The Treatment of Obstructive Sleep Apnea with Modafinil and Armodafinil

Abstract

This thesis aims to evaluate the safety and efficacy of wakefulness promoters modafinil and armodafinil in three obstructive sleep apnea (OSA) phenotypes; 1) mild-moderate OSA patients not using treatment, 2) OSA patients who remain sleepy despite using continuous positive airway pressure (CPAP) and 3) moderate to severe OSA patients who are unable to tolerate CPAP whilst undergoing a weight loss program. Chapter 2 describes a two-week, randomised, placebo-controlled crossover trial of modafinil in 32 sleepy male mild-moderate OSA patients not using treatment. The primary outcome, Epworth Sleepiness Scale (ESS) score, was significantly improved over placebo by 3.6 points (95%CI 1.3 to 5.8). Modafinil was well tolerated over this short period. A systematic review and meta-analysis of all trials of modafinil or armodafinil in patients with residual daytime sleepiness despite CPAP use is described in Chapter 3. Ten trials including 1466 patients showed a pooled reduction in ESS score of 2.2 points on modafinil/armodafinil over placebo (95%CI 1.5 to 2.9). Modafinil/armodafinil doubled the risk of suffering an adverse event, but the three trials which quantified blood pressure showed a non-significant increase on modafinil/armodafinil. Chapter 4 describes a randomised, parallel-group trial of armodafinil versus placebo adjunctive to weight loss in OSA patients unable to tolerate CPAP. The primary outcome, driving simulator steering deviation, was significantly improved on armodafinil over placebo at three months (12.7cm, 95%CI 4.3 to 21.1), but this was not sustained to the primary timepoint of six months (5.1cm, 95%CI -3.4 to 13.5). There was not a significant increase in risk of suffering an adverse event on armodafinil. Overall, these three trials provide sleep clinicians with an evidence base upon which they may decide to use modafinil or armodafinil to treat daytime sleepiness in patients who fall into any of the three described OSA phenotypes.