Certifications 

Prevalence 

Symptoms of ADHD 

Etiology 

Diagnosis 

MANAGEMENT
Pharmacologic Treatment of ADHD

Stimulants 

Antidepressants 

Alpha-2 Agonists 

CONCLUSION 

TABLES 

Table 1

Table 2

Table 3 

REFERENCES 

 
Support for this CE has been provided through an unrestricted educational grant by 
Medeva Pharmaceuticals 

Attention-Deficit Hyperactivity Disorder in Children and Adolescents

Linda G. Tolstoi, RPh, MS, MEd

Ms. Tolstoi is a visiting scientist with Boston University’s Center for Advanced Biotechnology in the Department of Biomedical Engineering and is a lecturer for the Pennsylvania State University Fayette Campus in Uniontown, Pennsylvania.

Introduction 

At the turn of the century, physicians were aware of young children who were active and impulsive.^1,2 In the 1930s, the modern history of attention-deficit hyperactivity disorder (ADHD) began when Dr. Charles Bradley and his successors began to systematically study a group of children who showed signs of inattention, distractibility, impulsivity, poor persistence, and disinhibition.² The physicians used names such as “minimal brain dysfunction” and “hyperkinesis” to describe the children’s behavior. In 1937, Bradley used the first stimulant drug (racemic amphetamine) to treat the hyperactivity.³ This was followed by dextroamphetamine (d-amphetamine) and, in the mid-1950s, methylphenidate.² 

Researchers are discovering that ADHD is not a disorder of attention, per se, as previously thought. Instead, they are finding that ADHD occurs as a result of a developmental failure in the brain circuitry that plays an important role in inhibition and self-control.⁴ Loss of one’s self-control adversely affects other brain functions that are crucial for maintaining attention, such as one’s ability to defer an immediate reward for a greater gain at a later time. However, it is only recently that the National Institute of Mental Health recognized the fact that ADHD is a psychological condition.⁵ 

ADHD is characterized by two types of behavior—inattention and a combination of hyperactivity and impulsivity.⁴ Most children, compared to adults, are more active, distractible, and impulsive. However, when children display these behaviors more significantly than their peers, it suggests that a problem exists.⁴

ADHD, one of the major clinical and public health problems in the United States, is associated with morbidity and disability in children and adolescents.⁶ It creates a serious burden on the health care system,⁶ which accounts for a significant number of referrals to family physicians, pediatricians, pediatric neurologists, and child psychiatrists.⁷ ADHD has an enormous impact on society in terms of financial cost, stress to families, disruption in schools, and its negative effect on self-esteem.⁶ Unfortunately, children with ADHD are at risk for developing psychiatric disorders (i.e., antisocial behaviors, alcoholism and substance abuse, and symptoms of depression and anxiety). 

Presently, controversy continues to exist regarding the definition, prevalence, diagnosis, etiology, and management of ADHD.⁸ The difficulty in defining ADHD is that learning disabilities and other neurologic or emotional problems can be associated with the disorder.⁵

Prevalence 

Epidemiologic studies of ADHD using standard diagnostic criteria provide evidence that 3% to 6% of school-aged children (including elementary through high school) may have the disorder¹—perhaps as many as 2 million American children.⁹   On the average, at least one student in every classroom requires help. Boys compared to girls are two to three times more likely to be affected with ADHD.⁹ Although the abnormal behavior usually begins to appear between 3 and 5 years of age, the symptoms may not develop until late childhood or early adolescence.⁴ 

Symptoms of ADHD

ADHD is the most common behavioral disorder diagnosed during childhood and adolescence.¹⁰ These children experience learning difficulties and behavioral problems that affect their social interactions, academic performance, and family.¹¹ Unfortunately, the abnormal behavior often continues into adulthood, where it is associated with an increased risk of psychological disorders, irresponsible and impulsive lifestyles, and sociopathic behaviors.¹¹ 

The three main signs of ADHD are inattentiveness, hyperactivity, and impulsivity.¹² The term “inattentive type” describes an individual who can’t seem to get focused or stay focused on a task or activity. A hyperactivity-impulsive type of individual is very active and often acts without thinking. An individual with the combined type of ADHD is inattentive, impulsive, and too active. Table 1 lists some of the behavioral characteristics of patients with ADHD.¹² From time to time, all children are inattentive, impulsive, and overactive. However, these signs of behavior are the rule and not the exception in children who have ADHD.¹² 

Table 1.  Some Behavioral Signs 
of Inattentiveness and 
Hyperactivity-Impulsivity

When a child exhibits signs of ADHD, he/she needs to be evaluated by a qualified professional to rule out other causes for the child’s behavior and to determine if the child has other disabilities that may accompany ADHD.¹² Although there is no quick cure for ADHD, the symptoms can be managed by pharmacologic and nonpharmacologic treatments.^9,12

Etiology

Although the etiology of ADHD is not known, researchers have suggested many possible theories.⁹ Recently, researchers have shown an increased interest in the genetic basis of ADHD.¹³ The results of their research studies suggest that ADHD is a familial disorder. Other genetic studies implicate faulty genes that govern the biochemical activity of neurotransmitters.^4,8 For example, dopamine, a neurotransmitter, communicates with brain structures affected in ADHD.⁴ However, a mutation in the genetic code for the dopamine receptor or dopamine transporter interferes with the ability of dopamine to convey messages from one nerve cell to another. 

Many different nongenetic or environmental factors have been linked to ADHD. One theory suggested that minor head injuries or undetectable brain damage as a result of early infection or birth complications were responsible for attention deficit disorders.⁹ However, this theory was rejected because of insufficient evidence.

It appears that maternal smoking is associated with a higher risk for ADHD.⁵ During pregnancy, the use of cigarettes and alcohol may be dangerous to the fetus’s developing brain, because the alcohol and nicotine may distort developing nerve cells.⁹ Many children who are born with fetal alcohol syndrome show behavioral characteristics similar to children with ADHD.⁹ 

Research studies suggest that drug abuse (e.g., cocaine) may harm brain receptors that play an important role in transmitting incoming signals (eg, skin, eyes, ears) and control one’s response to the environment.⁹ Damage to these receptors may lead to ADHD. 

Lead, an environmental toxin, is found in dust, soil, and flaking paint in areas where leaded gasoline and paint were previously used.⁹ Children who consume low amounts of lead display behavioral symptoms similar to ADHD.⁵ These children are easily distracted, disorganized, and have difficulty thinking in a logical manner. 

Dietary factors, such as refined sugar and food additives (eg, artificial flavorings and preservatives), have been implicated in causing hyperactivity and inattentiveness in children.⁹ In 1982, the National Institutes of Health concluded that the restricted diet only seemed to help approximately 5% of children with ADHD.⁹ Most of the children who benefitted from the restricted diet were either young children or children with food allergies.

Medical problems (i.e., hearing or vision problems, thyroid dysfunction, genetic disorders [eg, fragile X syndrome], and some types of seizure disorders) can cause ADHD-like symptoms.⁸

And finally, an unstable or dysfunctional home life has also been considered a factor.^9,14 However, researchers are finding evidence suggesting that a clear relationship between home life and ADHD does not exist; further research is needed.⁹ 

Diagnosis

Diagnosis of ADHD is difficult because it cannot be identified by particular organic signs or neurologic indicators.¹⁵ Also, the popularity of the disorder sometimes discourages parents, teachers, and physicians from searching for the possibility of other causes. 

Presently, children or adolescents who consistently show certain behavioral characteristics over a period of time may be diagnosed as having ADHD.⁹ It is important to note that everyone shows some of these behavioral characteristics at one time or another. Therefore, very specific diagnostic criteria for ADHD have been established by the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).¹⁶ 

Diagnosis of ADHD depends on the presence of inattention, hyperactivity, and impulsivity, or a combination of these characteristic behaviors. First, these behavioral characteristics must appear before the age of 7 and continue for at least 6 months.⁹ Second, in children, these behaviors must appear more frequently or be more severe compared with other children of the same age. And finally, these behavioral characteristics must create a real handicap in at least two areas of an individual’s life, such as school, home, work, or social settings.⁹ 

Since no specific tests for the diagnosis of ADHD exist, an accurate diagnosis depends on gathering information about the patient.¹⁴ For children, the following areas need to be evaluated: history (eg, family, medical, psychosocial, scholastic), sensory screening (eg, hearing), and examinations (eg, physical, neurologic).¹⁷

Diagnosis must differentiate between ADHD and other medical conditions that may cause symptoms similar to ADHD.⁸ A child may also be inattentive or occasionally overactive because of allergic symptoms or the effects of the drugs prescribed to control allergies.⁸

Management

Unfortunately, there is no cure or “quick fix” for ADHD.¹⁸ Table 2 lists different types of controversial treatments that have not been scientifically proven to be helpful in treating the majority of children with ADHD.⁹

Table 2. 
Some Types 
of Controversial Treatments for ADHD

The purpose of managing ADHD is to help patients focus their attention, build self-esteem, and function in new ways.⁹ Although drugs can be of value to patients with ADHD, this complex disorder requires a multiple therapeutic approach¹⁹ known as multimodal management (Table 3).¹⁸ A broader range of clinical symptoms may be treated by the multiple therapeutic approach than by either psychosocial intervention or pharmacological treatment alone.²⁰ Also, a lower dosage of the drug(s) and a less complicated program of psychosocial intervention may be possible than with either treatment alone.²⁰ 

Table 3. Multimodal Management of ADHD

Conditions That Coexist with ADHD

Psychological conditions that coexist with ADHD are symptomatically distinct disorders²¹; they include Tourette’s syndrome, oppositional defiant disorder (ODD), and conduct disorder (CD). Tourette’s syndrome, a rare disorder, occurs in a very small proportion of people with ADHD.⁹ Clinical symptoms include tics and other movements (ie, eye blinks or facial twitches) that cannot be controlled by the patient. ODD coexists in about half of the children (mostly boys) diagnosed with ADHD.⁹ These children are characterized by refusing to follow any or all instructions.⁵ Sometimes ODD can progress to more serious conduct disorders.⁹ Children with CD have a tendency to lie, cheat, and sneak to avoid obeying rules.²² 

Anxiety disorders (eg, obsessional disorders) and mood disorders (eg, depression) frequently co-exist with ADHD and affect attention.²¹ Children who are significantly depressed may experience the same characteristics as children with ADHD.²² Children with depression may be unhappy most of the time, may be irritable, show signs of negativity, are poorly motivated, and are unable to keep up with their schoolwork. However, these children tend to be hypoactive compared to children with ADHD.²²

Unfortunately, many professionals confuse learning and language disabilities (the conditions that most commonly coexist with ADHD⁸) with ADHD itself. Learning and language disabilities and ADHD are distinctly different in terms of their etiology and methods of diagnosis and therapy. Confusion occurs because children with ADHD also do poorly in school. 

Not all children with ADHD have a coexisting disorder.⁹ Conversely, not all patients with psychological disorders or learning disabilities have ADHD. However, it is important to watch for these disorders in children with ADHD, because they can seriously complicate the patient’s life.⁹ 

Pharmacologic Treatment  of ADHD

For more than 60 years, drugs have played a key role in managing ADHD.²³ Stimulant medications (eg, methylphenidate) are the drugs of choice because of their overall efficacy and safety. Since approximately 25% of the children with ADHD do not respond to the first stimulant drug prescribed, additional drugs usually must be prescribed before the patient achieves an adequate response.²² Alternative drugs (eg, antidepressants) play a very important role in managing children who do not respond to or cannot tolerate the adverse effects of the stimulant medications.¹⁹ 

When a drug is prescribed to treat ADHD, the initial dose should be low, with gradual, small increases¹⁷ to reduce the risk of overmedicating a child, to minimize adverse effects, and to reduce parental anxiety.²⁴

Stimulants

In the United States, stimulants account for more than 95% of the prescriptions written for ADHD.²³ This class of drugs includes methylphenidate (Schedule II), amphetamines (Schedule II), and pemoline (Schedule IV). Methylphenidate is the stimulant most commonly prescribed for children with ADHD.²² 

In general, this class of drugs produces its effect by stimulating the central nervous system (CNS) in areas of the brain that control impulses, self-regulation of behavior, and attention.¹⁹ Supposedly, these drugs help to “normalize” these functions in children with ADHD. Although the exact mechanism of these drug-induced responses is not well defined, it is probably related to the increased availability of the neurotransmitters (eg, dopamine, norepinephrine) at the neuronal synapses.¹⁹

When stimulants are administered orally, the drugs reach their peak plasma levels within a few hours.²⁵ Usually, methylphenidate and d-amphetamine are administered two to three times a day. Although the effects of methylphenidate and d-amphetamine become apparent quickly, it may take many weeks before maximum effectiveness of the drugs can be evaluated.¹⁷ 

Both methylphenidate and d-amphetamine are available in regular and sustained-release (SR) dosage forms. The SR tablet of methylphenidate has proven to be not as reliable as the regular tablet.²³ The slow onset of action (up to 2 hours) of the SR tablet can be offset by the coadministration of a 5- or 10-mg regular tablet.²³ The SR spansule (capsule) of d-amphetamine compared to the SR tablet of methylphenidate has been more reliable with an onset of action of 1 hour.²³ However, the beneficial effects from the SR dosage forms of both drugs have been shown to vary considerably compared to the short-acting forms.²⁵ An advantage of the SR dosage form is that it avoids the need for an in-school dose. The SR spansule of d-amphetamine allows greater flexibility in titrating the drug because the SR spansule is available in three strengths.²² However, it is important to advise patients not to chew the SR dosage forms, so that the extended-release properties of the drug may be maintained.²⁶ If a child has difficulty in swallowing the SR spansule, the capsule can be opened and the contents sprinkled onto applesauce.¹⁰

Just recently, ALZA Corporation announced that it has received approval from the FDA to market a new dosage form (extended-release tablets) of methylphenidate. The new dosage form requires once-daily dosing and eliminates the need for multiple doses of the drug throughout the day.

When a short-acting d-amphetamine tablet is prescribed, 5 mg is suggested as a reasonable initial dose.²⁴ However, it is recommended that one half of the starting dose (2.5 mg) be prescribed when treating preschool-aged or other small children.²⁴ Since d-amphetamine is twice as potent as methylphenidate, a 5-mg dose of SR d-amphetamine administered in the morning delivers the equivalent of a 5-mg dose of methylphenidate administered at breakfast and lunch.²⁴ 

Physicians hesitate to prescribe methylphenidate for children who are younger than 5 or 6 years.²² First, it may be difficult for the physician to establish a diagnosis of ADHD. Second, methylphenidate is not consistently effective in the preschool group. 

Pemoline has a longer half-life compared with the other stimulants, but it takes several days before a clinical response is apparent.²⁴ Although it is recommended that pemoline be administered once a day in the morning,¹⁷ research studies suggest that the drug is more effective when the total dose is split into two doses.²²

For pemoline, the suggested initial dose is 37.5 mg.²² However, it is recommended that an initial dose of 18.75 mg be prescribed for very small children.²² Although the drug is not available in a short-acting dosage form, it is available as a chewable tablet.

This class of drugs is not a perfect treatment for ADHD because of the usual need for frequent dosing, adverse effects, and other potential risks (eg, abuse, hepatotoxicity).²⁶ The SR dosage forms of d-amphetamine and methylphenidate also have relatively short half-lives.²² Therefore, the patient not only requires multiple dosing, but the potential for rebound hyperactivity exists.²² Many patients may experience the rebound effect in the afternoon when the pharmacologic effects of the stimulant subside.¹⁰ It can occur within several days or sometimes many months after the initiation of pharmacologic therapy. The symptoms include irritability, crankiness, increased aggression, overactivity, or crying.¹⁰ An additional dose of the stimulant is required at lunch time or in the afternoon to counteract the rebound effect.¹⁰ It is important to note that pemoline does not cause a rebound effect.²² 

In general, most of the adverse effects of stimulant drugs are related to dose and become apparent within the first few days or weeks of treatment.²⁴ When the drug is discontinued, most of the adverse effects disappear. In addition, many of the adverse effects improve or disappear when the dose is reduced.²⁴ 

Loss of appetite, difficulty sleeping, and emotional disturbances are the most common adverse effects of stimulant drugs.²² Some studies suggest that a slightly greater incidence of appetite suppression and sleep disturbances may occur with d-amphetamine compared with methylphenidate or pemoline.²⁴ Methylphenidate can cause emotional disturbances, such as depression, anger, irritability, or oppositional defiant behavior.²² D-amphetamine has about the same propensity to cause emotional problems in children with ADHD.²² It is important to be aware of the fact that individuals vary considerably with respect to adverse effects.²⁴ 

Appetite suppression is worse in the beginning of pharmacologic treatment, but it can continue until the drug therapy is discontinued.²⁴ Subsequent weight loss can vary from 0.5 to 2.25 kg.¹⁰ If the child’s weight loss exceeds 10%, it is recommended that a different stimulant be prescribed.²³ Therefore, the patient’s weight should be monitored prior to and during treatment with psychostimulants.²⁶ If the drug causes anorexia or abdominal pains, it may be beneficial to administer the drug after meals.²⁵ Parents should be reminded to provide well-balanced meals when the child is hungry.²³ Finally, stimulants are contraindicated for children when weight and caloric intake is a problem (eg, cystic fibrosis, insulin-dependent diabetes mellitus).²⁵

Many children with ADHD have sleep disturbances prior to treatment with stimulant drugs.²⁴ Usually, mild insomnia, a drug-related adverse effect, is worse during the first few days of drug therapy, but may continue throughout the period of treatment. If a child has difficulty sleeping, one solution to minimize the problem is to administer the last dose at least 5 hours before bedtime.²² Also, the patient’s physician may prescribe an additional drug (eg, clonidine).²⁴ Parents need to be advised that the safety of exogenous administration of melatonin at nighttime has not been studied in children.²⁴

Controversy exists regarding the possibility of developing abnormal motor movements or tics, an adverse effect of stimulant drugs.²⁷ It is estimated that less than 1% of the children who are treated with stimulants develop tics.²⁵ If the child with ADHD develops a tic, it is recommended that the drug be discontinued immediately.²⁴ Usually, the tic disappears within a few weeks, but it may be necessary to change to a different drug (eg, stimulant, nonstimulant) or adjust the dose of the initial stimulant.²⁴ Occasionally, stimulants may prematurely precipitate the symptoms (eg, tics) of Tourette’s syndrome.^23,24 Behaviors such as lip licking and throat clearing are examples of tics.²⁴

When a patient has a concomitant tic disorder, it is recommended that stimulants not be prescribed if alternative drugs (eg, tricyclic antidepressants [TCAs], clonidine) can be used successfully.²⁷ Since the natural course of tics is variable, parents need to be aware of the fact that tics can be exacerbated by both pharmacologic factors and nonpharmacologic factors (eg, stress).²¹ 

Although an increased baseline heart rate and blood pressure are common with stimulants, they are rarely of clinical significance.²³ However, patients who are treated with stimulants should have their blood pressure and heart rate monitored on a regular basis.²⁸ 

The potential for addiction is well documented for the stimulants, except for pemoline.²³ When the recommended doses for stimulants are prescribed for patients with ADHD, they do not experience euphoria, and the incidence of physiologic and psychological dependence is rare.²⁹ However, amphetamines are contraindicated in patients with a history of drug abuse.²⁸ 

Amphetamines and methylphenidate need to be used cautiously with certain drugs because of drug-drug interactions.²⁸ An increased dose of an amphetamine (eg, d-amphetamine) may be necessary when a TCA is prescribed, because the antidepressant may decrease the effects of the psychostimulant.³⁰ It has been reported that methylphenidate inhibits the metabolism of anticonvulsants (eg, phenobarbital, phenytoin, and primidone) and TCAs.³¹ Thus, methylphenidate may increase the serum concentrations of these drugs to toxic levels. Therefore, it may be necessary to decrease the dosage of these drugs.

The major disadvantage of pemoline is its potential to cause hepatotoxicity.³² Therefore, baseline and quarterly liver function tests are necessary when the drug is prescribed for patients with ADHD.¹⁰ Also, parents need to be educated about the signs (eg, fatigue, nausea, or vomiting) of liver toxicity.²⁷ Pemoline should not be prescribed for patients with any history of alcoholism, quiescent or ongoing liver dysfunction, or abnormal liver function tests.¹⁰ 

Antidepressants

Although antidepressants are the second line of treatment for ADHD, they are often helpful in combination with stimulants in managing associated mood and anxiety disorders.³³

Commonly prescribed TCAs include imipramine, amitriptyline, nortriptyline, desipramine, and clomipramine.³⁴ TCAs increase the concentration of neurotransmitters, such as norepinephrine and serotonin, at the synaptic cleft by inhibiting the reuptake of the neurotransmitters. Many clinical studies document the efficacy of various TCAs in treating the symptoms of ADHD at different doses, but the relationship to serum levels is unclear.⁶

Typically, TCAs reach a peak plasma level within 2 to 8 hours after rapid and complete absorption by the gastrointestinal (GI) tract.³⁴ Since TCAs are bound to plasma proteins, other drugs that compete for the protein-binding sites can affect the plasma levels of TCAs.³⁴ Aspirin, phenytoin, scopolamine, and phenothiazines can potentiate the effects of TCAs by increasing TCA plasma levels. In the liver, microsomal enzymes metabolize the TCAs.³⁴ However, hepatic metabolism of TCAs can be impaired by other drugs (eg, fluoxetine) that are metabolized by the liver.

Careful monitoring of the patient is required because of the serious adverse effects of TCAs.¹⁴ Initially, the daily dosage should be small and then gradually increased over time to minimize the adverse effects. An accidental overdose of TCAs can cause abnormal cardiac rhythms that are reflected on the electrocardiogram (ECG).³⁵ 

The anticholinergic symptoms are more apparent with imipramine, amitriptyline, and clomipramine compared with nortriptyline and desipramine.³⁴ Although the anticholinergic effects of TCAs are usually mild, they can be managed by appropriate treatment or by adjusting the dose of the TCA.³⁴ Some of the anticholinergic symptoms include dry mouth, blurred vision, urinary retention, and constipation. A decrease in the production of saliva may cause tooth decay in some children.

TCAs, except for desipramine, can cause excessive weight gain.³⁴ Therefore, the patient’s weight should be monitored when TCAs are prescribed.

When TCA therapy is stopped abruptly, the patient may experience flulike symptoms (ie, nausea, abdominal discomfort and pain, vomiting, and fatigue).³⁵ Usually, tapering the drug over a period of 10 to 14 days avoids or significantly diminishes the flulike symptoms.³⁵

Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, fluoxetine, and paroxetine, do not affect the core symptoms of ADHD.¹² However, SSRIs may be very effective in treating depression and obsessive-compulsive symptoms that can accompany ADHD.¹² The therapeutic margin of safety of SSRIs is extremely wide.¹⁰ Serious adverse effects and the potential for toxicity from overdose are rare, and the potential for abuse does not exist. The most common adverse effects include occasional headaches, insomnia, somnolence, and GI distress.¹⁰ Although these drugs are safe and effective, some SSRIs may increase the risk for impulsive behavior.⁵

Bupropion, an antidepressant of the aminoketone class, is not chemically related to other known antidepressants (eg, tricyclics, tetracyclics).³⁵ Bupropion is not as effective as stimulants or TCAs in treating ADHD.³⁶ The safety and efficacy of the drug has not been established officially for patients under 18 years of age.³⁶ Although clinical studies provide evidence that the drug is more effective in adolescents compared to children, the drug is not usually recommended for younger children.³⁶ The most common adverse effects of bupropion are agitation, dry mouth, insomnia, headaches, nausea, vomiting, constipation, tremors, and skin rash.³⁵

Alpha-2 Agonists

Clonidine, a third line of treatment for ADHD, is recommended when none of the stimulants or antidepressants is effective.³³ Clonidine, an alpha2-noradrenergic agonist,¹⁰ acts in the CNS to decrease the noradrenergic output.¹⁹ Initially, clonidine was reported to be of value in treating Tourette’s syndrome.^37,38 Also, some children with ADHD seemed to benefit from the drug. Clonidine is beneficial to patients who are hyperaroused, extremely overactive, oppositional defiant, or have conduct disorders.¹⁰ 

Clonidine at bedtime may be of value in treating sleep disturbances associated with ADHD or its treatment.^39,40 The effectiveness of clonidine in improving sleep in children and adolescents may be related to its potential to cause somnolence and its effect in reducing ADHD symptoms (eg, motoric hyperactivity).³⁹ The somnolent properties of the drug begin within 30 minutes after it is administered and generally last until the morning.³⁹ When children take the drug at nighttime for sleep disturbances, adverse effects such as morning sedation, hypotension, postural dizziness, confusion, or depression have not been reported.³⁹ When the drug is stopped abruptly, hypertension, diaphoresis, diarrhea, and tachycardia may occur.²⁵

Adverse effects have been associated with clonidine therapy. Adverse cardiac effects and abnormal ECGs have been associated with the combination of methylphenidate and clonidine.³⁷ When the dose of clonidine was reduced, the cardiovascular and ECG abnormalities disappeared. Clonidine is contraindicated for patients who have arrhythmias or cardiac abnormalities, because the drug decreases blood pressure and pulse rate.²⁵ 

Clonidine is available in two dosage forms, tablets and transdermal patch. It is necessary to stabilize the patient on oral clonidine before the patch can be used.¹⁰ Recently, two cases of unintentional overdose of transdermal clonidine in pediatric patients were reported.⁴¹ The safety and efficacy of the transdermal patch is not only dependent on the integrity of the transdermal system, but also on the condition of the dermal surface where the patch is applied. Patient education regarding appropriate precautions plays an important part in preventing toxicity associated with the clonidine patch in children and adolescents.⁴¹ Cardiovascular monitoring is recommended in children who are treated with clonidine alone or in combination with methylphenidate.⁴²

Although the half-life of clonidine is 8 to 12 hours in children, the behavioral effects of the drug appear to last 3 to 6 hours.⁴³ Therefore, the oral dosage form of the drug is prescribed three to four times a day. The transdermal therapeutic system (TTS) patch eliminates the need for multiple dosing.⁴³ Usually, the patch is applied on a clean, dry hairless area of the patient’s back. The transdermal patches are available in three strengths (eg, 0.1, 0.2, 0.3 mg).⁴³ A total daily oral dose of 0.1 mg is equivalent to the TTS-1 patch.⁴³ Contact dermatitis, a skin reaction to the patch, can be reduced by rotating sites on the body and treating the dermatitis with topical steroids.¹⁰ 

Guanfacine, a centrally acting antihypertensive agent, has selective alpha2A-adrenoreceptor agonist properties in contrast to clonidine, a less selective alpha2 agonist.³⁵ A preliminary study provides evidence that guanfacine appears to be helpful in reducing hyperactivity and enabling greater attention span with minimal adverse effects in patients with ADHD.⁴⁴ Guanfacine seems to be less sedating and also less hypotensive compared to clonidine.⁴⁵

Common adverse effects of guanfacine include sedation, sleep disturbances, and headache.⁴⁵ Sedation is associated with increases in dose. Patients may wake up 6 to 8 hours after the bedtime dose. Usually, these annoying adverse effects can be managed by slowly adjusting the dose upward, decreasing the dose, or changing the schedule of dosing.⁴⁵ 

Usually, the initial dose of guanfacine is 0.5 mg/day and is gradually increased every 4 to 5 days in 0.5-mg increments.⁴⁵ The daily dosage ranges from 1.5 to 3 mg in three divided doses.⁴⁵ 

Guanfacine is available in the oral dosage form of 1- and 2-mg tablets.⁴³ Therefore, it is important to be aware of the difference in the 0.1-mg dose of clonidine compared to the 1-mg dose of guanfacine.⁴³

Conclusion

During the past 40 years, ADHD, a childhood neuropsychiatric syndrome, has been thoroughly studied.¹ However, the pathophysiology remains unknown. Recently, researchers have been showing an increased interest in the genetic basis of the disorder, but ADHD is a complex multifactorial disorder, and environmental factors need to be considered as well.¹³ However, researchers know relatively little about the interaction between genes and environment.

Although most individuals do not outgrow ADHD, they can learn to adapt and live meaningful lives.⁹ Effective combinations of drugs, new skills, and emotional support can help these patients to develop ways to control their attention and minimize their disruptive behaviors.⁹ 

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Temple University School of Pharmacy is approved by the American Council on Pharmaceutical Education (ACPE) as a provider of continuing pharmaceutical education. Its CE programs are developed in accordance with the “Criteria for Quality and Interpretive Guidelines” of ACPE. This program is acceptable for 2.0 hours of Continuing Education Credits (0.2 CEU) through September 30, 2003. ACPE Pgm I.D.  057-999-00-017-H01.