Narcolepsy: current treatment options and future approaches

Abstract

Abstract:The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafi nil has replaced methylphenidate and amphetamine as the fi rst-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafi nil, but on no direct comparison of modafi nil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good effi cacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.

Current and Future Treatment Options for Narcolepsy: A Review

“…Stimulants, such as amphetamines/dextroamphetamines and methylphenidate, are the conventional medications prescribed for symptom management, particularly EDS 18 . These medications promote alertness by increasing monoaminergic activity, specifically targeting the neurotransmitters dopamine and norepinephrine 16 .…”

“…Stimulants have not been effective in treating most cases of cataplexy, particularly when the symptoms are more severe. Currently, amphetamines/dextroamphetamines and methylphenidate are typically prescribed as ancillary medications for narcolepsy treatment when the first-line forms of pharmacologic therapies (e.g., modafinil/armodafinil and sodium oxybate) are not fully effective in treating EDS, or patients are unable to take these medications 16,18 .…”

Dopamine neurons in the ventral periaqueductal gray modulate isoflurane anesthesia in rats

“…[4][5][6] In the clinic, methylphenidate and amphetamine, which elevate extracellular dopamine (DA) concentrations, are commonly applied for treating attention-deficit hyperactivity disorder and sleep disorders such as narcolepsy. [7][8][9] Additionally, systemic administration of D1 receptor agonist 10 or methylphenidate 11 strongly quickened the reanimation from isoflurane anesthesia in rats. 12 It is interesting to note that optogenetic activation of DA neurons in the VTA induces reanimation from isoflurane anesthesia to an awake state, which hinted that DA neurons in distinct regions play different roles depending on the general anesthetic agent used.…”

“…Importantly, dopaminergic pathways in the brain are vital for regulation of sleep and wake 4‐6 . In the clinic, methylphenidate and amphetamine, which elevate extracellular dopamine (DA) concentrations, are commonly applied for treating attention‐deficit hyperactivity disorder and sleep disorders such as narcolepsy 7‐9 . Additionally, systemic administration of D1 receptor agonist 10 or methylphenidate 11 strongly quickened the reanimation from isoflurane anesthesia in rats 12 .…”

Effects of Sleep Deprivation on Surgeons Dexterity

“…Among stimulants drugs, modafinil is used for the treatment of excessive sleepiness syndrome in shift work (117) and in narcolepsy (118). Particularly important in surgeons performance, this drug does not induce tremors, anxiety and nausea, that are instead associated to high dosages of caffeine (107).…”