.

Potential Disadvantages

The extended levels of amphetamines may extend the duration of side effects. The frequency (vs placebo) of the most common side effects is loss of appetite (22% vs 2%), insomnia (17% vs 2%), emotional lability (9% vs 2%), and nervousness (6% vs 2%).1 Patients with ADHD symptoms associated with acute stress should avoid amphetamines.

Comments

The efficacy of Adderall XR was established in 2 placebo-controlled, 3-week, parallel-group studies in children 6-12 years of age (n = 635). Patients were randomized to a fixed-dose of 10 mg, 20 mg, 30 mg, or placebo and extrapolated from immediate form of Adderall.1 In the studies, efficacy was based on teachers rating of attention and hyperactivity or behavior and performance. In general, mixed amphetamines have been shown to be comparable to methylphenidate in the management of ADHD.2,3 Mixed amphetamine salts have also been shown to be effective in adults. A 7-week, randomized, double-blind, placebo-controlled crossover study in 27 subjects reported a reduction in the ADHD rating scale of 30% or greater in 70% compared to 7% for placebo.4 At the same dose on mg/kg bases, children have a 30% less systemic exposure than adults.1 The clinical relevance of this phenomena is not clear. Adderall XR costs about $2/d regardless of the strength.

Clinical Implications

ADHD is often regarded as a disease of children and adolescents. However, it is often a lifelong condition and can affect adults who were diagnosed at childhood and has been an increasingly recognized disorder in adults.5,6 Psychostimulants and antidepressants are the primary treatment options.5,7,8 Adderall XR provides a once-daily formulation of mixed amphetamines. 

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Adderall XR product information. Shire US Inc, May 2002.

2. Manos MJ, et al. J Am Acad Child Adolesc Psychiatry. 1999;38:813-819.

3. Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2000;39:619-626.

4. Spencer T, et al. Arch Gen Psychiatry. 2001;58(8): 775-782.

5. Horrigan JP. Expert Opin Pharmacother. 2001;2: 573-586.

6. Wilens TE, et al. Annu Rev Med. 2002;53:113-131.

7. Wilens TE, et al. J Atten Disord. 2002;5(4):189-202.

8. Higgins ES. J Fam Pract. 1999;48(1):15-20.