Boele, F.W., Douw, L., de Groot, M., van Thuijl, H.F., Cleijne, W., Heimans, J.J., . . . Klein, M. (2013). The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: A multicenter randomized controlled trial. Neuro-Oncology, 15, 1420–1428.

To investigate the effects of modafinil on fatigue, depression, cognitive impairment, and health-related quality of life in patients with primary brain tumors

The intervention consisted of subjects receiving modafinil versus a placebo over six weeks. The week 1 dosage was 100 mg twice daily and the weeks 2–6 dosages were 200 mg twice daily. The cross-over occurred after the completion of week 6; thus, subjects who initially received the placebo followed the same dosing schedule over the next six weeks while those who had taken modafinil previously were given a placebo. Neuropsychological assessments and self-report measures were completed at baseline, six weeks, and 12 weeks.

• N = 37  
• AVERAGE AGE = 48.16 years (SD = 12.02 years)
• MALES: 37.8%, FEMALES: 62.8%
• KEY DISEASE CHARACTERISTICS: Gliomas and meningiomas with stable tumor status for six months
• OTHER KEY SAMPLE CHARACTERISTICS: Subjects had to score > 27 on the Checklist Individual Strength Test indicating the presence of fatigue. Exclusions include psychiatric disease or depressive disorders and medication interactions with modafinil.  

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: VU University Medical Center (Amsterdam), Academic Medical Center (Amsterdam), and Medical Center Haaglanden (Hague)

PHASE OF CARE: Multiple phases of care

Randomized, controlled, double-blinded clinical trial using a cross-over design. Measurements were performed at baseline, six weeks, and 12 weeks.

• Rey Auditory Verbal Learning Test (RAVLT)
• Memory Comparison Test
• Stroop Color and Word Test (Stroop)
• Letter Digit Substitution Test
• Concept Shifting Test (CST)
• Categorical Word Fluency Test
• Checklist Individual Strength (CIS)
• Center for Epidemiologic Studies Depression Scale (CES-D)
• Medical Outcomes Study Short-Form Health Survey (MOS SF-36)
• Medical Outcomes Study Subjective Cognitive Functioning Scale (MOS)

The CIS severity and reduced motivation scores for fatigue were lower after treatment with both modafinil (p = 0.01, p = 0.021) and placebo arms (p < 0.001, p = 0.027), but there was no difference in scores between trial arms. Significant improvements in working memory (p = 0.04, p = 0.043), information-processing (p = 0.036, p = 0.04), and attention (p = 0.015, p = 0.013) were found after treatment with modafinil and the placebo, respectively. There were no differences in scores between trial arms. Health-related quality of life measured by the physical component summary of the SF-36 was significantly improved for both modafinil (p = 0.001) and placebo arms (p = 0.008). There were no differences in depressive symptoms following modafinil or placebo.

The results indicate that there were no significant differences observed in fatigue, cognitive functioning, health-related quality of life, and mood between modafinil and a placebo. These findings may be related to the study design, duration of treatment, low study accrual, subject withdrawals, and lack of longitudinal follow-up.

• Small sample (< 100)
• Subject withdrawals ≥ 10%

Findings do not support the use of modafinil to improve fatigue, cognitive functioning, mood, and health-related quality of life in patients with brain tumors.