Armodafinil for sarcoidosis-associated fatigue: a double-blind, placebo-controlled, crossover trial

Abstract

Context: Fatigue has been identified in more than one-half of patients with sarcoidosis. Although fatigue is not synonymous with impaired quality of life, most studies of sarcoidosis identify fatigue as a major cause of impaired quality of life.

Objectives: To test the hypothesis that stimulants may have a role in the treatment of fatigued sarcoidosis patients, even without objective evidence of daytime sleepiness.

Methods: This was a double-blind, placebo-controlled, crossover study of sarcoidosis patients followed up in one sarcoidosis clinic Sarcoidosis patients with fatigue received either armodafinil or placebo with eight weeks of therapy for each arm and a two week washout period before crossover to the other treatment. Initial armodafinil dose was 150mg and increased to 250mg after four weeks. Patients underwent polysomnography and multiple sleep latency testing (MSLT) the following day. Patients with an apnea/hypopnea index <6/hour received either armodafinil or placebo. Polysomnography with MSLT was repeated after each treatment arm.

Results: Fifteen patients received the study drug. Fatigue was assessed using the Fatigue Assessment Scale (the lower the score, the less the fatigue) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) (the higher the score, the less the fatigue). After eight weeks of therapy, there was a significant improvement in the Fatigue Assessment Scale during armodafinil treatment (median -4.5, range -20, 5) compared with placebo treatment (median 3.5, range -9, 14, P<0.05) and for the FACIT-F (armodafinil: median 9, range -12, 26 vs. placebo: median -5, range -17, 11, P<0.005). This improvement in fatigue was seen for both those with and without shortened sleep onset latency time during the MSLT.

Conclusion: Armodafinil treatment led to a significant reduction in fatigue in sarcoidosis patients. This effect was seen even in patients who did not have excessive daytime somnolence.

Fig. 1

Flow diagram summarizing the double-blind, placebo-controlled, crossover design of the study. Overnight sleep studies followed by multiple sleep latency tests (MSLT) were performed prior to randomization and at the end of each eight-week treatment period.

Fig. 2

CONSORT diagram detailing the outcome of studied patients. Ten patients were unable or unwilling to undergo an initial sleep study. After the initial sleep study, five patients were excluded from further study because of inadequately controlled sleep apnea or restless leg syndrome. Fourteen patients completed all 19 weeks of the study as detailed in Fig. 1.

Fig. 3

The change of the Fatigue Assessment Scale (FAS) score after four or eight week of therapy compared with the baseline value (Week 1 or 11). There was a significant difference between armodafinil and placebo after eight weeks of therapy (P = 0.0295).

Fig. 4

The change of the Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) score after four or eight week of therapy compared with the baseline value (Week 1 or 11). There was a significant difference between armodafinil and placebo after four and eight weeks of therapy (P = 0.0149 and P = 0.0040, respectively).