​Most migraines can be effectively managed in primary care with the initiation of appropriate acute symptomatic treatment and first-line migraine preventives. Read all about the various forms of migraine and the appropriate management measures, and when referral for specialist care is needed.

Migraines are the second leading medical condition that contributes to years lived with disability and affects almost one billion people around the world.1 In a 2018 Singapore study, the direct and indirect costs due to migraines were estimated to be S$1.04 billion.2

The high prevalence of the disease, as well as economic burden from healthcare cost and loss of productivity makes it crucial for migraines to be treated effectively, with a growing demand for high quality healthcare access across all levels of the healthcare system in Singapore.

REVALENCE IN SINGAPORE

Migraines are common in Singapore, with a lifetime prevalence of 8.2% in one recent 2020 Singapore study.3

This prevalence is similar between boys and girls before puberty, at around 3-7%. However, postpuberty, due to the influence of hormones, the prevalence becomes higher in females, with migraines being three times more common than in males. This higher prevalence amongst females continues till menopause with a decline in statistics thereafter, but remains slightly higher than in males.4

In the 2020 Singapore study, it was also noted that the following groups were more likely to experience migraine headaches:

  • Malay ethnicity (compared to Chinese)
  • Diploma holders (compared to degree holders)
  • Younger age group of 18-34 years (compared to 65 years and above)
  • Employed people (compared to economically inactive people)

SYMPTOMS, HISTORY TAKING AND DIAGNOSIS

The mean age of onset of migraines in Singapore is 26.4 years,3 with a bimodal distribution of peaks in the late teens and twenties and around 50 years of age4.

However, patients with migraines can present at any age, and a careful history taking is needed to differentiate primary headache disorders, such as migraines and tension-type headaches, from secondary headache disorders.

Identifying red flags

Common red flags can be elicited from patients using the acronym 'SNNOOP10' to snoop for red flags (Table 1).5

 

​SNNOOP10 list of red and orange flags5

1​

​Sign or symptom

​Related secondary headaches (most relevant ICHD-3b* categories)

​Flag colour

2

Systemic symptoms including fever

Headache attributed to infection or nonvascular intracranial disorders, carcinoid or phaeochromocytoma

Red (orange for isolated fever)

​3

​Neoplasm in history

​Neoplasms of the brain; metastasis

​Red

4

Neurologic deficit or dysfunction (including decreased consciousness)

Headaches attributed to vascular, nonvascular intracranial disorders; brain abscess and other infections

​Red

​5

Onset of headache is sudden or abrupt

Subarachnoid haemorrhage and other headaches attributed to cranial or cervical vascular disorders

​Red

​6

​Older age (after 50 years)

Giant cell arteritis and other headache attributed to cranial or cervical vascular disorders; neoplasms and other nonvascular intracranial disorders

​Red

​7

Pattern change or recent onset of headache

Neoplasms, headaches attributed to vascular, nonvascular intracranial disorders

​Red

8

​Positional headache

​Intracranial hypertension or hypotension

​Red

9

Precipitated by sneezing, coughing or exercise

​Posterior fossa malformations; Chiari malformation

​Red

10

​Papilledema 

Neoplasms and other nonvascular intracranial disorders; intracranial hypertension

​Red

11

Progressive headache and atypical presentations

​Neoplasms and other nonvascular intracranial disorders

​Red

12

​Pregnancy or puerperium

Headaches attributed to cranial or cervical vascular disorders; postdural puncture headache; hypertension-related disorders (e.g., preeclampsia); cerebral sinus thrombosis; hypothyroidism; anaemia; diabetes

​Red

13

Painful eye with autonomic features

Pathology in posterior fossa, pituitary region, or cavernous sinus; Tolosa-Hunt syndrome; ophthalmic causes

​Red

14

Post-traumatic onset headache

Acute and chronic post-traumatic headache; subdural haematoma and other headache attributed to vascular disorders

​Red

15

Pathology of the immune system such as HIV

​Opportunistic infections

​Red

16

Painkiller overuse or new drug at onset of headache

​Medication overuse headache; drug incompatibility

​Red

​*ICHD-3b: International Classification of Headache Disorders 3b

Table 1

Past or current medical conditions of immunocompromised state, pregnancy, malignancy or recent head trauma can alert the physician to a possible secondary headache.

Headache characteristics such as those below are also suggestive of a potential intracranial pathology that may need to be further evaluated in a tertiary setting:

  • Early morning headaches
  • Presence of blurring of vision or focal neurological symptoms
  • Headache that changes with posture
  • Headache that worsens with the Valsalva manoeuvre

Diagnostic criteria

Based on the International Classification of Headache Disorders 3 (ICHD-3),6 migraines last about four to 72 hours and are characterised by a unilateral, throbbing-quality headache that is worsened with physical activity, and of moderate to severe intensity.

These may be associated with nausea and/or sensitivity to light, sound, smell or movements.

The criteria require two attacks for migraines with aura, and at least five attacks for migraines without aura.

It is useful to elicit the above characteristic features and associated symptoms during history taking, to assist in the diagnosis of migraines.

Migraine triggers

In addition to the diagnostic criteria, headaches with a clear trigger such as alcoholic beverages, menstruation, sleep deprivation, stress, missed meals, dehydration and other commonly known migraine triggers (Table 2) also give clues to the diagnosis of migraines.7

​Common migraine triggers7

Migraine trigger

​Percentage (%)

​Stress

​79.7

​Hormones

​65.1

​Missing a meal / hunger / fasting

​57.3

​Weather change

53.2​

​Sleep disturbance

​49.8

​Perfume or odour

​43.7

​Neck pain

​38.4

​Light

​38.1

​Alcohol

​37.8

​Smoking

​35.7

​Sleeping late

​32.0

​Heat

​30.3

​Food

​26.9

​Exercise

​22.1

​Sexual activity

​5.1

Table 2

Family history

Evaluating a patient’s family history for headache conditions also allows one to see the presence of familial aggregation and the patient’s genetic predisposition to migraines.

Migraines are commonly associated in first-degree relatives8, with one study showing that a strong family history predisposes an individual to a lower age at onset, higher number of medication days and presence of migraine with aura.9

Medication history

A careful medication history helps to evaluate for drugs that can potentially provoke a headache attack. Documenting the type and frequency of analgesia use helps to rule out the possibility of medication overuse headaches, which are often seen in patients with chronic migraine.10

Medication overuse headaches, by the diagnostic criteria of ICHD-3, are a secondary headache disorder that happens in patients with a pre-existing primary headache disorder, as a result of regular overuse of acute headache medications for more than three months.6

Hence it is important to identify this group of patients early, to allow for appropriate treatment.

TYPES OF MIGRAINE

By the ICHD-3 criteria, migraines can be subdivided into episodic migraines and chronic migraines.

  • Patients with episodic migraines experience migraines at a frequency of four to 14 days a month, over a period of at least three months.

  • Patients with chronic migraines have headache days occurring at more than 15 days a month over a period of three months.

Chronic migraines represent a more severe form of migraine, with neurophysiology studies and functional neuroimaging showing changes in the brain that are different from that of patients with episodic migraines or patients with no migraines.11

As such, treatment differs between patients with episodic migraines and patients with chronic migraines.

MANAGING MIGRAINES IN PRIMARY CARE

The treatment of migraines is largely divided into non-pharmacological and pharmacological management.

1. Non-pharmacological management

For the non-pharmacological approach, trigger identification and lifestyle modification play significant roles in limiting the progression and chronification of migraines.

A SMART lifestyle (Table 3) is advocated for migraine patients with low-frequency episodic migraines (four to nine headache days per month) or infrequent migraines (less than four headache days per month).

A healthy lifestyle with avoidance of triggers allows for less frequent attacks of headache, hence minimising the risk of chronification of migraines into that of higher frequency migraines or chronic migraines.

SMART lifestyle for migraine patients - NNI

Table 3 SMART lifestyle for migraine patients

2. Pharmacological management

The pharmacological approach comprises:

  • Acute symptomatic treatment for abortion of migraine attacks

  • Migraine preventive therapy, which is usually used for patients with high-frequency episodic migraines or chronic migraines to decrease the headache frequency and intensity over a period of time

Acute symptomatic treatment

Adequate abortive treatment is needed to ensure a good quality of life for the patient.

Physicians can consider acute pain management of migraines using either a step-care approach or a stratified-care approach.

  • In a step-care approach, patients are given first-line abortive treatments such as acetaminophen before escalating to nonsteroidal anti-inflammatory drugs (NSAIDs) or triptans should the first-line medications fail.

  • For a stratified-care regimen, physicians can use the Headache Impact Test-6 (HIT-6) or Migraine Disability Assessment (MIDAS) questionnaire12 to assess severity and disability from migraine attacks, and thereafter be better able to predict analgesia needs.
    A low MIDAS or HIT-6 score indicates that the patient is less likely to require escalation of treatment and can be started on acetaminophen or NSAIDs first. Patients with a higher score may respond better to migraine-specific treatments such as triptans as first-line therapy.13

Migraine preventive therapy

The choice to start preventive treatment requires proper discussion between the physician and patient. While it is common to start preventive treatment for patients with high-frequency episodic migraines or chronic migraines, preventive treatment can also be considered for low-frequency episodic migraine patients if each attack is severe, prolonged and debilitating.

The discussion needs to be based on the benefit of preventive treatment versus the harm from its side effects. The choice of preventive is largely dependent on the patient’s comorbidities, ease of administration and side effects.

Table 4 highlights some common migraine preventives used in tertiary centres, the starting doses and common adverse effects.

​Commonly used migraine preventives​ ​ ​ ​

Drug

Starting dose

Relative indications / comorbidities to consider

Adverse effects​

​Contraindications to consider

Propranolol

​10 mg BD

​Hypertension

​Lethargy, nausea, postural giddiness

Asthma, depression, congestive cardiac failure

Amitriptyline/
Nortriptyline

5-10 mg ON / 10 mg ON

Insomnia, depression, anxiety, pain disorders

​Drowsiness, dry mouth, weight gain

​Urinary retention, heart blocks

​Flunarizine

​5 mg ON

​Hypertension

Drowsiness, parkinsonism, weight gain, depression

​Parkinson disease, depression

​Topiramate

​25 mg ON

​Epilepsy, obesity

Paresthesia, altered taste, cognitive complaints

​Renal stones, glaucoma

Valproate

​200-500 mg BD

​Epilepsy, depression

​Weight gain, tremors, lethargy

​Liver disease, thrombocytopaenia

Table 4 ON: once every night; BD: twice daily

​CASE STUDY

Background

Ms Tan is a 32-year-old Chinese female holding a managerial role in a large company. She has no significant past medical history. 

Symptoms, history taking and diagnosis

She has had headaches since her school days, but reported noticing a recent increase in headache frequency for the past six months.

Her headache is characterised as throbbing in nature, with sensitivity to light and sound, as well as nausea. Her reported visual analogue scale (VAS) pain score was seven to eight out of ten.

Out of the four average attacks she has per month, about half of them are severe and debilitating enough to stop her from working, and can last up to two days. 

She also noticed a trend of headache attacks about one to two days prior to her menstruation, and those are usually more severe and prolonged headache attacks. She has no other red flags noted on history.

Based on the ICHD-3 criteria, she fulfils the diagnosis of low-frequency, episodic migraines.

Initial management

Using the stratified-care approach, sumatriptan 50 mg was recommended for her as abortive treatment

Although her current headache frequency was about four days per month, the attacks were severe and prolonged, hence there was a discussion of starting preventive treatment with the patient. However, the patient opted not to start preventive treatment yet. 

Patient education was provided to the patient to identify triggers and modify her lifestyle as much as possible, despite her busy work schedule.

Follow-up and management reviews

She was reviewed in the clinic again after six months. During the next clinic visit, she reported an increase in migraine frequency to four to five days a week, with frequent usage of sumatriptan.

The analgesia had helped to abort the attacks, but her headache would recur as soon as the analgesia effect wore off. As such, she was taking sumatriptan about 20 days a month to cope with her headache attacks. 

Migraine preventive medication was strongly advised in the clinic consult due to worsening migraine frequency and the concern of medication overuse headaches. She was started on topiramate 25 mg once every night due to her comorbidity of obesity.

She was also advised to concurrently cut down her analgesia usage due to diagnosis of medication overuse headaches in her situation.

In the next review four months later, her use of analgesics and her frequency of migraine reduced dramatically.


TREATMENT OPTIONS BY SPECIALISTS

Tertiary hospitals have a larger range of oral preventive treatments available in formulary, including preventives in the category of antidepressants, antihypertensives and antiepileptics.

In addition, Botox is also available for the treatment of chronic migraines.

The Health Sciences Authority (HSA) has in recent years approved the use of four calcitonin gene-related peptide (CGRP) monoclonal antibodies – erenumab, fremanezumab, galcanezumab and eptinezumab – in preventive treatment of migraines. Most of these CGRP monoclonal antibodies are available in tertiary hospitals.

These antibodies are specifically designed for the treatment of migraines, and hence are more targeted with less side effects and offer a non-oral route of administration.

In addition, at the time of writing, rimegepant, which is an oral CGRP small molecule antagonist, is also seeking approval from HSA for use in acute and preventive treatment of migraines.

THE GP’S ROLE IN TREATMENT

Evaluation

GPs can evaluate a patient’s migraine severity based on migraine questionnaires such as HIT-6 and/or MIDAS to assess its impact on the patients’ life.

Patient education and initial treatment

From there, we advocate patient education and a discussion with the patient on the need for migraine prophylaxis. Abortive treatment can be given to patients in a stratified-care regimen to allow for more tailored treatment. 

If a migraine preventive is initiated, it should be kept on a minimum duration of four to six months before tapering or stopping, with review in between to assess for efficacy and allow for titration of doses. 

Referral and shared care

If the patient fails to respond to the first-line preventives in Table 4, referral to a tertiary centre can be considered for further evaluation and treatment.

A shared care approach between the patient’s primary care physician and tertiary specialists can be considered during the period that the patient is on migraine preventives. Eventually, when the patient’s migraine is well controlled, the GP can be the patient’s primary healthcare provider to titrate preventives as and when needed during a patient’s lifetime, in the event of relapses.

WHEN TO REFER TO A SPECIALIST

Referral to a tertiary institution can be considered when patients present red flags of headaches and an underlying secondary headache disorder is suspected.

Most primary headaches can be managed at a primary care level with initiation of appropriate acute symptomatic treatment, as well as first-line migraine preventives.

However, migraines that are progressing and not responding to preventive medications that are of adequate doses and duration can be considered for tertiary institution referral.

Lastly, patients with medication overuse headaches are a special group of patients that requires patient education, analgesic withdrawal and concurrent initiation of preventive therapy. If withdrawal of medication is difficult and preventive treatment is inadequate, referral to a tertiary institution can also be considered.

MIGRAINE MANAGEMENT AT THE NATIONAL NEUROSCIENCE INSTITUTE

The National Neuroscience Institute (NNI) is the national centre for treatment of neurological diseases in Singapore, with its two main campuses located in Singapore General Hospital and Tan Tock Seng Hospital, and outpatient clinics in Changi General Hospital, Sengkang General Hospital and Khoo Teck Puat Hospital.

NNI sees at least 2,500 outpatient referrals for headaches a year, and is equipped to handle primary and secondary headaches as well emergency headache disorders. With expertise in neuroradiology and neurosurgery, NNI provides multidisciplinary management for our patients who require complex care.


GP survey - NNI

REFERENCES

  1. Vos T, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211–59.

  2. Ong, Jonathan J. Y., Devanshi Patnaik, Yee C. Chan, Oliver Simon, and Eric A. Finkelstein. “Economic Burden of Migraine in Singapore.” Cephalalgia Reports 3 (2020): 251581632090824.

  3. Jeyagurunathan, Anitha, Edimansyah Abdin, Janhavi A. Vaingankar, Boon Y. Chua, Saleha Shafie, Shi H. S. Chang, Lyn James, et al. “Prevalence and Comorbidity of Migraine Headache: Results from the Singapore Mental Health Study 2016.” Social Psychiatry and Psychiatric Epidemiology 55, no. 1 (2019;2020;): 33–43.

  4. Victor TW, Hu X, Campbell JC, Buse DC, Lipton RB. Migraine prevalence by age and sex in the United States: a life-span study. Cephalalgia. 2010 Sep;30(9):1065-72. doi: 10.1177/0333102409355601. Epub 2010 Mar 12. PMID: 20713557.

  5. Red and orange flags for secondary headaches in clinical practice: SNNOOP10 list - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/SNNOOP10-list-of-red-and-orange-flags_tbl1_329939433 [accessed 16 Sep, 2022]

  6. The International Classification of Headache Disorders 3rd edition [Internet]. 2018 [cited 2022 Sep 20]. Available from: https://ichd-3.org/

  7. Kelman, L. "The Triggers or Precipitants of the Acute Migraine Attack." Cephalalgia 27, no. 5 (2007): 394–402

  8. Cologno, D., A. De Pascale, and G. C. Manzoni. "Familial Occurrence of Migraine With Aura in a Population-Based Study." Headache 43, no. 3 (2003): 231–34.

  9. Pelzer, Nadine, Mark A. Louter, Erik W. van Zwet, Dale R. Nyholt, Michel D. Ferrari, Arn MJM van den Maagdenberg, Joost Haan, and Gisela M. Terwindt. "Linking Migraine Frequency with Family History of Migraine." Cephalalgia 39, no. 2 (2019;2018;): 229–36.

  10. Straube, A., V. Pfaffenrath, K-H Ladwig, C. Meisinger, W. Hoffmann, K. Fendrich, M. Vennemann, and K. Berger. "Prevalence of Chronic Migraine and Medication Overuse Headache in Germany—the German DMKG Headache Study." Cephalalgia 30, no. 2 (2010): 207–13.

  11. Mathew, Ninan T. "Pathophysiology of Chronic Migraine and Mode of Action of Preventive Medications." Headache 51, no. s2 (2011): 84–92.

  12. Sauro, Khara M., Marianne S. Rose, Werner J. Becker, Suzanne N. Christie, Rose Giammarco, Gordon F. Mackie, Arnoldas G. Eloff, and Marek J. Gawel. "HIT-6 and MIDAS as Measures of Headache Disability in a Headache Referral Population." Headache 50, no. 3 (2010): 383–95.

  13. Diamond, Merle L., Richard G. Wenzel, and George R. Nissan. "Optimizing Migraine Therapy: Evidence-Based and Patient-Centered Care." Expert Review of Neurotherapeutics 6, no. 6 (2006): 911–19.

  14. HEALTH PROMOTION BOARD LAUNCHES NATIONAL PHYSICAL ACTIVITY GUIDELINES [Internet]. 2011 [cited 2022 Sep 20]. Available from: https://www.hpb.gov.sg/article/health-promotion-board-launches-national-physical-activity-guidelines

 

Dr Zhao Yi Jing is a Consultant at the Department of Neurology, National Neuroscience Institute (Singapore General Hospital Campus) who specialises in the assessment, treatment and prevention of headaches and migraines in adult and adolescence. Dr Zhao is the Singapore representative principal investigator for several international and local clinical trials involving novel therapy for headaches. She also sits on several medical advisory boards for new migraine treatments in Singapore. She is the treasurer for the Headache Society of Singapore, and a member of the Asian Regional Consortium for Headache.

 

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