Narcolepsy is a medical term, a type of neurological disorder which is unusual among people. It is literally defined as “seized by somnolence” (1). This disorder can be seen in 1 in 2000 individuals and is described by unnecessary daytime sleepiness and cataplexy (literally means “struck down as if stupefied”)(2). Because of inadequate information on the cause of this disorder, it remains a major challenge in the field of narcolepsy therapeutics. Misunderstanding of the disease is common in the medical ground because of its various contrasting symptoms(3). It is an incurable and chronic disorder which remains a major challenge.
How To Prevent Narcolepsy?
As there is no cure for narcolepsy, most patients require lifelong pharmacologic management. To manage narcolepsy, patients must change their lifestyle such as behavior modifications like maintaining a regular sleep schedule. Sleep scheduling long naps or short naps (15–20 min) in the day have favorable effects on daytime performance. There is no established behavioral treatment for cataplexy, although patients can predict situations likely to trigger cataplexy attacks and act accordingly.
Therapeutics for Narcolepsy Syndrome
In the beginning, treatments for the narcolepsy include anti-epileptic potassium bromide, vasodilators picrotoxin, amyl nitrate vapors, apomorphine, and strychnine were recommended. However, these drugs were ineffective for this syndrome. Several alternative therapies such as hydrotherapy, electricity, and cauterization of the nape of the neck have shown minimal effect.
- Pharmacological mitigation of cataplexy was first documented in 1960 with the unexpected discovery that the tricyclic antidepressant imipramine significantly decreased the occurrence of cataplexy(7).
- Clomipramine were found to inhibit rapid eye movement sleep and also control sleep paralysis and hypnogogic hallucinations in addition to cataplexy.
- The US Food and Drug Administration (FDA) has approved five pharmacotherapeutics for the treatment of narcolepsy: sodium oxybate, modafinil, armodafinil, methylphenidate, and amphetamine(8)
ADX-N05 is a phenylalanine derivative with a dopaminergic and noradrenergic activity that has been assessed for treatment of daytime excessive daytime sleepiness (EDS) in narcolepsy. GABAB agonism with R-baclofen, an enantiomer-specific form of racemic baclofen has exerted greater anticataplectic efficacy. Novel approaches using pluripotent stem cells for the treatment of narcolepsy are also under development. Hypocretin deficiency is assumed to be the main cause of narcoleptic symptoms. Hypocretin replacement will be the most essential treatment for narcolepsy(9, 10, 11).
Problems Of The Future Development Of Narcolepsy Therapeutics
With a prevalence of 0.05%, there are approximately 150,000 individuals with narcolepsy in the US. Despite the advantages stated above, a number of obstacles remain problematic for the future development of narcolepsy therapeutics. Perhaps the paramount obstacle is the relatively low prevalence of this disorder which may limit the number of companies that are willing to invest in new therapeutic development for a disorder with a small market.
Narcolepsy Clinical Features
Irresistible sleepiness in the day time, emotionally-triggered muscle paralysis, head trauma, sleepless night, hallucinations, rapid eye movements while sleeping, vivid dreaming, lethargy and over-weight were all connected with narcolepsy disorder. The paralysis attack is different from epilepsy because no loss of consciousness is witnessed. Sleep paralysis is associated with this disease which involves incapability to move while sleeping or sometimes even after awakening. A sudden loss of muscle tone is seen in patients which are usually caused by positive emotional stimuli. Loss of muscle tone i.e., cataplexy occurs in 60–70% of narcoleptic patients(4, 5).
A major challenge in the development of narcolepsy therapeutics is the incomplete understanding of the etiology of this disorder. As there is no cure for narcolepsy, most patients require lifelong pharmacologic management. To manage narcolepsy, patients must change their life style such as behavior modifications like maintaining a regular sleep schedule. The US Food and Drug Administration (FDA) has approved five pharmacotherapeutics for the treatment of narcolepsy: sodium oxybate, modafinil, armodafinil, methylphenidate, and amphetamine. Clinical Physician believes that future therapies like the use of immune compound, stem cell therapy and hypocretin replacement therapy will be the most essential treatment for managing narcolepsy.
- Gélineau J. De la Narcolepsie. Gaz Hop (Paris) 1880
- Guilleminault C et al. Narcolepsy and Hypersomnia. Informa Healthcare USA; New York, NY: 2007.
- Black SW et al. Challenges in the development of therapeutics for narcolepsy. Prog Neurobiol. 2017.
- Anic-Labat et al. Validation of a cataplexy questionnaire in 983 sleep-disorders patients.1999.
- Yoss Re et al. Criteria for the diagnosis of the narcoleptic syndrome.Proc Staff Meet Mayo Clin. 1957
- Billiard M et al. EFNS guidelines on management of narcolepsy. Eur J Neurol 2006.
- Akimoto et al. Pharmacotherapy in narcolepsy.1960.
- CDER. The Voice of the Patient: Narcolepsy, Ed. Silver Spring; MD, U.S. FDA: 2013
- Black SW et al. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep. 2013.
- Bogan RK et al. A double-blind, placebo-controlled, randomized, cross-over study of the efficacy and safety of ADX-N05 for the treatment of excessive daytime sleepiness in adult subjects with narcolepsy. Sleep. 2013.
- Xie et al. Gamma-hydroxybutyrate hyperpolarizes hippocampal neurones by activating GABAB receptors.1992.
- Narcolepsy: Symptoms, Causes, Diagnosis, Treatment- Drugs, Short Naps
- Impact of Narcolepsy On The School Life of Children
- Can You Legally Drive If You Have Narcolepsy?
- Is Narcolepsy Considered A Disability?
- What Happens To A Person With Narcolepsy?
- Are There Different Levels Of Narcolepsy?
- How To Catch Narcolepsy In The Initial Stages?
- Can You Be Misdiagnosed With Narcolepsy?