Overview of ADHD.
Article Type: Disease/Disorder overview
Subject: Attention-deficit hyperactivity disorder (Diagnosis)
Attention-deficit hyperactivity disorder (Care and treatment)
Attention-deficit hyperactivity disorder (Research)
Dopamine (Agonists)
Dopamine (Usage)
Dopamine (Health aspects)
Authors: Sajid, Ayesha
Poor, Maria C.
Diaz, David R.
Pub Date: 09/22/2010
Publication: Name: Annals of the American Psychotherapy Association Publisher: American Psychotherapy Association Audience: Academic; Professional Format: Magazine/Journal Subject: Psychology and mental health Copyright: COPYRIGHT 2010 American Psychotherapy Association ISSN: 1535-4075
Issue: Date: Fall, 2010 Source Volume: 13 Source Issue: 3
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 242897533

The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) has come a long way from the first description by physician Sir George Frederick Still in 1902. He called it a "defect of moral control." Dr. Still believed this "defect" to be a medical disorder beyond the sufferer's control. After several terminology changes, in 1980 the new DSM III officially recognized the disorder as Attention Deficit Disorder, with or without Hyperactivity. ADHD has been defined by Russell A. Barkley as a disorder of response inhibition and executive dysfunction leading to deficits in self-regulation, impairment in the ability to organize behavior toward present and future goals, and difficulty adapting socially and behaviorally to environmental demands.

In 1937, Dr. Charles Bradley, while treating headache in children with Benzedrine, realized it had a calming effect resulting in increased productivity in children with severe behavior issues. Use of stimulants in a child who is already hyperactive may seem counterintuitive. In recent times, the neurotransmitter dopamine has been identified as playing a role not only in the causation of attention deficit/hyperactivity disorder, but also in its treatment.

Stimulants are dopamine agonists, are the best researched medications currently indicated for ADHD, and are a highly efficacious treatment option. With reported 65% to 75% clinical improvement in double-blinded placebo-controlled trials in both children and adults, they are considered as first-line therapy. The stimulants are available in short-acting (3-4 hours) and long-acting (8-12 hours) formulations and include methylphenidate, which promotes release of stored dopamine from pre-synaptic vesicles and blocks the return of dopamine into pre-synaptic nerve endings. Amphetamine blocks dopamine reuptake but appears to selectively promote the release of newly synthesized dopamine. An alternative formulation is available as a combination of amphetamine salts.

Short-acting stimulants are inexpensive alternatives and may be prescribed in children weighing less than 35 pounds (16kg) for whom sufficiently low doses do not exist in a long-acting form. They also can be used in conjunction with long-acting stimulants for early in the morning when the long-acting preparation has yet to start working and during homework time or other after-school activities that require focus and concentration after the long-acting has worn off. Short-acting stimulants have to some extent been displaced by long-acting formulations because of the need to be dosed three to four times each day. These longer-acting formulations include some forms of methylphenidate, mixed salts amphetamine, and an amphetamine prodrug, lisdexamfetamine. These medications remove the stigma of being medicated at school and tend to result in increased compliance. Additional convenience of dosing is offered by patches, pumps, and extended-release tablets that can be opened and sprinkled on soft food.

Before prescribing any medication, a full history should be taken. In the case of stimulants, it is especially important to check for a personal or family history of heart conditions and arrhythmias. Of course, a complete physical examination is also required, with referral to a cardiologist if indicated from information in the history. Methylphenidate and amphetamine have been equally linked to small but statistically significant and dose-related reduction in the rates of height and weight gain in children. These generally revert once the stimulant is stopped, so regular growth monitoring is recommended while stimulants are being taken.

Prescribers now have several non-stimulant options to consider for treatment of those refractory to stimulants. Though not first line, these are available if the patient experiences tics, mood lability, or if substance abuse liability is an issue. Atomoxetine, approved by the FDA for treatment of ADHD, works by blocking presynaptic uptake at noradrenergic neurons. It may be considered as a first-line therapy for patients with substance abuse issues and anxiety symptoms. It has a long-lasting therapeutic effect, but it takes longer to begin to work, reaching peak efficacy over 2-6 weeks. Its efficacy is about 30 percent less than stimulants. One potential side effect, included as a black box warning, is suicidal ideation.

Bupropion, tricyclic antidepressants (TCA), and alpha-agonists lack an FDA-approved indication for ADHD but are often used and thought to be effective in many cases. Among alpha-agonists, clonidine and guanfacine are the most familiar. They are primarily used in conjunction with stimulants to treat core symptoms of ADHD (comorbid aggression, or to combat side effects of tics or insomnia) with longer therapeutic availability in the form of guanfacine extended release preparation and clonidine patch. Orthostatic hypotension is the most common limiting side effect. If alpha-agonists are to be discontinued at any point, they should be slowly reduced in order to prevent abrupt increases in blood pressure.

Bupropion, a well-known noradrenergic antidepressant that showed modest efficacy for ADHD, is available in immediate release and long-acting forms. It lowers seizure threshold and so its usage has been limited in children with seizure disorder or those weighing less than 55 pounds (25 kg). Tricyclics have been prescribed with some success, most commonly imipramine and nortriptyline. They carry a stern caution, especially for children, for cardiac arrhythmia. It is recommended that an EKG be done prior to initiation of treatment and with every increase in dose. Once a stable TCA dosage is established, a level should be drawn to ensure it is not within toxic ranges.

Treatment of ADHD should be individualized. Current guidelines recommend long-acting stimulants or combination salts of short-acting stimulants as the first step. If these fail, then a non-stimulant alone or in conjunction with stimulants can be tried with caution. The decision to withdraw treatment is as crucial as the one to initiate it. There is not a large body of evidence available supporting treatment discontinuation, though certain parameters have been recommended. These parameters include being symptom-free for one year, no dosage adjustment required with growth, and lack of deterioration during drug holidays. If the decision is to stop, a tapering could commence while assigning cognitively demanding tasks to determine whether remission has indeed occurred. If there is a notable decline in functional productivity, the medication should be resumed.

Treatment of ADHD can be a long and frustrating journey for families, and a one-size-fits-all approach certainly does not apply. It is important to couple medications with lifestyle modifications and behavioral changes in order to maximize the benefit. The ultimate goal that patients, families, and prescribers need to understand and strive for is not a cure, but rather the management of the symptoms and productivity.


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By Ayesha Sajid MD, Maria C. Poor MD, David R. Diaz, MD
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