Vol.III, No.V
November/December 2000
Margaret Peters,
Pharm.D.
Return to
Pharmacotherapy
Update Index
|
Concerta™ for
Attention-Deficit/Hyperactivity Disorder
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.
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.
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™.
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.
References Available Upon Request
|
