Recommendations for research

In 2012 the guideline committee made the following recommendations for research.

1 Amitriptyline to prevent recurrent migraine

Is amitriptyline a clinically and cost effective prophylactic treatment for recurrent migraine?

Why this is important

Effective prevention has the potential to make a major impact on the burden of disability caused by recurrent migraine. There are few pharmacological agents that have been proven to prevent recurrent migraine.

Amitriptyline is widely used, off‑label, to treat chronic painful disorders, including migraine. The updated evidence review (2015) found evidence comparing amitriptyline with topiramate, but not with placebo, and there was uncertainty about the effectiveness of amitriptyline as a prophylactic treatment. A double‑blind randomised controlled trial (RCT) is needed to assess the clinical and cost effectiveness of amitriptyline compared with placebo. The definition of migraine used should be that in the International classification of headache disorders II or this guideline. Outcomes should include change in patient‑reported headache days, responder rate and incidence of serious adverse events.

2 Pizotifen to prevent recurrent migraine

Is pizotifen a clinically and cost effective prophylactic treatment for recurrent migraine?

Why this is important

There are few data to inform guidance on the prevention of migraine in children and young people.

Pizotifen is a popular treatment for migraine prevention in the UK, especially in children and young people. It has been in use since the 1970s and appears to be well tolerated. Inadequate evidence was found in the review for this guideline for the effectiveness of pizotifen in the prophylaxis of migraine. A double‑blind RCT either head‑to‑head with best available treatment, or placebo controlled, is needed to assess the clinical and cost effectiveness of pizotifen in young people aged under 18 and adults. The trial should enrol people aged under 18 and adults. The definition of migraine used should be that in the International classification of headache disorders II or this guideline. Outcomes should include change in patient‑reported migraine days, responder rate and incidence of serious adverse events. If pizotifen is shown to be effective, it will widen the range of therapeutic options, in particular for young people in whom recommended medications are ineffective or not tolerated.

3 Topiramate to prevent recurrent cluster headache

Is topiramate a clinically and cost effective prophylactic treatment for recurrent cluster headache?

Why this is important

Cluster headache is an excruciatingly painful and highly disabling disorder. The management of cluster headache includes the use of preventive treatments to stop the attacks as quickly and safely as possible. There is a significant unmet clinical need for effective preventive treatments in cluster headache and few data to inform guidance on prophylaxis of cluster headache. Although numerous agents including verapamil, topiramate, lithium, methysergide and gabapentin are used in routine clinical practice, this is largely based on clinical experience as very few RCTs have been performed.

Several open‑label studies have reported on the efficacy of topiramate in the preventive treatment of cluster headache. There is therefore a need for a high‑quality RCT of topiramate in the prevention of cluster headaches.

4 Psychological interventions to manage chronic headache disorders

Does a psychological intervention such as cognitive behavioural therapy (CBT) improve headache outcomes and quality of life for people with chronic headache disorders?

Why this is important

Psychological interventions such as CBT are widely recommended for people with chronic painful disorders. An effective psychological intervention based on cognitive behavioural principles for people with chronic headache disorders has the potential to substantially improve their quality of life. There are few data to support the use of these interventions to manage chronic headache disorders.

A pragmatic RCT is needed to assess the impact of a psychological intervention compared with an active control. Mood disorders are commonly comorbid with headache disorders, but the trial needs to address the impact of a psychological intervention on headache alone, using appropriate headache outcomes such as change in patient‑reported headache days and headache‑specific quality of life.

5 Pharmacological treatments for headache prophylaxis to aid withdrawal treatment in medication overuse headache

Does a course of steroid treatment or pharmacological treatments used for headache prophylaxis help people with medication overuse headaches withdraw from medication?

Why this is important

Medication overuse headache is a common disorder. Current best advice is for abrupt withdrawal without any supportive pharmacological treatment. Many people with medication overuse headache find it difficult to withdraw abruptly because in the short term their headaches can become much worse. The use of steroids may aid withdrawal and for those who have an underlying headache disorder such as migraine or tension‑type headache, appropriate prophylaxis may assist in treating the headache.

Double‑blind RCTs are needed in people with suspected medication overuse headache who have an identifiable primary headache disorder. There should be two separate trials, one to investigate withdrawal of medication with placebo versus withdrawal of medication with steroid treatment, and the other to investigate withdrawal of medication with placebo versus withdrawal of medication with appropriate pharmacological prophylaxis. Outcomes should include change in acute medication use, proportion of patients who no longer have suspected medication overuse headache, change in patient‑reported headache days and headache‑specific quality of life.

  • National Institute for Health and Care Excellence (NICE)