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STIMULANTS

Depressive disorders are extremely common in medically ill patients including those with heart disease, stroke, Parkinson's disease, diabetes, and stimulants, amphetamine, methylphenidate, dextroamphetamine, Ritalin, ritelin, ritalen The tricyclic antidepressants (TCAs) are associated with anticholinergic side effects (e.g., dry mouth, constipation, urinary retention, tachycardia); cardiac conduction system abnormalities (e.g., increased QTC interval); orthostatic hypotension; sedation; and weight gain. In addition, they are toxic in overdose. In fact, in one study [96]

TCAs and the newer standard antidepressants also have a long latency of response (i.e., up to 3 to 4 weeks) that interferes with compliance and rehabilitation attempts. Hence, psychostimulants (i.e., dextroamphetamine, methylphenidate, pemoline) offer an attractive alternative for the treatment of depression among the medically ill.

Unfortunately, barriers (e.g., myths regarding addiction, abuse, and tolerance, and anorectic effects) to the prescription of psychostimulants by clinicians exist. Physicians distrust stimulants because of their checkered history;

CHEMISTRY AND PHARMACOLOGY OF THE PSYCHOSTIMULANTS

Amphetamine, racemic beta-phenylisopropylamine (see Fig. 1) , has powerful central stimulant effects in addition to peripheral alpha- and beta-receptor actions common to sympathomimetic drugs.

In the central nervous system, amphetamine acts in general to produce wakefulness, alertness, elevation of mood and self-esteem, and increased motivation and initiative resulting in improved cognitive and physical performance.

Amphetamine exerts most of its effects by increasing the concentration of catecholamines in the synaptic cleft principally by releasing cathecholamines from intraneuronal storage sites. The central psychostimulant actions are primarily dependent on interaction with dopaminergic fibers in the ventral tegmentum and mesolimbic system,

Dextroamphetamine

Amphetamine is a racemic mixture of levo- and dextrorotatory isomers. The dextrorotatory form is marketed in the United States as dextroamphetamine (DAMP) (Dexedrine) and is three to four times more potent than the 1-isomer.

Methylphenidate

Methylphenidate (MPD) has a profile of clinical activity that is indistinguishable from that of DAMP, although there is considerable interindividual variability of response. [70] [89] [110] Clinical response to one agent does not

The distinctive qualities of MPD are pharmacologic and account for dosage and dosing patterns that are different than those of DAMP. The structure of MPD is similar to that of other phenylethylamines (Fig. 2) (Figure Not

Pemoline

Pemoline (P), a mild stimulant and performance enhancer, [48] has been used successfully but less frequently than the other psychostimulants for the treatment of secondary depression in the medically ill. It has features, however, that recommend its wider use. P has been approved by the Food and Drug Administration (FDA) and traditionally

USE OF PSYCHOSTIMULANTS

Patients with General Medical Illness

Although the first major review of amphetamine therapy was published in 1939, it was not until the mid- to late 1970s that their use for the depressed medically ill was advocated. At the 1978 annual meeting of the American Psychiatric Association, Dr. Thomas Hackett outlined 10 important indications for amphetamine use. In addition to