Topamax added to the PBS for migraine prophylaxis

Migraine is a common, underdiagnosed and often inadequately treated condition, affecting approximately 6% of males and 18% of females.1 Most migraine sufferers use simple over-the-counter analgesics to manage acute attacks which is in accordance with current recommended guidelines.1 However, overmedication of acute migraine can lead to chronic migraine, hence the need for appropriate prophylactic agents. The "gold standard" drugs to prevent migraine are Topamax (topiramate), propranalol, amitriptyline, valproate and timolol.3 Topamax (a versatile anti-convulsant) will become available on the PBS by authority script from December 1st 2007.2

Migraine is a common and distressing disorder characterised by moderate to severe headaches (frequently unilateral and pulsating) and associated symptoms such as nausea, photophobia and phonophobia. Migraines are divided into classic and common migraines depending on the presence or absence of a preceding aura respectively. The pathophysiology of migraines is debated but they are thought to be partly caused by abnormal vasospasms of cranial vasculature. Common triggers for migraine attacks include chocolate, caffeine, menstruation, weather changes and sleep deprivation.

Recurrent migraines can be disabling and impair a patient’s overall quality of life. Absenteeism from work and impaired performance also cause financial and economic burdens.³ Therefore it is recommended that patients should be evaluated for prophylactic therapy following management of acute attacks.³ Preventative therapy is indicated in patients who experience two or more migraines, lasting three or more days per month, where acute treatments are contraindicated, ineffective or cause side effects.³ Evidence has accumulated demonstrating the safety and efficacy of a number of agents including propranolol, timolol, amitriptyline, divalproex, sodium valproate, and topiramate as first-line agents for migraine prevention.³

A study by Stark et al. as part of the BEACH (Bettering the Evaluation and Care of Health) program found that approximately three quarters of patients who would benefit from prophylaxis were not receiving appropriate treatment.¹ Furthermore, general practitioners (GPs) were also noted to use only a limited range of prophylactic agents. Pizotifen and propranolol were the most common first line agents but very few patients were trialled on other agents such as anti-convulsants if these treatments failed.¹ This may reflect a lack of familiarity with alternatives (despite supporting research and guidelines) or lack of confidence in using these drugs.¹ Further concern highlighted by the study was that approximately 9% of patients used acute agents (analgesics, triptans and ergotamines) inappropriately as prophylactics. This contributed to medication-overuse headaches and transformation to chronic migraines in such patients.¹

A separate study by Modi and Lowder found that preventive therapy can reduce the frequency of migraines by 50% or more, but is used by fewer than half of people with migraine. As first-line preventive agents the authors recommend topiramate, propranolol, timolol, amitryptiline and sodium valproate.³

Results of these studies have urged efforts to make migraine prophylactic agents more available to Australians. Although many drugs have been regarded as first or second line agents for prophylaxis, several had not yet been TGA approved or PBS listed for migraine prophylaxis in Australia.¹ These factors may have deterred GPs from prescribing these medications to avoid increased out-of-pocket expenses for patients.^1,5

In March this year, the Pharmaceutical Benefits Advisory Committee’s (PBAC) recommended the listing of topiramate (Topamax) on the PBS for migraine prophylaxis.⁴ This decision is a welcomed development in the overall management of migraines. As you are aware, topiramate is a versatile anti-epileptic agent that has been available on the PBS for seizure treatment since 1997. Topiramate is an appropriate monotherapy for partial epilepsies and as an add-on therapy for primary generalised tonic-clonic seizures or drop attacks associated with Lennox-Gastaut syndrome.² More recently several open-label and controlled studies have found that that topiramate is effective in migraine prophylaxis, and it is considered a first-line agent for this use.³

Despite rejecting the submission in July 2006 for ‘uncertain benefits’ and ‘uncertain cost-effectiveness,’ the PBAC has now recommended that topiramate tablets, 25 mg and 50 mg (maximum quantity 60, with provision of 5 repeats) are available as an authority script for "Prophylaxis of migraine in a patient who has experienced an average of three or more migraines per month over a period of at least six months, and who:⁴

1. has a contraindication to beta-blockers, as described in the relevant TGA-approved Product Information; OR
2. has experienced intolerance of a severity necessitating permanent withdrawal during treatment with a beta-blocker; AND
3. is overweight (as defined by body mass index of >30 kg/m²); OR
4. has experienced intolerance of a severity necessitating permanent withdrawal during treatment with pizotifen.

The recommendations will come into effect on December 1st, 2007 when topiramate receives its official authority listing.

This addition to the PBS is exciting news for the 11% of Australians who currently suffer from migraines.¹ Not only will patients be able to access a safe, effective and versatile drug at a subsidised price but hopefully the listing will encourage GPs to prescribe migraine prophylactic agents more effectively. GPs now have access to a wider choice of prophylactic agents and can target therapy more effectively to their individual patients. Furthermore, it is hoped that future clinical practice and prescribing will more adequately reflect clinical guidelines and research findings.  

References:

1. Stark R, Valenti L, Miller G. Management of migraine in Australian general practice. MJA 2007; 187(3): 142-6.
2. MIMS online – Prescribing Information, Topamax (Topiramte), MIMS Australia Pty Ltd 2003.
3. Modie M, Lowder D. Medications for migraine prophylaxis. American Family Physician. 2006; 73: 72-8, 79-80.
4. PBAC – Public Summary Document, PBAC Meeting, 2007.
5. Prosser H, Almond S, Walley T. Influences on GPs’ decision to prescribe new drugs – the importance of who says what. Fam Pract 2003; 20: 61-8.