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Treating chronic migraine

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Considerable advances in the treatment of chronic migraine have occurred in the past decade. Despite this, the optimisation of migraine treatment in sufferers is still wanting. Practitioners face the challenge of developing individualised management plans from the increasing number of available medical treatments and incorporating non-traditional approaches to migraine management.1

Dr Karl Ng, Consultant Neurologist at Royal North shore Hospital and Conjoint Senior Lecturer at the University of Sydney, says that there are no ‘textbook’ rules for treating chronic migraine.

“Despite many pharmacological and other interventions, there is no one drug that works dramatically in all patients, not to mention without significant side-effects,” said Dr Ng.

Modern approaches to chronic migraine management aim to prevent pain and reverse progression of episodic to chronic migraine through prophylactic treatment, rather than simply aborting acute migraine attacks. As such, attention to the individualised nature of migraine patterns and progression is required. Optimal management of chronic migraine also requires a chronic disease approach, which recognises the importance of identifying and addressing migraine-related health problems.1

The challenge of developing optimal treatment regimens for chronic migraine is considerable. However, the potential benefits for patients who experience this highly debilitating condition are potentially immense.1

A severely debilitating condition

Chronic migraine is a type of daily headache, migrainous in nature and occurring in the absence of medication overuse. By definition, sufferers experience these headaches on at least 15 days each month.2 It is a severely debilitating condition.3 Migraine (including episodic and chronic forms) is the 19th leading cause of disability overall, but when only females are considered, migraine ranks as the 12th leading cause of disability. Female migraine sufferers outnumber male sufferers by almost 3 to 1.4 Migraine is also a leading cause of workplace absenteeism.5

Chronic migraine affects both physical and emotional parameters of health. The more frequently headaches occur, the more likely negative health effects are. Individuals who experience chronic migraines are more likely to miss school or work as a result of their headaches than those who experience episodic migraines (< 15 days per month). They are also more likely to experience disruption to other daily activities including social and leisure activities and family life. Chronic migraine has also been reported to impair financial capacity and interfere with patients’ sex lives.4 According to Dr Ng, pain is at the core of the psychological impact of chronic migraine.

“Aside from fear of a sinister cause, most of the psychological burden stems from intractable pain,” Dr Ng said.

Chronic, progressive and commonly comorbid

Once conceived as an episodic disorder, the chronic, progressive and debilitating nature of migraine has received increasing attention in the past 2 decades.1 Up to 14% of individuals with episodic migraine will progress to experiencing more frequent, and eventually chronic, headaches which occur ≥ 15 days per month.6 However, the functional impairment of chronic migraine persists even between acute episodes of headache. Anxiety about future migraine attacks is a significant contributing factor which may, for example, cause sufferers to limit their activities (e.g. travelling alone) due to the possibility of migraine occurring.4

Individuals with chronic migraine also typically experience a greater burden of comorbid disease. They are at increased risk of psychological conditions including depressive, anxiety and panic disorders and obsessive-compulsive disorder.4 While these comorbidities also affect episodic migraine sufferers, those with chronic migraine have a greater risk. Chronic migraineurs also have a greater risk of physical comorbidities including asthma, chronic obstructive pulmonary disease, diabetes, obesity and other cardiac risk factors.7

Treatment

Understanding the quality of life impact of migraine is an important aspect of developing an optimal treatment plan. One goal of treatment is to reduce disruption to daily life and it is important that the impact of comorbid conditions and functional impairment be understood and considered when developing or evaluating the impact of the patient’s individualised management plan. Typically, such a plan incorporates prophylactic and abortive therapies.4

Prophylactic treatment

Prophylaxis is an important component of chronic migraine treatment and aims to reduce the frequency of migrainous headaches, and the associated impairment and medication use.8 Eligibility for prophylaxis is determined based on the severity and frequency of migraines and, by virtue of their very common migraines, individuals with a diagnosis of chronic migraine are eligible for, and should receive, prophylactic therapy.4 Some would advocate that prophylaxis should be considered when migraine is experienced > 3 times a month. However, Dr Ng urges caution.

“In Australia, the use of codeine either alone or in compound analgesic preparations is one of the commonest causes of medication overuse headache, and it is not advocated for the prophylaxis of migraine,” Dr Ng said.

Pharmacotherapy
A range of medications have an established role in prophylactic therapy. However, evidence of their effectiveness relates mainly to use in episodic, rather than chronic migraine prophylaxis.3 Many pharmacotherapies used in the treatment of episodic migraine have either not been studied, or have produced inconclusive results in trials for the prophylaxis of chronic migraine. The aetiology of episodic and chronic migraine is thought to differ. Whereas acute pain is thought to have a protective function, chronic pain is not thought to exert such protection and instead leads to neuroplastic tissue changes which have an overall detrimental effect on health. Chronic migraine is also more refractory to treatment, including migraine-specific triptan therapy.9

The best evidence for prophylaxis of chronic migraine is for the anticonvulsant topiramate, which has been reported to significantly reduce headache days compared to placebo. However, studies of topiramate have not determined whether or not the reduction in headache days also reduces the need for acute medication use.3,10 Other medications which have been shown to reduce the frequency of headache amongst chronic migraine sufferers include gabapentin, tizanidine, sodium valproate,8 and botulinum toxin A (BTX-A).11 While prophylactic gabapentin has been demonstrated to be effective in reducing headache-associated disability,8 and prophylactic BTX-A in improving health-related quality of life in this group of patients,12 neither of these medications has been shown to significantly reduce the need for acute medication use in chronic migraine.8,11


BTX-A
Botulinum toxin A (Botox) was recently approved for the chronic migraine prophylaxis indication in the US, UK9 and Australia,13 making it the first treatment specifically approved for migraine prophylaxis.9 BTX-A works by inhibiting neurotransmission via prevention of acetylcholine release. The result is paralysis of the targeted muscles and inhibited release of pro-inflammatory factors, including those which innervate the skin and muscles, as well as those involved in central sensitisation and pain.9

However, similar to other therapies, not all patients respond to BTX-A. Muscle tenderness and allodynia seem to predict response to BTX-A, and clinical examination of patients may involve neck and shoulder palpation to identify trigger points which can be targeted with BTX-A therapy. Another possible approach is targeting the trigeminal nerve to inhibit innervation of the entire head and neck, although the efficacy of this approach has not been established.9  A recent multicentre randomised placebo-controlled study (PREEMPT) utilising more than 1,300 patients demonstrated that BTX-A can be effective for treating chronic migraine, primarily in reducing the number of headache days.11 This study utilised injection of 155 U of Botox into 31 different sites on the head and neck at 3 monthly intervals for 5 cycles (3 blinded, 2 open label with crossover), measuring headache days as the primary endpoint, and several other common secondary endpoints. Improvements were noted, albeit modestly in the primary outcome (8.8 vs 6.6 headache days per month), but also significantly in 6 of 7 other secondary outcome measures. This accords the author’s experience of patients who often report not only less diarised headache days, but also reduced headache length, severity, and improved general well-being.11


Non-pharmacological treatment
A range of non-pharmacological treatments are also used for chronic migraine including cognitive behavioural therapy (CBT), biofeedback and other bio-behavioural strategies (e.g. relaxation, stress management), physical therapy, health and lifestyle education and modification (e.g. avoiding migraine triggers14) and information and education about the condition.4 It is important to educate all patients about the incurable nature of the disease and that treatment aims to reduce its impact rather than provide a cure.15 Nevertheless, our understanding of its natural history may give patients some comfort that the condition may lessen in severity with age and certain scenarios (e.g. pregnancy).


Occipital nerve stimulation
An emerging non-pharmacologic option, occipital nerve stimulation, while still under-development, has demonstrated feasibility for the treatment of refractory chronic migraine and is a promising treatment option for this group of patients. The treatment involves implantation of a pulse generator in the subcutaneous tissue at the level of the first cervical vertebra (C1).6

A recent study reported that 39% individuals fitted with a self-programmed stimulator device experience a ≥ 50% reduction in headache pain, compared to only 6% of those with a pre-programmed stimulator device and 0% of those who continued with medication-only management of refractory chronic migraine. The response rate amongst the treatment group was similar to that recorded with popular chronic migraine pharmacotherapies. The difference in response rates between treatment and control groups was statistically significant. The self-stimulation group also experienced associated improvements in functional ability, mood, treatment satisfaction, pain severity and medication use, although these differences did not reach statistical significance.6

While occipital nerve stimulation via an implanted device appears effective and feasible, it is associated with a relatively high rate of adverse events. For example, in a feasibility study 56 adverse events were reported from 51 individuals using the device. Three serious events in which the treated patients required hospitalisation were reported while 9% of the treatment group also experienced worsening migraines. While further development is required to optimise the safety and efficacy of this therapy, occipital nerve stimulation may provide an important alternative for patients with intractable chronic migraine, and further research to develop the treatment is warranted.6

 

Abortive treatment

While prophylaxis may reduce the frequency of headaches, chronic migraineurs continue to experience acute episodes of migraine which require abortive therapy. The majority (70%) of individuals who experience chronic migraine use pharmacotherapy to treat acute attacks.16 Early intervention with pharmacotherapy has been shown to reduce headache frequency and is thus associated with reduced medication use in the long term. However, there remains considerable debate regarding which medicine to choose, and at what point in a headache episode medications should be administered (e.g. before or after the onset of severe pain) to reduce the likelihood of medication overuse occurring.17

A broader range of pharmacotherapies are available for the treatment of acute migraine attacks in comparison to migraine prohpylaxis,5 including analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, triptans, ergotamines,3 and anti-emetic dopamine agonists.5 A typical approach to within-attack treatment is to “step up”, beginning with simple analgesics and, when these are ineffective, combining other non-specific painkillers (e.g. NSAIDs) or migraine-specific pain relievers (e.g. triptans).4


Self-administered abortive treatment
Oral medications may be prescribed for patient administration at the onset of, or during, an acute attack; however, these are more effective when taken early in the course of an acute episode. Bear in mind that the pylorus closes during acute migraine episodes, limiting the absorption and effects of orally administered medication. As such, non-oral administration (e.g. anal suppository), or sublingual transmucosal delivery systems may be required.14

The patient’s previous experience with migraine medication should be considered when determining the best agent, as many patients will be familiar with which medications are and are not effective. Simple analgesics are recommended for treatment early in an acute episode. If these are ineffective for the patient, more potent pain relief medication should be prescribed.18

Oral opioids should be avoided, or only used rarely.14 Ergotamines have been used in the treatment of acute migraine for over a century; however, in recent decades, triptans, which have greater specificity for serotonin receptors, have largely replaced them. Triptans are agonists of serotonin 1B/1D receptors.5 The therapy is migraine-specific and effective in most patients when administered early in the course of acute migraine, as monotherapy or in combination with simple analgesics.15 The medication  is relatively costly, and there is some concern that, like compound analgesics (containing codeine in Australia in particular), triptans may play a role in some cases of medication overuse headache.


Abortive therapy in the emergency setting
When experiencing a particularly acute episode of migraine, chronic migraineurs may present for emergency treatment. In emergency settings, opioids are most commonly used as abortive migraine therapy, although they are less effective than other options and are associated with a high rate of adverse events. While they should not be withheld on principle, they are generally not recommended for first-line treatment.5

The use of triptans in emergency therapy is limited by the lack of injectable forms (sumatriptan is the only triptan available for injection). However, where subcutaneous administration is possible, it provides rapid (often within 5–7 minutes) and complete migraine relief and enables patients to return to daily activities promptly. The best option for acute relief appears to be a single 6 mg dose of subcutaneous sumatriptan.5 There are other types of triptans available on the market in Australia, including sublingual wafers (rizatriptan).

Dihydroergotamine (0.5–1 mg slow intravenous infusion) may be useful for acute migraine treatment in the emergency setting, particularly for patients with a history of headache recurrence, which is common with sumatriptan and less likely with dihydroergotamine. Concomitant prescription of an anti-emetic is recommended. Anti-emetic dopamine agonists are a further option and amongst them a 2.5 mg droperidol had the best demonstrated efficacy and safety. Headache relief rates of 100% 2 hours after dosing have been reported. Metoclopramide is an appropriate choice for acute migraine treatment in pregnant women.5

Conclusion

Migraine treatment options are increasing, and new therapies like BTX-A and occipital nerve stimulation are likely to provide further alternatives in the near future. While effective treatments exist, the challenge of matching the right treatment to individual patients and instituting therapy at the right time remains. Developing individualised management plans which consider not only the acute symptoms but also the ongoing functional impairments chronic migraine causes is the best strategy. According to Dr Ng, allowing patient response to guide therapy is the most effective approach.

“The trick is to find what works for a patient, being guided by their profile as to the therapy order of selection,” said Dr Ng.

While simple analgesics and migraine-specific pain relievers are effective for many patients, not all satisfactorily respond to these medications. These patients are particularly likely to benefit from the further development of emerging treatment, including BTX-A and occipital nerve stimulation.

 

Headache picture

For more information about headache syndromes, including how they can be differentiated and treated, see Headache.

 

 

Article kindly reviewed by:
Dr Karl Ng MB BS (Hons I) FRCP FRACP CCT Clinical Neurophysiology (UK)
Consultant Neurologist and licensed botulinum toxin administrator, Sydney North Neurology and Neurophysiology (download referral form and map)
Conjoint Senior Lecturer, University of Sydney; and Editorial Advisory Board Member of the Virtual Neuro Centre.

References

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  2. Olesen J, Bousser MG, Diener HC, et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia. 2006; 26(6): 742-6. [Abstract]
  3. Silberstein SD, Lipton RB, Dodick DW, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007; 47(2): 170-80. [Abstract | Full text]
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  13. Product Information: Botox. Gordon, NSW: Allergan Australia Pty Ltd; 24 March 2011.
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Posted On: 8 June, 2012
Modified On: 19 March, 2014

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