Treatment of Mood Disorders: Psychostimulants
Psychostimulants have been used effectively in the treatment of depression in patients with illnesses that vary from stroke to HIV. Psychostimulants exert their effect in rapid fashion and are of use when a quick antidepressant response is needed. The action of the stimulants is via an increase in the neurochemical concentration of catecholamines and dopamine. This occurs with a relative lack of production of active metabolites. The only notable liver/CYP effect occurs with concomitant use of either TCAs or thyroid hormone, which can lead to increased serum stimulant levels. The three most commonly used agents include methylphenidate, dextroamphetamine, and pemoline. These medications are best used as short-term adjuncts to conventional therapy and should be reserved for patients whose conditions are highly treatment-resistant. One exception here is the apathetically depressed patient in whom activation is necessary for clinical improvement.

Dextroamphetamine is excreted primarily through the renal system and thus avoids CYP interaction for the most part. Dextroamphetamine’s plasma half-life is approximately 12 hours. Methylphenidate, metabolized to ritalinic acid in the liver, is excreted primarily by the kidney and has a half-life of approximately 2 hours. Pemoline has also been used in elderly depressed patients primarily because of its lack of cardiovascular side effects. Although psychostimulants are generally well tolerated, they can cause or lead to increases in blood pressure, cardiac arrhythmias, anorexia, insomnia, and rarely, psychosis. Short-term therapy is usually preferred secondary to tolerance that would require escalating dosage and risking the side effects mentioned. Concern for dependency within this population has been studied, and potential for abuse appears to be quite low. Drug interactions include increasing circulating levels of phenobarbital, primidone, and phenytoin.