Baclofen Improves Excessive Daytime Sleepiness in Narcolepsy

Baclofen can be an effective treatment for excessive daytime sleepiness and sleep fragmentation in patients with narcolepsy, according to results of an analysis of case presentations of 5 adolescents with narcolepsy type 1. The findings were published in Pediatric Neurology.

The investigators studied the cases of 5 patients with narcolepsy associated with severe daytime sleepiness who had failed, had an inadequate response to, or had intolerable adverse effects associated with their first-line therapies. All patients who were evaluated had a positive response to treatment with baclofen, defined as improved sleep consolidation and reduction in excessive daytime sleepiness. Overall, 3 adolescent men (13, 16, and 17 y) and 2 adolescent women (14 and 15 y) were assessed.

With no current cure available for narcolepsy, first-line therapy for the disorder generally involves treatment with the wake-promoting agents modafinil or armodafinil. Traditional stimulants, including methylphenidate and amphetamines, are second- and third-line therapies. An alternative treatment for narcolepsy is sodium oxybate — a gamma-aminobutyric acid (GABA)-beta receptor agonist. Treatment goals of narcolepsy therapy are directed at specific relief of symptoms, including excessive daytime sleepiness, sleep fragmentation, and cataplexy.

Baclofen is a centrally acting GABA-beta agonist that is frequently used in pediatric patients for the treatment of dystonia, rigidity, and spasticity, which are associated with a variety of disorders, including cerebral palsy, multiple sclerosis, and poststroke symptomatology. Evidence suggests that baclofen may offer sleep benefits by reducing sleep latency and increasing slow-wave sleep. The use of baclofen has also been shown to increase total sleep time — both rapid eye movement (REM) and non-REM sleep duration — and has been associated with a significant reduction in the time spent awake after sleep onset.

Variations in patient response to baclofen therapy may reflect differences in the dosing regimens that are used. On average, the adolescent patients in the current analysis were exposed to a higher dose of baclofen and continued their other narcolepsy treatments as well. Thus, the beneficial responses reported may be related to the higher baclofen dose or to possible synergy with other therapies.

Baclofen is an inexpensive medication with a known safety profile in all age groups, thus providing additional benefits in terms of its use for increasing slow-wave sleep and improvement in sleep consolidation. Adverse effects associated with the use of baclofen include depression, hallucinations, dizziness, sensory disturbances, and nausea.

The investigators concluded that future studies are warranted, in which the use of baclofen at higher doses, both with and without other narcolepsy therapies, is evaluated. All 5 adolescents who were part of this analysis reported a response to baclofen therapy.

Reference

Morse AM, Kelly-Pieper K, Kothare SV. Management of excessive daytime sleepiness in narcolepsy with baclofen [published online November 22, 2018]. Pediatr Neurol. doi: 10.1016/j.pediatrneurol.2018.10.020