A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease

Background: Fatigue is a commonly encountered symptom of human immunodefici ency virus (HIV) disease, associated with significant psychological and fun ctional morbidity and poor quality of life. Preliminary studies on the trea tment of fatigue from the cancer and multiple sclerosis literature suggest that psychostimulants may be effective in reducing fatigue. Objective: To compare the efficacy of 2 psychostimulant medications, methyl phenidate hydrochloride (Ritalin) and pemoline (Cylert), with a placebo int ervention for the treatment of fatigue in patients with HIV disease. Methods: In this double-blind trial, 144 ambulatory patients with HIV disea se and persistent and severe fatigue were randomized to treatment with meth ylphenidate, pemoline, or placebo. Medications were titrated up to a maximu m dose of 60 mg of methlyphenidate hydrochloride, 150 mg of pemoline, or 8 capsules of placebo daily. Fatigue was measured using 2 self-reported ratin g scales, the Piper Fatigue Scale (PFS) and the Visual Analogue Scale for F atigue (VAS-F). We also used the timed isometric unilateral straight leg-ra ising task, a measure of muscular endurance. Quality-of-life and psychologi cal well-being measures included the Beck Depression Inventory, the Brief S ymptom Inventory, and the 36-Item Short-Form Medical Outcomes Study Health Status Survey. Side effects were monitored using the Systematic Assessment for Treatment Emergent Events and the Extra-pyramidal Symptom Rating Scale. All measures were rated weekly. Results: One hundred nine subjects completed the 6-week trial; 15 patients (41%) receiving methylphenidate and 12 patients (36%) receiving pemoline de monstrated clinically significant improvement compared with 6 patients (15% ) receiving placebo. Patients receiving methylphenidate or pemoline demonst rated significantly more improvement in fatigue on several self-reported ra ting scales (PFS total score, P = .04; affective subscale, P = .008; sensor y subscale, P=.04; and VAS-F energy subscale, P = .02). Analysis of the reg ression slopes by means of hierarchical linear modeling demonstrated a sign ificantly greater rate of improvement in PFS total scores among patients re ceiving psychostimulants compared with the placebo group (P = .02). There w ere no significant differences in the efficacy between methlyphenidate and pemoline on any outcome measure studied. Improvement in fatigue was also si gnificantly correlated with improvement in measures of depression, psycholo gical distress, and overall quality of life. Severe side effects were relat ively uncommon among this sample, and only hyperactivity or jitteriness occ urred significantly more often among subjects receiving active medication. Conclusions: Many patients with HIV- and acquired immunodeficiency syndrome -unrelated fatigue respond favorably to treatment with methylphenidate or p emoline. Both psychostimulants appear to be equally effective and significa ntly superior to placebo in decreasing fatigue severity with minimal side e ffects. Moreover, improvement of fatigue was significantly associated with improved quality of life and decreased levels of depression and psychologic al distress.