Moss, E. L., Simpson, J. S., Pelletier, G., & Forsyth, P. (2006). An open-label study of the effects of bupropion SR on fatigue, depression and quality of life of mixed-site cancer patients and their partners. Psycho-Oncology, 15, 259–267.

Bupropion sustained release (SR) was administered for four weeks at the maximum tolerated dose. Dosing was initiated at 100 mg in the morning and adjusted in increments of 50 mg, based on tolerability and effects, to a maximum of 300 mg daily. It was given in divided doses of either 100 or 150 mg. The dose was not increased if the maximum tolerable dose had been identified. The dose was 300 mg per day until the Brief Fatigue Inventory (BFI) score had dropped to less than 50% of the initial value. Following dose escalation, a four-week, fixed-dose phase occurred at the maximum tolerated dose, during which efficacy and safety measures were assessed every two weeks. The average dose for bupropion SR was 214 mg per day (standard deviation = 80 mg).

• The study included 21 patients (52% male) with a mean age of 40.4 years.
• All patients had persistent fatigue as a prominent symptom (scoring at least 4 out of 10 on the BFI fatigue interference scale). Nine patients scored 7 or greater on the BFI, which indicated severe fatigue.
• One-third of the patients had a primary brain tumor, and approximately 25% had breast cancer. Patients with brain tumors were overrepresented because the sample included a specific recruitment of this patient population.
• Patients were ineligible if they were receiving erythropoietin or had received it in the past six weeks, were using psychostimulants or antidepressants, or identified a medical cause for fatigue (e.g., thyroid dysfunction, adrenal insufficiency) on screening tests or on review of systems.

• Outpatient
• Large comprehensive cancer center

The study used a prospective, variable dose, open-label trial design.

• BFI scores were measured every two weeks and were used for dose escalation and then were measured twice for evaluation of treatment effects during the four-week, fixed-dose phase of the study.
• Other constructs measured included depression and health-related quality of life.

• A statistically significant improvement (p = 0.001) in fatigue was found when the baseline fatigue score was compared to the fatigue score obtained after four weeks of the fixed-dose treatment with bupropion.
• At baseline, fatigue and depression were not significantly correlated (r = 0.21).
• Four patients withdrew during treatment due to intolerable side effects (n = 1), perceived lack of efficacy (n = 2), and scheduled surgery for cholecystitis and cholelithiasis (n = 1).

• The trial was open-label and nonrandomized.
• The sample size was small, which made it difficult to establish a relationship between depression and fatigue.
• Overrepresentation of patients with brain tumors limited generalizability.
• The lengths of treatment and follow-up were brief.
• Side effects experienced at dose limits were not described; one patient withdrew because of side effects, but no details were reported.
• Cost was incurred to acquire the drug.