Medications for Attention-Deficit / Hyperactivity Disorder
(June 2005)


Attention-deficit/hyperactivity disorder (ADHD) is a chronic condition for which there is no cure. The primary treatment goal is to optimize functioning in different domains that have been impaired and cause continued distress. For more than 60 years, stimulant therapy has been the single most effective treatment approach for children with ADHD.(1) Stimulants are the most extensively studied ADHD medications and are still considered first-line drugs.(2) Numerous studies have documented the efficacy of stimulants in reducing the core symptoms of ADHD in approximately 70 to 80 percent of affected children.(3) Stimulants are generally considered safe medications with few contraindications to their use.(4)

The three types of stimulants currently available include methylphenidate, dextroamphetamine and mixed salts of amphetamine. Each of these stimulants has similar side effects and can be grouped according to their approximate duration of action: short-acting (effects lasting 3 to 4 hours); intermediate-acting (effects lasting 6 to 8 hours); and long-acting (effects lasting 8 to 12 hours).(5) New delivery systems have increased the stimulants’ duration of action.(6)

This article aims to present an overview of stimulants for treating ADHD and will highlight key features of the newer medications. This may assist primary care physicians in choosing the stimulant that best suits the needs of their patients with minimal side effects.

Short-Acting Stimulants for ADHD
Short-acting stimulants include Ritalin®, Methylin®, Focalin®, Dexedrine® and Dextrostat®.(5)
We advise first trying patients on short-acting Ritalin — the most widely studied stimulant medication — before considering other stimulants. Methylin, a branded generic methylphenidate preparation, is both lactose- and dye-free. This may be better tolerated by children who have food sensitivities. Focalin is the d-isomer of methylphenidate and is supposedly less rapidly metabolized and degraded following oral administration. It is generally given at half the usual methylphenidate dose and its duration of action is under 6 hours.(6) Dexedrine and Dextrostat are short-acting dextroamphetamine products which offer beneficial effects similar to Ritalin.

Intermediate-Acting Stimulants for ADHD
Intermediate-acting stimulants include Ritalin-SR, Methylin ER, Metadate ER and Adderall tablets.(4,5) Ritalin-SR, the original sustained-release methylphenidate preparation, has a highly variable duration of action. Methylin ER (a lactose and dye-free generic methylphenidate preparation) and Metadate ER (a generic preparation of Ritalin-SR) have pharmacokinetic profiles similar to that of Ritalin-SR.(6) Adderall, a mixed amphetamine salts preparation, is an effective alternative stimulant that also has a variable duration of action. These stimulants may not be ideal for children who need consistent coverage throughout the 8-hour school day. These children should perhaps try a long-acting stimulant or a combination of intermediate- and short-acting stimulants. However, given the variability of clinical response to medication across patients, there will always be some children who benefit from intermediate-acting stimulants.

Long-Acting Stimulants for ADHD
The past four years have seen new, long-acting stimulant preparations. Ritalin LA® is a new methylphenidate preparation designed to provide once-a-day dosing throughout the school day. It uses bead technology and has a biphasic release, i.e., 50% immediate-release beads and 50% modified-release beads. Four hours after ingestion, methylphenidate diffuses out of the modified-release beads through pores in the outer polymer coating, resulting in a bimodal release profile. This creates smoother peaks and troughs compared with short-acting Ritalin administered B.I.D.(6)

Metadate CD® is a new sustained-release methylphenidate formulation that also uses bead technology and has a biphasic release. 70% of the dose is continuously released and 30% is rapidly released. It is designed to provide coverage throughout the school day but not after school. It can be sprinkled over food and is ideal for children who have difficulty with pills.(5,6)

Concerta® is an extended-release medication that uses a different delivery system, i.e., an oral osmotic therapeutic system designed to achieve a 12-hour duration of action. There is release of methylphenidate from the outer covering immediately after oral intake. This is followed by a progressive 8-hour release of medication through the osmotic pump. In each tablet, there are two separate drug sub-compartments with different drug concentrations.(5,6) This set-up ensures an increasing concentration of medication in the bloodstream in the afternoon. It allows for once-a-day dosing and eliminates the need for midday dosing, thereby reducing the potential for diversion and addressing social issues in older children and adolescents.

Adderall XR® is a new long-acting version of Adderall which has a drug delivery system similar to Ritalin LA. Fifty percent of the dose is delivered through immediate-release beads and the remaining 50% is released though other beads 4 hours after intake.(4,6) It is designed for once-a-day dosing and may have beneficial effects that last for 10 to 12 hours. Its absorption may be influenced by food, e.g., decreased drug delivery with a high-fat diet.

In general, methylphenidate and amphetamine preparations are equally effective in treating ADHD. Though most children respond well to both types of stimulants, some may respond better to one type than the other. Just as there is no preferred drug for ADHD, there is no single medication that meets the needs of all children. Primary care physicians should help parents to make informed decisions regarding medications while being open to trials of ADHD stimulants until optimal results are achieved with minimal side effects. In general, one can expect a beneficial response within one month of starting a new medication or increasing doses. In the event that treatment failure occurs, the existence of co-morbidities and a review of the diagnosis, adherence to treatment, and appropriateness of target outcomes need to be considered.(4,8)

References

1. Adesman, Andrew. Effective Treatment of Attention-Deficit/Hyperactivity Disorder: Behavior Therapy and Medication Management. Primary Psychiatry 2003. 10(4):55-60.
2. Nickel, R, Desch, L. The Physician’s Guide to Caring for Children with Disabilities and Chronic Conditions (2000). Baltimore: Paul H. Brookes Publishing Co.
3. Parker, S, Zuckerman, B, and Augustynn, M. Developmental and Behavioral Pediatrics. A Handbook for Primary Care (2nd ed). Philadelphia: Lippincott Williams and Wilkins.
4. American Academy of Pediatrics Subcommittee on ADHD, Committee on Quality Improvement. Clinical Practice Guidelines: Treatment of the School-Aged Child with Attention-Deficit/Hyperactivity Disorder. Pediatrics 2001. 108 (4). 1033-1044.
5. Wolraich, Mark. Disorders of Development and Learning. Oklahoma (2003): BC Decker, Inc.
6. Adesman, Andrew. New Medications for Treatment of Children with Attention-Deficit/Hyperactivity Disorder: Review and Commentary. Pediatric Annals 2002. 31 (8): 514-522.
7. Wender, EH. Managing Stimulant Medication for Attention-Deficit/Hyperactivity Disorder: An Update. Pediatrics in Review 2002. 23:234-236.
8. Wender, Paul. ADHD: Attention-Deficit/Hyperactivity Disorder in Children, Adolescents, and Adults (2002). New York: Oxford University Press.


This information provided by Lalaine Dimagiba-Sebastian, M.D. Child Development Center
Tel. (415) 600-6200