The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C) are defined at the end of the "Major Recommendations" field.
Drug Treatment of Migraine Attacks
Analgesics
Table. Analgesics with Evidence of Efficacy in at Least One Study on the Acute Treatment of Migraine. The level of recommendation also considers side effects and consistency of the studies.
| Substance |
Dose |
Level of Recommendation |
Comment |
| Acetylsalicylic acid (ASA) |
1000 mg (oral)
1000 mg (intravenous [i.v.])
|
A
A
|
Gastrointestinal side effects, risk of bleeding |
| Ibuprofen |
200 – 800 mg |
A |
Side effects as for ASA |
| Naproxen |
500 – 1000 mg |
A |
Side effects as for ASA |
| Diclofenac |
50 – 100 mg |
A |
Including diclofenac-K |
| Paracetamol |
1000 mg (oral)
1000 mg (suppository)
|
A
A
|
Caution in liver and kidney failure |
| ASA plus, paracetamol plus and caffeine |
250 mg (oral),
200 – 250 mg
and 50 mg
|
A |
As for ASA and paracetamol |
| Metamizol |
1000 mg (oral)
1000 mg (i.v.)
|
B
B
|
Risk of agranulocytosis
Risk of hypotension
|
| Phenazon |
1000 mg (oral) |
B |
See paracetamol |
| Tolfenamic acid |
200 mg (oral) |
B |
Side effects as for ASA |
Antiemetics
Table. Antiemetics Recommended for the Acute Treatment of Migraine Attacks
| Substance |
Dose |
Level |
Comment |
| Metoclopramide |
10-20 mg (oral), 20 mg (suppository), 10 mg (intramuscular, intravenous, and subcutaneous) |
B |
Side effect: dyskinesia; contraindicated in childhood and in pregnancy |
| Domperidon |
20-30 mg (oral) |
B |
Side effects less severe than in metoclopramide; can be given to children |
Ergot Alkaloids
The advantage of ergot alkaloids in some patients is a longer half life time and a lower recurrence rate. Therefore, these substances should be restricted to patients with very long migraine attacks or with regular recurrence. The only compound with sufficient evidence of efficacy is ergotamine tartrate 2 mg (oral or suppositories).
Triptans (5-HT1B/1D-agonists)
Table. Different Triptans for the Treatment of Acute Migraine Attacks (Order in the Time of Marketing). Not all doses or application forms are available in all European countries
| Substance |
Dose |
Level |
Comment |
| Sumatriptan |
25, 50 and 100 mg (oral including rapid-release) |
A |
100 mg sumatriptan is reference to all triptans |
| 25 mg (suppository) |
A |
| 10 and 20 mg (nasal spray) |
A |
| 6 mg (subcutaneous) |
A |
| Zolmitriptan |
2.5 and 5 mg (oral including disintegrating form)
2.5 and 5 mg (nasal spray)
|
A
A
|
|
| Naratriptan |
2.5 mg (oral) |
A |
Less but longer efficacy than sumatriptan |
| Rizatriptan |
10 mg (oral including wafer form) |
A |
5 mg when taking propranolol |
| Almotriptan |
12.5 mg (oral) |
A |
Probably less side effects than sumatriptan |
| Eletriptan |
20 and 40 mg (oral) |
A |
80 mg allowed if 40 mg not effective |
| Frovatriptan |
2.5 mg (oral) |
A |
Less but longer efficacy than sumatriptan |
Migraine Prophylaxis
There is no commonly accepted indication for starting a prophylactic treatment. In the view of the Task Force, prophylactic drug treatment of migraine should be considered and discussed with the patient when
- The quality of life, business duties, or school attendance are severely impaired
- Frequency of attacks per month is two or higher
- Migraine attacks do not respond to acute drug treatment
- Frequent, very long, or uncomfortable auras occur
Table. Recommended Substances (Drugs of First Choice) for the Prophylactic Drug Treatment of Migraine
| Substances |
Daily Dose |
Level |
| Betablockers |
| Metoprolol |
50–200 mg |
A |
| Propranolol |
40–240 mg |
A |
| Calcium channel blockers |
| Flunarizine |
5–10 mg |
A |
| Antiepileptic drugs |
| Valproic acid |
500–1800 mg |
A |
| Topiramate |
25–100 mg |
A |
Table. Drugs of Second Choice for Migraine Prophylaxis (Evidence of Efficacy, but Less Effective or More Side Effects than Drugs of the Table above)
| Substances |
Daily Dose |
Level |
| Amitriptyline |
50–150 |
B |
| Naproxen |
2 x 250–500 |
B |
| Petasites |
2 x 75 |
B |
| Bisoprolol |
5–10 |
B |
Table. Drugs of Third Choice for Migraine Prophylaxis (Only Probable Efficacy)
| Substances |
Daily Dose |
Level |
| Acetylsalicylic acid |
300 mg |
C |
| Gabapentin |
1200–1600 mg |
C |
| Magnesium |
24 mmol |
C |
| Tanacetum parthenium |
3 x 6.25 mg |
C |
| Riboflavin |
400 mg |
C |
| Coenzyme Q10 |
300 mg |
C |
| Candesartan |
16 mg |
C |
| Lisinopril |
20 mg |
C |
| Methysergide |
4–12 mg |
C |
Migraine in Pregnancy
If migraine occurs during pregnancy, only paracetamol is allowed during the whole period. Non-steroidal anti-inflammatory drugs (NSAIDs) can be given in the second trimester. These recommendations are based on the advices of the regulatory authorities in most European countries. There might be differences in some respect between different countries (in particular, NSAIDs might be allowed in the first trimester).
For migraine prophylaxis, only magnesium and metoprolol are recommended during pregnancy (level B recommendation).
Definitions:
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
