In Europe, modafinil used to be available as a treatment for the excessive daytime sleepiness (EDS) associated with idiopathic hypersomnia (IH). However, in 2010, the European Medicines Agency (EMA, the equivalent of the Food and Drug Administration [FDA] in the United States) changed the labeling, and the drug is now approved for use only in narcolepsy. Amphetamines are available in Europe for the treatment of excessive daytime sleepiness (EDS), but are not labeled for treatment of sleepiness associated with IH in any European country.
Who were the researchers?
Mayer and the other researchers were from three different research institutes in Germany.
What was the purpose of the study?
The primary aims of this study were to assess changes in sleepiness using theEpworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT). The secondary aims were to measure changes in the Clinical Global Impression (CGI) rating scale (item: severity of illness), laboratory tests, and vital signs and to measure the number and type of adverse events, number of unintended daytime naps, and responder rates (defined as ESS scores ≤10 at final visit on medication).
What was the study design?
Who took part in the study?
Thirty-three patients with IH without long sleep who were older than 18 years, had IH for more than 2 years, had an onset of IH symptoms between the ages of 10 and 30 years, had a Beck Depression Inventory score of less than 16, and had more than 110 pg mL-1 of hypocretin-1 in cerebrospinal fluid (if this measurement was performed) originally agreed to take part in the study. One subject did not complete the study and one was ruled ineligible, leaving 31 patients who completed the study (17 received modafinil and 14 received placebo).
What did the research subjects do?
The research subjects stopped taking their usual medicines for at least one week and then completed the ESS during the baseline visit (V2), day 8 (V3), day 14 (V4), and day 21 (V5). They also completed the MWT during visits V2, V3, and V5, and kept a sleep-wake diary throughout the study. In the morning and at noon, they took either placebo or 100 mg of modafinil for three weeks and then no medication for one week.
What did the researchers do?
At V2, V3, V4, and V5, the researchers completed the CGI. At the end of the study, they calculated the difference between baseline values and end-of-treatment values for the sleep latency on the MWT, the ESS scores, and the CGI scores for each patient.
What were the results?
Compared with placebo, modafinil reduced daytime sleepiness significantly, as measured by the ESS (modafinil: > 5 points vs placebo: 1.8 points). The sleep latency according to the MWT did not improve significantly in the modafinil or placebo groups (the difference between sleep latency on V2 and V5). The results of laboratory tests and vital signs did not change throughout the study and did not differ between the modafinil and placebo groups. The CGI severity-of-illness score changed significantly more in the modafinil group from baseline to V5 than in the placebo group. According to the data from the sleep-wake diaries, performance and exhaustion improved significantly at weeks 2 and 3 in the subjects who received modafinil, with no changes in these scores in subjects who received placebo, and the number of reported naps and duration of daytime sleepiness decreased significantly. Subjects in the modafinil group and placebo group were equally likely to experience at least one side effect, but headaches and gastrointestinal distress were more commonly experienced by subjects taking modafinil.
Mayer G, Benes H, Young P, Bitterlich M, Rodenbeck A. Modafinil in the treatment of idiopathic hypersomnia without long sleep time-a randomized, double-blind, placebo-controlled study. J Sleep Res. 2014 Sep 5. doi: 10.1111/jsr.12201. [Epub ahead of print] PubMed PMID: 25196321.