Clinical experience suggests that modafinil is an effective and safe treatment for paediatric narcolepsy

Narcolepsy with cataplexy is a chronic, life-long, disabling condition that occurs during childhood in approximately onethird of subjects. It usually begins during the first or second decade of life, and symptoms may develop rapidly over a few weeks or months, with excessive daytime sleepiness (EDS) and cataplexy being the most dramatic and observable symptoms. Pharmacological treatments in children with narcolepsy are mostly based on empirical data and clinical experience; randomized clinical trials are lacking and treatment guidelines have not yet been established in narcoleptic children (Ivanenko et al., 2003; Nevsimalova, 2009). Based on the experience of all the undersigned, wakepromoting medications have significantly improved the symptoms and well-being of young patients with narcolepsy. However, all available treatments are delivered off-label in the paediatric population (Aran et al., 2010; Peraita-Adrados et al., 2011). Modafinil is a non-amphetamine type stimulant that acts as a wakefulness-promoting drug, and is approved for managing EDS due to narcolepsy in adults. Following the findings of a safety review, the European Medicines Agency has recently recommended that the use of medicines containing modafinil should be restricted to sleepiness associated with narcolepsy only, with all other indications to be removed from product information. In addition, the Committee for Medicinal Products for Human Use recommended that the product information carry a recommendation stating that modafinil should not be prescribed to children, as the risk of developing serious skin and hypersensitivity adverse reactions appears to be higher in this age group. As an international group of paediatric sleep specialists with over two decades of experience using modafinil, we were surprised by this decision. Our concerns were that this decision might be based on the absence of safety data from well-conducted trials in children. This recommendation has the potential to adversely affect our ability to use of one of the few efficient and safe drugs available for the treatment of narcolepsy in children and adolescents. Based on our clinical experience, we collected all cases providing here a description of efficacy and side-effects. Summarizing the data from all authors, 205 children and adolescents (99 M; 106 F) with narcolepsy were treated with modafinil; the age range was 4–18 years, and the prescribed dose of modafinil varied from 50 to 600 mg (Table 1). Patients have been treated for more than 10 years in the majority of the Centres, with the longest period of treatment of 19 years in France. According to literature, increasing modafinil doses above 400 mg has not usually conferred any additional benefit, and most co-authors used a maximum daily dose of 400 mg. In the French paediatric cohort, the average daily dose of modafinil was 388 ± 140 mg. In some rare cases, and for adolescents over 16 years old, modafinil had progressively been titrated to twice-daily 300 mg doses. In these cases, increasing the dose was beneficial, safe and well tolerated. We found modafinil to be effective in more than 85% of patients, and in the remaining cases lack of efficacy, habituation or mild adverse effects led to drug discontinuation. The most frequent side-effects were represented by headache in 13.7% of cases, nervousness and irritability in 6.5%, and loss of appetite in only 2.2%. No severe hypersensitivity reactions were reported by any author, and particularly no serious skin reactions were recorded. Although these data are based on clinical experience and cannot replace randomized studies, the number of patientyears we have accrued suggests modafinil can be used safely in children and adolescents. Prior to this recommendation the major limitation for utilization of modafinil within different countries was related to the availability and price of the compound. For instance, in France, modafinil was used for decades as the first-line treatment for adults with narcolepsy before sodium oxybate was licensed. In Italy it is the only first-line treatment for narcolepsy in children, as methylphenidate is licensed only for attention deficit hyperactivity disorder. In Spain it is a highcost treatment, as the public health system refunds only 60% of the price of modafinil. The Spanish Narcolepsy Association has lobbied both to the Health National Service and the Health Commission in Parliament without success. A specific Working Group for Narcolepsy in Children has been recently constituted as part of the European Network of Rare Pediatric Neurological Diseases (http://www.neuro ped.eu). Its far-reaching aims are to identify current research, treatment and patient care challenges, to develop a registry for observational and prospective studies, and to disseminate recommendations on diagnosis and treatment on narcolepsy in children. Although not specific for children, the European Narcolepsy Network (http:// www.narcolepsy-network.eu) is another non-profit organization with the purpose of gaining a better insight into narcolepsy and related hypersomnias by pooling the resources of a variety of Sleep Centres, and creating an international database of patients with narcolepsy and hypersomnias. Together these initiatives will provide additional valuable information about the safety of modafinil. Across our European Centres, both the young people we treat and their careers attest to the potential for modafinil to restore a high quality of alertness and attention throughout J. Sleep Res. (2012) 21, 481–483 Modafinil and paediatric narcolepsy