Narcolepsy: Evolutions in Pharmacotherapy

Lillian Smith, PharmD, MBA, CPh; Juan F. Mosley II, PharmD, CPh, AAHIVP; Megan Ford, PharmD Candidate; Thomas Barwick, PharmD Candidate; David Brooks, PharmD Candidate; Wileta Luckett, PharmD Candidate


US Pharmacist. 2016;41(1):40-44. 

In This Article

Abstract and Introduction


Narcolepsy, a complex and often debilitating neurologic disease, is characterized by cataplexy, sleep paralysis, and hypnagogic and/or hypnopompic hallucinations. Several treatments are available, such as amphetamines, modafinil, and sodium oxybate, but current therapy is limited to symptom management and does not affect the underlying process. Recognition and a better understanding of the role of autoimmunity in type 1 narcolepsy have provided a means for early diagnosis, thus creating the potential for new interventions, such as hypocretin replacement and IV immunoglobulin therapy. However, larger-scale studies need to be conducted in order to prove the efficacy of these therapies.


Narcolepsy is a complex and often debilitating neurologic disease characterized by excessive daytime sleepiness, uncontrollable sleep attacks, hypnagogic (drowsiness preceding sleep) and hypnopompic (semiconsciousness preceding waking) hallucinations, and sleep paralysis. In many cases, cataplexy (sudden, brief, episodic loss of muscle tone) occurs. Narcolepsy affects one in every 1,000 to 2,000 Americans and is slightly more prevalent among men.[1] This disorder can interfere with the ability to independently perform normal daily activities such as studying, driving, and working. Symptoms usually manifest within the second decade of life and increase in severity during the third and fourth decades.[1]

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, divides primary hypersomnolence syndromes into three types: narcolepsy caused by hypocretin (also known as orexin) deficiency, Kleine-Levin syndrome, and syndromes with hypersomnolence unexplained by hypocretin abnormalities (generally without cataplexy).[2] Kleine-Levin syndrome, a rare disorder that typically affects adolescent males, is characterized by recurring bouts of excessive sleep separated by weeks or months, along with altered behavior.[3,4] The International Classification of Sleep Disorders, Third Edition, classifies narcolepsy as type 1 or type 2. Type 1 narcolepsy is differentiated from type 2 by the presence of cataplexy and/or hypocretin deficiency (<110 pg/mL) in the cerebrospinal fluid (CSF).[5] Since narcoleptic patients can have deficiencies in hypocretin-producing neurons, an autoimmune process may be responsible for the destruction of hypocretin-producing cells.