Sympathomimetics are the first-line drugs for treatment of ADHD in children and are effective about 75 percent of the time. Methylphenidate and dextroamphetamine are equally effective and work within 15 to 30 minutes. Pemoline requires 3 to 4 weeks to reach its full efficacy; however, it is rarely used because of toxicity. Sympathomimetic drugs decrease hyperactivity, increase attentiveness, and reduce impulsivity. They may also reduce comorbid oppositional behaviors associated with ADHD. Many persons take these drugs throughout their schooling and beyond. In responsive persons, use of a sympathomimetic may be a critical determinant of scholastic success.

Sympathomimetics improve the core ADHD symptoms of hyperactivity, impulsivity, and inattentiveness and permit improved social interactions with teachers, family, other adults, and peers. The success of long-term treatment of ADHD with sympathomimetics, which are efficacious for most of the various constellations of ADHD symptoms present from childhood to adulthood, supports a model in which ADHD results from a genetically determined neurochemical imbalance that requires lifelong pharmacologic management.

Methylphenidate is the most commonly used initial agent, at a dosage of 5 to 10 mg every 3 to 4 hours. Dosages may be increased to a maximum of 20 mg four times daily or 1 mg/kg a day. Use of the 20-mg sustained-release
formulation to achieve 6 hours of benefit and eliminate the need for dosing at school is supported by many experts, although other authorities believe it is less effective than the immediate-release formulation. Dextroamphetamine is about twice as potent as methylphenidate on a per milligram basis and provides 6 to 8 hours of benefit. Some 70 percent of nonresponders to one sympathomimetic may benefit from another. All of the sympathomimetic drugs should be tried before switching to drugs of a different class. The previous dictum that sympathomimetics worsen tics and therefore should be avoided by persons with comorbid ADHD and tic disorders has been questioned. Small dosages of sympathomimetics do not appear to cause an increase in the frequency and severity of tics. Alternatives to sympathomimetics for ADHD include bupropion (Wellbutrin), venlafaxine (Effexor), guanfacine (Tenex), clonidine (Catapres), and tricyclic drugs. Further studies are needed to determine whether modafinil improves the symptoms of ADHD.

Short-term use of the sympathomimetics induces a euphoric feeling; however, tolerance develops for both the euphoric feeling and the sympathomimetic activity. Importantly, tolerance does not develop for the therapeutic effects in ADHD.

Narcolepsy consists of sudden sleep attacks (narcolepsy), sudden loss of postural tone (cataplexy), loss of voluntary motor control going into (hypnagogic) or coming out of (hypnopompic) sleep (sleep paralysis), and hypnagogic or hypnopompic hallucinations. Sympathomimetics reduce narcoleptic sleep attacks and improve wakefulness in other types of hypersomnolent states. Modafinil is approved as an antisomnolence agent for treatment of narcolepsy, for people who cannot adjust to night shift work, and for those who do not sleep well because of obstructive sleep apnea.

Other sympathomimetics are also used to maintain wakefulness and accuracy of motor performance in persons subject to sleep deprivation, such as pilots and military personnel. Persons with narcolepsy, unlike persons with ADHD, may develop tolerance for the therapeutic effects of the sympathomimetics.

In direct comparison with amphetaminelike drugs, modafinil is equally effective at maintaining wakefulness, with a lower risk of excessive activation.

Sympathomimetics may be used for treatment-resistant depressive disorders, usually as augmentation of standard antidepressant drug therapy. Possible indications for use of sympathomimetics as monotherapy include depression in elderly persons, who are at increased risk for adverse effects from standard antidepressant drugs; depression in medically ill persons, especially persons with AIDS; obtundation caused by chronic use of opioids; and clinical situations in which a rapid response is important but for which electroconvulsive therapy is contraindicated. Depressed patients with abulia and anergia may also benefit.

Dextroamphetamine may be useful in differentiating pseudodementia of depression from dementia. A depressed person generally responds to a 5-mg dose with increased alertness and improved cognition. Sympathomimetics are thought to provide only short-term benefit (2 to 4 weeks) for depression because most persons rapidly develop tolerance for the antidepressant effects of the drugs. However, some clinicians report that long-term treatment with sympathomimetics can benefit some persons.

Sympathomimetics increase alertness, cognition, motivation, and motor performance in persons with neurologic deficits caused by strokes, trauma, tumors, or chronic infections. Treatment with sympathomimetics may permit earlier and more robust participation in rehabilitative programs. Poststroke lethargy and apathy may respond to long-term use of sympathomimetics.