CLINICAL CASE

Presented by:

Carlo Lisotto 

Headache Centre

Department of Neurosciences

University of Padua, Italy

Woman with long-lasting migraines

and high rates of relapse

IDENTIFICATION

• 39-year old woman with episodic migraine without aura and infrequent migraine with aura

• She took several NSAIDs, without any benefit

PAST CLINICAL HISTORY AND FAMILY HISTORY

• She suffered from headaches since her late teens• The headaches gradually increased in duration and intensity and

currently occur 2-3 times a month, last 3 to 4 days, and are extremely severe

• The headaches reach peak intensity on average within 2-3 hours• Premonitory symptoms consist in fatigue, yawning, stiff neck,

concentration problems and irritability• The headaches are frequently associated with pallor, nausea,

phonophobia, photophobia, osmophobia and, sporadically, with vomiting

• Mental strain, anxiety, lack of sleep, missing meals, exertion and changes in weather make the headaches worse

• She reports 5 episodes of visual aura• Her grandmother had migraine, which resolved a few years after her

menopause

DIAGNOSTIC PROCEDURES

• Physical and neurological examinations with fundoscopy showed no abnormalities

• BP 120/80 mmHg • Pericranial muscles were slightly stiff and tender, and their

tenderness was increased by digital pressure • No sign of temporomandibular dysfunction (TMD)• MRI with angiography of the brain showed small foci of

hyperintensity in the deep white matter of both hemispheres; these abnormalities were considered non-specific and clinically unremarkable (Fig.1)

• Tests for disorders of coagulation were normal• MIDAS score of 22 indicates severe disability

Figure 1: THE PATIENT’S BRAIN MRI

DIAGNOSIS

• Migraine without aura + migraine with aura

PAST TREATMENT

• The patient had been treated unsuccessfully with NSAIDs and then given oral rizatriptan 10 mg with remarkable benefit

• Rizatriptan was selected because of its rapid onset of action, taking into consideration that the patient’s attacks reach peak intensity within 2-3 hours on average

• Rizatriptan 10 mg acted quickly in relieving the head pain and associated symptoms, thus rapidly restoring the patient’s functions

• She was almost constantly pain-free within 2 hours, but unfortunately the pain tended to recur, usually 6 hours after taking the first dose

TREATMENT

• In the light of the relapses, the patient was recommended treatment with frovatriptan 2.5 mg once per day. If migraine recurs after initial relief it may be taken a second dose at a 2-h interval and not within the same attack. The total daily dose should not exceed 5 mg per day

FOLLOW-UP VISIT

• Assessment after 6 months:- rizatriptan and frovatriptan were equally effective (pain

free 2 hrs after the first dose)- headache recurrence was much less frequent after

taking frovatriptan than after rizatriptan use- fewer frovatriptan doses were required to treat her

prolonged attacks

• Consequently, the patient preferred frovatriptan:- favourable sustained effect with a lower rate of relapse- prevents the worsening of migraine attacks and

reduces their severity

COMMENTS (I)

• White matter hyperintensities (brain MRI): - more prevalent in migraineurs than in the general

population (12-47% of all patients)- more frequent in female patients and in migraineurs

with aura- pathogenesis and clinical significance are still unclear

• Long-lasting untreated severe migraine attacks result in significant disability and compromised function in a substantial proportion of patients (Fig. 2)1

1. Lipton RB, et al. Neurology 2007;68:343-349.

Figure 2: MIGRAINE-ASSOCIATED DISABILITY

0

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Functionnormally

Severe impairmentor bed rest

Someimpairment

Lipton RB, et al. Neurology 2007;68:343-349.

COMMENTS (II)

Migraine attacks• Almost three quarters of women have headaches that last

over 24 hours, whereas only 50% of men have such long-lasting attacks 1

• The mean duration of women’s headaches was found to be 31 hours, while in men the mean duration was shorter, being 19 hours 2

• In clinical practice there is a huge inter-individual variability of migraine attacks in terms of severity, duration, associated symptoms and time to peak intensity

• Usually attacks with a gradual-onset are long-lasting and are frequently associated with headache relapse 3

1. Kelman L. Headache 2006;46:942-953; 2. Pryse-Phillips W, et al. Headache 2006;46:1480-1486;3. Lipton RB, et al. J Headache Pain 2004;5:123-130.

COMMENTS (III)

Triptans • Triptans with the shortest Tmax are believed to provide the

fastest speed of action 1

• Triptans with longer half-lives seem to provide the lowest rates of headache relapse, with there being a significant inverse correlation between half-life and recurrence rate (Fig. 3) 2

• In clinical trials, responses to frovatriptan and rizatriptan were consistently similar in terms of pain-free at 2 hours rates, but frovatriptan was associated with a significantly lower incidence of recurrence (Fig. 4) 3,4

1 Johnston MM, Rapoport AM. Drugs 2010;70:1505-1518; 2.Géraud G, et al. Headache 2003; 43:376-388; 3. Tfelt-Hansen P, et al. Cephalalgia 2012;32:6-38; 4. Savi L, et al. J Headache Pain 2011;12: 219-226.

Figure 3: INVERSE CORRELATION BETWEEN TRIPTANS HALF-LIVES AND RECURRENCE

RATE

Geraud G, Keywood C, Senard JM. Headache 2003; 43:376-388.

Rizatriptan

Sumatriptan

Zolmitriptan

Almotriptan

Eletriptan

Naratriptan

Frovatriptan

Inci

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%)

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Rizatriptan 40

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25

23

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1726

6

5

3.5

3

2.5

Figure 4: PERCENTAGE OF RELAPSES (IHS) IN THE ITT POPULATION (N=125)

Savi L, et al. J Headache Pain 2011;12: 219-226.

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COMMENTS (IV)

Recurrence and frovatriptan• Relapse is one of the two main reasons for patients’

dissatisfaction with migraine treatment, together with incomplete pain relief 1

• The pivotal importance of this attribute was clearly pointed out by 86% of patients in a survey by Lipton et al. 2

• Frovatriptan provided in this patient rapid efficacy comparable to that of rizatriptan

• Conversely, the relapse rate was significantly lower after taking frovatriptan and the patient expressed a clear preference for this triptan, based on this crucial effect

1. Malik SN, et al. Headache 2006;46:773-780.; 2. Lipton RB, et al. Headache 2002;42(Suppl 1):S3-S9.

COMMENTS (V)

In conclusion• Frovatriptan seems to be unique in the triptan class,

having the longest duration of action and the lowest recurrence rate

• Compared to the other triptans, frovatriptan offers the advantage of a lower risk of relapse and therefore a more sustained effect

• Frovatriptan represents a particularly favorable option for treating migraine attacks with a high rate of relapse