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Medication

Drug treatment is according to the diagnosis (hence the diagnosis must be right). Acute and/or preventative medication may be appropriate (ref 143).

Migraine

Acute intervention

  • Drug treatment should be selected for each patient according to his or her need and response to it.
  • Since little basis other than trial and error exists for achieving this, patients should climb a treatment ladder (stepped management). This is a reliable strategy for achieving correctly individualised

Step one:

  • simple oral analgesia (aspirin 900mg [adults only], paracetamol 1000mg, ibuprofen 400-600mg)
  • in soluble or mouth-dispersible formulations
  • taken early in the attack
  • plus, if necessary, metoclopramide 10mg or domperidone 20mg as antiemetics and to promote gastric emptying.

Step two:

  • parenteral administration to bypass the stomach
  • diclofenac suppositories 100mg for pain plus domperidone suppositories 30mg (if needed) for nausea/vomiting.

Step three:

  • triptans should be offered, unless contra-indicated, to all patients failing steps one and two available triptans differ somewhat (ref 153), but there are unpredictable individual variations in response to them; patients should try several, and choose between them
  • triptans are associated with return of symptoms within 48 hours (relapse) in up to 40% of patients who have initially responded.

Triptans include:

  • Sumatriptan tablets (50mg and 100mg), nasal spray (10mg [licensed for adolescents] and 20mg) or self-administered subcutaneous injection (6mg). The last is appropriate when a rapid response is important above all, or if vomiting precludes oral therapy.
  • Zolmitriptan tablets (2.5mg), mouth-dispersible tablets (2.5mg) (two of either may be taken if needed) or nasal spray (5mg). The last may be useful despite vomiting since absorption is through the nasal mucosa.
  • Rizatriptan tablets (5mg [to be used when propranolol is being taken] and 10mg) or mouth-dispersible wafers (10mg).
  • Naratriptan tablets (2.5mg). It has slower onset of effect but may be appropriate when other triptans cause undue side-effects.
  • Almotriptan tablets (12.5mg).
  • Eletriptan tablets (20mg and 40mg: 2 x 40 mg may be taken if needed). Unlike other triptans, eletriptan exhibits a clear dose-response relationship for efficacy, in the range 20-80mg.
  • Frovatriptan tablets (2.5mg).

Contraindications:

There are specific precautions attached to some triptans. As a class, triptans should be avoided in:

  • uncontrolled hypertension
  • coronary heart disease, cerebrovascular disease and peripheral vascular disease
  • presence of risk factors for coronary or cerebrovascular disease.

Treatment of relapse: a second dose of a triptan is usually effective for relapse. The second dose may lead to further relapse: in some people, repeated dosing gives rise to repeated relapse (ref 6). Diclofenac may be an effective alternative. Ergotamine tartrate, with prolonged duration of action, may be useful for this purpose; it should not be used within 12 hours after any triptan.

Prophylaxis

Prophylactic therapy is added when best acute therapy gives inadequate symptom control. The judge of this is usually the patient. In children, an index is frequency of absence from school.

Over-frequent use of acute therapy is also a criterion for prophylaxis, but prophylactic drugs are inappropriate and will be ineffective for medication overuse headache.

Poor compliance is a major factor impairing efficacy of migraine prophylactics. Once-daily dosing is preferable. Otherwise, there are no sound criteria for choice of prophylactic drug except those of comorbidity and contraindications.

The dose of each should, usually, start low in the suggested range and be increased in the absence of troublesome side-effects.

  • Beta-adrenergic blockers without partial agonism (ref 154): atenolol 25-100mg bd, propranolol LA 80mg od-160mg bd. Avoid in asthma, heart failure, peripheral vascular disease and depression. Propranolol has best evidence of safety during pregnancy and lactation (ref 155).
  • Sodium valproate 0.6-2.5g daily (ref 156). Avoid during pregnancy and when pregnancy may occur, and use with care in children.
  • Pizotifen 1.5mg at bedtime. Avoid when weight gain is undesirable.
  • Amitriptyline 10-150mg at bedtime (or 2-4 hours before). Use when migraine coexists with TTH, depression or sleep disturbance. It may be used concomitantly with a beta-blocker. Explain the choice of this drug to patients who do not consider themselves depressed or they may reject it.
  • Methysergide 1-2mg tds (hospital use only). This is held in reserve because of its association with retroperitoneal fibrosis but seems not to have this side-effect in courses of less than 6 months.

In children: beta-blockers or pizotifen (available as an elixir) may be tried. Some paediatricians use sodium valproate or amitriptyline. Dosage is adjusted according to age.

Duration of use of prophylaxis:

  • prophylaxis is required for periods of exacerbation
  • if effective it should be continued for 4-6 months, then withdrawn (abruptly or tapered) to establish continued need
  • prophylactic drugs that are apparently not effective should not be discontinued too soon lest patients be labelled non-responders prematurely; 3-4 weeks may be the minimum.

If prophylaxis fails

  • review the diagnosis
  • review compliance and concordance
  • review other medication, especially for overuse
  • if prophylaxis still fails to have measurable benefit, discontinue it.

Tension-type headache

Drug therapy has limited scope but is effective in some patients:

  • symptomatic treatment with over-the-counter analgesics is appropriate for episodic TTH occurring on <2 days per week: aspirin 600-900mg (ref 157), ibuprofen 400mg or paracetamol 1000mg
  • codeine and dihydrocodeine should be avoided
  • as the frequency of headaches increases, so does the risk of medication overuse
  • these treatments are inappropriate in chronic TTH, but a 3-week course of naproxen 250-500mg bd may interrupt frequently recurring or unremitting headaches
  • amitriptyline is otherwise the prophylactic treatment of choice for frequent episodic or chronic TTH; intolerance is reduced by starting at 10mg at night and incrementing by 10-25mg each 1-2 weeks usually into the range 50-150mg at night
  • sodium valproate 0.6-2.5g daily is an alternative; avoid during pregnancy and use with care in children.

Duration of use of prophylaxis:

  • withdrawal may be attempted after improvement has been maintained for 4-6 months.

If prophylaxis fails

  • failure may be due to subtherapeutic dosage or insufficient duration of treatment
  • review compliance and concordance: patients who are not informed that they are receiving medication often used as an anti-depressant, and told why, may default when they find out
  • review other medication, especially for overuse
  • when prophylaxis still fails to have measurable benefit, discontinue it.


Cluster headache

The objective in both episodic and chronic CH, not always achievable, is total attack suppression. In most cases, preventive drugs are the mainstay of treatment.

Acute therapies

  • sumatriptan 6 mg subcutaneously is the only proven highly-effective acute treatment
  • oxygen 100% at 7 l/min (requires a special mask and regulator) helps some people
  • analgesics have no place in treating CH.

Prophylaxis

Prophylaxis of episodic CH should begin early after the start of a new cluster bout.

The following are used by specialists. Failure of one drug does not predict failure of others. Combinations may be tried (ref 158), but the potential for toxicity is obviously high.

  • verapamil 240-960 mg/day (ref 159)
  • prednisolone 60-80 mg/day for 2-4 days, discontinued by dose reduction over 2-3 weeks
  • lithium carbonate 600-1600 mg/day
  • ergotamine 2-4 mg/day per rectum, usually omitted every 7th day
  • methysergide 1-2mg tds

 Duration of use of prophylaxis:

  • apart from prednisolone, treatment should be discontinued 2 weeks after full remission

Medication-overuse headache

Prevention is ideal, with education the key factor.

Once MOH has developed, early intervention is important since the long-term prognosis depends on the duration of medication overuse (ref 160).

  • Treatment is withdrawal of the suspected medication(s).
  • Although this will lead initially to worsening headache, with forewarning and explanation it is probably most successfully done abruptly (ref 161).
  • Within 2-3 weeks, usually, the headache shows signs of improvement. Patients should be reviewed at this time to ensure withdrawal has been achieved.
  • Improvement may be slow but continues for weeks to months.
  • 50-75% of patients revert to their original headache type which may be migraine (usually) or TTH. This headache should be reviewed after 2-3 months and managed appropriately.
  • Most patients require extended support: the relapse rate is around 40% within five years.

References

143 British Association for the Study of Headache. Guidelines for all doctors in the diagnosis and management of migraine and tension-type headache, 2nd edition (revised). BASH 2003 at http://www.bash.org.uk.

153. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001; 358: 1668-1675.

154. Ramadan NM, Schultz LL, Gilkey SJ. Migraine prophylactic drugs: proof of efficacy, utilization and cost. Cephalalgia 1997; 17: 73-80.

155. Hopkinson HE. Treatment of cardiovascular diseases. In Rubin P (ed), Prescribing in pregnancy. London: BMJ Publishing Group 1995, p. 98.

156. Rothrock JF. Clinical studies of valproate for migraine prophylaxis. Cephalalgia 1997; 17: 81-83.

157. Steiner TJ, Lange R, Voelker M. Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol. Cephalalgia 2003; 23: 59-66.

158. Kudrow L. Treatment of cluster headache. Headache Quart 1993; 4: 42-47.

159. Gabai IJ, Spierings ELH. Prophylactic treatment of cluster headache with verapamil. Headache 1989; 29: 167-168.

160. Schnider P, Aull S, Baumgartner C et al. Long-term outcome of patients with headache and drug abuse after inpatient withdrawal: five-year follow-up. Cephalalgia 1996; 16: 481-485. 161. Hering R, Steiner TJ. Abrupt outpatient withdrawal of medication in analgesic-abusing migraineurs. Lancet 1991; 337: 1442-1443.

161. Hering R, Steiner TJ. Abrupt outpatient withdrawal of medication in analgesic-abusing migraineurs. Lancet 1991; 337: 1442-1443.

Last edited: 6/2/2004


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