Incidence	Cause
Most likely	Tension-type headache
Likely	Migraine, sinusitis, eye strain
Unlikely	Cluster headache, medication-overuse headache, temporal arteritis, trigeminal neuralgia, depression
Very unlikely	Glaucoma, meningitis, subarachnoid haemorrhage, raised intracranial pressure

Headache classification

If the pharmacist is to advise on appropriate treatment and referral then it is essential to make an accurate diagnosis. However, with so many disorders having headache as a symptom pharmacists should endeavour to follow an agreed classification system. The third edition (2010) of the International Headache Society (IHS) classification is now almost universally accepted (Table 4.2). The system first distinguishes between primary and secondary headache disorders. This is useful to the community pharmacist, as any secondary headache disorder is symptomatic of an underlying cause and would normally require referral. In the IHS system, primary headaches are classified on symptom profiles, relying on careful questioning coupled with epidemiological data on the distribution a particular headache disorder has within the population.

Table 4.2

The International Headache Society classification of headache

Source: adapted by the British Association of Headache (BASH) from the International Headache Society Classification Subcommittee, The International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004, Blackwell Publishing, reproduced with permission.

Table 4.3

Specific questions to ask the patient: Headache

Clinical features of headache

In a community pharmacy the overwhelming majority of patients (80–90%) will present with tension-type headache. A further 10% will have migraine. Very few will have other primary headache disorders and fewer still will have a secondary headache disorder (see Table 4.1).

Tension-type headache

Tension-type headaches can be classed as either episodic or chronic. Episodic tension-type headache can be further subdivided into infrequent and frequent forms. Most patients will present to the pharmacist with the infrequent episodic form. Headaches last from 30 minutes to up to 7 days in duration and often the patient will have a history of recent headaches. They might have tried OTC medication without complete symptom resolution or say that the headaches are becoming more frequent. Pain is bifrontal or bioccipital, generalised and non-throbbing (Fig. 4.1). The patient might describe the pain as tightness or a weight pressing down on their head. The pain is gradual in onset and tends to worsen progressively through the day. Pain is normally mild to moderate and not aggravated by movement, although it is often worse under pressure or stress. Nausea and vomiting are not associated with tension-type headache and rarely causes photo or phonophobia. Overall, the headache has a limited impact on the individual.

Fig. 4.1 Location of pain in headache.

Patients who have frequent episodic tension-type headaches suffer more frequent headaches that last longer and over time these can develop into chronic tension-type headache. Headaches occur for more than 15 days per month, and might be daily which last for at least 3 months. These types of headaches can severely affect the patient’s quality of life and should not be managed by the community pharmacist.

Migraine

There are an estimated 5 million migraine sufferers in the UK, half of whom have not been diagnosed by their GP. The peak onset for a person to have their first attack is in adolescence or as a young adult. Migraines are rare over the age of 50 and anyone in this age group presenting for the first time with migraine-like symptoms should be referred to the GP to eliminate secondary causes of headache. If this is not their first attack they will normally have a history of recurrent and episodic attacks of headache. Attacks last anything between a few hours and up to 3 days. The average length of an attack is 24 hours. The IHS classification recognises several subtypes of migraine but the two major subtypes are migraine with aura (classical migraine) and migraine without aura (common migraine). A migraine attack can be divided into three phases:

• Phase one: premonitory phase (prodrome phase), which can occur hours or possibly days before the headache. The patient might complain of a change in mood or notice a change in behaviour. Feelings of well being, yawning, poor concentration and food cravings have been reported. These prodromal features are highly individual but are relatively consistent to each patient. Identification of ‘triggers’ is sometimes possible (Table 4.4).

Table 4.4

Triggers and strategies to reduce migraine attacks

Trigger	Strategy
Stress	Maintain regular sleep pattern Take regular exercise Modify work environment Relaxation techniques, e.g. yoga
Diet Any food can be a potential trigger but food implicated includes: Cheese Citrus fruit Chocolate	Maintain a food diary. If an attack occurs within 6 h of food ingestion and is reproducible it is likely that it is a trigger for migraine Eat regularly and do not skip meals Note: Detecting triggers is complicated because they appear to be cumulative, jointly contributing to a ‘threshold’ above which attacks are initiated.

• Phase two: headache with or without aura,

• Phase three: as the headache subsides the patient can feel lethargic, tired and drained before recovery, which might take several hours and is termed the resolution phase.

Headache with aura (classic migraine)

This accounts for less than 25% of migraine cases. The aura, which are fully reversible, develop over 5 to 20 min and can last for up to 1 h. It can either be visual or neurological. Visual auras can take many guises, such as scotomas (blind spots), fortification spectra (zig-zag lines) or flashing and flickering lights. Neurological auras (pins and needles) typically start in the hand, migrating up the arm before jumping to the face and lips. Within 60 min of the aura ending the headache usually occurs. Pain is unilateral, throbbing and moderate to severe. Sometimes the pain becomes more generalised and diffuse. Physical activity and movement tends to intensify the pain. Nausea affects almost all patients but less than a third will vomit. Photophobia and phonophobia often mean patients will seek out a dark quiet room to relieve their symptoms. The patient might also suffer from fatigue, find concentrating difficult and be irritable.

Headache without aura (common migraine)

The remaining 75% of sufferers do not experience an aura but do suffer from all other symptoms as described above.

Other likely causes of headache

Eye strain: People that perform prolonged close work, for example VDU operators, can suffer from frontal aching headache. In the first instance, patients should be referred to an optician for a routine eye check.

Sinusitis: The pain tends to be relatively localised, usually orbital, unilateral and dull. A course of decongestants could be tried but if treatment failure occurs referral to the GP for possible antibiotic therapy would be needed. For further information on sinusitis see page 13.

Unlikely causes

Cluster headache: Cluster headache is predominantly a condition that affects men over the age of 30. Typically the headache occurs at the same time each day with abrupt onset and lasts between 10 minutes and 3 hours, with 50% of patients experiencing night-time symptoms. Patients are woken 2 to 3 h after falling asleep with very intense unilateral orbital boring pain. Additionally, conjunctival redness, lacrimation, nasal congestion (which laterally becomes watery) are observed on the pain side of the head. Patients tend to be restless and irritable and move about to relieve the pain.

The condition is characterised by periods of acute attacks, typically lasting a number of weeks to a few months with sufferers experiencing between one to three attacks per day. This is then followed by periods of remission, which can last months or years. During acute phases, alcohol can trigger an attack. Nausea is usually absent and a family history uncommon. Referral is required, as sumatriptan, the drug of choice, does not have an OTC licence for cluster headache.

Medication-overuse headache: Patients with long-standing symptoms of headache who regular medicate can develop medication-overuse headache. Pain receptors (nociceptors) instead of being ‘switched off’ when analgesics are taken are in fact ‘switched on’. The consequence is a cycle where patients take more and more painkillers that are stronger and stronger in order to control the pain. Patients will experience daily or near daily headaches that are described as dull and nagging. Obviously in these cases a medication history is essential and should prompt the pharmacist to refer the patient to the GP. Treatment is to stop all analgesia for a number of weeks and requires careful planning.

Temporal arteritis: The temporal arteries that run vertically up the side of the head, just in front of the ear, can become inflamed. When this happens, they are tender to touch and might be visibly thickened. Unilateral pain is experienced and the person generally feels unwell with fever, myalgia and general malaise. Scalp tenderness is also possible, especially when combing the hair. It is most commonly seen in the elderly, especially women. Prompt treatment with oral corticosteroids is required as the retinal artery can become compromised, leading to blindness. Urgent referral is needed.

Trigeminal neuralgia: Pain follows the course of either the second (maxillary; supplying the cheeks) or third (mandibular; supplying the chin, lower lip and lower cheek) division of the nerve leading to pain experienced in the cheek, jaws, lips or gums. Pain is short lived, usually lasting only a couple of minutes but is severe and lancing and is almost always unilateral. It is three times more common in women than men.

Depression: A symptom of depression can be tension-type headaches. However, other more prominent symptoms should be present. The DSM-IV criteria are often used to aid a diagnosis of depression. The pharmacist should check for a loss of interest or pleasure in activities, fatigue, inability to concentrate, loss of appetite, weight loss, sleep disturbances and constipation. If the patient exhibits some of these characteristics then referral to the GP would be necessary. Recent changes to the patient’s social circumstances, for example loss of job, might also support your differential diagnosis.

Very unlikely causes

Glaucoma: Patients experience a frontal/orbital headache with pain in the eye. The eye appears red and is painful. Vision is blurred and the cornea can look cloudy. In addition, the patient might notice haloes around the vision. For further information on glaucoma see page 48.

Meningitis: Severe generalised headache associated with fever, an obviously ill patient, neck stiffness, a positive Kernig’s sign (pain behind both knees when extended) and latterly a purpuric rash are classically associated with meningitis. However, meningitis is notoriously difficult to diagnose early and any child that has difficulty in placing their chin on their chest, has a headache and running a temperature above 38.9°C (102°F), should be referred urgently.

Subarachnoid haemorrhage: The patient will experience very intense and severe pain, located in the occipital region. Nausea and vomiting are often present and a decreased lack of consciousness is prominent. Patients often describe the headache as the worse headache they have ever had. It is extremely unlikely that a patient would present in the pharmacy with such symptoms but if one did then immediate referral is needed.

Conditions causing raised intracranial pressure: Space-occupying lesions (brain tumour, haematoma and abscess) can give rise to varied headache symptoms, ranging from severe chronic pain to intermittent moderate pain. Pain can be localised or diffuse and tends to be more severe in the morning with a gradual improvement over the next few hours. Coughing, sneezing, bending and lying down can worsen the pain. Nausea and vomiting are common. After a prolonged period of time neurological symptoms start to become evident, such as drowsiness, confusion, lack of concentration, difficulty with speech and paraesthesia.

Any patient with a recent history (lasting 2 to 3 months) of head trauma, headache of long-standing duration or insidious worsening of symptoms, especially associated with decreased consciousness and vomiting must be referred urgently for fuller evaluation.

Figure 4.2 (and summary table in Case Study 4.1) will help in the differentiation of serious and non-serious causes of headache.

Trigger points indicative of referral

Headache

Symptoms/signs	Possible danger/reason for referral
Headache in children under 12 who have a stiff neck or skin rash	Meningitis?
Headache occurs after recent (1 to 3 months) trauma injury	Haematoma?
Nausea and/or vomiting in the absence of migraine symptoms Neurological symptoms, if migraine excluded, especially change in consciousness New or severe headache in patients over 50 Progressive worsening of headache symptoms over time Very sudden and/or severe onset of headache	All can suggest sinister pathology and require further investigation
Headache unresponsive to analgesics	Simple analgesia is effective, therefore if they have not worked the patients’ symptoms require further investigation
Headache that has lasted for more than 2 weeks	Most acute (or uncomplicated) cases will last less than 2 weeks. Further investigation required

Fig. 4.2 Primer for differential diagnosis of headache.
Age
Caution should be exercised in children who present with headache. Although the majority of headaches will not have an organic cause, children under 12 are probably best referred if they show no signs of a systemic infection (e.g. fever, malaise).
Referral for suspected sinister pathology
With increasing age it is more likely that a sinister cause of headache is responsible for the symptoms, especially if the patient has not experienced similar headache symptoms before. Mass lesions (tumours and haematoma) and temporal arteritis should be considered.
Referral for suspected sinister pathology
Nausea and vomiting in the absence of migraine-like symptoms should be treated seriously. Mass lesions and subarachnoid haemorrhage need to be eliminated.

Evidence base for over-the-counter medication

Simple analgesia (paracetamol, aspirin and ibuprofen) have shown clinical benefit in relieving migraine attacks. A recent Cochrane review (Derry et al 2010) found that a single oral dose of paracetamol 1000 mg was effective in relieving moderate to severe migraine symptoms, compared with placebo. Approximately 20% of patients will be pain free in 2 hours (reduced from moderate to severe) and approximately 60% of patients can expect a reduction in the severity of pain from moderate/severe to mild pain by 2 hours. (Note that addition of metoclopramide saw efficacy equivalent to 100 mg sumatriptan – such products are available OTC in other countries, e.g. Australia.)

For episodic tension-type, a systematic review by Verhagen et al (2006) investigated the comparative efficacy of simple analgesics. The authors concluded that all simple analgesics had similar efficacy (measured as >50% pain relief).

Combinations of simple analgesics with codeine are available (page 263); however, there is doubt whether the amount of codeine in these preparations is sufficient to provide any additional pain relief. Further, there is growing evidence of problems with the over-use of these products resulting from dependence on the codeine components (Frei et al 2010). In response to the ongoing concerns about the over-use of codeine-containing products, the MHRA, in 2009, issued new guidance to restrict codeine-containing products for the short term (3 days) treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

In summary, simple analgesia should be tried as first-line options for the relief of pain in migraine and tension-type headache.

Additionally, four UK products are specifically marketed to aid relief from pain and/or nausea associated with migraine: Migraleve; Midrid; Buccastem; and Imigran Recovery. The evidence for these products is reviewed.

Migraleve

Migraleve is available as either Migraleve Pink tablets, which contain a paracetamol codeine combination (500/8) plus buclizine 6.25 mg or Migraleve Yellow tablets, which contain only the analgesic combination. A number of trials have investigated Migraleve Pink tablets against placebo, buclizine and ergotamine products in an attempt to establish clinical effectiveness.

A review of two trials in which Migraleve was compared against buclizine (Jorgensen 1974) and placebo (Scopa et al 1974) showed Migraleve was as effective as buclizine and superior to placebo in reducing severity of migraine attacks. However, patient numbers were small (n = 21 and 20 respectively) and statistical significance was not reported. Migraleve has also been compared to ergotamine-containing products; the standard drug at the time the trial was conducted. Results from a GP research group (Anon 1973) concluded that Migraleve was equally effective as Migril in treating migraine. However, results should be viewed with caution because the trial suffered from poor design, lacked randomisation, placebo or proper blinding. A further trial by Carasso and Yehuda (1984) also reported beneficial effects of Migraleve. The most recent trial (Adam 1987) was well designed, being double-blind, randomised and placebo controlled. The author concluded that, compared with placebo, Migraleve did reduce the severity of attacks significantly but not their total duration.

Midrid

Midrid capsules contain isometheptene mucate 65 mg and paracetamol 325 mg. A number of trials have investigated the effect of Midrid on reducing the severity of migraine attacks. Trials date back to 1948, although it was not until the 1970s that soundly designed trials were performed. Two studies (Diamond 1975, 1976) using similar methodology investigated isometheptene versus placebo and paracetamol. Both were double blind, placebo controlled and had identical inclusion criteria. The 1975 trial concluded that isometheptene was superior in relieving headache severity compared to placebo, although the dose of isometheptene used was double that found in Midrid. The 1976 trial also concluded that isometheptene was significantly superior to placebo and appeared to be better than paracetamol alone, but this did not reach statistical significance. A further trial (Behan 1978) compared Midrid against placebo and ergotamine. Fifty patients who suffered four or more migraine attacks per month were recruited to the study. Diary cards were completed for six attacks in which patients rated relief from headache on a four-point rating scale. The author concluded that Midrid was as effective as ergotamine and that both were more beneficial than placebo, although it is unclear whether this was statistically significant.