Concerta™ for Attention-Deficit/
Hyperactivity Disorder

Volume III, Number 5 | November/December 2000
Margaret Peters, Pharm.D.

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Introduction

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder of childhood, estimated to affect between 4 to 10% of all children. Unfortunately, the cause of this disorder remains unknown. Boys are two to three times more likely to be diagnosed with ADHD than girls, and the abnormal behavior usually begins to appear between 3 and 5 years of age. Children with ADHD exhibit excessive activity, cannot pay attention in the classroom, act impulsively, are more prone to injury, and engage in disruptive behaviors. These symptoms can persist into early adolescent years and, if left untreated, can lead to higher rates of antisocial personality and substance abuse in adulthood.

Diagnosis

While an independent diagnostic test for ADHD does not exist, three subtypes of the disorder can be diagnosed based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). These subtypes include hyperactive-impulsive type, inattentive type, and combined type. Despite these DSM-IV classifications, the diagnosis and subsequent treatment of ADHD remains controversial. In May 2000, the American Academy of Pediatrics released the first of two sets of guidelines to provide recommendations on ADHD intended for use by primary care physicians. The first publication of clinical practice guidelines focuses on the assessment and diagnosis of school-aged children with ADHD. The second set of guidelines will address the issue of treatment of children with ADHD. Unfortunately, these recommendations are not yet available. Nevertheless, the focus of this article will be current drug treatment options for ADHD, particularly the newest formulation of methylphenidate, Concerta™.

Table 1 contains FDA-approved stimulant drugs for the treatment of ADHD, as well as the dosages of these agents in children 6 years of age or older. Of these stimulants, methylphenidate is the most commonly prescribed agent.

Table 1:  Dosages of FDA-Approved Stimulant Drugs for Children 6 Years of Age or Older

Also available as a chewable tablet; QD=once daily; BID=twice daily, TID=three times daily.
Adapted from product labeling

Mechanism of Action, Adverse Drug Reactions, and Drug-Drug Interactions

The potential mechanism of action for methylphenidate in ADHD involves the blockade of dopamine reuptake and possibly norepinephrine and serotonin. The most common side effects associated with methylphenidate include headache, nausea, vomiting, anorexia, dizziness, and insomnia. Tics have been reported with methylphenidate, as well as growth suppression.

Methylphenidate may also lower the seizure threshold and increase blood pressure. Drug interactions with methylphenidate include decreased metabolism of drugs such as warfarin, phenobarbital, phenytoin, primidone, tricyclic antidepressants, and selective serotonin reuptake inhibitors (e.g., Prozac®, Luvox®, Celexa™, Paxil®, and Zoloft™). Additionally, methylphenidate should not be used with monoamine oxidase inhibitors (e.g., Parnate® and Nardil®).

Methylphenidate

Methylphenidate is available in three formulations: immediate-release (Ritalin®), sustained-release (Ritalin SR®), and now extended-release (Concerta™). Table 2 details the pharmacokinetics of the various formulations.

Table 2:  Pharmacokinetics of Methylphenidate Formulations

Concerta™

Concerta™ is a unique formulation of methylphenidate which uses an advanced OROS® patterned-release delivery system. The design of this system is similar to that of the Nifedipine Gastrointestinal Therapeutic System (GITS), except for the fact that Procardia XL® only consists of a two layer core. In contrast, the Concerta™ system contains a trilayer inner core surrounded by a semipermeable membrane with an immediate-release overcoat. This technology features a semipermeable rate-controlling membrane surrounding an osmotic core, which contains a push layer and a drug layer. Once in the gastrointestinal tract, water enters the osmotic system and dissolves or suspends the drug in the tablet's core. The drug is then released via osmotic pressure through a laser-drilled hole in the membrane at a controlled rate.

The benefit of this type of delivery system is extended symptom relief and reduction in the number of daily doses compared to conventional therapies. Another advantage to the Concerta™ formulation is that the outer layer of medication provides an immediate-release of methylphenidate within one hour. Compared to Ritalin SR®, which is formulated for a delayed onset of effect, Concerta™ has a quicker onset of action and alleviates the need to add another immediate-release product to Ritalin SR®.

When switching patients from the immediate- and sustained-release methylphenidate formulations to Concerta™, the dose depends upon the current regimen. Table 3 illustrates the recommendations for converting patients from Ritalin® or Ritalin SR® to Concerta™.

Table 3:  Dosage Conversions of Various Methylphenidate Formulations

QD = once daily, BID=twice daily, TID=three times daily, QAM=every morning
Adapted from product labeling

Conclusion

While controversy exists regarding the diagnosis and etiology of attention-deficit/hyperactivity disorder in children and adolescents, current management strategies include behavioral and pharmacological treatment. Stimulant medications are the drugs of choice because of their overall safety and efficacy. Of the stimulants available, methylphenidate is the most commonly prescribed agent for children with ADHD. When methylphenidate is prescribed, initial doses should be low, with small, gradual increases to reduce the risk of overmedicating and adverse effects. Currently, there are three formulations of methylphenidate, including immediate-release (Ritalin®), sustained-release (Ritalin SR®) and extended-release (Concerta™). Careful dosage adjustments are necessary when converting patients from one formulation to another. See Table 4 for information on pricing of the various methylphenidate formulations.

Table 4: AWP of Various Formulations and Dosages of Methylphenidate

Adapted from 2000 Drug Topics® Red Book®
AWP= Average wholesale price

References Available Upon Request

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