The Debatable Relationship Between Migraine and Narcolepsy

Written by: Kylie Petrarca, RN, BSN

Medically Reviewed by: Dr. Michael Thorpy

Edited by: Leigh Serth

What is Narcolepsy?

Narcolepsy is a chronic neurological disorder characterized by an inability to regulate normal patterns of wakefulness and sleep. Key features of narcolepsy include daytime sleepiness, cataplexy (type 1 narcolepsy), sleep paralysis and sleep related hallucinations.¹ The daytime sleepiness symptoms can cause impairment of daily activities due to the inability to stay awake. Patients are often unable to control when they fall asleep and can have sleep attacks.

There are two types of narcolepsy: type 1, and type 2, sometimes called idiopathic narcolepsy. 

• Type 1 narcolepsy is known as narcolepsy with cataplexy. Cataplexy is defined as a loss of muscle control and occurs while someone is awake, typically after a strong emotional response to laughter, excitement, fear or stress. An episode of cataplexy can range from mild to severe and normally lasts for a few minutes, resolving on its own. People with type 1 narcolepsy will commonly experience excessive daytime sleepiness and have low cerebrospinal fluid levels of an important hypothalamic sleep hormone called hypocretin. 
• Type 2 narcolepsy, is known as narcolepsy without cataplexy. The sleepiness may be less severe than type 1. People with type 2 can have sleep paralysis and sleep-related hallucinations but have normal levels of hypocretin.

Narcolepsy can be secondary to a neurological disorder when there is damage to the hypothalamus, an area of the brain that regulates sleep and wake cycles. People will still experience the symptoms of type 1 and type 2 narcolepsy but may sleep for longer periods of time.²

Narcolepsy is diagnosed after a thorough medical, psychological, sleep and family history followed by a polysomnogram and a multiple sleep latency test. A polysomnogram is an overnight sleep study that measures heart rate, oxygen saturation, sleep, respiration, muscle tone and eye movements. This test evaluates the amount and quality of sleep and helps exclude other sleep disorders.³ Next, a multiple sleep latency test is performed to determine the severity of daytime sleepiness and the presence of sleep onset REM periods (SOREMPs). In this test, a person is given the opportunity to nap 4-5 times during the day. The test measures how long it takes the person to go to sleep and the stages of sleep achieved. This is the most important test for diagnosing narcolepsy.

The Relationship Between Migraine and Narcolepsy – An Overview of Studies

The relationship between migraine and narcolepsy is somewhat debatable as one study disproves their relationship but 4 other studies demonstrate a connection. The first study that identified a connection between migraine and narcolepsy was by Dahmen, et. al who interviewed 68 people diagnosed with idiopathic narcolepsy (narcolepsy with an unknown cause).⁴ They found 81% of the study group had headaches and 54% of the study group met the IHS criteria for migraine.⁴ A few years later, the same author conducted another study with 100 people and found that 44.4% of women and 28.3% of men with narcolepsy also had migraine.⁵ They concluded that migraine was 2 – 4 times more prevalent among people with narcolepsy.⁵ In addition, they found that on average the first migraine symptom occurred 12.3 years after the first narcolepsy symptom.⁵

A third study found that migraine was more prevalent among people with narcolepsy (23.5%) and idiopathic hypersomnia (a variant of narcolepsy) (41.2%) compared to the control group.⁶ People who live with migraine were also more likely to have excessive daytime sleepiness compared to the control group.⁶ 

Lastly, one study found that children with migraine were over 5 times more likely to live with narcolepsy.⁷ See the Migraine, Narcolepsy and Children section for more information.

On the other hand, there was a study by Evers and the DMKG Study Group that did not find a correlation between migraine and narcolepsy, however, they did find a relationship between narcolepsy and tension headache.⁸ There were 96 people enrolled in the study who had idiopathic narcolepsy.⁸ The frequency of migraine was not statistically significant compared to the control group.⁸ Tension headache was reported to be higher in the study group (60.3%) than the control group (40.7%), which was statistically significant.⁸

What Is The Connection?

Although it is not completely understood how narcolepsy and migraine are related, there are a few common factors including issues with the hypothalamus, REM sleep disturbances, genetics and the dysregulation of different areas in the brainstem. 

The hypothalamus is an important area in the brain that keeps the body in balance. It regulates a persons’ sleep wake cycle, temperature, thirst, appetite, mood and sex drive.⁹ Interestingly, during the prodrome phase of a migraine, researchers found that there is increased activity in the hypothalamus. The hypothalamus is likely involved in many migraine symptoms such as mood changes, temperature changes, fatigue, food cravings and loss of appetite.¹⁰ In narcolepsy, the hypothalamus is also involved. The hypothalamus produces the sleep hormone hypocretin which is typically deficient in most people with narcolepsy. This hormone is produced throughout the day to promote wakefulness. It also suppresses REM sleep. People who are deficient in hypocretin may have trouble staying awake during the day and can enter REM sleep while awake.

Dysregulation of REM sleep is involved in the pathophysiology of narcolepsy. People with this condition may enter REM sleep while awake, and experience cataplexy, sleep paralysis, hallucinations and other symptoms.⁶ REM sleep is also thought to be involved in migraine attacks because many people with migraine have longer periods of REM sleep and migraine attacks commonly occur during REM sleep.⁶ 

Genetics may be another contributing factor to the relationship between narcolepsy and migraine. There has been an association between migraine without aura and the orexin (hypocretin) receptor 1 gene.⁶

Lastly, the brainstem may also be involved in the relationship between narcolepsy and migraine. “A dysregulation of brainstem areas, including the periaqueductal gray, the dorsal raphe nucleus, and the locus coeruleus has been proposed as a possible pathophysiological link between migraine and narcolepsy.“¹¹

Migraine, Narcolepsy and Children

The onset of narcolepsy can begin at any age but most often occurs in children, adolescents and young adults. According to a study by Yang et. al, children with migraine had a 5.3 fold increased risk of narcolepsy.⁷ The risk of narcolepsy was the highest in children who have migraine with aura compared to migraine without aura.⁷ Males who live with migraine were found to have a 6.68 fold increased risk of developing narcolepsy compared to males without migraine.⁷ 

The study also identified other risk factors for narcolepsy in children with migraine.⁷

• Aged 12-17 years old
• Use of NSAIDS
• Use of acetaminophen
• Other comorbidities

Treatment of Narcolepsy

Wake promoting medications are typically used to help people with narcolepsy stay awake during the day but do not treat cataplexy. Some examples include modafinil, armodafinil, and solriamfetol. Pitolisant treats both sleepiness and cataplexy. Sodium oxybate is the only FDA approved medication used to treat daytime sleepiness, disturbed nocturnal sleep and cataplexy in people with narcolepsy but people on this medication should limit their sodium intake. A new formulation of oxybate, mixed salts oxybate, has less sodium. Cataplexy, hallucinations, disrupted nighttime sleep and sleep paralysis can be treated with antidepressant medications such as norepinephrine reuptake inhibitors (NERIs) or selective serotonin reuptake inhibitors (SSRIs).¹² It should be noted that narcolepsy medications can cause headaches.

Warnings for Treating Migraine in People Also Living With Narcolepsy*

• Tiptans can cause drowsiness if taken during the day.¹³ 
• Some antidepressants and anti-seizure medications can cause sleepiness. If tricyclic antidepressants are used, they are better tolerated when taken at night.¹³ 
• Beta blockers can cause nightmares and frequent awakening during sleep which may be a concern for someone living with narcolepsy.¹³ 
• Ubrogepant may cause sleepiness.

Recommended Medications for Migraine Disease in Someone Living With Narcolepsy*

• CGRP monoclonal antibodies
• Certain neuromodulation devices such as non-invasive vagus nerve stimulation and remote electrical neuromodulation
• OnabotulinumtoxinA
• Vitamins and supplements
• Many over the counter combination analgesics contain caffeine which may be helpful for people with excessive daytime sleepiness or narcolepsy. 

Sleep Tips for Migraine and Narcolepsy

• Create a sleep schedule: go to sleep and wake up at the same time every day
• Avoid using electronics before bed
• Avoid caffeine, nicotine, large meals and exercise before bed
• Sleep in a dark, quiet and cool room
• Try using relaxation techniques before sleep such as meditation, guided imagery, etc.

*Always discuss treatment options with your doctor. Never start or stop a medication without first consulting with your provider.

What Type of Doctor is Recommended for Migraine and Narcolepsy?

Migraine is best treated by a clinician who specializes in headache medicine. A sleep medicine specialist and/or a neurologist is recommended to diagnose and treat narcolepsy. 

A Note To Patients and Providers

Migraine and narcolepsy are two conditions that can be extremely debilitating and can result in profound impairment. Both conditions can affect people at any age but narcolepsy onset most often occurs in people less than 18 years old. Treatment for narcolepsy and migraine may be difficult but providers may want to opt for migraine medications that do not cause drowsiness. People with narcolepsy should report extreme sleepiness and any adverse events from migraine medications. Sleep hygiene is incredibly important for managing both migraine and narcolepsy. Providers may want to assess for migraine in people living with narcolepsy due to the high prevalence of people with headache disorders in this population. If you live with narcolepsy and/or migraine, consider donating your brain to research. Learn more here.

Thank you to our sponsor Axsome Therapeutics!

Resources 

1. Join a support group
2. Facts about narcolepsy
3. Participate in a clinical trial

References

1. Golden, Erin C., and Melissa C. Lipford. “Narcolepsy: Diagnosis and Management.” Cleveland Clinic Journal of Medicine, vol. 85, no. 12, 2018, pp. 959–969., https://doi.org/10.3949/ccjm.85a.17086. 
2. https://www.ninds.nih.gov/narcolepsy-fact-sheet
3. https://healthysleep.med.harvard.edu/narcolepsy/diagnosing-narcolepsy/narcolepsy-testing#:~:text=The%20diagnosis%20of%20narcolepsy%20is,Sleep%20Latency%20Test%20(MSLT).&text=A%20polysomnogram%20helps%20your%20physician,when%20REM%20activity%20is%20occurring.
4. Dahmen N, Querings K, Grün B, Bierbrauer J. Increased frequency of migraine in narcoleptic patients. Neurology. 1999 Apr 12;52(6):1291-3. doi: 10.1212/wnl.52.6.1291. PMID: 10214764.
5. Dahmen N, Kasten M, Wieczorek S, Gencik M, Epplen JT & Ullrich B. Increased frequency of migraine in narcoleptic patients: a confirmatory study. Cephalalgia 2003; 23:14–19. London. ISSN 0333-1024
6. Suzuki K, Miyamoto M, Miyamoto T, Inoue Y, Matsui K, Nishida S, Hayashida K, Usui A, Ueki Y, Nakamura M, Murata M, Numao A, Watanabe Y, Suzuki S, Hirata K. The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study. PLoS One. 2015 Sep 29;10(9):e0139229. doi: 10.1371/journal.pone.0139229. PMID: 26418536; PMCID: PMC4587931.
7. Yang C-P, Hsieh M-L, Chiang J-H, Chang H-Y, Hsieh VC-R (2017) Migraine and risk of narcolepsy in children: A nationwide longitudinal study. PLoS ONE 12(12): e0189231. https://doi.org/10.1371/journal.pone.0189231
8. Evers S. Migraine and Idiopathic Narcolepsy – A Case-Control Study. Cephalalgia. 2003;23(8):786-789. doi:10.1046/j.1468-2982.2003.00594.x
9. https://my.clevelandclinic.org/health/articles/22566-hypothalamus#:~:text=Your%20hypothalamus%2C%20a%20structure%20deep,system%20or%20by%20managing%20hormones.
10. May A, Burstein R. Hypothalamic regulation of headache and migraine. Cephalalgia. 2019 Nov;39(13):1710-1719. doi: 10.1177/0333102419867280. Epub 2019 Aug 29. PMID: 31466456; PMCID: PMC7164212.
11. Tiseo, C., Vacca, A., Felbush, A. et al. Migraine and sleep disorders: a systematic review. J Headache Pain 21, 126 (2020). https://doi.org/10.1186/s10194-020-01192-5
12. https://my.clevelandclinic.org/health/diseases/12147-narcolepsy#:~:text=Diagnosis%20and%20Tests&text=Two%20essential%20sleep%20studies%20to,and%20require%20an%20overnight%20stay
13. Korabelnikova, E.A., Danilov, A.B., Danilov, A.B. et al. Sleep Disorders and Headache: A Review of Correlation and Mutual Influence. Pain Ther 9, 411–425 (2020). https://doi.org/10.1007/s40122-020-00180-6
14. https://braindonorproject.org/

*The contents of this blog are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The writer does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.