Attention-Deficit/Hyperactivity Disorder: An Overview

Attention-deficit/hyperactivity disorder (ADHD), a common psychiatric disorder that affects all age groups, has been a subject of interest due to the increase in cases diagnosed. Researchers estimate that ADHD affects 4% to 12% of school-age children in the United States^1,2 and 4% of college-age students and adults.³ The ratio of boys to girls in children diagnosed with ADHD is 3:1.^1,2 If the disorder is left untreated, the societal impact is considerable, resulting in conduct problems, poor academic performance, and difficulties with personal relationships and employment,⁴ as well as a greater risk of a range of psychiatric problems and/or substance abuse.⁵

Diagnosing ADHD

The diagnosis and treatment of ADHD remain controversial subjects within the media and among health care professionals, yet ADHD has been consistently and reliably diagnosed both in children and adults.^2,6 The current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defines the criteria for diagnosing ADHD, which include 6 or more symptoms of inattention or of hyperactivity and impulsivity (Table 1).⁷ Adult ADHD presents itself with similar symptoms. Nearly 50% of childhood patients continue the symptoms and illness into adulthood, experiencing academic, social, and work-related underachievement.^8-10 Interestingly, many ADHD patients exhibit comorbid disorders, such as anxiety, depression, bipolar disorder, and even Tourette's syndrome.¹¹ Adults with ADHD usually manifest comorbidity in a similar fashion, especially anxiety, depression, and substance abuse.^2,12

Basically, the diagnosis of ADHD is derived from observation of the patient, family history, academic records, and medication history.¹³ In essence, the patient must meet the DSM-IV criteria, including the presence of some hyperactive-impulsive or inattentive symptoms before the age of 7, as well as impaired functioning at school, home, or work that is not related to another medical condition.⁷

Treatment Considerations

Once the diagnosis of ADHD has been established, a treatment approach typically is implemented. The treatment generally consists of some behavioral therapy prior to or in conjunction with medication, whereby a network among teachers, physicians, and parents is established to improve the chances of a better therapeutic outcome.

Yet, pharmacologic therapy??consisting of psychostimulants, antidepressants, and even antihypertensives??usually is the way to proceed in treating ADHD. The FDA has approved various stimulants as well as atomoxetine (Strattera), a nonstimulant, for use in children. Only amphetamine compounds and atomoxetine have been approved for use in adults.² The mechanism of action of agents used to treat ADHD generally is unknown. It is thought, however, that the neurotransmitters dopamine and norepinephrine play a role in the efficacy of these drugs by helping patients organize their thoughts and improve concentration and attention??albeit with unpleasant side effects. Whereas stimulants and atomoxetine have proven effective as single agents in treating ADHD, combined therapy may be required by some patients.¹⁴

Psychostimulants

Psychostimulant drugs, generally considered first-line therapy and an effective way to treat ADHD, often are the agents of choice for children, whereas other alternatives may be considered for adults where drug abuse may be a concern.¹² Stimulants are prescribed far more frequently than any other class of drugs for treating ADHD. They exert their action on the nervous system by targeting the function of certain neurotransmitters,⁵ primarily elevating the transmission of norepinephrine and dopamine.² The goal of therapy is ultimately to achieve a response while controlling the unwanted side effects associated with the drugs. The side effects commonly experienced include insomnia, decreased appetite, irritability, and nervousness, yet these effects appear to be well tolerated by most patients. Arriving at optimal dosing is crucial; however, patients are started at low doses and titrated to achieve a therapeutic outcome. Many of the immediate-release agents, which require multiple dosing throughout the day, are being replaced by longer-acting, extended-release formulations, which have proven to be clinically useful.¹⁵

Methylphenidate

Methylphenidate is a commonly used drug in many patients with ADHD, dating back to the 1950s when it gained approval for narcolepsy and lethargy in general. A mild central nervous system (CNS) stimulant, it blocks reuptake of both dopamine and norepinephrine into the presynaptic neuron.^13,16 Methylphenidate is available in short-acting, intermediate-acting, and long-acting formulations.

Ritalin and Methylin, immediate-release forms of methylphenidate, are dosed 2 to 3 times daily, with an approved range of between 10 and 60 mg daily. Dexmethylphenidate (Focalin), an isomer of methylphenidate, is dosed twice daily, with a maximum of 10 mg twice daily, dosed at least 4 hours apart.

Ritalin SR, Metadate ER, and Methylin ER are intermediate- acting agents with multiple daily dosing, generally once to twice daily.

Ritalin LA, Concerta, and Metadate CD are long-acting formulations of methylphenidate. Ritalin LA has a bimodal release system, with each capsule containing half the dose for immediate release and the other half for delayed release (approximately 4 hours after administration). Concerta, available in 18-, 27-, 36-, and 54-mg formulations, uses an OROS osmotic technology delivery system that releases medication at a controlled rate, resulting in a decrease in the peak-trough fluctuations seen with immediate-release formulations. (It is not unusual to see the empty shell in the stool.) Metadate CD exerts its effect with 30% of the dose by immediate release and 70% providing extended-release effects.

Amphetamine Salts

These formulations are about twice as potent as the methylphenidate compounds.²

Adderall is a psychostimulant made up of d-amphetamine and l-amphetamine. The recommended dose for patients 3 to 5 years of age is 2.5 mg per day. For patients ??6 years of age, the dose is 5 mg once or twice daily, with increases at weekly intervals and a maximum dose of 40 mg per day.

Adderall XR is a long-acting, sustained-release formulation available in 5-, 10-, 15-, 20-, 25-, and 30-mg strengths. It is the only stimulant with FDA approval for treating ADHD in adults.¹⁶

Dextroamphetamine, the d-isomer of amphetamine, is approximately twice as potent as methylphenidate, with a similar side-effect profile.² It is available in an immediate-release form, Dexedrine??dosed once to twice daily, with a maximum daily dose of 40 mg??as well as Dexedrine Spansules, a sustained-release formulation usually dosed once daily in the morning.

Pemoline (Cylert) is a mild CNS stimulant that is structurally different from methylphenidate and the amphetamines but has a similar mechanism of action. This agent is used only in refractory cases due to its side-effect profile, particularly hepatic failure.

Nonstimulants

With the concern about possible drug dependence with stimulants, the first noncontrolled, nonstimulant drug has been approved by the FDA to treat ADHD in children and adults. Atomoxetine is believed to exert its therapeutic effect by inhibiting the reuptake of norepinephrine, yet the exact mechanism of action is unknown. Atomoxetine is dosed once or twice daily. Some reports show an onset of action in ~1 week,¹⁷ but optimal effects appear within 4 to 6 weeks.² The side-effect profile includes sleep disorders, dizziness, and stomach upset.

Other agents used include bupropion, selective serotonin reuptake inhibitors, venlafaxine, and alpha-2 antagonists, such as clonidine and guanfacine (Table 2).

ADHD in Adults

The prevalence of ADHD in adults remains a topic of clinical significance and interest, because almost 50% of childhood patients continue with the illness into adulthood.⁸ Whereas in childhood prevalent symptoms of ADHD are inattention, hyperactivity, and impulsivity, adults manifest the illness mostly by way of inattention, as well as an inability to process information. Adults are treated with the same medications as children, yet only Adderall XR and atomoxetine are FDA-approved for use in adults. Fear of drug addiction and abuse has been an issue in treating adults with stimulants, yet certain studies have demonstrated a decrease in later substance abuse with early treatment.¹⁸ Atomoxetine remains a good alternative, especially in patients with anxiety or tic disorders.¹⁹

Role of the Pharmacist

ADHD continues to be a complex disorder that affects both genders of children and adults and appears to linger through adulthood in many patients, as stated above. Pharmacists, as members of the health care team, are in a position to assist patients by monitoring side effects and by encouraging compliance to ensure optimal outcomes in therapy. Adults and also parents of children with ADHD should be counseled with regard to consistency in the dosing schedule, the best time of day to administer medication, how to best manage adverse side effects, and possible drug-drug interactions. Although ADHD has no known cure to date, emphasis must be placed on integrating behavior therapy with pharmacotherapy in treating the symptoms and improving the impaired functioning of the patient.

Dr. Pelegrin is the pharmacy manager of a Publix Pharmacy in Miami, Fla.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@mwc.com.