The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial.
BACKGROUND
Fatigue, cognitive deficits, and depression are frequently reported but often undertreated symptoms that can profoundly affect daily life in patients with primary brain tumors (PBTs). To evaluate the effects of the psychostimulant modafinil on fatigue, depression, health-related quality of life (HRQOL), and cognitive functioning in PBT patients, we performed a multicenter, double-blind placebo-controlled crossover trial.


METHODS
Patients randomly received either 6 weeks of treatment with modafinil (up to 400 mg/day) or 6 weeks with placebo. After a 1-week washout period, the opposite treatment was provided. Assessments took place at baseline and immediately after the first and second condition. Patients completed self-report questionnaires on fatigue (Checklist Individual Strength [CIS]), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), HRQOL (Short-Form Health Survey [SF-36]), and self-perceived cognitive functioning (Medical Outcomes Study [MOS]). They also underwent comprehensive neurocognitive testing.


RESULTS
In total, 37 patients participated. Relative to baseline, patients reported lower fatigue severity (CIS) and better motivation (CIS) in both the modafinil (P = .010 and P = .021, respectively) and the placebo condition (P < .001 and P = .027, respectively). The same held for physical health (SF-36 Physical Component Summary score; P = .001 and P = .008, respectively), working memory (P = .040 and P = .043), and information processing capacity (P = .036 and P = .040). No improvement in depressive symptoms was found in either condition.


CONCLUSIONS
Modafinil did not exceed the effects of placebo with respect to symptom management. Patient accrual was slow, and relatively many patients dropped out during the trial, due mostly to side effects. Other, preferably nonpharmacologic intervention studies should be considered to improve symptom management of PBT patients.
Corresponding Author: Florien W. Boele, MSc, Department of Medical Psychology, D-345, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands. f.boele@vumc.nl.
Florien W
FW
Boele
Linda
L
Douw
Marjolein
M
de Groot
Hinke F
HF
van Thuijl
Wilmy
W
Cleijne
Jan J
JJ
Heimans
Martin J B
MJ
Taphoorn
Jaap C
JC
Reijneveld
Martin
M
Klein
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003072:Cognition Disorders / Q000139:chemically induced*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D000077408:Modafinil; D019964:Mood Disorders / Q000139:chemically induced*; D060787:Neoplasm Grading; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D011795:Surveys and Questionnaires; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects
D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
HRQOL; brain tumor; cognitive functioning; fatigue; modafinil; mood