1. “My migraine always comes back” Presented by: Julio Pascual Neuroscience Area, Service of Neurology, University Hospital Central de Asturias and Ineuropa, Oviedo, Asturias, Spain CLINICAL CASE

2. IDENTIFICATION This 34-year old otherwise healthy woman presented with a long history of headache attacks that lasted 2 days and were difficult to treat

3. PAST CLINICAL HISTORY AND FAMILY HISTORY No personal antecedents 18-year history of headache attacks Frequency: two episodes/month One of the episodes usually prior to menstruation Hemicranial (both sides) pulsating headaches Pain develops in 2 h and she has to go to bed during its peak Accompanying symptoms: nausea, phonophobia and photophobia No aura symptoms Family history: mother with migraine attacks until menopause

4. DIAGNOSTIC PROCEDURES General clinical and neurological examinations were unremarkable Routine laboratory determinations without abnormal findings MRI, performed due to her headaches 4 years earlier, was within normal limits

5. DIAGNOSIS Migraine without aura

6. PAST TREATMENT (I) The main reason for consulting us was difficulty in managing her migraine attacks: –Simple analgesics: no improvement –Ergot drugs: increase in nausea and vomiting –NSAIDs (e.g. naproxen, ibuporfen): moderate and inconsistent improvement

7. PAST TREATMENT (II) Treatment with triptans after 4 years: Sumatriptan, zolmitriptan and rizatriptan relieved pain and nausea by 3 hours Moderate-severe pain recurred within 15-20 hours Pain also recurred with both sumatriptan and zolmitriptan intranasal formulations Recurrence usually responded well to triptans

8. TREATMENT Theoretical options: Initiating preventative treatment –Frequency of attacks is lower Combining a NSAID and a triptan –Good option in terms of efficacy and decrease in recurrence rate, but increased risk of overuse and adverse events Long-acting triptan: –A long-duration triptan would be able to reduce recurrence Oral frovatriptan, 2.5 mg, at the beginning of her migraine attacks was recommended

9. FOLLOW-UP VISIT Assessment after 3 months: –7 migraine attacks treated with frovatriptan –No subjective adverse events –Pain-free always by 2 h –Recurrence on just one occasion, after 28 h and with mild pain, which responded well to a second dose of frovatriptan –She was told to continue taking frovatriptan for future attacks

10. COMMENTS (I) Abortive treatment is mandatory for migraine attacks as they are invalidating Drugs not recommended: –Simple analgesics: low efficacy –Combination analgesics and opioids: rebound headache –Ergot drugs: rebound headache and adverse events NSAIDs could be useful for mild-moderate attacks Triptans should be the standard therapy of choice for moderate-severe attacks or for those attacks which do not respond to NSAIDs Evers S, et al. Eur J Neurol 2009;16:968-81; Tfelt-Hansen P, et al. Brain 2000;123:9-18.

11. Figure 1: AN ALGORITHM FOR THE TREATMENT OF MIGRAINE Evers S, Lisotto C. World Congress of Neurology, Vienna, Austria, 2013.

12. COMMENTS (II) Triptans In contrast to ergot drugs, they are selective for 5- HT1B/1D receptors All 7 available triptans share the same mechanism of action and almost identical pharmacodynamics However, their quite different pharmacokinetic profiles and metabolism make each of them preferable or not, depending on the characteristics of the attack/patient to be treated

13. COMMENTS (III) Frovatriptan Frovatriptan is a potent 5-HT1B/1D agonist Frovatriptan response rates are comparable to those of the standard triptans and this triptan is very well tolerated 1,2 Frovatriptan has the longest half-life among triptans 1,3 (Fig. 2), which translates in a remarkably low recurrence rate (17% in phase III trials) 2 1. Sanford M. CNS Drugs 2012; 26: 791-811, 2. Cortelli P, et al. Neurol Sci 2011; 32 (Suppl 1): S95-98; 3. Tfelt-Hansen P, et al. Drugs 2000;60(6):1259-87.

14. Figure 2: HALF-LIFE OF THE DIFFERENT TRIPTANS Hours Tfelt-Hansen P, et al. Drugs 2000;60(6):1259-87.

15. COMMENTS (IV) Frovatriptan and recurrence Pain recurrence within a migraine attack (<3 days) is interpreted by the patients as a treatment failure and requires further symptomatic treatment This is costly and can contribute to overuse and migraine chronification Therefore, frovatriptan is a triptan of choice for the acute treatment of prolonged migraine attacks at risk of relapse Lisotto C, et al. J Headache Pain 2013;14:96.