Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache continued

• Tension-type headache (TTH) may be stress-related or associated with functional or structural cervical or cranial musculoskeletal abnormality

• Most patients seek medical advice because TTH is becoming frequent (possibly no longer responding to painkillers)

• Episodic TTH:
• occurs at a variable, low frequency in attack-like episodes mostly lasting no more than several hours
• headache generalised (may be unilateral), described as a pressure or tightness
• rarely disabling
• lacks the specific features and associated symptom complex of migraine

• Chronic TTH:
  • occurs on >15 days a month, may be daily
  • this condition is disabling

• If it is difficult to distinguish between migraine and TTH in patients with frequent headaches as there may be a mixture of the two. Management for the two conditions needs to be considered separately

Differential diagnosis

• Diagnosis by treatment is not recommended as drugs are neither totally effective nor specific to certain headache types

• Headache at any site may arise from functional or structural derangement of the neck

• Headache should not be attributed to sinus disease in the absence of symptoms

• Headaches caused by errors of refraction are mild, frontal and in the eyes themselves, and absent on waking

• Headache should not be considered secondary to conditions affecting the ears, jaw, or teeth, unless indicated by other symptoms suggestive of it

• Warning features in the history:
• headache that is new or unexpected in an individual patient
• thunderclap headache (intense headache with abrupt or 'explosive' onset)
• headache with atypical aura (duration >1 hour, or including motor weakness)
• aura occurring for the first time in a patient during use of combined oral contraceptives
• persistent morning headache with nausea
• progressive headache, worsening over weeks or longer
• headache associated with postural change
• new onset headache in a patient:
• older than 50 years—consider giant cell (temporal) arteritis
• younger than 10 years
• with a history of cancer
• with a history of HIV infection

Serious causes of headache

• New or recently changed headache calls for especially careful assessment. All healthcare professionals must be alert to warning features in the history (see above)

• Serious causes of headache such as intracranial lesions (tumours, subarachnoid haemorrhage, and meningitis) give rise to specific features in their histories that should bring them to mind

• In reality, intracranial lesions are uncommon (studies show that the 1-year risk of a malignant brain tumour was only 0.045%)

Medication overuse headache (MOH)

• Headache secondary to chronic overuse of medication intended for headache treatment:
  • symptoms are often worst on waking and increase after physical exertion
  • medication is often taken pre-emptively
  • combination analgesics containing barbiturates, caffeine, and codeine are the prime candidates for the development of MOH. Aspirin, paracetamol, and tripans are also associated with MOH
    • low doses daily carry greater risk than larger doses weekly

• Patients complaining of frequently-recurring headache should give a detailed account of medication use (including over the counter medication)—a diary can be of use here

• MOH masks other headaches and should be managed first to reveal other conditions

Cluster headache (CH)

• CH affects mostly men (6:1) in their 20s or older, and very often smokers

• Unilateral intense headaches occurring in 6–12-week bouts every 1–2 years

• Headaches typically occur at a similar time each day (often 1–2 hours after falling asleep), last 30–60 mins with associated ipsilateral autonomic symptoms (drooping eyelid, blood-shot eye, tearing, runny or blocked nose)

Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache continued

Management of migraine

Objectives

• Cure is not a realistic aim and patients need to understand this. Optimal management should control symptoms and minimise their impact on the patient's life

Basic principles

• If patients experience more than one type of headache, treat each individually

• Work through treatment options in a stepwise manner, starting at step one (see below), until certain that the most suitable solution has been found

• Progress to the next treatment step only after at least three treatment failures

• Acute drug therapy should be accompanied by rest and sleep, provided that it does not interfere with the patient's normal activities

• Follow-up will ensure that optimum treatment has been established

• Migraine varies with time and the patient's needs may change as a result

• In children, good management requires:
• conservative management initially
• reassurance of parents
• referral of troublesome migraine to a paediatrician with an interest in headache

• In adults, good management requires:
• correct and timely diagnosis
• explanation and reassurance
• trigger factor identification and avoidance (see box below)
• intervention (drug or non-drug)

Acute drug intervention

Step one: simple oral analgesic ± antiemetic

• Aspirin 600–900 mg or ibuprofen 400–600 mg in buffered soluble or orodispersible formulations, taken early in the attack to promote absorption
  • not codeine, dihydrocodeine or paracetamol
  • prochlorperazine 3–6 mg buccal tablet, or domperidone 10 mg for nausea and vomiting

• Simple oral analgesia as above or non-steroidal anti-inflammatory drugs (NSAIDs; tolfenamic acid rapid release 200 mg, naproxen 750–825 mg or diclofenac potassium 50–100 mg) combined with a prokinetic antiemetic:
  • metoclopramide 10 mg
  • domperidone 20 mg

• Contraindications to step one:
  • adults:none (unless NSAIDs contraindicated)
  • children <16 years: aspirin, metoclopramide, and prochlorperazine not recommended

Step two: rectal analgesic ± antiemetic

• Diclofenac suppositories 100 mg for pain plus domperidone suppositories 30–60 mg (if needed) for nausea/vomiting

• Contraindications to step two:
  • peptic ulcer (misoprostol 800 µg or omeprazole 20–40 mg daily may give limited gastroduodenal protection)
  • lower bowel disease
  • diarrhoea during acute migraine may prevent use
  • suppositories unacceptable to some patients

Step three: specific anti-migraine drugs

• Triptans:
  • first line:
    • sumatriptan (50 mg tablet or rapid-dispersal tablet) or
    • zolmitriptan (2.5 mg tablet or oro-dispersible tablet) or
    • almotriptan (12.5 mg oral)
    • eletriptan (40 mg oral)
  • second line (more potent):
    • sumatriptan (100 mg tablet or rapid-dispersal tablet, or 20 mg nasal spray; if vomiting or for greater speed, 6 mg sc self-injection) or
    • zolmitriptan (5 mg oral or 5 mg nasal spray if vomiting) or
    • rizatriptan (10 mg tablet or oro-dispersible wafer) or
    • eletriptan (80 mg oral)
  • second line (less potent):
    • naratriptan (2.5 mg oral) or
    • frovatriptan (2.5 mg oral)
  • individual responses to different triptans vary, so it is reasonable for patients to try each and judge for themselves
  • triptans should be taken at the start of the headache phase
  • it is suggested that metoclopramide or domperidone is taken with oral triptans

• Ergotamine tartrate 1–2 mg (preferably rectally) if relapse is a particular problem
  • greater potential for toxicity and misuse
  • should not be taken concomitantly with any triptan; probably safe after 12 hours
  • ergotamine taken with beta-blockers can cause digital gangrene

• Contraindications to step three:
  • uncontrolled hypertension
  • risk factors for coronary heart disease or cerebrovascular disease (refer if uncertain)
  • children <12 years (neither safety nor efficacy established)
  • specific contraindications for particular triptans

• If step three fails:
  • review diagnosis
  • review compliance and manner of use
  • may be worth trying step four
  • consider prophylaxis

Step four: combinations

• Although there is no formal evidence for combinations, it may be worth trying:
  • step one + step three, followed by
  • step two + step three

• Although not common practice, self-injected im diclofenac 75 mg may be tried

Emergency treatment

• The following recommendations apply to emergency treatment of patients at home, or of those visiting A&E. Use a previously effective therapy, if established, otherwise:
  • narcotics are not recommended
  • im diclofenac 75 mg and, if needed, im chlorpromazine 25–50 mg
  • im or iv metoclopramide 10 mg, as an alternative
  • early follow-up is suggested

Treatment of relapse within the same attack after initial efficacy

• Symptomatic medications (steps one and two) should be repeated within dosage limitations

• If using triptans, a second dose may be effective, but repeated dosing may give rise to repeated rebound. Naproxen 500 mg or tolfenamic acid 200 mg may be preferable for the first or second relapse

• If patients consistently experience relapse:
  • naratriptan, eletriptan, and frovatriptan are also associated with relatively low recurrence rates
  • ergotamine is associated with significantly less relapse and is a fall-back option
  • naproxen or tolfenamic acid may be used pre-emptively if relapse is anticipated

Slowly developing migraine

• Simple analgesics during early stages

• Triptans should only be used once it is certain that the headache is migrainous

Drugs to avoid in acute intervention

• Opiates and opioids increase nausea, promote systemic shutdown, and can be addictive. There is no evidence that codeine or dihydrocodeine in combination preparations are of benefit, and they are implicated in MOH

Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache continued

Prophylactic drug intervention

• Indications:
  • over-frequent use of acute therapy:
    • use on >2 days/week is inappropriate (risk of MOH)
    • use on >1 day/week calls for close enquiry

• Prophylaxis therapy:
  • used to reduce the number of attacks in which symptoms are inadequately controlled by acute therapy
  • used in addition to, not instead of, acute therapy
  • only required for periods of migraine exacerbation: effective drugs should usually be continued for 4–6 months and then withdrawn over 2–3 weeks

• Drug choice should be on the grounds of efficacy, comorbidity, and contraindications; once-daily dosing can improve compliance

• First-line prophylactic drugs:
  • β-adrenergic blockers without partial agonism (e.g. atenolol 25–100 mg bd)
  • amitriptyline 10–150 mg daily if:
    • migraine coexists with TTH or another chronic pain condition
    • sleep is disturbed
    • there is associated depression

• Second-line prophylactic drugs:
  • sodium valproate 300–1000 mg bd
  • topiramate 25 mg od–50 mg bd

• Third-line prophylactic drugs:
  • gabapentin 300 mg od–800 mg tds
  • methysergide 1–2 mg tds (may cause rebound)
  • β-blocker + amitriptyline (see above)

Drugs with limited or uncertain efficacy:

• verapamil modified release 120–240 mg bd
• selective serotonin reuptake inhibitors
• onabotulinumtoxinA is licensed for prophylaxis of patients with >15 headache days/month, of which at least eight days are with migraine

Prophylaxis for hormone-related migraine

• The effect of hormones on migraine is common; oestrogen withdrawal is implicated in some cases

• Prophylaxis should be tried for at least three cycles in maximum dose before being deemed ineffective. There are three options:
  • non-hormonal prophylaxis with mefenamic acid* 500 mg tds–qds, from onset of menstruation to last day of bleeding
  • frovatripan* 5 mg bd on day 1; 2.5 mg bd days 2–6, starting 2 days before expected onset of migraine
  • hormone supplements: transdermal oestrogen* 100 µg or oestradiol gel* 1.5 mg in 2.5 g gel starting 3 days before onset of menses for 7 days
  • combined oral contraceptives (pills, patches, vaginal ring), oral desogestrel, subdermally implanted etonogestrel, or injectable depot progestogens

* unlicensed indication

Management of TTH

• Long-term remission is the objective of management of very frequent episodic or chronic TTH. Where this is unachievable, avoidance of aggravation by medication overuse and the recognition and treatment of contributory factors are important

Basic principles:

• reassurance is important and effective
• effective treatment depends on identification of contributory factors, and either or both of:
  • stress
  • functional or structural cervical or cranial musculoskeletal abnormality
• distinguish between episodic and chronic TTH based on frequency; chronic TTH may have one of the following in the background:
  • MOH
  • clinical depression

• First measures
  • regular exercise is worth recommending
  • physiotherapy is the treatment of choice for musculoskeletal symptoms
  • stress-reducing lifestyle changes and relaxation therapy, cognitive training, yoga and meditation, should improve stress-related TTH

• Drug therapy
  • TTH occurring <2 days/week can be treated symptomatically using simple analgesia:
    • aspirin 600–900 mg
    • ibuprofen 400 mg
    • codeine/dihydrocodeine should be avoided
  • treat chronic TTH prophylactically; amitriptyline is the drug of choice; attempt withdrawal after improvement has been maintained for 4–6 months

Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache continued

Management of cluster headache

• Cluster headache (CH) management is usually better left to experienced specialists who see this disorder frequently

• While CH may spontaneously enter long-term remission, there is no present prospect of a cure. Realistically, the aim is to shorten the cluster period in episodic CH and to reduce the frequency and/or severity of attacks in both episodic and chronic CH

• Basic principles:
  • patients experiencing their first attacks will be greatly concerned, and need reassurance
  • drug treatment is always necessary. In most cases, prophylactic drugs are the mainstay of treatment
  • prophylactic drugs should be commenced as early as possible after the start of a new cluster period
  • treatment found effective in a previous cluster period should be rapidly reintroduced at the start of the next
  • patients may benefit from being given a supply before the next cluster period is anticipated
  • early review is recommended in such cases. Unfortunately, what has worked well before may not do so again

Prophylactic drug intervention

• Evidence base for all drugs listed below is limited, but expert opinion strongly supports their use. Not all experts use them in the same order, but the following is recommended

• Drugs with efficacy:
  • verapamil 80 mg tds or qds may be effective but up to 960 mg daily is sometimes required
  • prednisolone 60–100 mg, once daily for 2–5 days; dose reduction is initiated after 2–5 days and continued, in 10 mg decrements each second or third day, so that treatment is discontinued after 2–3 weeks
  • lithium carbonate should be considered in episodic or chronic CH if verapamil is not effective
    • in episodic form, with short-duration treatment courses (<12 weeks) expected, higher doses of 800–1600 mg daily may be needed
    • chronic CH, needing long-term treatment, may benefit from lower daily doses in the range of 600–900 mg
    • serum concentrations must be frequently monitored, both to ensure adequate dosing and to guard against overdosing
  • methysergide 1–2 mg tds may be effective in up to 70% of patients with episodic CH and is worth trying when other treatments fail
  • ergotamine tartrate 1–2 mg rectally

Drugs with uncertain efficacy or limited value:

• topiramate* ≥100 mg daily
• melatonin* 10 mg daily
• frovatriptan* 2.5 mg bd
• pizotifen 1.5–3 mg daily
• Duration of use:
  • with the exception of prednisolone, prophylaxis should be continued in episodic CH until the patient has been headache-free for at least 14 days
  • drugs should be withdrawn by progressive dosage reduction rather than ceased abruptly

* unlicensed indication

Acute drug intervention

• Drugs with efficacy:
  • sumatriptan 6 mg sc
  • oxygen 100% at 10–15 l/min for 10–20 min
  • zolmitriptan 5–10 mg nasal spray

• Analgesics have no place in treating CH. Ergotamine tartrate and all orally-administered triptans are of no use as acute therapy

Management of MOH

• Objectives of management:
  • achieve withdrawal from the overused medication
  • recovery from MOH
  • review and reassess the underlying primary headache disorder (migraine or TTH), which will probably become unmasked and may or may not need a treatment plan according the principles above
  • prevent relapse, which has a rate of around 40% within 5 years and is most likely to occur within the first year after withdrawal

• Basic principles:
  • prevention, through education, is better than cure
  • once MOH has developed, early intervention is important. The long-term prognosis depends on the type of primary headache and the type of overused medication
  • the only treatment of established MOH is withdrawal of the suspected medication(s)
  • some patients are psychologically dependent upon their medication

• Management of withdrawal:
  • patients must be motivated, understanding that their 'treatment' for headache is actually the cause
  • abrupt withdrawal is most likely to be successful
  • forewarn patients that withdrawal initially aggravates symptoms. Withdrawal should be planned in advance to avoid disruption
  • a diary to record symptoms and medication use during withdrawal is strongly recommended
  • good hydration should be maintained

• Follow-up:
  • review is advised after 2–3 weeks to ensure withdrawal has been achieved
  • recovery continues slowly for weeks to months. Further follow-up is necessary
  • most patients revert to their original headache type (migraine or TTH) within 2 months. Overused medications (if appropriate) may be reintroduced after 2 months, with explicit restrictions on frequency of use
  • relapse is common, and many patients require extended support to prevent it. The majority of relapses occur within the first year after withdrawal. The main risk factors for relapse are:
    • male sex
    • intake of combined analgesic drugs
    • TTH as the primary headache disorder
  • behavioural therapies (CBT, stress reduction, biofeedback) may help

• Inability to cope with emergent aggravation can be managed by offering:
  • naproxen, 250 mg tds or 500 mg bd, to be taken regularly whether symptoms are present or not, for a course of 3–4 weeks, and not repeated
  • prednisolone 60 mg/day for 2 days, 40 mg/day for 2 days and 20 mg/day for 2 days
  • amitriptyline 10–75 mg at night, which is then continued as long-term prophylaxis

• When recovery does not follow withdrawal, the diagnosis of MOH is presumptive. Once medication overuse has been eliminated, preventative drugs may become effective

Management of multiple coexistent headache disorders

• Symptomatic medication should be restricted to no more than 2 days/week. Where migraine coexists with episodic TTH and prophylaxis is considered, amitriptyline 10–150 mg daily is the drug of choice

• Where migraine occurs in association with other, the more troublesome headache (usually chronic TTH or MOH) should be treated first. Improvement in migraine often occurs concomitantly

Predisposing and trigger factors

Factor	Management summary
PREDISPOSING FACTORS
Stress	Lifestyle change; stress reduction/coping strategies
Depression/anxiety	Specific therapy
Menstruation	See prophylaxis of hormone-related migraine
Menopause	Hormone replacement therapy
Head or neck trauma	Physiotherapy
TRIGGER FACTORS
Relaxation after stress, especially at weekends or on holiday	Stress avoidance; lifestyle change
Other change in habit: missing meals; missing sleep; lying in late; long distance travel	Avoidance if possible; avoidance of other cumulative triggers
Bright lights and loud noise (both perhaps stress inducing)	Avoidance
Dietary: certain alcoholic drinks; some cheeses; citrus fruits; possibly chocolate	Avoidance if indicated
Unaccustomed strenuous exercise	Keeping fit/avoidance
Menstruation	See prophylaxis of hormone-related migraine

full guidelines available from…
British Association for the Study of Headache; http://www.bash.org.uk/

British Association for the Study of Headache. Guidelines for Healthcare Professionals in the Diagnosis and Management of Migraine, Tension-Type, Cluster and Medication-Overuse Headache. 3rd edition (1st revision). Updated 2011