For Clinicians
Helpful guide
The primary purpose of the clinician section is to help you care for patients suffering from primary headache disorders (though it also includes educational components, advice on discussing pros and cons of imaging). As well as supplementing clinical care you may also find this site useful for triage.
How to use:
- Clinical assessment and common primary headaches sections are relatively didactic.
- The treatment tables are taken from the British Association for the Study of Headache guidelines recommended therapies section.
- The information sheets provide standardised information on treatments- including issues of analgesic overuse, suggested start and stop criteria, dosing, pregnancy/breast feeding etc, and you may find it helpful to provide these to your patients.
- For patients who wish to find out more about research, we have included an area to assist with signposting.
If you would like to download the BASH guidelines in their entirety please click here. This contains information about additional treatment options.
Headaches are classified by the International Headache Society as primary or secondary headaches (www.ichd-3.org).
The majority of headache is primary (such as migraine). Primary headache is the best validated within this classification system.
Secondary headaches are precipitated by another condition or disorder, local or systemic1-3 . Serious causes of secondary headache are uncommon.
Using the temporal pattern of headache to help differentiate primary from secondary headache
While we acknowledge that not all the following descriptors have tight definitions, we have tried to consider different temporal clinical patterns that the ‘jobbing’ clinician might frequently encounter and recognise.
Sudden onset headache
Sudden onset headache reaching maximum intensity within 5 minutes is called thunderclap headache 4-6,15-17. Thunderclap headache has the greatest probability of a secondary precipitant 4-6.
Recent onset and progressive headache
Evolution of headache over days to weeks. If associated systemic features and/or focal neurological signs there is an increased probability of secondary precipitant 4,7,8.
Recurrent episodic headache
Recurrent episodic headache in isolation is most likely due to a primary headache disorder 13,18.
Headache which occurs on the majority of days in a month
Headache present for at least 15 days per month for over 3 months in isolation is most likely due to a primary headache disorder 18.
Laterality and site of headache
Strictly unilateral (right or left but never bilateral) headache most consistently occurs in the Trigeminal Autonomic Cephalalgias (TACS) (www.ichd-3.org). 11.5- 20% of migraine sufferers experience unilateral headache 19,20.
Bilateral headache more commonly occurs in migraine, and is a more consistent defining feature of tension-type headache 21-23.
In most primary headache disorders the pain is experienced in the distribution of the first division of the trigeminal nerve and second cervical root. Neck pain can therefore be a feature of a migraine attack 22,24-31.
Associated symptoms
Prominent features in migraine include nausea, vomiting, photophobia, phonophobia and motion sensitivity (a tendency for the headache to be exacerbated by head movement or mild exertion) 21,23,32-35.
Cranial autonomic features, such as lacrimation, conjunctival injection, rhinorrhoea, and nasal blockage, are characteristic of the TACs, but can occur in up to 25% of migraine sufferers 36,37.
Unlike migraine sufferers who are frequently motion sensitive and generally prefer to remain still during an attack, patients with cluster headache and to a lesser extent TACs tend to be restless during an attack 25-27,38
Aura can be experienced in all headache disorders, but is by far most common in migraine 39.
Examination
The presence of abnormal neurological signs significantly increases the chance of an intracranial abnormality. Therefore, an appropriate neurological examination including fundoscopy is required when assessing the patient presenting with headache.
Useful and brief ways to perform the neurological examination:
Table 1 shows a comparative table to distinguish between common primary headaches.
MIGRAINE | TENSION TYPE-HEADACHE | CLUSTER HEADACHE |
|---|---|---|
Episodic | ||
Unilateral
(although often bilateral)
| Bilateral | Unilateral (never bilateral) |
Pulsating
| Pressing, tightening, non-pulsating | |
Moderate or severe
| Mild or moderate but not disabling | Very severe |
Aggravated by, or causing avoidance of, routine physical activity
| No aggravation by, or avoidance of, routine physical activity | Restlessness No aggravation by physical activity |
No aggravation by, or avoidance of, routine physical activity
Restlessness
No aggravation by physical activity
Nausea and/or vomiting
Photophobia
Phonophobia
| No nausea, vomiting, photophobia, or phonophobia | Ipsilateral to pain, there may be:
|
Attacks last hours to days
(usually 4-72 hours)
| Attacks last hours to days | Attacks last from 15 mins to 3 hours |
Frequency 1-2 attacks per month
| Frequency 1-3 attacks per day (up to 8) and usually occur daily for 2-3 months at a time | |
Chronic
| ||
Chronic migraine or chronic tension-type headache: At least 15 headache days per month for >3 months with the above clinical description, in the absence of medication overuse
| Chronic cluster headache: Attacks occurring for more than 1 year without remission, or remission periods lasting <3 months | |
Medication-Overuse Headache
| ||
Ergotamine, triptans, or opioids taken on 10 or more days per month, or 15 days for simple analgesics, for >3 months. Chronic migraine is fulfilled 2 months after medication has been withdrawn without improvement
| No medication overuse headache Medication-overuse headache only reported in patients with a predisposition to migraine and/or tension-type headache; clinical syndrome of the headache exacerbated by the acute-relief medication overuse is of the migraine and/or tension-type headache 50 |
The most consistent indicators for serious secondary headache are:
- Thunderclap (sudden onset) headache 4-6
- Associated focal neurological deficit 4,7,8
- Associated systemic features 4,7,8
- Patients over the age over 50 years 9,10
The history is the key to diagnosis in headache. The neurological examination is also helpful in differentiating primary from secondary headache 4,7,8. For example, patients with migraine (with or without typical aura) or tension-type headache and a normal neurological examination do not have an increased likelihood of a secondary precipitant relative to the background population 11-13.
For other isolated headache syndromes with normal neurological examination there is insufficient data to enable a definitive conclusion 14.
People suffering from headache can be anxious about the possibility of a brain tumour. Outside of an emergency setting, current data indicates that the risk of finding serious secondary pathology in patients with isolated headache and a normal neurological examination is similar to that in people who do not have headache 8,11,12,51.
Normal imaging can reduce subsequent health care utilisation in the short term (less than one year) presumably because of reassurance. The effect however does not appear to be sustained in patients with anxiety and depression 8,52.
Moreover, there is a significant potential for uncovering incidental findings in 6-15% patients, which may not necessarily require further management but can themselves increase anxiety 1-3, and even potentially affect insurance coverage/premiums for that individual.
An information sheet can be useful to act as an ‘aide memoire’ when discussing these issues.
Migraine is the most common disabling headache disorder, ranked as 7th highest among specific causes of disability globally and is responsible for 2.9% of all years of life lost to disability 105.
The global lifetime prevalence is 10% in men and 22% in women 106.
Peak prevalence increases to the age of 40 years and declines thereafter in both women and men, though can present de novo later in life 107-109.
Chronic migraine is a highly disabling primary headache disorder that affects 2% of the population 110,111, with reduced quality of life 112, increased risk of anxiety, depression and chronic pain and greater use of healthcare resource 113.
Around two-thirds of patient with chronic migraine have medication overuse 114.
Migraine is characterised by recurrent episodes of moderate to severe headaches, unilateral or bilateral and frequently throbbing. There may be associated nausea/vomiting, and light, noise and/or motion sensitivity 21,23,32-35. (IHS classification).
Attacks can last 4-72 hours with freedom from symptoms in between, and vary in frequency from one per year to a few times per month 33,40,41,115.
The median frequency is one to two attacks per month 116.
Headache on 15 or more days per month for 3 consecutive months, of which at least 8 days have features of migraine, is termed chronic migraine (IHS classification).
The most sensitive and specific features of migraine are 117:
- Nausea
- Disability (limitation of activity
- Photophobia
Prior to the onset of headache, patients can frequently experience premonitory symptoms, the most common of which are feeling tired (72%), difficulty concentrating (51%), and a stiff neck (50%) 118.
After the headache has ended patients often experience postdrome symptoms of a similar nature. In most attacks (93%), there was return to normal within 24 hours 119.
Aura affects around a third of migraine sufferers 120,121.
A typical aura comprises of fully reversible visual and/or sensory/ and/or speech symptoms, evolving over minutes with a total duration of up to 60 minutes (IHS classification).
Aura may occur without headache particularly in older patients122.
Aura usually precedes, but may occur during, or after the headache.
Aura is not unique to migraine. It may occur in other forms of primary headaches 39.
General Principles
Validate the impact the condition has on the individual and family.
Manage expectations: Patients may have low or unrealistic expectations of what is achievable. Explain that most headache disorders cannot be cured but can be effectively managed in most cases.
Reassurance: Patients often worry about an underlying serious disorder. Explaining the nature of the condition to the patient can be of therapeutic value 125.
Empower the patient to help promote self-management.
Brain Scans and Primary Headache
Outside of an emergency setting, current data indicates that the risk of finding serious secondary pathology in patients with isolated headache and a normal neurological examination is similar to that in people who do not have headache
Normal imaging can reduce subsequent health care utilisation in the short term (less than one year) presumably because of reassurance. The effect however does not appear to be sustained in patients with anxiety and depression.
Moreover, there is a significant potential for uncovering incidental findings in 6-15% patients, which may not necessarily require further management but can themselves increase anxiety, and even potentially affect insurance coverage/premiums for that individual.
An information sheet can be useful to give to the patient to act as an ‘aide memoire’ when discussing these issues- available from this site.
When considering medication
Potential issues of medication overuse, both with respect to the impact on headache and side effects should be discussed.
Prescribing decisions should be made with reference to the patient’s current clinical situation and their future plans (e.g. pregnancy or contraception).
A daily headache diary for at least three months may be helpful able to establish the patterns of headache- a template diary is available from this site.
Ensure that the patient does not take painkillers too often. Taking painkillers on more than 2 days per week can cause a medication overuse headache.
In medication overuse – the headache improves in about 70% of people once pain killers are reduced and adequate preventative treatment established.
If there is difficulty restricting use of pain killers to less than 2 days per week, consider referral to clinical psychologist/pain team to develop pain management skills to be able to manage the pain better.
If the patient is experiencing migraine on more than 4 headache days a month which need treating with some sort of pain killer, a prescribed preventative medication might be appropriate – please make an appointment see your GP with your headache diary and this information sheet.
Validate the impact the condition has on the individual and family.
Manage expectations: Patients may have low or unrealistic expectations of what is achievable. Explain that migraine cannot be cured but can be effectively managed in most cases 123,124.
Reassurance: Patients often worry about an underlying serious disorder. Explaining the nature of the condition to the patient can be of therapeutic value 125.
Empower the patient to help promote self-management 126.
Prescribing decisions should be made with reference to the patient’s current clinical situation and their future plans (e.g. pregnancy or contraception). Potential issues of medication overuse, both with respect to the impact on headache and side effects should be discussed.
Cognitive behavioural therapy has shown a greater reduction in migraine associated disability compared to drug therapy alone 127.
When prescribing acute treatments there are two broad strategies 128:
- Stepped approach: start with simple analgesics and if ineffective step-up e.g. to a triptan
- Stratified approach: target treatment based on attack severity
The stratified approach is associated with better health related outcomes and lower indirect costs (e.g. GP and hospital visits) 128,129.
Adding an anti-emetic to an acute treatment improves efficacy unrelated to nausea and/or vomiting130 and can improve gastric motility and hence drug absorption 131-133.
The end point of an effective treatment is a significant response at two hours, because the natural history for most attacks is to spontaneously improve in 4 hours 134.
If a treatment is not effective at 2 hours, then it is unlikely to work in that attack at that dose and considering an alternative acute treatment or combination treatment would be reasonable 135.
Lack of response to one triptan does not predict response to other triptans 135.
Triptans are most effective when taken early in the headache phase of the attack 136.
Triptans are less likely to be effective at treating the headache if taken during the preceding aura 137-139.
After 2 treatment failures with a particular triptan a trial with an alternative triptan is recommended. This rationale is based on the finding that in patients who experienced treatment failure in two attacks, 70% failed to respond in the third attack. Around 30% patients do not respond to any triptan 140.
Acute treatments can be associated with the development of medication overuse headache 141.
Opioids are not recommended for the treatment of acute headache because of the significant risk of medication overuse and the most protracted withdrawal 141.
For patients attending the emergency department parenteral NSAIDs or subcutaneous sumatriptan should be considered, and evidence also supports the use of antiemetics 142. Opioids have not been shown to be significantly effective and should not be used 143.
Recommended acute treatments are included in tables 3 and 4.
Choosing a triptan
Sumatriptan 6 mg subcutaneous remains the most rapid and effective treatment for pain relief but has a higher risk of adverse events than other formulations.
Combination of a triptan and an NSAID with a long half-life, such as naproxen, is better than monotherapy 178.
In comparison to sumatriptan 100 mg 171,179-181:
- Lower adverse events: naratriptan 2.5 mg, almotriptan 12.5 mg and frovatriptan 2.5 mg
- Better 2-hour pain response: eletriptan 80 mg and rizatriptan 10 mg, almotriptan 12.5 mg
- Lower recurrence rate: frovatriptan 2.5 mg, and eletriptan 40 mg
Contraindications to triptans include ischaemic heart disease, cerebrovascular disease, previous myocardial infarction, and uncontrolled or severe hypertension. The cardiovascular risk of triptans is very low in the absence of these contra-indications 182.
The NNTs for therapies to achieve the outcome of pain freedom at two hours from a baseline of moderate to severe pain can be accessed by the SIGN guideline.
General Principles
Prescribing decisions should be made with reference to the patient’s current clinical situation and their future plans (e.g. pregnancy or contraception).
Preventive treatment should be offered as an option to patients with 4 or more migraine days a month as this frequency is associated with significant disability. Such an approach will also mitigate the risk of escalation of acute treatment and consequent development of medication overuse headache.
Acute treatment on more than 2 days per week is associated with medication overuse, which renders preventive treatment less effective 183.
As there are relatively few head to head comparative studies, the choice of preventive depends primarily upon the side-effect profile of the drug and co-existing morbidities.
Preventive medications must be titrated slowly to an effective or maximum tolerable dose and continued for at least 6-8 weeks to adequately assess effect 184,185.
A headache diary may help evaluate response to treatment.
Consider gradual withdrawal after 6-12 months of effective preventive 184.
Monitor quality of life through validated tools such as HIT-6186. The HIT-6 score can be downloaded or can be found in the information sheet section of these guidelines (Patient reported outcome measure HIT-6).
Treatment options
In selecting a preventative treatment, a reasonable strategy would be to consider which options might be most suitable for the individual patient, given their previous treatment, medical and other co-morbidities, personal preferences, and side effect profiles of the various treatments.
Table 5 shows the dose and titration regimen for recommended preventive treatments in both episodic and chronic migraine.
Table 6 shows dose and treatment regimen for recommended preventive treatments in chronic migraine only.
All preventive treatments with randomised placebo-controlled trial data are listed as an appendix.
Onabotulinumtoxin A
The efficacy and safety of Onabotulinumtoxin A for prophylaxis of Chronic Migraine has been shown through in the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical programme.
Patient selection: Treatment is licensed for adult patients with chronic migraine. Treatment is not effective in episodic migraine (< 15 days a month).
BASH considers it good practice to address medication overuse prior to commencing Botox treatment. Patients are advised to restrict their acute headache medication to no more than two days a week on a regular basis.
As 60% of patients failed two oral preventive treatments in the PREEMPT trial, BASH recommends considering use of 2-3 oral preventive treatments prior to Botox therapy.
Treatment response should be monitored using quality of life measures, for example HIT-6.
A proportion of women suffer from migraine attacks in association with the menstrual cycle, termed menstrual related migraine (MRM). MRM occurs between days -2 and +3 of the first day of menstruation (which is +1) in at least 2 out of 3 menstrual cycles.
Women with MRM will also have attacks at other times.
Less than 10% of women report migraine exclusively with menstruation and at no other time (‘pure’ menstrual migraine) 247-253
Acute Treatment
The acute treatment of menstrual related attacks is no different to non-menstrual attacks.
Head-to-head studies do not show clear superiority of one triptan over any other 254.
Recommended short term preventive treatments for menstrual related migraine, or pure menstrual migraine.
Targeted oestrogen supplementation
Menstrually targeted oestrogen supplementation (assuming no contraindications) has been found in some studies to offer benefit in menstrual related migraine 260-262.
However, a rebound increase in migraine attack frequency has been found when the effect of this strategy has been considered over the whole menstrual cycle 263.
The risk of stroke in migraine with aura, when taking oestrogen-containing contraceptives.
Females suffering migraine with aura have an inherent increased risk of stroke 264.
Use of the oestrogen contraceptive pill is also associated with increased risk of stroke in all individuals. The incidence of stroke in females with migraine with aura, who are also taking the oestrogen-containing contraceptive pill is additionally increased.
Consequently, contraceptive methods other than oestrogen containing contraception are advised for women with migraine with aura. There is no established additional risk in migraine without aura.
Treatment in pregnancy & breast feeding
- In the majority of women, migraines improve during pregnancy 265,266
- Caution is advised and checking with British National formulary data and pregnancy register is recommended especially when prescribing in pregnancy, breast feeding, and considering contraception. The resource Best Use of Medicine in Pregnancy (BUMPS) may also be of help to patients (www.medicinesinpregnancy.org)
- Paracetamol is not generally considered to be associated with a significantly elevated risk throughout pregnancy and lactation 267
- The Sumatriptan & Naratriptan Pregnancy Registry found no evidence of teratogenicity associated with major birth defects for sumatriptan 268-271
Epidemiology & Diagnosis
In patients with migraine or tension-type headache, regular frequent use of acute treatment can result in exacerbation of the pre-existing primary headache 272.
Medication overuse headache (MOH) is classified as a chronic headache disorder. The headache occurs on more than 15 days a month for at least 3 months, affecting between 1-2% of the general population and, up to 20-50% of the chronic headache population 105,106,273-276.
MOH has been recognized since the 1940s and is a worldwide issue resulting from an interaction between frequently used acute headache medication in a susceptible patient 277,278.
Majority of patients improve on withdrawal of the overused medication 279-283.
All medications used to treat an acute headache can result in medication overuse headaches. Triptans, opioids and combination analgesics are likely to result in development of MOH more rapidly (treatment taken on 10 days or more per month) as compared to simple analgesics such as paracetamol (treatment taken on 15 days or more per month) 141,272,284-286.
MOH occurs primarily in individuals with migraine or tension type headache and is generally of the same phenotype 141.
Overuse of triptans has been shown to cause MOH faster and with fewer doses compared with analgesics. The average interval between the first intake and daily MOH was 1.7 years for triptans, 2.7 years for ergots and 4.8 years for analgesics 141.
Patients must provide details of their usage of both prescription medications and of treatments taken over the counter.
Clinicians must specifically ask how many days in a month the patient takes medication for treating the acute headache and preferably correlate this with a headache diary.
In patients with a history of migraine or tension type headaches pain killer medication taken regularly for non-headache pain, such as joint or back pain, can result in medication overuse headaches 278,287.
The association between analgesic overuse and chronic pain is strongest for chronic migraine (odds ratio of 10.3) 288.
Clinical features
Triptan overuse may result in daily migraine like headache or an increase in migraine frequency, whereas overuse of other analgesics may lead to daily headache with features of both migraine and tension type headache 141.
Many patients continue to take their acute medications despite the apparent lack of effect, while also reporting significant rebound in headache when acute medications are not taken 279-283.
The prevalence of comorbid psychiatric disorders, including depression and anxiety, is greatly increased in patients with MOH. In patients with medication overuse headache with pre-existing episodic tension type headache 67.7% have comorbid psychiatric disorders while in those with pre-existing migraine these were present in 53.7%. Depression and anxiety themselves also be risk factor 289.
Migraine is comorbid with depression and anxiety and these may be risk factors for developing MOH 290,291.
Dependence related behaviour is noted in 60–70% patients and relapses are common 290.
Management
Patient education
An important aspect in the management of MOH is to increase awareness of the condition amongst health care providers as well as the general population.
Patients must be advised that restricting their acute headache medications to no more than 2 days in a week minimizes the potential of developing MOH 292.
Educational intervention is crucial and results in improvement in headache 293.
Comparison of advice alone with a structured detoxification program in patients with MOH is similarly effective 294.
The use of rescue medications, including steroids, does not improve outcomes 294-297.
Patients should be encouraged to seek preventive treatments for migraine as this can prevent the conversion from episodic to chronic migraine thereby reducing the risk of development of MOH 298.
Medication withdrawal
The MOH is unlikely to resolve unless the offending medication is stopped 299.
There is no difference in outcome with either abrupt or gradual withdrawal of the causative drug 300.
Outpatient medication withdrawal is as effective as inpatient detoxification 294,301,302.
Withdrawal headache usually lasts for 2-10 days from the time of complete cessation of the overused medication 114,303,304.
After medication withdrawal patient’s headaches gradually improve. This improvement can take up to 12 weeks 286.
The average duration of withdrawal headache appears to be shortest in patients overusing triptans (4 days) 305.
Response to acute and preventive medications improves following withdrawal of the overused medication 299,306.
Prognosis
At 8 weeks following medication withdrawal 45% of patients report improvement in headaches while in 48 % the headaches remain unchanged 299 (though it must be noted that this data is from a single trial).
Between 22 – 45% patients relapse back into MOH within 1 year, and 40 – 60% within 4 years of withdrawing from their overused medications 307,308.
The relapse rate is lower for patients with migraine and for individuals overusing triptans rather than analgesics (21% vs 71%) 308.
Comorbid anxiety and depression can be associated with difficulty in medication withdrawal and a high risk of relapse following withdrawal of medication 290.
Response to migraine preventive medications improves following withdrawal of the overused acute headache medication 299,309.
There is no difference in outcome if preventive medication is started during or after withdrawal, as long as the acute medication is withdrawn. Preventive treatment is more effective once the overused medication is withdrawn 183,201,306,310.
The most important step in MOH management is to identify the diagnosis and inform the patient of the importance of reducing or stopping the offending medication, and no further measures may then be required 311-313.
Epidemiology
Tension-Type Headache (TTH) is the most common primary headache disorder with a mean global lifetime prevalence of 42% (Range 19-83%) 314. Chronic tension-type headache affects 0.5 - 4.8 % of the worldwide population 315.
Clinical Features
TTH is characterised by mild-moderate and not severe, headache. It is bilateral and often described as pressing or tightening like a vice or tight band.
It typically lacks the specific features that characterise migraine such as nausea, light and noise sensitivity.
The headache is not aggravated by routine physical activity and this is a key criterion for diagnosis 21,316-318.
Duration of pain can be variable with a range from half an hour to several days. TTH on 15 or more days per month for at least 3 months is termed chronic TTH.
Disabling TTH is rare. Most patients diagnosed with disabling TTH have migraine, and respond to triptans 319,320.
Management
Reassurance may suffice in the majority of patients.
Individual attacks can be treated with simple analgesics (see table 8).
Table 8. Recommended acute treatments in tension-type headache
ANALGESIC | SINGLE DOSE | MAXIMUM DAILY DOSE |
|---|---|---|
Paracetamol 321-323
| 1000mg | 4000mg |
Aspirin 324,325
| 500-1000mg (UK doses are 300-900mg) | 4000mg (for oral dosing) |
Preventive treatment is rarely necessary, though can be considered if symptoms are causing significant disability (see table 9).
Table 9. Recommended preventive treatment in tension-type headache.
DRUG | STARTING DOSE | TITRATION | MAXIMUM DOSE |
|---|---|---|---|
Amitriptyline 326-330
| 10mg | 10-25mg | 150mg |
Appendix 3. All acute treatments in tension-type headache.
TREATMENT | SINGLE DOSE | MAX DAILY DOSE |
|---|---|---|
Aspirin 324,325,331
| 500-1000 mg (UK doses are 300-900 mg) | 4000 mg (for oral dosing) |
Diclofenac 332
| 25-75 mg | 150 mg |
Ibuprofen 331,333,334
| 400 mg | 2400 mg |
Ketoprofen 334-338
| 50 mg | 300 mg |
Naproxen 339 | 250-500 mg | 1000 mg |
Paracetamol 321-323
| 1000 mg | 4000 mg |
Appendix 4. All preventive treatments in tension-type headache.
TREATMENT | STARTING DOSE | TITRATION | MAXIMUM DAILY DOSE |
|---|---|---|---|
Acupuncture 340-347
| 6 treatment sessions | ||
Amitriptyline 326-329
| 10 mg | 10-25 mg | 150 mg |
The trigeminal autonomic cephalalgias are a group of headache disorders with prominent autonomic features and a shared pathophysiology 348,349.
There are four trigeminal autonomic cephalalgias. Each disorder can be either episodic or chronic. The trigeminal autonomic cephalalgias are uncommon headache disorders. Therefore, there is a high misdiagnosis rate 350,351 and few randomised-controlled treatment trials.
The clinical characteristics of the trigeminal autonomic cephalalgias as defined by the International Classification of Headache Disorders are based upon the published cases reports and series apart from cluster headache which has population-based data.
The trigeminal autonomic cephalalgias are:
- Cluster headache
- Paroxysmal hemicrania
- SUNCT/SUNA (Short-lasting neuralgiform attacks with conjunctival injection and tearing/Short-lasting neuralgiform attacks with cranial autonomic features)
- Hemicrania continua
Epidemiology
Cluster headache has a prevalence of about 0.1% 352
The peak age of onset is between the 3rd and 4th decades 25,42,353-356
The disorder is four times more common in men 352
Cluster headache sufferers are often smokers 25,43,348
Epidemiology
Cluster headache has a prevalence of about 0.1% 352
The peak age of onset is between the 3rd and 4th decades 25,42,353-356
The disorder is four times more common in men 352
Cluster headache sufferers are often smokers 25,43,348
Clinical Features
The current classification of cluster headache is well validated (www.ichd-3.org).
Attacks are characterised by excruciating strictly unilateral and strictly unilateral headache. However, attacks can change side, across different bouts, within the same bout and rarely within an acute attack 26,27,37,38,42,353,355,357.
Bilateral pain in cluster headache is rare 25,42,358-360.
The attacks are accompanied by ipsilateral cranial autonomic features which are primarily parasympathetic and can most commonly include lacrimation, conjunctival injection, rhinorrhoea, nasal congestion, drooping or swelling of the eyelid. The presence of cranial autonomic features in headache does not necessarily indicate cluster headache or another TAC. For example, these features can also occur in migraine.
One of the most distinguishing features during the cluster attack is restlessness. Patients typically walk up and down, or rock to and fro, clutching the affected side, unlike migraineurs who are motion-sensitive and prefer to remain still 25-27,38.
Attack duration is usually between 15 minutes to 3 hours and attack frequency 1-2 a day. Cluster headache can be episodic or chronic. Episodic cluster bouts usually last between 2 weeks and 3 months and most often occur once every 1-2 years. Ten to 20% of sufferers experience chronic cluster headache, which is currently defined as attacks occurring without a remission period, or with remissions lasting < 3 month, for at least 1 year 38,42,44,353-355,357.
Active bouts of cluster headache can be seasonal and at the same time each year. During an active bout, sufferers can experience attacks at set times during the day for weeks or months. The pattern can change or become less predictable 25,45,353,355,361,362.
Cluster attacks often wake patients from sleep, usually about 1.5-2 hours after they have fallen asleep 25,27,37,363,364.
Some individuals can exclusively have nocturnal attacks 37.
In between attacks of pain patients can experience a background dull ache in the same distribution of the cluster attacks. The interparoxysmal pain tends to settle when the cluster bout resolves 365.
During an active cluster bout some patients can be exquisitely sensitive to alcohol triggering an attack, usually within an hour. The propensity does not occur out of the bout 366.
Clinically relevant commonalities and differences between migraine and cluster headache include:
- Cluster sufferers can have nausea and vomiting, photophobia and phonophobia 25-27,38
- Up to 25% of migraine sufferers can experience autonomic features during an attack 37
- Aura can be experienced in up to 23% of cluster headache sufferers 27,38,360,367 (though in practice is rare)
- 20-40% of migraine sufferers experience strictly unilateral headache 19,24
- The duration of untreated migraine attacks in adults is invariably longer than 4 hours 35,41
- A key feature in cluster headache is restlessness and lack of motion sensitivity, while migraine sufferers prefer to be still 25-27,38
Appendix 7: Classification of cluster headache (www.ichd-3.org)
CLUSTER HEADACHE DIAGNOSTIC CRITERIA
- Severe/very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 minutes (untreated)
- Either or both of the following:
- At least one of the following symptoms or signs, ipsilateral to the headache:
- Conjunctival injection and/or lacrimation
- Nasal congestion and/or rhinorrhoea
- Eyelid oedema
- Forehead and facial sweating
- Forehead and facial flushing
- Sensation of fullness in the ear
- Miosis and/or ptosis
- A sense of restlessness or agitation
- Attack frequency between one every other day up to 8/day for > half the time the disorder is active
EPISODIC CLUSTER HEADACHE
- Attacks fulfilling criteria for Cluster headache and occurring in bouts (cluster periods)
- At least two cluster periods lasting from 7 days to one year (when untreated) and separated by pain-free remission periods of three months
CHRONIC CLUSTER HEADACHE
Attacks fulfilling criteria for Cluster headache and occurring without a remission period, or with remissions lasting < 3 months, for at least 1 year.
Management - Acute
The most effective acute treatment is the sumatriptan 6mg subcutaneous injection with significant relief within 15 minutes 368.
The maximum limit is two 6mg injections a day 369.
The treatment is generally well tolerated, without tachyphylaxis 370,371.
Patients who have cluster headache rarely develop medication overuse headache 370,371.
Patients who also have migraine may develop exacerbation of their migraine disorder whilst using a triptan effectively for their cluster attacks 50,372.
High flow oxygen 100% at 7-15 litres/minute for 15-20 minutes, using a non-rebreathable mask, is effective in aborting acute attacks of cluster headache 373,374.
There is no limit to the use of high flow oxygen, though obvious cautions around smoking/flames/fire hazards near oxygen need to be considered/addressed. Oxygen is often used together with triptans in patients with multiple attacks.
Table 10 shows recommended acute cluster attack treatments.
Treatment | Formulation | Strength | Maximum Daily Dose |
|---|---|---|---|
Oxygen 373,374
| Inhalation through non-rebreathable mask | 7-15 L/min | No limit |
Sumatriptan 368 | Subcutaneous injection | 6 mg | 12 mg |
Sumatriptan 375
| Nasal spray | 20 mg | 40 mg |
Zolmitriptan 376-378
| Nasal spray | 5 mg | 15 mg |
Non-invasive vagal nerve stimulation 379
| Transcutaneous | As per specialist recommendation |
Appendix 5: All acute cluster attack treatments.
Name | Formulation | Strength | Maximum Daily Dose | Comment |
|---|---|---|---|---|
Lidocaine 380
| Nasal spray | 4% | Not specified | Self –administered using a nasal dropper |
Octreotide 381
| Subcutaneous injection | 100 mcg | Not specified | |
Oxygen 373,374
| Inhalation through non-rebreathable mask | 7-15 L/min | No limit | |
Sphenopalatine Ganglion Stimulation (SPG) 382,383 | Implantable device | As per specialist recommendation | ||
Sumatriptan 368
| Subcutaneous injection | 6 mg | 12 mg | |
Sumatriptan 375
| Nasal spray | 20 mg | 40 mg | |
Zolmitriptan 376-378
| Nasal spray | 5 mg | 15 mg |
Management - Preventive
Verapamil is an effective preventive treatment in cluster headache 384.
The doses required to suppress cluster headache attacks can be higher than those used to treat cardiac disorders. Clinically significant cardiac rhythm disturbances can occur and are neither dose nor time dependent 385,386. It is possible for patients to develop cardiac conduction abnormalities even after they have been on a stable dose for a long period.
BASH recommends an ECG done at baseline and following each increase in dose. At a stable dose ECG should be done once every six months. Any cardiac rhythm disturbance may require dose reduction or drug withdrawal 385.
In episodic cluster headache, once control has been achieved, towards the end of the expected bout, the preventive can be slowly withdrawn. If attacks recur the preventive should be re-established.
Oral corticosteroids have been shown to be effective in the prevention of cluster headache attacks 387.
The response should be seen within 48 hours. Given the high adverse effect profile corticosteroid use is best restricted as a short-term measure in patients with multiple daily attacks, which cannot be treated effectively acutely, whilst an alternative preventive is being introduced.
Suboccipital nerve block (i.e. suboccipital depot steroid and local anaesthetic injection) has shown a significant reduction or resolution of attacks compared to placebo and despite a high placebo response rate 388,389.
Table 11: Recommended preventive treatments for cluster headaches.
Name | Start Dose | Titration | Max Daily Dose | Comments |
|---|---|---|---|---|
Greater occipital nerve block 388,389
| Depot steroid + local anaesthetic | Not applicable | Not applicable | Different formulations of steroid & anaesthetic used* |
Verapamil 384
| 80 mg TDS | Increase 80 mg every 2 weeks | 960 mg | ECG monitoring recommended |
*There does not seem to be a difference between different local anaesthetics.
Appendix 6: All preventive treatments for cluster headaches
Name | Start Dose | Increment | Max Daily Dose | Comments |
|---|---|---|---|---|
Greater occipital nerve block 388,389
| Depot steroid + local anaesthetic | Not applicable | Not applicable | Different formulations of steroid & anaesthetic used* |
Lithium 390
| 200 mg/day | 200 mg/week | According to serum lithium levels. Note preparations vary widely in bioavailability | Monitor levels as per BNF |
Melatonin 391
| 10 mg | 10 mg | ||
Non-Invasive Vagal Nerve Stimulation 379
| As per specialist recommendation | |||
Prednisolone/prednisone 387,392
| 40mg for 10-14 days | Taper thereafter | Short term interim use only | |
Sphenopalatine Ganglion Stimulation 383,393
| As per specialist recommendation | |||
Verapamil 384
| 80 mg TDS | Increase 80 mg every 2 weeks | 960 mg | ECG monitoring recommended |
Epidemiology
Population-based data on the prevalence of paroxysmal hemicrania is sparse and has been cited as 0.05% in the 18-65-year age group 394 . Total published cases remain less than 200. There may be a slight female preponderance with ratios ranging between 1.1 to 2.36. Mean age of onset is between the 4th and 5th decades 46,395,396 .
Clincial Features
The pain is strictly unilateral with associated ipsilateral autonomic features (www.ichd-3.org).
The classification of paroxysmal hemicranias is shown as an appendix.
Attack duration ranges between 2-30 minutes and frequency of attacks is reported up to 50 a day. The mean lies between seven and 13 attacks per day 46,395 . A greater proportion present with chronic paroxysmal hemicrania. The disorder has an absolute response to indomethacin 46,47,395-397.
The attacks are shorter and more frequent than in cluster headaches and longer and less frequent than in SUNCT/SUNA.
The typical circadian characteristics seen in cluster headache are less prominent in paroxysmal hemicrania. All attacks are spontaneous unlike SUNCT/SUNA, in which attacks are often triggered immediately by various sensory stimuli. The key distinction is the clear therapeutic response to Indomethacin. The main differential diagnoses are shown are shown as an appendix.
Management
There are no RCTs for preventive treatment in paroxysmal hemicranias.
Acute Treatment
The attacks of paroxysmal hemicrania are usually too short to respond to any oral acute treatment. Open label observation suggests that sumatriptan 6mg subcutaneous injection and high flow oxygen are generally not effective 398,399.
Preventive Treatment
By definition paroxysmal hemicrania is an indomethacin-responsive disorder.
The effective dose range is between 25-300mg daily dose 46,397 .
Although most patients show a rapid response to indomethacin, some patients can take up to a week to demonstrate a response to an effective dose. Based upon this BASH recommends indomethacin 25mg PO TDS for 7 days, 50mg TDS 7 days, up to 75mg TDS. We recognise and emphasise the higher dose is above the BNF quoted maximum of 200mg per day, and should only be considered if clinically required, after appropriate counselling with the patient, and with clear criteria for dose reduction.
Dose requirements can change over time and some patients may go into remission 400 .
Therefore, once symptoms are well controlled for a period of time gradual dose reduction should be tried to maintain the lowest effective dose or, if there is no recurrence on each dose reduction, withdrawal during remission periods. Gastrointestinal side effects with indomethacin are common and may preclude use of the drug. A concomitant proton-pump blocker or H2-antagonist can be used.
The original description of this disorder was termed SUNCT, short-lasting unilateral neuralgiform attacks with conjunctival injection and tearing 48 .
Conjunctival injection and tearing (lacrimation) are the most common autonomic symptoms in all the TACs 26,27,30,38,42,395,396 .
The terminology SUNA was proposed based on the fact that a number of patients were noted to lack one or both of these symptoms 49,401 .
The distinction remains within the ICHD classification. From a clinical perspective, management remains the same. The distinction remains within the ICHD classification. BASH recommends this as a research tool and for current clinical purposes will adopt the terminology of SUNA to encompass both groups 49.
Epidemiology
SUNCT/SUNA is rare 401,402 .
The mean age of onset is 48 years with a slight male preponderance 1.5403 .
Clinical Features
The attacks are the shortest and most frequent of all the TACs. Attacks can be either spontaneous or induced by cutaneous triggers. Mean duration is about one minute (range 1-600 seconds) with frequency up to 30 attacks in an hour 31 .
The character of the attacks can vary: attacks can occur in single stabs, a group of stabs or a long attack with a ‘saw-tooth’ pattern of stabs between which the pain does not return to baseline. Other features of TACs may be present, such as agitation. SUNCT/SUNA can be misdiagnosed as Trigeminal Neuralgia. However, the location of the pain, autonomic features, duration of attacks and spontaneity of attacks in SUNCT/SUNA, differentiate between the two (See appendix Table. Differential diagnosis of The Trigeminal Autonomic Cephalalgias).
Management
There are no RCTs for preventive treatment in SUNCT/SUNA.
Acute treatment
Because of the short attack duration there are no effective acute treatments in SUNCT/SUNA
Preventive treatment
The most effective reported treatment is lamotrigine with dose range up to 400 mg. Topiramate may be effective in SUNCT 385 . Carbamazepine and gabapentin may also be effective 31,49,404.
Epidemiology
Hemicrania continua is an uncommon disorder with estimated prevalence of 0.8-1.5% however it is acknowledged that this is compounded by diagnostic inaccuracy 408,409 .
The disorder seems to be more common in women. Mean age of onset is between the 3rd and 4th decade 410,411 .
Clinical Features
Hemicrania continua is characterized by strictly unilateral pain of moderate severity with ipsilateral autonomic features which may be more prominent during exacerbations. Hemicrania continua has both clinical and pathophysiological overlap with migraine 412.
Thus, although more than half of cases can be restless during the attacks, others experience motion sensitivity 30,410,411,413,414. Although the disorder is defined by chronicity it can present in a relapsing and remitting (thus episodic) form 415-420.
Management
There are no RCTs for preventive treatment in hemicrania continua.
Acute treatment
Medication overuse can occur in hemicrania continua. Thus, analgesics should be withdrawn prior to assessing response to indomethacin 421,422.
Preventive treatment
Hemicrania continua is an indomethacin-sensitive disorder. The effective dose range is between 25-300mg daily dose 46,395-397.
Although most patients show a rapid response to Indomethacin, some patients can take up to a week to demonstrate a response to an effective dose. Based upon this BASH recommends Indomethacin 25mg TDS for 7 days, 50mg TDS 7 days, up to 75mg TDS.
Dose requirements can change over time and some patients may go into remission 400.
Therefore, once symptoms are well controlled for a period of time gradual dose reduction should be tried to maintain the lowest effective dose or, if there is no recurrence on each dose reduction, withdrawal during remission periods.
Gastrointestinal side effects with Indomethacin are common and may preclude use of the drug. A concomitant proton-pump blocker or H2-antagonist can be used.
What you can do to help yourself and help your doctor.
Headache sufferers can use this diary to keep a track of how often they have headaches and how severe they are.
When are brain scans needed for a headache?
This is a guide to the phenomenon of 'incidental findings' - discoveries on scans that the doctors were not looking for.
What is migraine and how common is it?
Guide to common symptoms of migraine.
How to treat migraine attacks when they happen.
Treatments that can prevent migraine attacks starting.
Menstrual migraine treatment options.
Migraine treatment options during and after pregnancy.
Information about how migraine affects the chances of having a stroke.
A guide to amitriptyline use for migraine
A guide to candersartan use for migraine.
A guide to propranolol use for migraine.
A guide to topiramate use for migraine.
A guide to using triptans for migraine.
A guide to verapamil use for cluster headache.
A guide to GON block for headache.
A guide to botox injections for chronic migraine.
Table 3. Recommended acute treatments – simple analgesics and antiemetics.
DRUG | DOSE | MAXIMUM DAILY DOSE | INFORMATION |
|---|---|---|---|
Simple Analgesics
| |||
ASPIRIN 144-148
| 600-1000 mg (UK doses are 300-900 mg) | 4000 mg (for oral dosing) | |
DICLOFENAC 149-152
| 25 mg | 150 mg | |
IBUPROFEN 153-155
| 400-600 mg | 2400 mg | |
KETOPROFEN 156,157
| 75-150 mg | 150 mg | |
NAPROXEN 158-160
| 250 mg | 1000 mg | |
PARACETAMOL 133,161
| 1000 mg | 4000 mg | |
TOLFENAMIC ACID 162
| 200 mg | 400 mg | |
Antiemetics
| |||
DOMPERIDONE 133 | 10 mg | 30 mg | Safety alert: MHRA-Domperidone |
PROCHLORPERAZINE 163-165 | 10 mg | 30 mg | |
METOCLOPRAMIDE 132,166,167
| 10 mg | 30 mg | Safety alert: MHRA-Metoclopramide |
Table 4. Recommended acute treatments – triptans
DRUG | FORMULATION | STRENGTH | SINGLE DOSE | MAX/24 HOURS |
|---|---|---|---|---|
ALMOTRIPTAN 168,169
| TABLET | 12.5 mg | 12.5 mg | 25 mg |
ELETRIPTAN 170
| TABLET | 40 mg | 40 mg | 80 mg |
FROVATRIPTAN 171
| TABLET | 2.5 mg | 2.5 mg | 5 mg |
NARATRIPTAN 172
| TABLET | 2.5 mg | 2.5 mg | 5 mg |
RIZATRIPTAN 173
| TABLET ORODISPERS LYPOPHILLISATE | 5 mg/10 mg 10 mg 10 mg | 10 mg 10 mg 10 mg | 20 mg 20 mg 20 mg |
SUMATRIPTAN 137,174
| TABLET SPRAY SUBCUT INJ | 50 mg/100 mg 100 mg/ml or 200 mg/ml 6 mg | 50-100 mg 10 - 20 mg 6 mg | 300 mg 12 mg |
ZOLMITRIPTAN 175-177
| TABLET ORODISPERS SPRAY | 2.5 mg/5 mg 2.5 mg/ 5 mg 50 mg/ml | 5 mg 5 mg 5 mg | 10 mg 10 mg 10 mg |
Table 5. Recommended preventive treatments in episodic and chronic migraine.
DRUG | START DOSE | TITRATION | TRIAL STUDIED DAILY DOSE |
|---|---|---|---|
Amitriptyline 187-191
| 10-25 mg OD | 10 -25 mg | 25-150 mg |
Candesartan 192,193
| 2 mg OD | 2 mg | 8-16 mg total/day |
Propranolol 187,194,195
| 10 mg BD | 10-20 mg BD | 120-240 mg total/day |
Topiramate 196-205
| 25 mg daily | 25 mg od | 25-200 mg total/day |
CGRP Monoclonal Antibodies
| |||
Erenumab 206-209
| 70-140 mg monthly | Max dose as per licensed indication | |
Fremanezumab 210
| 225 mg monthly 675 mg three-monthly | Max dose as per licensed indication | |
Galcanezumab 211-213
| 120-240 mg monthly | Max dose as per licensed indication |
Table 6. Recommended preventive treatments for chronic migraine only.
Onabotulinumtoxin A214-218. 155-195 IU intramuscularly, as per PREEMPT protocol. Every 12 weeks
Table 7. Recommended triptans for short term prevention of menstrual related migraine or pure menstrual migraine.
DRUG | FORMULATION | STRENGTH |
|---|---|---|
FROVATRIPTAN 255,256
| TABLET | 2.5 mg twice daily on the days migraine is expected (generally from two days before until three days after bleeding starts). |
ZOLMITRIPTAN 257
| TABLET | 2.5 mg twice or three times a day on the days migraine is expected (generally from two days before until three days after bleeding starts). |
Table 8. Recommended acute treatments in tension-type headache.
ANALGESIC | SINGLE DOSE | MAXIMUM DAILY DOSE |
|---|---|---|
Paracetamol 321-323
| 1000 mg | 4000 mg |
Aspirin 324,325
| 500-1000 mg (UK doses are 300-900 mg) | 4000 mg (for oral dosing) |
Table 9. Recommended preventive treatment in tension-type headache.
DRUG | STARTING DOSE | TITRATION | MAXIMUM DAILY DOSE |
|---|---|---|---|
Amitriptyline 326-330
| 10 mg | 10-15 mg | 150 mg |
Table 10. Recommended Acute Cluster attack treatments.
TREATMENT | FORMULATION | STRENGTH |
|---|---|---|
Oxygen 373,374
| Inhalation through non-rebreathable mask | 7-15 L/min |
Sumatriptan 368
| Subcutaneous injection | 6 mg |
Sumatriptan 375
| Nasal spray | 20 mg |
Zolmitriptan 376-378
| Nasal spray | 5 mg |
Non-invasive vagal nerve stimulation 379
| Transcutaneous | As per specialist recommendation |
Table 11: Recommended preventive treatments for cluster headaches.
NAME | START DOSE | TITRATON | MAX DAILY DOSE | COMMENTS |
|---|---|---|---|---|
Greater occipital nerve block 388,389
| Depot steroid + local anaesthetic | Not applicable | Not applicable | Different formulations of steroid & anaesthetic used* |
Verapamil 384
| 80 mg TDS | Increase 80 mg every 2 weeks | 960 mg | ECG monitoring recommended |
*There does not seem to be a difference between different local anaesthetics
People suffering from headache conditions are understandably interested in the research that is being done into their condition.
Research in the NHS
The NHS is committed to the use of research to improve care (www.gov.uk/government/publications/the-nhs-constitution-for-england).
The National Institute for Health Research network regards headache as a key area for even closer co-operation between patients, charities, neurologists and research networks (www.nihr.ac.uk/nihr-in-your-area/neurological/).
BASH is keen to help people access opportunities to be involved in research if they wish.
If you are interested in headache research either as a patient or a professional please contact us and we will send you information on currently available studies and how you could get involved should you wish.
Other useful links
The Migraine Trust (www.migrainetrust.org/finding-a-cure/take-part-in-research/) is another useful contact point for people wishing to learn more about research opportunities, and the process of taking part in research trials.
The UK clinical trials gateway is a searchable site (ukctg.nihr.ac.uk/) and may be helpful to find out about which trials that may be available.