Guideline:
EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias
Bibliographic Source(s)
- May A Leone M Afra J Linde M Sandor PS Evers S Goadsby PJ EFNS Task Force. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol 2006 Oct;13(10):1066-77. [143 references] PubMed
Guideline Status
This is the current release of the guideline.
Guideline Category
Assessment of Therapeutic Effectiveness
Management
Prevention
Treatment
Intended Users
Physicians
Guideline Objective(s)
To give evidence-based recommendations for the treatment of cluster headache paroxysmal hemicranias and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome
Target Population
Patients suffering from cluster headache paroxysmal hemicranias and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome
Interventions and Practices Considered
Treatment
Cluster Headaches
- 100% oxygen
- Triptans (e.g. sumatriptan zolmitriptan)
- Intranasal lidocaine
- Subcutaneous octreotide
Prevention
Cluster Headaches
- Verapamil
- Steroids
- Lithium carbonate
- Methysergide
- Topiramate
- Ergotamine tartrate
- Valproic acid
- Melatonin
- Baclofen
Paroxysmal Hemicrania
- Indomethacin
- Verapamil
- Non-steroidal anti-inflammatory drugs (NSAIDs)
Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Syndrome
- Lamotrigine
- Topiramate
- Gabapentin
Major Outcomes Considered
- Effectiveness of treatment
- Prevention of attacks
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 keywords used were 'cluster headache' 'paroxysmal hemicrania' 'SUNCT' 'treatment' and 'trial' (last search in January 2006). All papers published in English German or French were considered if they described a controlled trial or a case series on the treatment of at least five patients (or less in paroxysmal hemicrania or short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing [SUNCT] syndrome). Papers discovered by this search were reviewed as were references cited therein. In addition review books the German treatment recommendations for cluster headache were consulted and abstracts with new data from the most recent congress of the International Headache Society (HIS) (Kyoto October 2005) were hand searched.
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
Systematic Review
Description of the Methods Used to Analyze the Evidence
The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies (EFNS) resulting in level A B or C recommendations and good practice points (see the "Availability of Companion Documents" field in this summary).
Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations
All authors performed an independent literature search. All members of the task force read the first draft and discussed changes by email. All recommendations had to be agreed on by all members of the task force unanimously. The background of the research strategy and of reaching consensus and the definitions of the recommendation dosages used in this paper follow the European Federation of Neurological Societies (EFNS) guidelines (see "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.
Good practice point Where there was a lack of evidence but consensus was clear the Task Force has stated their opinion as good practice points (GPPs).
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" field).
Major Recommendations
The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C good practice point) are defined at the end of the "Major Recommendations" field.
Table 5. Treatment Recommendations for Cluster Headache Paroxysmal Hemicrania and Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Syndrome
| Treatment of Choice | |||
|---|---|---|---|
| Therapy | Cluster Headache | Paroxysmal Hemicrania | SUNCT Syndrome |
| Acute | 100% oxygen 15 l/min (A) Sumatriptan 6 mg subcutaneous (A) Sumatriptan 20 mg nasal (A) Zolmitriptan 5 mg nasal (A/B) Zolmitriptan 10 mg nasal (A/B) Zolmitriptan 10 mg oral (B) Zolmitriptan 5 mg oral (B) Lidocaine intranasal (B) Octreotide (B) |
None | None |
| Preventative | Verapamil (A) Steroids (A) Lithium carbonate (B) Methysergide (B) Topiramate (B) Ergotamine tartrate (B) Valproic acid (C) Melatonin (C) Baclofen (C) |
Indomethacin (A) Verapamil (C) Non-steroidal anti-inflammatory drugs (NSAIDs) (C) |
Lamotrigine (C) |
For exact doses see original guideline document (A denotes effective B denotes probably effective C denotes possibly effective).
Treatment of Cluster Headache
Level A Recommendation
The first option for the treatment of acute attacks of cluster headache should be the inhalation of 100% oxygen with at least 7 l/min over 15 min (class II trials) or with the subcutaneous injection of 6 mg sumatriptan (class I trials). An alternative would be sumatriptan 20 mg nasal spray or zolmitriptan 5 mg nasal spray (one class I trial each) with the disadvantage of a slower onset and the advantage of being able to treat more attacks in 24 hours than with injected sumatriptan.
Prophylaxis of cluster headache should be tried first with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability electrocardiogram [ECG] controls are obligatory with increasing doses). Although no class I or II trials are available steroids are clearly effective for treating cluster headache. Therefore the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or up to 500 mg intravenously (i.v.) per day over 5 days (then tapering down) is recommended.
Level B Recommendation
Intranasal lidocaine (4%) and subcutaneous octreotide (100 micrograms) can be tried for treating acute cluster headache attacks if level A medication is ineffective or contraindicated. Oral administration of zolmitriptan at 5 to 10 mg is effective in some patients (class I trial) but high doses produce more side effects and limit practical use.
Methysergide and lithium are drugs of second choice if verapamil is ineffective or contraindicated. Corticosteroids can be used for short periods where bouts are short or to help establish another medication. Topiramate is promising but only open trials exist at this point. Melatonin is useful in some patients. Except for lithium the maximum dose depends on efficacy and tolerability. Ergotamine tartrate is recommended for short-term prophylaxis (class III studies). Despite positive class II studies pizotifen and intranasal capsaicin should only be used in rare cases because of side effects.
Level C Recommendation
Baclofen 15 to 30 mg and valproic acid showed possible efficacy and can be tried as drugs of third choice.
Good Practice Point
Surgical procedures are not indicated in most of the patients with cluster headache. Patients with intractable chronic cluster headache should be referred to centres with expertise in both destructive and neuromodulatory procedures to be offered all reasonable alternatives before a definitive procedure is conducted.
Treatment of Paroxysmal Hemicrania
Paroxysmal hemicrania is to be treated with indomethacin up to 200 mg (level A recommendation). Alternatively verapamil and other NSAIDs can be tried (level C recommendation).
Treatment of Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Syndrome
Recent large case series outcomes suggest that lamotrigine is the treatment of choice in SUNCT followed by topiramate and gabapentin.
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.
Good practice point Where there was a lack of evidence but consensus was clear the Task Force has stated their opinion as good practice points (GPPs).
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 treatment of cluster headache paroxysmal hemicranias and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome
Potential Harms
Adverse Effects of Medications
- The most uncomfortable side effects of sumatriptan are chest pain and distal paresthesia
- Side effects of verapamil are bradycardia ankle oedema constipation gastrointestinal discomfort gingival hyperplasia and dull headache. Regular echocardiographic (ECG) controls are required to control for an increase in cardiac conduction time reflected in a prolongation of the PR interval. Sometimes ECG may be necessary because of the negative inotropic effects of verapamil.
- Major side effects of lithium are hyperthyreosis tremor and renal dysfunction. The plasma level should be monitored and kept between 0.6 and 1.2 mmol/l. Regular control of liver renal and thyroid function and of electrolytes is required.
- Methysergide should be used with caution when patients are receiving other ergotamine derivatives or triptans. As there is a definite incidence of pulmonary and retroperitoneal fibrosis under long-term use the continuous use of methysergide is limited to 6 months.
- Main side effects of topiramate are cognitive disturbances paresthesias and weight loss.
- A proton pump inhibitor should be given with indomethacin as gastrointestinal discomfort and bleeding are the major side effects of indomethacin.
Contraindications
- Contraindications to sumatriptan are cardio- and cerebrovascular disorders and untreated arterial hypertension.
- Topiramate is contraindicated in nephrolithiasis.
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)
- May A Leone M Afra J Linde M Sandor PS Evers S Goadsby PJ EFNS Task Force. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol 2006 Oct;13(10):1066-77. [143 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 Treatment of Cluster Headache and other Trigeminal Autonomic Cephalalgias
Composition of Group that Authored the Guideline
Task Force Members: A. May Department of Systems Neuroscience University of Hamburg Hamburg Germany; M. Leone Instituto Neurologico Carlo Besta Milan Italy; J. Áfra National Institute of Neurosurgery Budapest Hungary; M. Linde Cephalea Pain Centre and Institute of Neuroscience and Physiology Sahlgren Academy Göteborg University Göteborg Sweden; P. S. Sándor Department of Neurology University of Zurich Zurich Switzerland; S. Evers Department of Neurology University of Münster Münster Germany; P. J. Goadsby Institute of Neurology Queen Square London UK
Financial Disclosures/Conflicts of Interest
The present guidelines were developed without external financial support. None of the authors declares a conflict of interests. The authors report the following financial supports:
Arne May: Salary from the University Hospital of Hamburg; honoraries and research grants by Almirall AstraZeneca Bayer Vital Berlin Chemie GlaxoSmithKline Janssen Cilag MSD Pfizer.
Massimo Leone: Salary from the Istituto Nazionale Neurologico C. Besta; honoraries by GlaxoSmithKline Almirall Medtronic.
Judit Áfra: Salary by the Hungarian Ministry of Health; honoraries by GlaxoSmithKline.
Mattias Linde: Salary from the Swedish government; honoraries by AstraZeneca GlaxoSmithKline MSD Nycomed Pfizer.
Peter S. Sándor: Salary from the University Hospital of Zurich; honoraries by AstraZeneca GlaxoSmithKline Janssen Cilag Pfizer Pharm Allergan.
Stefan Evers: Salary from 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.
Peter J. Goadsby: Salary from the University College of London; honoraries by Almirall AstraZeneca GlaxoSmithKline MSD Pfizer Medtronic Advanced Bionics.
Guideline Status
This is the current release of the guideline.
Guideline Availability
Electronic copies: Available to registered users from the European Federation of Neurological Societies Web site.
Print copies: Available from Arne May MD Department of Systems Neuroscience Universitäts-Krankenhaus Eppendorf (UKE) Martinistr. 52 D-20246 Hamburg Germany; Phone: 040 42803 9189; Fax: 040 42803 9955; E-mail: a.may@uke.uni-hamburg.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 11 2007. The information was verified by the guideline developer on May 15 2007.
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This NGC summary is based on the original guideline which is subject to the Blackwell-Synergy copyright restrictions.
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