French consensus. Management of patients with hypersomnia: Which strategy?

Abstract

Central hypersomnias principally involves type 1 narcolepsy (NT1), type 2 narcolepsy (NT2) and idiopathic hypersomnia (IH). Despite great progress made in understanding the physiopathology of NT1 with low cerebrospinal fluid hypocretin-1 levels, current treatment remains symptomatic. The same applies to NT2 and IH, for which the physiopathology is still largely unknown. Controlling excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep are key therapeutic targets in NT1. For IH and NT2, reducing EDS is the main objective. Based on European and American directives for the treatment of narcolepsy, we propose French recommendations for managing central hypersomnias as well as strategies in the case of drug-resistance. Stimulating treatments target EDS, and Modafinil is the first-line treatment. Other stimulants such as methylphenidate, pitolisant, and exceptionally dextro-amphetamine can be prescribed. Selective serotonin and noradrenaline reuptake inhibitor antidepressants are effective for the management of cataplexy in NT1. Sodium oxybate is an effective treatment for several symptoms, including EDS, cataplexy and disturbed night-time sleep. Treatment of central hypersomnia must also take into consideration frequent cardiovascular, metabolic and psychiatric comorbidities, particularly in NT1. New therapies are currently under study with the development of new stimulants and anti-cataplectics. The next few years will see innovative emerging therapies, based on a physiopathological approach, aiming to restore hypocretinergic transmission or to interrupt the autoimmune processes causing the loss of hypocretin neurons.

Introduction

Central hypersomnias principally involve type 1 narcolepsy (NT1, hypocretin deficiency syndrome, characterised by excessive daytime sleepiness or EDS and cataplexy), type 2 narcolepsy (NT2, narcolepsy without cataplexy with normal hypocretin-1 in the cerebrospinal fluid), and idiopathic hypersomnia [1], [2], [3], [4], [5]. Excessive daytime somnolence (EDS) is often the most disabling symptom and the most frequent reason for consultation. Cataplexy may be a highly disabling NT1-specific symptom, and the best clinical diagnostic marker of the disease. Other symptoms such as sleep-related hallucinations, sleep paralysis, even if non-specific to narcolepsy, are frequent and found in 50% of patients with narcolepsy but rarely in patients with IH. To date, no cure is available to treat central hypersomnias, and treatment is purely symptomatic and therefore long term, especially for patients suffering from NT1. European and American directives for the treatment of narcolepsy were developed a few years ago [6], [7]. Stimulant treatments target EDS, antidepressants target cataplexy, and sodium oxybate acts on both symptoms. While the ANSM, the French National Agency for Drug Safety, and the EMA, the European Drug Agency, approve the use of some pharmacological stimulants (market approval/product licence), other molecules are prescribed off-label due to their recognised usefulness in treating the symptoms of central hypersomnia. The management and follow-up of these patients should ideally be conducted in a Hypersomnia-Narcolepsy Reference or Competence Centre.