Early RX of Migraines
Timing 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 STRATEGIES
THE RATIONALE FOR EARLY INTERVENTION
PRESENTED BY THE NATIONAL HEADACHE FOUNDATION
FACULTY
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 and
failed prescriptions.
3- Patients and physicians may become discouraged
and the patient may lapse from care.
4- Overuse of medications may lead to chronic daily
headache 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. Over
a 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 Keywood
Authors and Disclosures
Posted: 10/21/2004; Curr Med Res Opin. 2004;20(9) © 2004 Librapharm Limited
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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 remedication (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, Resear
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 Sumatriptan Scholpp 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 AB
Article 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.
30
In a placebo-controlled study of 112 patients with migraine
2-hour pain-free response was greater when Maxalt was taken when the
headache pain was still mild
2- Hour Pain-Free Response (%)
•
Treating With Maxalt Early in the
Migraine Attack (1)
Placebo
Rizatriptan
100
P<0.01
P<0.01
80
72%
70%
60
42%
40
22%
25%
16%
20
0
n (attacks) = 109 216
Total
100
194
Mild
9
22
Moderate/Severe
Pain severity at time medication was taken
Adapted from Mathew NT et al. Headache. 2004;44:669–673.
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 Nback 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.