Auret, K. A., Schug, S. A., Bremner, A. P., & Bulsara, M. (2009). A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. Journal of Pain and Symptom Management, 37, 613–621.

To test the hypothesis that use of dexamphetamine in fatigued patients with advanced cancer would produce a clinically significant improvement with minimal side effects.

Patients with a prognosis of more than two months and fatigue rated at least 4 out of 10 were randomized to receive either dexamphetamine or lactose placebo. Patients were given a daily dose of 20 mg in two doses daily at 8 am and noon. Patients were contacted daily by telephone if at home to record acceptability and improve compliance. If the dose was not tolerated, it was reduced by 50%. The trial was conducted for eight days, and measurement was repeated every two days.

• In total, 50 patients (36 men, 14 women) were enrolled, and 39 completed the study.
• Patients had advanced cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 3.
• Mean age was 67.8 years for the control group and 73.3 years for the experimental group. 
• Diagnoses varied, but all patients were in palliative care.
• Patients were excluded if they were currently receiving chemotherapy, had anxiety requiring medication, had untreated depression, had recently used monoamine oxidase inhibitors (MAOIs), had an untreated medical condition, or had a hemoglobin less than 100 mg/dL with transfusion planned.

Single multisite study in a palliatve care service in Australia

The study was a randomized, double-blind, placebo-controlled trial.

• Brief Fatigue Inventory (BFI)
• McGill Quality of Life Questionnaire
• ECOG Performance Status
• Self-reported and clinician-reported side effects.
• It was identified from previous work that a two-point decrease in fatigue levels on a 10-point scale was clinically relevant, and this was used for power analysis in sample size planning. A 20% drop-out rate was incorporated in planning for 90% power.
• Other measurements and tools used included albumin levels, hemoglobin levels, oxygen saturation on room air, and other medications.

A transient improvement was observed in fatigue in the dexamphetamine arm (p = 0.039) only on day 2 of the trial. No other significant differences existed between groups. Age and sex were significant predictors of severity of fatigue; those who were younger (p = 0.03) and male (p = 0.047) had more severe fatigue. Both groups had nonsignificant improvement in quality of life measures on some subscales, indicating a potential overall placebo effect. Medication was associated with an increased pulse rate, suggesting that the dosage given had a physiologic effect.

Although well tolerated, 20 mg of dexamphetamine does not improve fatigue or quality of life in patients with advanced cancer. This study agreed with null effects reported by others. Short-term results seen may indicate a response to initiation of a psychostimulant, and changing the dosage over time may have more effect.

• A significant number of drop-outs resulted in a small final sample size.
• Although the authors stated planned approaches to monitor patient compliance with the medication regime, no relevant findings were identified, so actual medication adherence is unknown.
• No longer-term follow-up was conducted. 
• Patients studied were very ill, with low performance status. Findings may not be applicable for individuals with less severe disease.

Optimum dosage across studies has not been defined.