Early RX of MigrainesTiming is Everything

Do it, NOW.

Why treat early?

Allow me to demonstrate why.

If not now, then when? When it is too late?

Our function is to diagnose, treat promptly and minimize suffering.

Who amongst us would do otherwise?

My Clinical Experience

My patients are instructed to take their abortive triptans or ergots at the first sign of a migraine headache and within 20 minutes of the onset of the headache when it is mild. Otherwise when it becomes moderate or severe, allodynia sets in, the triptans and the ergots are not nearly as effective, they usually become incapacitated and will probably see another Neurologist.

MIGRAINE TREATMENT STRATEGIESTHE RATIONALE FOR EARLY INTERVENTION

PRESENTED BY THE NATIONAL HEADACHE FOUNDATIONFACULTY

Elizabeth W. Loder, MD, FACP Spaulding Rehabilitation Hospital 125 Nashua Street Boston, MA 02114. Steen B. Graff-Radford, DDS The Pain Center Cedars Sinai Medical Center 444 South San Vincenter Blvd Suite 1101 Los Angeles, CA 90048 Timothy R. Smith, MD, RPh 1585 Woodlake Drive Suite 200

Chesterfield, MO 63017

1- Successful treatments may be delayed, resulting in unnecessary suffering.2- Resources may be wasted on follow-up visits andfailed prescriptions.3- Patients and physicians may become discouragedand the patient may lapse from care.4- Overuse of medications may lead to chronic dailyheadache or rebound headache.

Summary and Conclusions

There is compelling evidence supporting intervention early in the pain phase of migraine with migraine-specific medications.

Pain-free response is significantly higher; furthermore, migraineurs who progress to the late headache phase often end up in hospital emergency departments or acute care centers.

These patients present a considerable cost burden. Over years of migraine attacks, early intervention may also ease the substantial burden of disability, with fewer missed days of school and work and fewer trips to emergency departments.

It may mean a patient performs better at work and isn’t exposed to barbiturate or opiate rescue medications.

During a single attack, early intervention can save hours of unnecessary pain. Overa lifetime, it can have a cumulative and very important benefit on a patient’s quality of life.

Frovatriptan

Two studies demonstrating the effectiveness of early treatment.

Randomized, Placebo-Controlled Comparison of Early Use of Frovatriptan in a Migraine Attack Versus Dosing After the Headache Has Become Moderate or Severe

Roger Cady; Arthur Elkind; Jerome Goldstein; Charlotte KeywoodAuthors and Disclosures

Posted: 10/21/2004; Curr Med Res Opin. 2004;20(9) © 2004 Librapharm Limited

• Main outcome measures: Freedom from pain at 2h for frovatriptan versus placebo as Dose 1; use of Dose 2 and/or rescue medication, pain severity, functional impairment and headache recurrence.

• Results: In 241 patients who each treated 2 migraine attacks, Dose 1 frovatriptan was more effective than placebo in terms of the proportion of patients who were pain free at 2h (28% vs 20%, p = 0.04). This benefit was sustained up to 4h post-dose (p = 0.003). Early use of frovatriptan significantly reduced re-medication (p < 0.001). Twenty-four-hour headache recurrence was low in both early (4%) and later use (6%) groups. Sustained pain-free response occurred in 40% of frovatriptan early use patients compared with 31% of later use patients (p < 0.05). Early use prevented headache progression: 69%-78% had mild/no headache 2-4h after Dose 1 frovatriptan compared with 54%-63% taking Dose 1 placebo (p < 0.001). Early use reduced pain burden and functional disability (p ≤ 0.001). More patients rated early use of frova triptan as excellent or good (57% vs 46%).

• Conclusions: Early use of frovatriptan resulted in a higher, earlier and sustained pain-free response, prevented progression to moderate/severe headache and reduced pain burden and functional disability.

• Waiting for the headache to become moderate or severe with sufficient associated symptoms to formally diagnose migraine may force patients to endure hours of unnecessary suffering. Furthermore, our study suggests that prompt treatment with a triptan may reduce the time required to abort a migraine attack and significantly reduce functional impairment.

The Migraine Intervention Score - a tool to improve efficacy of triptans in acute migraine therapy: the ALADIN study

Authors: Göbel, H.; Heinze, A.Source: International Journal of Clinical Practice, Volume 65, Number 8, 1 August 2011 , pp. 879-886(8)

Background:  The `Migraine Intervention Score' (MIS) is a new self-administered scale that can be used to quantify the severity of specific migraine symptoms. The objective of this study was to determine if MIS could be used to improve the efficacy of frovatriptan 2.5 mg in the early treatment of migraine attacks for clinical practice.

Methods:  In this prospective observational study, patients suffering from migraines with or without aura were enrolled and permitted to choose the time of self-medication with frovatriptan 2.5 mg. At the time of intake of medication, patients evaluated the severity of individual migraine symptoms using MIS. The scores for each symptom were then totalled to provide an overall level of symptom severity. A total of 1620 patients completed the treatment of three migraine attacks with frovatriptan. A total of 1518 patients could be analysed with respect to the documented efficacy parameters of the third attack. Patients initiating treatment at low symptom severity levels were compared with those initiating treatment at high symptom severity levels.

Results:  Time to the achievement of the primary endpoint (headache response) was significantly lower in patients who initiated treatment at low vs. high symptom severity levels (42.06 ± 32.33 vs. 49.25 ± 34.92 min; p = 0.0023). Likewise, patients who initiated treatment at low symptom severity levels achieved complete headache relief more rapidly (79.37 ± 65.33 vs. 96.05 ± 100.85 min; p = 0.0109) and required escape medication less frequently (3.88% vs. 13.73%; p < 0.0001).

The Migraine Intervention Score - a tool to improve efficacy of triptans in acute migraine therapy: the ALADIN study International Journal of Clinical Practice,

07/20/2011 Clinical Article

Conclusions

Treatment with frovatriptan at low severity of migraine symptoms is more effective than starting therapy at higher symptom levels.

This results in low recurrence headache rate, decreased necessity for escape medication and low number of tablets needed.

Sumatriptan/Naproxen

Three studies demonstrating the effectiveness of early treatment.

OPTIMIZING EFFICACY IN THE ACUTE TREATMENT OF MIGRAINE: EVALUATION OF THE CLINICAL BENEFITS OF TREATMENT PARADIGM AND COMBINATION THERAPY

(FIXED SINGLE-TABLET FORMULATION OF SUMATRIPTAN 85MG RT TECHNOLOGYTM AND NAPROXEN SODIUM 500MG, SumaRT/Nap)JL Brandes1, P Winner2, SA McDonald3, S Lener 3

1Nashville Neuroscience Group, Nashville, TN, USA, 2 Palm Beach Headache Care Center, West Palm Beach, FL, USA, 3GlaxoSmithKline, Research Triangle Park, NC, USA

Conclusions SumaRT/Nap was well-tolerated in both early and late treatment

paradigms (totalling 4 studies).

Subjects who treated their migraine “early” were more likely to obtain sustained pain free response compared to “late” intervention.

Subjects who treated their migraine with combinationtherapy (SumaRT/Nap) were more likely to obtain a sustained pain free response compared to monotherapy (SumaRT).

To optimize efficacy, patients should treat their migraine early with combination therapy.

Early Treatment of a Migraine Attack while Pain is Still Mild Increases the Efficacy of SumatriptanScholpp J, Schellenberg R, Moeckesch B, Banik N.Posted: January 2005 Cephalalgia 2004; 24:925-933

To investigate the hypothesis that early treatment of a migraine attack with sumatriptan, while pain is still mild, results in higher pain free rates in comparison to delayed treatment, when pain is at least moderate, we performed a prospective, controlled and open label study. Migraineurs with or without aura who fulfilled the diagnostic criteria recommended by the International Headache Society were enrolled in the study and randomly assigned to either ‘early’ or ‘late’ treatment with sumatriptan 100 mg. tablets. In the early treatment group significantly more patients were pain free at all times measured during two hours after dosing than in the late treatment group. Furthermore, patients in the early treatment group became pain free significantly sooner after dosing than patients who delayed treatment. It is concluded that migraineurs, who are able to differentiate between a migraine attack and other forms of headache, benefit from early intervention with sumatriptan 100 mg. tablets.

Sumatriptan–Naproxen Migraine Efficacy in Allodynic Patients: Early Intervention

Stephen Landy MD, Rebecca Hoagland MS, Nancy A. Hoagland ABArticle first published online: 29 AUG 2011

Sumatriptan–Naproxen Migraine Efficacy in Allodynic Patients: Early Intervention

Objective.— This study evaluated the effectiveness of a single fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan–naproxen) using a very early treatment paradigm in migraine patients whose attacks were historically accompanied by cutaneous allodynia.Background.— Evidence suggests that allodynic migraineurs may demonstrate a better response when treated prior to developing central sensitization, and that these patients are treated more effectively with a compound of sumatriptan and naproxen sodium than either drug alone. This study targeted patients who have accompanying allodynia using a very early treatment paradigm where treatment was initiated while symptoms were still mild.Methods.— This was an open-label prospective, outpatient study of adult migraineurs who had screened positive for cutaneous allodynia and typically experienced moderate to severe pain preceded by an identifiable mild pain phase. Patients were treated with sumatriptan–naproxen using a very early intervention paradigm in 4 test migraines over 12 weeks where dosage occurred within 30 minutes of symptom onset. Data from diaries and questionnaires were used to evaluate the primary endpoints of sustained pain-free response at 24 hours post dose (using no second dose of study drug and no other rescue drugs), and overall satisfaction with sumatriptan–naproxen.Results.— Forty allodynic migraineurs enrolled in this study and reported a total of 160 migraines. Of these migraines, 78 (49%) achieved sustained pain-free at 24 hours and 94 (59%) were reported as pain-free at 2 hours. The number of patients who rated their Overall Satisfaction following treatment with sumatriptan–naproxen as “Satisfied” (satisfied or very satisfied) was 32 (80%) after the first migraine and 25 (63%) after 3 or more migraines.Conclusions.— In this open-label study, allodynic patients reported that their migraine attacks responded well and they achieved a high degree of satisfaction following treatment with a fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg administered in a very early treatment paradigm.

Rizatriptan

Another study demonstrating the effectiveness of early treatment.

Treating With Maxalt Early in the Migraine Attack

This study by Mathew et al evaluated the pain-free response obtained with rizatriptan 10 mg when taken early in the migraine attack when the pain was still mild.

A total of 112 rizatriptan-naïve patients aged 20–64 years with a history of migraine attacks that progressively worsened when left untreated were assigned to receive rizatriptan 10 mg or placebo. Patients were instructed to treat 3 migraine attacks as early as possible during each attack, while the pain was still mild.

Pain-free response (the primary endpoint) at 2 hours occurred in 70% of attacks in the rizatriptan group and 22% of attacks in the placebo group (P<0.01). When the attacks were categorized by headache severity at the time of treatment (as recorded by patients in their headache diaries), the pain-free response at 2 hours was greater for mild attacks than for moderate or severe attacks (P<0.01).

A possible explanation for the benefits of early treatment is that treating migraine pain when it is mild prevents the pain from becoming more severe. In addition, gastroparesis, which is associated with migraine, is thought to impair absorption of oral medication.

Thus, the earlier migraine is treated, before gastroparesis is established, the more complete the absorption of the drug and the greater the probability of response.

Treating With Maxalt Early in the Migraine Attack (1)

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• 2-hour pain-free response was greater when Maxalt was taken when the headache pain was still mild

Pain severity at time medication was taken

PlaceboRizatriptan

Total Mild Moderate/Severe

109 216 100 194 9 22n (attacks) =

In a placebo-controlled study of 112 patients with migraine

Adapted from Mathew NT et al. Headache. 2004;44:669–673.

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The impact of a migraine attack and its after-effects on perceptual organization, attention, and working memory

Introduction: Many migraine patients report cognitive complaints during the first hours or days following a migraine attack. The aim of this study was to assess whether and which cognitive (perceptual, attentional, or memory) processes are impaired during the first 48 hours after a migraine attack.Methods: Three different cognitive tasks (global-local task, the attentional network task, and N-back task) were administered to 16 migraine patients (13 migraine without aura; mean age 58 years, 15 female) and 18 controls (59 years, 15 female), matched on age, gender, and educational level. Tasks were administered at three time points; during the first headache free day following a migraine attack (first session), 24 hours later (second session), and 12 days after the attack (third session).Results: The attentional network and N-back tasks showed no significant differences between migraineurs and controls. In the global-local task, controls showed faster reaction times to global than to local stimuli, which is the standard global-precedence effect. This effect was absent in the migraineurs in all three sessions, especially if they used prophylaxis.Conclusion: Migraineurs had no impaired attentional or working-memory functioning in the 2 days after an attack. They did show impairments in the processing of global visual features compared with controls, both between and immediately after an attack.

Summary

Early treatment of migraine improves efficacy of triptans and ergots.

Early treatment staves off allodynia, disability and reduces unnecessary ER visits, and hence is cost effective.

Early treatment reduces unnecessary suffering and improves patient satisfaction.

Early treatment may well prevent post migraine visual perceptual issues.