According to the latest Global Burden of Diseases, Injuries, and Risk Factors Report, headache disorders rank among the top 15 most common conditions across all age groups globally.1

Patients with migraine wait more than 17 years before being referred to a headache specialist.

A 2022 study by Stovner et al showed that tension-type headaches are the most common form (26%), followed by migraine (14%). Furthermore, headache accounts for one in 10 general practitioner consultations, one in three neurology referrals and one in five acute medical admissions.2,3,4

Migraine: more than just a headache

The International Headache Society (IHS) classifies headache disorders as primary or secondary. A primary headache has no known underlying cause. Secondary headache is the result of another condition causing traction on or inflammation of pain-sensitive structures.5

Patients with migraine are known to have a high lifetime prevalence of psychiatric comorbidities including major depressive disorders, panic disorders, and generalised anxiety disorder and higher suicidal ideation.7,8

About 90% of patients with migraine report having moderate or severe pain,  75% report functional disability during a migraine attack, more than 30% require bed rest during their attacks and 50% need help from family or friends.4,6

Migraine has a substantial impact on the economy as well as work and school productivity. On average patients with migraine lose between 3.2 and 89.2 work-equivalent days per year. Furthermore, 10.6% of school-aged children suffer from migraine and miss on average 4.1 school-days per year. This also impact parents and other caregivers productivity and quality of life (QoL).9

The treatment of migraine also imposes a financial burden on patients and healthcare systems. A  2018 American study found that the total cost of episodic migraines was around $2649 (R42 000) per year, and that the cost of chronic migraine was around $8243 (R130 000). In this study, 60%-64% of migraine costs was due to direct medical ones.9

Diagnosis of migraine

The main subtypes are migraine with and without aura. The IHS defines migraine with aura as recurrent attacks, lasting minutes, of unilateral fully-reversible visual, sensory, or other central nervous system symptoms that usually develop gradually and are usually followed by headache and associated migraine symptoms10

Diagnostic criteria for migraine with aura include:

a. At least two attacks fulfilling criteria b and c
b. One or more of the following fully reversible aura symptoms:
1. Visual (90% of patients)
2. Sensory
3. Speech and/or language
4. Motor
5. Brainstem
6. Retinal.
c. At least three of the following six characteristics:
1. At least one aura symptom spreads gradually over ≥5 minutes
2. Two or more aura symptoms occur in succession
3. Each individual aura symptom lasts five to 60 minutes
4. At least one aura symptom is unilateral
5. At least one aura symptom is positive
6. The aura is accompanied, or followed within 60 minutes, by headache.
d. Not better accounted for by another diagnosis.

Diagnostic criteria for migraine without aura:

a. At least five attacks fulfilling criteria b-d
b. Headache attacks lasting four to 72 hours (untreated or unsuccessfully treated)
c. Headache has at least two of the following four characteristics:
1. Unilateral location
2. Pulsating quality
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)
d. During headache at least one of the following:
1. Nausea and/or vomiting
2. Photophobia and phonophobia
e. Not better accounted for by another diagnosis.

Episodic versus chronic migraine

Progression from episodic to chronic migraine can occur and has been associated with the overuse of certain medications (eg opioids, barbiturates, nonsteroidal anti-inflammatory drugs [NSAIDs], and triptans) and excessive consumption of caffeine. Medicine overuse is defined as taking pain medications for more than 10 days a month.12,13

About 31% of patients develop chronic migraines. Chronic migraines are defined as a headache occurring on 15 or more days/month for more than three months, which, on at least eight days/month, has the features of migraine headache.6,10

The diagnostic criteria for chronic migraine include:10

a. Headache (migraine-like or tension-type-like) on ≥15 days/month for >3 months, and fulfilling criteria b and c
b. Occurring in a patient who has had at least five attacks fulfilling criteria b-d for migraine without aura and/or criteria b and c for migraine with aura
c. On ≥8 days/month for >3 months, fulfilling any of the following:

1. Criteria c and d for migraine without aura
2. Criteria b and c for Migraine with aura
3. Believed by the patient to be migraine at onset and relieved by a triptan or ergot derivative
d. Not better accounted for by another diagnosis.

Episodic migraine is everything else, so anything up to 14 headache days per month. This threshold, however, is currently a hot topic of debate.10

Management challenges

Despite the availability of effective acute and preventative treatments for migraine, a 2019 study found that about 50% of patients and 30% of those who suffer from definite migraines do not believe that headache is a disease and do not require medical care – especially men – and prefer to self-medicate, which may result in medication overuse and progression to chronic migraine as mentioned above.13,14

The American Headache Society (AHS) acknowledges that because symptoms and intensity vary, optimising treatment for particular patients is challenging. As mentioned above migraine treatment involves acute (abortive) – also known as symptomatic treatment – and preventive (prophylactic) measures. The society recommends that all patients with a confirmed diagnosis of migraine should be offered a trial of acute pharmacological and/or nonpharmacologic treatment.14

Effective acute treatment can reduce the pain, associated symptoms, and disability associated with attacks. Suboptimal acute treatment is associated with higher migraine-related disability and risk of disease progression(eg chronic migraine).14

About 56% of patients with episodic migraine reported inadequate response to acute treatment at two hours for at least half of their migraine headaches, and an additional 26% reported recurrence within 24 hours after initial benefit.15

Studies show that less than 13% of migraine patients are believed to be on prophylactic therapy, whereas it is estimated that around 38% of episodic migraine patients would actually benefit from prophylactic therapy. Prophylactic migraine treatment should be considered in patients with >3 migraine headaches per month or at least eight headache days in one month.16

Goals of preventative treatment

According to the AHS, the principles of preventive treatment include using evidence-based treatments, titrating until clinical benefits are achieved, giving each treatment a trial of at least two to three months, and avoiding overuse of acute treatments.14 

The goals of migraine prevention are to:14

  • Reduce attack frequency, severity, duration, and disability
  • Improve responsiveness to and avoid escalation in use of acute treatment.
  • Improve function and reduce disability
  • Reduce reliance on poorly tolerated, ineffective, or unwanted acute treatments.
  • Reduce overall cost associated with migraine treatment
  • Enable patients to manage their own disease to enhance a sense of personal control
  • Improve health-related QoL
  • Reduce headache-related distress and psychological symptoms.

Patients with migraine should be considered for preventive treatment in any of the following situations:14

  • Attacks significantly interfere with patients’ daily routines despite acute treatment
  • Frequent attacks
  • Contraindication to, failure, or overuse of acute treatments
  • Adverse events with acute treatments
  • Patient preference.

According to Mungoven et al, the only currently available pharmacotherapies that have demonstrated efficacy in chronic migraine prophylaxis are botulinum toxin type A, topiramate and newly approved calcitonin gene-related peptide targeted monoclonal antibodies.17

How effective is botulinum toxin type A treatment?

In 2000, Binder et al evaluated the efficacy of pericranial botulinum toxin type A administration and improvement of migraine symptoms. They showed that 51% of participants reported a complete response with a mean response duration of 4.1 months, 38% reported partial response with a mean  response duration of 2.7 months and seven out of 10 true migraine patients treated acutely reported complete response with improvement one to two hours after treatment.18

Silbertein et al (2001) showed that patients treated botulinum toxin type A experienced significantly fewer migraine attacks per month, a reduced maximum severity of migraines, a reduced number of days using acute migraine medications, and reduced incidence of migraine-associated vomiting.19 

In a pooled analysis of the REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) studies,botulinum toxin type A 155U or placebo was administered as 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. At the investigator’s discretion, an additional 40U could be administered using a ‘follow-the-pain’ strategy.20

There was a large mean reduction from baseline in the frequency of headache days in both treatment groups. However, botulinum toxin type A was statistically significantly more effective than placebo in reducing the mean frequency of headache days at every visit in the double-blind phase starting at the first post-treatment study visit (week four) and including the week 24 primary endpoint (botulinum toxin type A−8.4, placebo −6.6).20

A significantly greater percentage of patients treated with botulinum toxin type A, compared to those treated with placebo, had at least a 50% decrease from baseline in the frequency of headache days at all time points, starting at the first post-treatment study visit (week four) and including week 24 (botulinum toxin type A 47.1% vs placebo 35.1%).20

Secondary endpoint findings:20

  • Mean change from baseline in frequency of moderate/severe headache days (-7.7 vs -5.8)
  • Mean change from baseline in cumulative hours of headache on headache days (-119.7 vs 80.5)
  • Mean change from baseline in frequency of headache episodes (-5.2 vs -4.9).
  • Mean change from baseline in frequency of migraine episodes (-8.2 vs-6.2)
  • Per cent patients with severe impact at baseline: botulinum toxin type 5% group versus 92.7%.

Both treatment arms showed an overall mean reduction in acute pain medication intakes. In a post-hoc analysis, there was statistically significant less use of triptans as acute pain medication at week 24 in the botulinum toxin type A group than in the placebo group.20

Botulinum toxin type A was approved for prophylaxis of chronic migraine in 2010 in the United States and has subsequently become a mainstream therapy for chronic migraine.21

Conclusion

There is a need for increased awareness about migraine among both patients and physicians. Patients believe that migraine do not require medical treatment and tend to self-medicate, which can result in medicine overuse and progression to chronic migraine (about 3%). A 2020 study found that only about 20% of headache patients were effectively managed in primary care, resulting in medicine overuse, unnecessary hospital emergency admissions and inappropriate use of brain imaging.22

A Brazilian study showed that patients with migraine wait more than 17 years before being referred to a headache specialist. As mentioned above, migraine severely impacts patients’ and caregivers’ QoL, resulting in decreased productivity, and high healthcare-related costs, reinforcing the need of specialised treatment for migraine patients.23

REFERENCES:

  1. Vos T, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 2020.
  2. Stovner LJ, et al. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 2018.
  3. Stovner LJ, et al. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. The Journal of Headache and Pain, 2022.
  4. Ahmed F. Headache disorders: differentiating and managing the common subtypes. Br J Pain, 2012.
  5. International Headache Society. Part II. Secondary headaches. https://ichd-3.org/5-headache-attributed-to-trauma-or-injury-to-the-head-andor-neck/
  6. Sajobi TT, et al.Global assessment of migraine severity measure: preliminary evidence of construct validity. BMC Neurology, 2018.
  7. Senaratne R, et al. The prevalence of migraine headaches in an anxiety disorders clinic sample. CNS Neurosci Ther, 2010.
  8. Lin Y-K, et al. Association of Suicide Risk With Headache Frequency Among Migraine Patients With and Without Aura. Frontiers in Neurology, 2019.
  9. Leonardi M and Raggi A. A narrative review on the burden of migraine: when the burden is the impact on people’s life. The Journal of Headache and Pain,
  10. International Headache Society. The International Classification of Headache Disorders 3rd Edition, 2018. https://ihs-headache.org/wp-content/uploads/2020/05/ICHD-3-Pocket-version.pdf
  11. Ishii R, et al.Chronic versus episodic migraine: The 15-day threshold does not adequately reflect substantial differences in disability across the full spectrum of headache frequency. Headache, 2021.
  12. Walter K. What Is Migraine? JAMA,
  13. Brusa P, et al. Self-medication for migraine: A nationwide cross-sectional study in Italy. PLoS One, 2019.
  14. Ailani J, et al. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache, 2021.
  15. Burch R and Rayhill M. Acute Treatment for Migraine: Contemporary Treatments and Future Directions. JAMA, 2021.
  16. Kumar A and Kadian R. Migraine Prophylaxis. [Updated 2021 Oct 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507873/
  17. Murgoven T, et al. Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives. Frontiers Pain Research, 2021.
  18. Binder WJ, et al. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg, 2000.
  19. Silberstein S, et al. Botulinum Toxin Type A as a Migraine Preventive Treatment. Headache, 2001.
  20. Diener HC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia, 2010.
  21. Becker WJ. Botulinum Toxin in the Treatment of Headache. Toxins (Basel), 2020.
  22. Fejes E, et al. Characteristics of Patients Referred To A Specialized Headache Clinic. Scientific Reports, 2020.
  23. Peres MFP, et al. Migraine patients’ journey until a tertiary headache center: an observational study. The Journal of Headache and Pain, 2019.