Use of medications for migraine in Aotearoa New Zealand

Despite being a common and disabling condition, with a global prevalence of 14%, migraine disease is often inappropriately or under-treated.¹ This is due to a combination of low consultation rates for headache (for reasons including cost, system barriers or not prioritising getting help for headache),² failure among health professionals to accurately diagnose migraine and poor delivery of evidence-based migraine treatment.^3–5

There are two elements to migraine treatment: management of acute attacks and instigation of a preventive medication. Appropriate management of migraine attacks is important not only to ameliorate the pain and disability of the attack but also because inadequate treatment may contribute to the development of chronic migraine (headache on 15 days or more a month for at least 3 months).⁶

Over-the-counter medication such as non-steroidal anti-inflammatory drugs (NSAIDs) and prescription-only triptans are first-line treatments for migraine attacks. Triptans were developed in the 1990s specifically to treat migraine and are recommended for moderate to severe headache or when NSAIDs are ineffective.¹ Of the seven triptans used globally, two (sumatriptan and rizatriptan) are currently available in Aotearoa New Zealand. International surveys report that only between 6–23% of people with migraine are currently using a triptan,^3,7 and although this is higher in people with chronic migraine,⁸ it suggests that under-utilisation of triptans is widespread.³ However, NSAIDs and triptans do not work or are not suitable for all people with migraine.⁹ NSAIDs have gastrointestinal and cardiovascular side effects and triptans may be contraindicated in as many as a fifth of people.^9,10

Opioids (e.g., codeine, tramadol, oxycodone) are not recommended for migraine attacks because they are not as effective as first-line options, have significant side effects, a risk of addiction and are associated with an increased risk of chronic migraine and medication overuse headache (MOH).¹¹ MOH is a chronic secondary headache that develops in people with migraine (or another primary headache disorder) who have headache for 15 days or more a month and have used (for at least 3 months):

• Simple analgesics on ≥15 days a month (including paracetamol, NSAIDs, combination analgesics and caffeine).
• Opioids or triptans on ≥10 days a month.¹²

Hence, inappropriate management of migraine attacks includes not only under-use of migraine-specific triptans where indicated, but over-use of triptans and analgesics, and any use of opioids.⁹

The second element of migraine management, prevention, is recommended for those with frequent and/or disabling headache. The goals of preventive treatment are to reduce frequency and severity of attacks, reduce disability, improve response to acute treatments and prevent or treat MOH.¹³ However, preventive medications for migraine are often under-used.⁴ For example, a large United States (US) study of people with migraine calculated that 40% were eligible for preventive treatment but only 17% were currently using it.³ This is often due to the poor tolerability/adverse effects and relatively poor efficacy of these medications.^9,14,15

Despite affecting an estimated 642,000 people in Aotearoa New Zealand and causing significant impacts on work, life and physical and mental health,¹⁶ there are no published data on acute or preventive medication use in people with migraine in Aotearoa New Zealand, nor any published data on whether migraine management in Aotearoa New Zealand adheres to evidence-based recommendations. We undertook a survey of people with migraine to explore:

• Current and previous use of acute and preventive migraine medications.
• Under-use and misuse of medications, including risk of acute medication overuse.
• Need for new types of migraine medication, specifically the monoclonal antibodies developed to treat migraine by targeting calcitonin gene-related peptide (CGRP).

Methods

The online Migraine in Aotearoa New Zealand Survey ran from 22 August to 7 October 2022, via SurveyMonkey. Recruitment was through website and/or social media platforms of Migraine Foundation Aotearoa New Zealand (MFANZ), Healthify, Neurological Foundation and New Zealand Pain Society, via media articles and through personal networks of MFANZ co-founders.

The survey was piloted by six individuals, five with migraine disease. Responses were anonymous and informed consent was assumed by initiation of the survey (information about the survey was provided on the landing page). Ethical approval was granted by the University of Otago Human Ethics Committee (D23/156).

Respondents were asked about acute medications taken for migraine: paracetamol, NSAIDs, triptans, opioids, anti-emetics and caffeine, with response options of currently use, previously used—stopped because of side effects, previously used—stopped because it didn’t work, previously used—stopped for another reason, never used—would like to try, never used—don’t want to try. Respondents were asked on how many days in the last month they had used paracetamol, NSAIDs, triptans or opioids and were classified as at risk of medication over-use if used 15 days or more a month (for paracetamol and NSAIDs) or 10 days or more a month (for opioids and triptans).

Respondents were also asked about use of prescribed preventive medications (same response options as above) that are listed in international guidelines on migraine treatment, including melatonin (which is often a prescription medication) and onabotulinumtoxinA (Botox^TM) injections. We derived the number of oral preventive medications currently or previously used through a count of all listed medications, excluding Botox^TM and CGRP monoclonal antibody injections.

We determined that respondents were “eligible” for preventive treatment if they had:

• Eight or more headache days a month, and/or
• Moderate to severe disability, as measured by the Migraine Disability Assessment Scale (MIDAS), which measures the impact of migraine on daily life through questions about limitations on work/study, household work, social/family life in the last 3 months, with a score of 21 or more indicating severe disability.¹⁷

We also asked whether a GP or neurologist had been seen about migraine, with response options including seen in the last 12 months.

The survey included an open-ended question about the new CGRP monoclonal antibody medications, noting that only erenumab and galcanezumab were available in Aotearoa New Zealand. Respondents were asked about their experience with these and why they would or would not try one in the future. More details about other questions in the survey are published elsewhere¹⁶ and a copy of the questionnaire is available in the Appendix.

The final dataset included 530 respondents, after removal of duplicates (n=4) and responses completing <6% of survey questions (n=33). Only people with a positive ID-Migraine test^TM (n=513), which has a sensitivity of 84% and specificity of 76%,¹⁸ or a migraine diagnosis from a health professional (n=17) were included.

As the survey was a convenience, self-selected sample, only descriptive and unweighted statistics were calculated, using Microsoft Excel version 2403. Missing data were excluded from analyses; respondents were able to skip individual questions, so response rates for each question varied. The qualitative data from the open-ended question were coded for themes relating to reasons for or against trying the new medication. Three main themes around barriers to uptake of these medications were identified. Quotes to illustrate the themes include the gender, age group and ethnicity of the respondent.

Results

The survey sample was predominantly female (82%) and NZ European (77%) (Table 1). Over a fifth (22%) had chronic migraine, who were more likely to report severe migraine disability and poor self-rated health than those with episodic migraine.

View Table 1–2, Figure 1.

Acute medications

Use of acute medications for migraine is detailed in Table 2. Most people had used NSAIDs or paracetamol and around half or more currently used NSAIDs, caffeine, triptans and paracetamol. Almost half had stopped using paracetamol because it did not work. Fifty-five percent were currently using one or both of the triptans, 23% had never used either of the triptans and 22% had previously used one or both of the triptans but had stopped for some reason. For each individual triptan, the most common reason for stopping was that they did not work.

Over a quarter of respondents were currently using opioids and only a third had never used them for migraine attacks (9% said they would like to try opioids). Of the 139 survey respondents who were currently using opioids for migraine, 36 had previously used a triptan but stopped, 30 had never used a triptan and the remainder were concurrently using a triptan.

Risk of medication over-use

Overall, 27% of survey respondents had over-used at least one acute medication in the last month (i.e., paracetamol or NSAIDs on 15 days or more, triptan or opioids on 10 days or more). This was higher in people with chronic migraine (70%) than episodic migraine (15%). By medication type, triptans were most commonly over-used, with 30% of those currently using triptans taking more than the recommended amount in the last month (Figure 1). Nearly one fifth of those currently using opioids were taking more than recommended. All the rates of over-use were much higher in those with chronic migraine than episodic migraine.

Preventive medications

A total of 496 respondents answered questions on migraine preventive medication. Half of these respondents (n=249) were currently taking at least one preventive. The most commonly used class of preventive was antidepressants, currently taken by 28% of survey respondents (36% previously used). Antihypertensives, including beta-blockers, were the next most commonly used medication, currently taken by 17% of respondents (25% previously used). Only 8% of survey respondents were currently taking an antiepileptic for migraine prevention but 30% had previously taken one.

The most common currently used medications were amitriptyline, nortriptyline, melatonin, venlafaxine, propranolol and topiramate, each taken by 5% or more of respondents (Table 2). For all medications, a much higher proportion of respondents had previously tried and stopped the medication, because of lack of efficacy, side effects or another reason, than were currently using it. Side effects were most notable for amitriptyline, topiramate, fluoxetine, propranolol, nadolol, pizotifen and sodium valproate, where those who stopped due to side effects were nearly or more than double the proportion of those currently using them.

Current preventive medication use was higher in people with chronic migraine (72%) than episodic migraine (44%). Only 5% of those with chronic migraine had not previously used any preventives compared with 30% of those with episodic migraine. People with chronic migraine had previously used an average of four oral preventive medications. Of those who had previously used any preventives, 12% had tried seven or more.

Under-use of preventives

Nearly three quarters (74%, n=393) of all survey respondents were “eligible” for preventive medication, according to our stringent criteria of 8 headache days or more a month and/or presence of moderate–severe migraine disability. Of these, 369 respondents provided information about preventive medication use. Only 57% of people “eligible” for preventive treatment were currently taking it, while nearly two thirds (64%) of those not currently taking a preventive were “eligible” for one. Over a quarter (28%) of people with chronic migraine were not receiving preventive treatment.

Consultation with a health professional provides an opportunity for preventive treatment to be reviewed and instigated. In those who were “eligible” for preventive treatment, a higher proportion of people currently taking a preventive (compared with those not taking a preventive) had seen a neurologist (28% compared with 11%) and a GP (89% compared with 71%) about migraine in the last 12 months.

New treatments

There were 435 responses to the open-ended question about CGRP monoclonal antibodies. Many respondents reported that their migraine attacks were so severe or poorly controlled they “would try anything” to reduce the impact of migraine attacks on their lives. The new medications represented hope for those who had found little relief from other preventives or had experienced intolerable side effects.

“I would love to try Emgality [galcanezumab]. I get horrible side effects from the propranolol ... I have awful exercise tolerance due to my low blood pressure and everyday activities can be difficult. I have not reacted well or had benefit from other prevention medications so am stuck with this.” – 18–24 years, Female, Māori

Respondents identified three main barriers to use of the new medications. The prohibitive cost (up to NZ$325 a month for Emgality), uncertainty about effectiveness and side effects, and lack of awareness of their existence, in both patients and doctors.

All three of these barriers may need to be addressed for new medications to be accessible:

“I … would try one in the future if I knew enough about it, if it was publicly funded and my doctor discussed it with me.” – 25–34 years, Female, Asian

Discussion

This survey of people with migraine in Aotearoa New Zealand reveals several areas where best practice in migraine prescribing was not being followed. For management of acute attacks, opioids were being inappropriately used in over a quarter of respondents. A similar proportion were at risk of MOH, through over-use of one or more acute treatments. Nearly a quarter had never used a triptan, which suggests a level of under-use, but may also include those with contraindications for triptan use. Over two fifths (43%) of those assessed as “eligible” for preventive medication were not currently taking a preventive, including 28% of those with chronic migraine, all of whom would benefit from effective preventive treatment.

Among people diagnosed with migraine, US research suggests that appropriate treatment is received by only 54–60%¹⁹ and many general practitioners (GPs) are not aware of or adhere to best practice on managing migraine.^20,21 For example, a survey of GPs in the US found that only 28% were familiar with the American Academy of Neurology guidelines on preventive treatment, only a third knew that opioids can cause MOH and few recommended non-pharmacological treatments, despite these being included in evidence-based guidelines.²⁰ The knowledge of GPs in managing migraine in Aotearoa New Zealand is unknown and deserves additional research to establish the role of prescribers in contributing to MOH and under-use of preventive medications. Ineffective migraine treatment increases the risk of developing chronic migraine and increases healthcare utilisation and costs.^6,22,23 A stronger emphasis on the importance of avoiding opioids in the treatment of migraine is needed in Aotearoa New Zealand, for both health professionals, especially prescribers, and patients.

The prevalence of MOH in Aotearoa New Zealand is unknown. Estimates from international studies range from 0.5–2.6%,²⁴ with most cases associated with migraine.²⁵ As many as a third of people with episodic migraine and three quarters of people with chronic migraine may be at risk of MOH,¹⁹ which is consistent with our survey results that 15% of those with episodic and 70% of those with chronic migraine had over-used medication in the last month. MOH is avoidable with appropriate migraine management and is also treatable with effective preventive medications.²⁶ Knowledge about MOH among the public, people with migraine and health professionals is often low,^24,25 including awareness of the risk of a person with migraine developing MOH if taking regular analgesics for another condition (e.g., back pain). Education of patients about MOH can reduce medication over-use and prevent MOH.²⁴

The high use of opioids and high rates of acute medication over-use in survey respondents also highlights the need for more options to treat migraine attacks that are safe and effective. Insufficient response to triptans can occur in around 30% of people with migraine,⁹ which could contribute to increased use of opioids as an alternative. In cases of initial triptan non-response, trying two or more different triptans is recommended.⁹ However, only two of the seven triptans on the market are available in Aotearoa New Zealand and only one is in a formulation that bypasses the stomach, which is beneficial for people with severe nausea or vomiting during a migraine attack. New, alternative treatments are available overseas (but not in Aotearoa New Zealand), including the ditan lasmiditan, which has a similar action to triptans but without the side effect of vasoconstriction, and has demonstrated efficacy for those in whom triptans are contraindicated or ineffective.²⁷ Gepants (such as rimegepant, ubrogepant and zavegepant) are small molecule CGRP receptor antagonists taken orally or as a nasal spray that have few side effects and do not appear to induce MOH, unlike triptans.⁹

The survey also highlighted issues with the use of migraine preventive medications. These were much more likely to have been used in the past, and stopped because they were ineffective or intolerable, than to be currently used. Most people who had used preventives had tried more than one—one respondent had tried 18 different medications. International research has found that among people with migraine who have ever used preventive medication, the average number used was four for people with chronic migraine and three for people with episodic migraine,¹⁵ which was the same as in our survey. Close to half of respondents were not taking preventive medication despite frequent and disabling headaches. Many of those who were on preventive medication still had a high headache frequency, indicating that these medications were not working well. Adherence to migraine preventives has been shown to be low in many countries,¹⁴ with one study finding that only 17–20% of people continued with a preventive at 12 months.²⁸

New and more effective medications to prevent migraine attacks, that have fewer side effects, are needed to reduce migraine disability and chronification. Of the new migraine medications that target CGRP and can be used for prevention (the monoclonal antibodies and several gepants), only two monoclonal antibodies are currently available in Aotearoa New Zealand and neither are yet funded. In a recent systematic review, the CGRP medications outclassed other drugs used for migraine prevention in both safety and efficacy.²⁹ Early and effective preventive treatment has the potential to not only improve quality of life for people with migraine but also reduce healthcare and other costs and improve work and other functioning.³⁰ However, these new drugs do not work for all people with migraine, and more research into the underlying pathophysiological causes of migraine and development of additional targeted treatments is still needed.

At the time of this survey, respondents identified cost, lack of awareness about the existence of the medication and uncertainty around effectiveness and side effects as barriers to use. The latter two issues should resolve as awareness spreads across health professionals and people with migraine, but cost remains a considerable obstacle, particularly for those who are unable to work. In December 2023, three CGRP medications (galcanezumab, erenumab and atogepant) were recommended for funding at a high priority by Pharmac’s Neurological Advisory Committee, and in June 2023, these were added to Pharmac’s Options for Investment list.

Strengths and limitations

This was the first survey of people with migraine undertaken in Aotearoa New Zealand and provides a snapshot of medication use in this sample. However, it was a non-representative survey, delivered online, and cannot be used to estimate prevalences at a population level. Responses from Māori and Pacific peoples were low, and more research is needed to explore potential ethnic inequities in migraine management.

We asked about medication use in the last month to minimise error from recall bias and reduce respondent burden from multiple questions. Since the diagnosis of MOH requires 3 months of medication over-use, our results only identify people at risk of MOH and will likely over-estimate the true risk. We provided names of commonly used medications but recall of previous medications may have led to an under-count of these.

Our estimate of eligibility for preventive medication was based on headache frequency and migraine disability, but is a conservative estimate because prevention is often appropriate for people with fewer than 8 headache days a month (e.g., if disability is high, if acute medications are ineffective or not well tolerated, or for specific types of migraine). Hence, our results will under-estimate the true number of “eligible” people and the proportion of those who are “eligible” but not using preventive medication.

Many non-prescription and non-medication approaches to migraine management (e.g., supplements, biofeedback, neurostimulation, acupuncture, lifestyle changes) are recommended for use, often in conjunction with medication.⁹ These were not included in this analysis but merit further research.

Conclusions

Many people with migraine in Aotearoa New Zealand are not receiving best practice prescribing of acute and preventive migraine medications. More awareness is needed among health professionals and patients about the risk of MOH with acute treatments, especially opioids and triptans. There is a clear need for more effective acute and preventive medications, with fewer side effects. The lack of availability and affordability of new migraine-specific medications in Aotearoa New Zealand means that people with migraine in Aotearoa New Zealand are likely to experience higher migraine disability and lower quality of life than those in countries with a broader range of treatment options.

View Appendix.