Modafinil for the treatment of idiopathic hypersomnia – results of a randomized, double-blind, placebo controlled study

Abstract

The European Medicines Agency withdrew modafinil for the indications idiopathic hypersomnia (IH) and narcolepsy in children due to the lack of sufficient evidence based literature. The literature provides mainly retrospective data. Lavault et al. (Sleep Medicine 2011) found modafinil to be the medication of first choice in 96% of IH patients resulting in a reduction of ESS of 2.6–3 points. The purpose of our study was to study the effects of modafinil on ESS and sleep latency in the MWT (primary variables) of IH patients. In this investigator initiated study only drug naïve IH patients without long sleep according to ICSD2 criteria were included. Disease onset had to be before the age of 30 years. Patients were consecutively recruited from 3 German Sleep Centers and randomized to placebo or 200 mg modafinil once daily in the morning. Visit 1 on day 1 (drug naïve) included vital signs, ESS, medical history, physical investigation and laboratory tests. Throughout the 28 days patients filled in evening morning protocols. Patients were on medication from days 8–21. On days 7, 14 and 21 MWT, ESS and CGI were performed. 14 IH were randomized to modafinil (10 m, 4f, mean age 38.4 ± 12.7 years), 17 (9 m, 8f, mean age 34.8 ± 13.5 years) to placebo. One patient was excluded due to protocol violation. In the intention to treat analysis ESS was significantly reduced in the modafinil group by 5.4 points, compared to 1.9 points in the placebo group ( p < 0.023, effect size 0.64), sleep latency in the MWT was not significantly prolonged (4.9 vs. 1.5 min.), CGI was significantly improved (−01.4 vs. −0.36, p < 0.028, effect size 0.61). Manovas showed no interaction of gender and ESS, but the differences were smaller for men than for women. There was no age effect. Modafinil 200 mg improves ESS and CGI significantly when compared to placebo. The increase of sleep latency in the MWT is not significant. There is no interaction with age and gender. Modafinil is an effective medication in adult patients with idiopathic hypersomnia without long sleep. This investigator initiated study was financed by Cephalon Germany.