Treatment Options for Narcolepsy

Abstract

Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated.