Is there any evidence to support the use of Vyvanse (lisdexamfetamine) in the treatment of narcolepsy?

Comment by InpharmD Researcher

Evidence supporting Vyvanse (lisdexamfetamine) in treatment of narcolepsy is limited to a single case series detailing its use. While the case series reported successful management of excessive daytime sleepiness, it is important to note that this evidence is anecdotal and derived from a small sample size (N= 5), hindering its generalizability. Additionally, while reviews suggest lisdexamfetamine as a potential alternative medication for narcolepsy, guidelines do not incorporate it into their recommendations. Overall, there is a need for more robust data regarding lisdexamfetamine in the treatment of narcolepsy.

Background

According to the American Academy of Sleep Medicine Report and the European Federation of the Neurological Societies, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate can effectively treat daytime sleepiness associated with narcolepsy. These medications have a long-standing history of effectiveness in clinical practice. However, there is limited information available regarding their benefit-to-risk ratio. According to a 2015 review article, lisdexamfetamine (Vyvanse) is used off-label because of its recognized utility in managing daytime sleepiness symptoms. However, the societal guidelines did not offer a specific recommendation regarding the specific use of this medication for the management of narcolepsy. [1], [2], [3]

A 2020 case series reported use of lisdexamfetamine in the management of narcolepsy based on experience from five narcoleptic patients in Brazil. Each patient received individualized doses and durations of treatment to help manage excessive daytime sleepiness (EDS) and weight control; weight gain is a common complication in narcoleptic patients, sometimes resulting in increased comorbidities such as metabolic syndrome and cardiovascular risk. Four of the included patients were women, and one was male, ranging in age from 22 to 51 years. Patients met the International Classification of Sleep Disorders, 3rd edition (ICSD-3) criteria for narcolepsy, characterized by an average sleep latency of ≤ 8 minutes and presence of two or more episodes of sleep-onset rapid eye movement (REM) periods. All patients were treated with lisdexamfetamine due to refractory EDS despite treatment with stable doses of methylphenidate or modafinil for at least 3 months. The duration of lisdexamfetamine therapy ranged from 2 to 20 months, with a median of 3 months. The most commonly utilized dosage was 50 mg/day, but one patient was administered 30 mg/day. This particular patient (see Patient 4 on Table 1) experienced the most limited decrease in EDS per the Epworth Sleepiness Scale (ESS). Overall, mean ESS scores decreased from 18.2 to 10.8 after at least 8 weeks of lisdexamfetamine treatment. All patients reported reduced appetite, and four of five reported weight loss. Overall, lisdexamfetamine was concluded to be well tolerated and successful for management of EDS and weight. [4]

References:

[1] Morgenthaler TI, Kapur VK, Brown T, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin [published correction appears in Sleep. 2008 Feb 1;31(2):table of contents]. Sleep. 2007;30(12):1705-1711. doi:10.1093/sleep/30.12.1705
[2] Billiard M, Bassetti C, Dauvilliers Y, et al. EFNS guidelines on management of narcolepsy. Eur J Neurol. 2006;13(10):1035-1048. doi:10.1111/j.1468-1331.2006.01473.x
[3] Thorpy MJ. Update on therapy for narcolepsy. Curr Treat Options Neurol. 2015;17(5):347. doi:10.1007/s11940-015-0347-4
[4] Aguilar AC, Frange C, Pimentel Filho LH, Reis MJ, Tufik S, Coelho FMS. Lisdexamfetamine to improve excessive daytime sleepiness and weight management in narcolepsy: a case series. Braz J Psychiatry. 2020;42(3):314-316. doi:10.1590/1516-4446-2019-0544

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there any evidence to support the use of Vyvanse (lisdexamfetamine) in the treatment of narcolepsy?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Table 1 for your response.


 
Clinical characteristics of the sample before and after intervention with lisdexamfetamine
Patient Age (years) Gender Narcolepsy type HCT-1 (pg/mL) SOREMP MSLT (mins) Maximum dose (mg) Treatment duration (months) BMI (kg/m2) Epworth Sleepiness Scale
                  Pre Post Pre Post
#1 28 M 2 350 2 7′ 50 2 28.4 27.7 19 10
#2 22 F 2 305 4 1′48″ 50 3 28.8 26.8 19 8
#3 27 F 2 NM 2 8′ 50 5 28 24 15 11
#4 51 F 1 58 3 1′5″ 30 2 26.6 28.2 23 20
#5 44 F 1 40 4 5′ 50 20 36.2 30.4 15 5

BMI = body mass index; F = female; HCT-1 = hypocretin-1; M = male; MSLT = multiple sleep latency test; NM = not measured; SOREMP = sleep-onset rapid eye movement episodes

Epworth Sleepiness Scale scores range from 0-24; 0-9 indicates no sleepiness symptoms, while > 10 indicates daytime sleepiness.

 
References:

Adapted from:
Aguilar AC, Frange C, Pimentel Filho LH, Reis MJ, Tufik S, Coelho FMS. Lisdexamfetamine to improve excessive daytime sleepiness and weight management in narcolepsy: a case series. Braz J Psychiatry. 2020;42(3):314-316. doi:10.1590/1516-4446-2019-0544