Guideline:
EFNS guideline on the drug treatment of migraine
Bibliographic Source(s)
- Members of the task force: Evers S Afra J Frese A Goadsby PJ Linde M May A Sandor PS. EFNS guideline on the drug treatment of migraine - report of an EFNS task force. Eur J Neurol 2006 Jun;13(6):560-72. [171 references] PubMed
Guideline Status
This is the current release of the guideline.
These recommendations should be updated within 2 years and should be complemented by recommendations for the non-drug treatment of migraine.
Guideline Category
Assessment of Therapeutic Effectiveness
Prevention
Treatment
Intended Users
Physicians
Guideline Objective(s)
To give evidence-based recommendations for the drug treatment of migraine attacks and migraine prophylaxis
Target Population
Adults children and adolescents with migraine
Interventions and Practices Considered
Treatment/Prevention
- Analgesics
- Antiemetics
- Ergot alkaloids
- Triptans
- Treatment of menstrual migraine: naproxen sodium
- Migraine in pregnancy: paracetamol NSAIDs
- Migraine in children and adolescents: ibuprofen paracetamol domperidon sumatriptan nasal spray
- Prophylaxis of migraine
- Drugs of first choice (e.g. beta blockers calcium channel blockers antiepileptic drugs)
- Miscellaneous drugs of second and third choice (see the "Major Recommendations" field for details)
- Prophylaxis of menstrual migraine
- Prophylaxis in pregnancy: magnesium and metoprolol
- Prophylaxis in children and adolescents: flunarizine and propranolol
Note: The non-drug management (e.g. behavioral therapy) is not included in this guideline although it is regarded as an important part of migraine treatment.
Major Outcomes Considered
- Effectiveness of treatment in pain relief headache recurrence severity of pain and analgesic requirements
- Adverse effects of medications used to treat migraine
Methods Used to Collect/Select Evidence
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods used to Collect/Select the Evidence
A literature search was performed using the reference databases MedLine Science Citation Index and the Cochrane Library; the key words used were 'migraine' and 'aura' (last search in January 2005). All papers published in English German or French were considered when they described a controlled trial or a case series on the treatment of at least five patients. In addition a review book and the German treatment recommendations for migraine were considered.
Number of Source Documents
Not stated
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence
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
Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence
Not stated
Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations
All authors performed an independent literature search. The first draft of the manuscript was written by the chairman of the task force. All other members of the task force read the first draft and discussed changes by e-mail. A second draft was then written by the chairman which was again discussed by e-mail. All recommendations had to be agreed to by all members of the task force unanimously. The background of the research strategy and of reaching consensus and the definitions of the recommendation levels used in this paper have been described in the European Federation of Neurological Societies (EFNS) recommendations (see the "Availability of Companion Documents" field).
Rating Scheme for the Strength of the Recommendations
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.
Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.
Method of Guideline Validation
Peer Review
Description of Method of Guideline Validation
The guidelines were validated according to the European Federation of Neurological Societies (EFNS) criteria (see "Availability of Companion Documents").
Major Recommendations
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.
Clinical Algorithm(s)
None provided
Type of Evidence supporting the Recommendations
The type of supporting evidence is identified and graded for selected recommendations (see "Major Recommendations").
Potential Benefits
Appropriate drug treatment and prophylaxis of migraine
Potential Harms
Analgesics
- Acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal side effects and risk of bleeding.
- Paracetamol and Phenazon should be given with caution in liver and kidney failure.
- Metamizol is associated with risk of agranulocytosis and hypotension
- In order to prevent drug overuse headache the intake of simple analgesics should be restricted to 15 days/month and the intake of combined analgesics to 10 days/month.
Antiemetics
- Metoclopramide is associated with dyskinesia
- Domperidon has less severe side effects compared to metoclopramide and can be given to children.
Ergot Alkaloids
- Major side effects of ergot alkaloids include nausea vomiting paresthesia and ergotism.
- Ergot alkaloids can induce drug overuse headache very fast and in very low doses. Therefore their use must be limited to 10 days/month.
Triptans
- The use of triptans is restricted to maximum 10 days/month. Otherwise the induction of a drug overuse headache is possible for all triptans.
- General side effects for all triptans: chest symptoms nausea distal paresthesia fatigue.
- After application of sumatriptan severe adverse events have been reported such as myocardial infarction cardiac arrhythmias and stroke.
Antidepressants
In several small studies amitriptyline showed central side effects.
Miscellaneous Drugs
Methysergide is recommended for short-term use only (maximum 6 months per treatment period) because of potentially severe side effects
Contraindications
- Metoclopramide is contraindicated in childhood and pregnancy.
- Ergot alkaloids are contraindicated in cardiovascular and cerebrovascular diseases Raynaud's disease arterial hypertension renal failure and pregnancy and lactation.
- Triptan contraindications: arterial hypertension (untreated) coronary heart disease cerebrovascular disease Raynaud's disease pregnancy and lactation age under 18 (except sumatriptan nasal spray) and age above 65 years severe liver or kidney failure.
Qualifying Statements
This guideline provides the view of an expert task force appointed by the Scientific Committee of the European Federation of Neurological Societies (EFNS). It represents a peer-reviewed statement of minimum desirable standards for the guidance of practice based on the best available evidence. It is not intended to have legally binding implications in individual cases.
Description of Implementation Strategy
The European Federation of Neurological Societies has a mailing list and all guideline papers go to national societies national ministries of health World Health Organisation European Union and a number of other destinations. Corporate support is recruited to buy large numbers of reprints of the guideline papers and permission is given to sponsoring companies to distribute the guideline papers from their commercial channels provided there is no advertising attached.
IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness
Bibliographic Source(s)
- Members of the task force: Evers S Afra J Frese A Goadsby PJ Linde M May A Sandor PS. EFNS guideline on the drug treatment of migraine - report of an EFNS task force. Eur J Neurol 2006 Jun;13(6):560-72. [171 references] PubMed
Adaptation
Not applicable: The guideline was not adapted from another source.
Source(s) of Funding
European Federation of Neurological Societies
Guideline Committee
European Federation of Neurological Societies Task Force on the Drug Treatment of Migraine
Composition of Group that Authored the Guideline
Task Force Members: S. Evers Department of Neurology University of Münster Münster Germany; J. Áfra National Institute of Neurosurgery Budapest Hungary; A. Frese Department of Neurology University of Münster Münster Germany; P. J. Goadsby Headache Group Institute of Neurology The National Hospital for Neurology and Neurosurgery London UK; M. Linde Cephalea Pain Center Läkarhuset Södra vägen Gothenburg Gothenburg Sweden; A. May Department of Neurology University of Hamburg Hamburg Germany; P. S. Sándor Department of Neurology University of Zurich Zurich Switzerland
Financial Disclosures/Conflicts of Interest
The present guidelines were developed without external financial support. The authors report the following financial supports:
Stefan Evers: Salary by the government of the State Northrhine-Westphalia; honoraries and research grants by Almirall AstraZeneca Berlin Chemie Boehringer GlaxoSmithKline Ipsen Pharma Janssen Cilag MSD Pfizer Novartis Pharm Allergan Pierre Fabre. Judit Áfra: Salary by the Hungarian Ministry of Health; honoraries by GlaxoSmithKline. Achim Frese: Salary by the government of the State Northrhine-Westphalia; no honoraries. Peter J. Goadsby: Salary by the University College of London; honoraries by Almirall AstraZeneca Glaxo- SmithKline MSD Pfizer Medtronic. Mattias Linde: Salary by the Swedish government; honoraries by AstraZeneca GlaxoSmithKline MSD Nycomed Pfizer. Arne May: Salary by the University Hospital of Hamburg; honoraries by Almirall AstraZeneca Bayer Vital Berlin Chemie GlaxoSmithKline Janssen Cilag MSD Pfizer. Peter S. Sándor: Salary by the University Hospital of Zurich; honoraries by AstraZeneca GlaxoSmithKline Janssen Cilag Pfizer Pharm Allergan
Guideline Status
This is the current release of the guideline.
These recommendations should be updated within 2 years and should be complemented by recommendations for the non-drug treatment of migraine.
Guideline Availability
Electronic copies: Available to registered users from the European Federation of Neurological Societies Web site.
Print copies: Available from Stefan Evers Department of Neurology University of Münster Albert-Schweitzer-Str. 33 48129 Münster Germany; Phone: +49-251-8348196; Fax: +49-251-8348181; E-mail: everss@uni-muenster.de
Availability of Companion Documents
The following are available:
- Brainin M Barnes M Baron JC Gilhus NE Hughes R Selmaj K Waldemar G; Guideline Standards Subcommittee of the EFNS Scientific Committee. Guidance for the preparation of neurological management guidelines by EFNS scientific task forces – revised recommendations 2004. Eur J Neurol. 2004 Sep;11(9):577-81. Electronic copies: Available in Portable Document Format (PDF) from the European Federation of Neurological Societies Web site.
- Guideline papers. European Federation of Neurological Societies. Electronic copies: Available from the European Federation of Neurological Societies Web site.
Patient Resources
None available
NGC STATUS
This NGC summary was completed by ECRI on April 6 2007. The information was verified by the guideline developer on May 15 2007. This summary was updated by ECRI Institute on November 9 2007 following the U.S. Food and Drug Administration advisory on Antidepressant drugs.
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