Full text of DOI:10.2165/00044011-200121120-00008

Clin Drug Invest 2001; 21 (12): 853-860
1173-2563/01/0012-0853/$22.00/0
OUTCOMES RESEARCH
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Adis International Limited. All rights reserved.
Improvement in Health-Related Quality of
Life with Rizatriptan 10mg Compared with
Standard Migraine Therapy
1
2
3
4
William C. Gerth, Kevin H. Ruggles, Stuart R. Stark, Glenn M. Davies and
4
Nancy C. Santanello
1
2
3
4
Outcomes Research, Merck & Co., Inc., Whitehouse Station, NJ, USA
Department of Neurology, Marshfield Clinic, Marshfield, WI, USA
Innovative Clinical Research Center, Alexandria, VA, USA
Department of Epidemiology, Merck & Co., Inc., West Point, PA, USA
Abstract
Objective: To compare the effects of rizatriptan and patients’ usual migraine
medication(s) on health-related quality of life.
Design and Setting: The study was a non-blinded, parallel-group, extension trial
in which patients who had completed a randomised, placebo-controlled trial of
the treatment of migraine with rizatriptan at 23 study sites in the United States
were randomly assigned in a 4 : 1 ratio either to rizatriptan or to standard care.
Patients: 265 migraineurs, 18 to 65 years of age.
Interventions: Patients received either rizatriptan 10mg or their usual migraine
medication(s).
Main Outcome Measures and Results: The main outcome measures were:
(
a) migraine-specific quality of life during the 24-hour period of an attack, as
determined by the 24-Hour Migraine-Specific Quality-of-Life Questionnaire
24-HrMQoLQ), for attacks in the first month; (b) general health-related quality
(
of life as determined by the eight domain scores and the Mental and Physical
Component Scales of the Short Form Health Survey (SF-36) after 2, 6 and 12
months. The 24-HrMQoLQ domains were scored from 3 to 21, and the SF-36
from 0 to 100, higher scores indicating better performance for both instruments.
Patients receiving rizatriptan had significantly better scores in all five domains
of the 24-HrMQoLQ compared with patients receiving standard care. Mean
scores (standard error) forthe rizatriptan and usual care groups were, respectively:
Work Functioning, 13.9 (0.4), 12.5 (0.8), p = 0.05; Social Functioning, 13.6 (0.4),
1
1.8 (0.8), p = 0.015; Energy/Vitality, 13.7 (0.5), 11.6 (0.8), p < 0.01; Feelings/
Concerns 13.3 (0.4), 10.6 (0.8), p < 0.001; and Migraine Symptoms 14.1 (0.4),
2.1 (0.7), p < 0.01. There was a trend for patients receiving rizatriptan to have
higher scores on the Mental Component Scale of the SF-36: mean score (SE) 50.3
0.6) for rizatriptan, 48.0 (1.1) for usual care, p = 0.068. There was no difference
between the treatment groups in the Physical Component Scale: mean score (SE)
8.4 (0.6) for rizatriptan, 49.7 (1.1) for usual care, p = 0.202.
1
(
4
Conclusion: Quality of life in the 24-hour period following a migraine attack
was better in patients treated with rizatriptan 10mg than in patients treated with
their usual migraine medication.

8
54
Gerth et al.
Migraine is a chronic neurovascular disorder
and standard care in HR-QoL between migraine
attacks, as measured with a generic HR-QoL in-
strument, the Short Form Health Survey (SF-36).
characterised by recurrent episodes of intense
headache pain with associated symptoms of nausea
and/or vomiting, photophobia, and phono-
[
1]
Patients and Methods
phobia. Migraine attacks have a negative effect
on health-related quality of life (HR-QoL). During
a migraine attack, headache pain and associated
symptoms interfere with the ability of migraineurs
to work, enjoy daily activities, and interact so-
cially.[ Several studies have demonstrated that the
HR-QoL of migraineurs is significantly impaired
Patients
All patients completing a randomised, triple-
blinded, placebo-controlled, crossover trial of the
treatment of four consecutive headache attacks
2]
[
7]
with rizatriptan (the 025 trial) were invited to
participate in the extension study. Of 313 patients
invited, 265 (85%) elected to enter the study.
[
3,4]
even between migraine attacks.
Migraine attacks have traditionally been treated
with a variety of drugs, including analgesics,
nonsteroidal anti-inflammatory drugs (NSAIDs),
opioids, corticosteroids and ergot derivatives.[
Triptans, which are serotonin receptor 5-HT1B/1D
agonists, have recently become the gold standard
of migraine treatment. Rizatriptan is a selective 5-
HT1B/1D receptor agonist. In several multicentre,
randomised, placebo-controlled trials, rizatriptan
Study Design
1]
This was a 12-month, parallel-group, non-
blinded extension trial in which patients were
randomly assigned in a 4 : 1 ratio either to
rizatriptan 10mg or to their usual migraine therapy
[
medication(s) used routinely to relieve their mi-
graine attacks, as prescribed by the investigators].
The efficacy and safety results of this US-based
trial (the 025 extension) and two other extension
1
0mg produced rapid pain relief and freedom
frompain, and reduced the incidence of migraine-
associated symptoms.[
5-8]
In randomised trials
[11]
trials have been described previously.
comparing rizatriptan with oral sumatriptan,
Patients in the rizatriptan group were not to use
sumatriptan, ergot derivatives or isometheptine for
24 hours before or after treating a migraine attack
with the test drug; monoamine oxidase inhibitors
and methysergide were prohibited for the duration
of the study. Most patients (66%) in the usual care
group used sumatriptan (oral or subcutaneous) for
treatment of most (80%) attacks, either alone or in
combination with other therapies. Other frequently
used abortive therapies in the standard care group
included (given as the percentage of patients treat-
ing at least one attack; percentage of attacks
treated): NSAIDs (70%; 45%), barbiturates (40%;
rizatriptan provided faster pain relief and reduced
nausea to a greater extent.[
8-10]
Patients completing
three of these trials entered three long-term
extension trials in which patients were randomly
assigned to rizatriptan or standard care.[ Stand-
ard care in the extension trials was most often
sumatriptan, but also included NSAIDs, paraceta-
mol (acetaminophen), barbiturates and opioids.
We report HR-QoL data from one of the exten-
sion trials of rizatriptan 10mg versus standard
11]
[
7,11]
care.
We hypothesised that rizatriptan 10mg
would improve HR-QoL to a greater extent than
standard care during a migraine attack, and that
rizatriptan might improve some aspects of HR-QoL
between migraine attacks. Results using a migraine-
specific instrument, the 24-Hour Migraine-Specific
Quality-of-Life Questionnaire (24-HrMQoLQ),[
indicate that rizatriptan improved HR-QoL over
standard care during migraine attacks. There
was no dramatic difference between rizatriptan
6
5
6%), paracetamol (40%; 66%) and opioids (30%;
2%).
Migraine Diary
12,13]
After initiating migraine therapy for each
moderate or severe migraine attack during the 12-
month duration of the extension study, patients
completed a migraine attack diary card. The diary
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Clin Drug Invest 2001; 21 (12)

Quality of Life with Rizatriptan in Migraine
855
card recorded the migraine headache severity (no
headache, mild, moderate or severe), functional
disability (normal, mildly impaired, severely im-
paired or unable to perform activities and requiring
bed rest), and associated symptoms (nausea,
vomiting, photophobia, phonophobia). Patients
recorded this information at initiation of study
therapy and 2 and 4 hours after drug admini-
stration. They recorded the need for additional
migraine medications and adverse experiences as
they occurred.
Data Analysis
Between-group differences in domains of the
4-HrMQoLQ were analysed in a mixed model.
[15]
2
Subjects were treated as random effects, and age,
gender, study site and baseline severity (i.e. sever-
ity at the beginning of a migraine attack) were
treated as fixed effects. Wald F tests were used to
test for differences between the rizatriptan and
usual care groups while controlling for these
baseline co-variates. Analysis of variance (ANOVA)
was used to analyse between-group differences in
SF-36 change-from-baseline scores adjusting for
age, gender and study site. Individuals with base-
line and at least one follow-up measurement were
analysed, and the average of available follow-up
scores was used. Statistical significance was de-
fined as p ≤ 0.05.
2
4-Hour Migraine-Specific Quality of Life
Questionnaire
Patients completed the 24-HrMQoLQ over the
first month of the extension. The 24-HrMQoLQ
assesses the impact of migraine and migraine
therapy on the quality-of-life decrement associated
with an acute migraine attack in the 24-hour period
following headache onset.[
12,13]
The 24-HrMQoLQ
Results
consists of 15 questions, with three questions
each in five domains: Work Functioning, Social
Functioning, Energy/Vitality, Symptoms and
Feelings/Concerns. The domain scores range from
a minimum of 3 (worst possible functioning/
migraine symptoms all of the time) to a maximum
of 21 (best possible functioning/no symptoms).
Patients were instructed to complete the 24-
HrMQoLQ 24 hours after initiating therapy for
a migraine headache that they rated as moderate or
severe, and to consider their entire migraine ex-
perience over the 24-hour period.
Patient Population
Fifty subjects were randomised to receive their
usual migraine therapy and 215 to receive
rizatriptan. The demographics of these patients at
baseline are shown in table I. Patients were pre-
dominantly female (83.4%) and their mean age
was 41 years.
Table I. Patient demographics
Short Form Health Survey
Characteristic
Rizatriptan
(n = 215)
Usual treatment
(n = 50)
The SF-36 is a generic health survey question-
naire consisting of eight domains, each scored
from 0 to 100, with 100 representing the best
possible health-related quality of life. Mental
Health and Physical Health Summary scores can
be computed from the eight domains, based upon
principal components analysis of data from a sur-
vey of the US population.[ The SF-36 was com-
pleted during a clinic visit at baseline and at
months 2, 6 and 12 (± 30 days from the scheduled
visit).
Age (y)
Mean (SD)
Range
41 (10.2)
19-65
42 (9.5)
19-60
Gender [no. (%)]
Female
177 (82.3)
38 (17.7)
44 (88)
6 (12)
Male
Race [no. (%)]
White
14]
207 (96.2)
3 (1.5)
45 (90)
1 (2)
Black
Other
5 (2.3)
4 (8)
SD = standard deviation.
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Clin Drug Invest 2001; 21 (12)

8
56
Gerth et al.
Table II. Headache severity and functional disability by treatment
group
Migraine-Specific Quality of Life
Characteristic
Rizatriptan
n = 214)
Usual treatment
(n = 48)
Patients randomised to receive rizatriptan 10mg
had statistically significantly better scores in all
five domains of the 24-HrMQoLQ instrument
(
Severity
No.
684
98
(
figure 1). The magnitude of the increases ranged
Moderate (%)
Severe (%)
59.2
40.8
66.3
33.7
from 11.2% in the Work Functioning domain to
25.5% in the Feelings/Concerns domain.
Functional disability
No.
678
3.4
97
Normal (%)
3.1
Short Form Health Survey
Mildly impaired (%)
Severely impaired (%)
Required bed rest (%)
52.4
29.9
14.5
53.6
25.8
17.5
There were no statistically significant between-
group differences in average follow-up scores,
over the three timepoints in the extension, in any
of the eight SF-36 domains except Mental Health,
where the rizatriptan group scored higher than the
control group (p = 0.048). Average mean follow-up
scores rose by 0.8% to 7.2% points from the base-
line values for seven, and declined by 1.1% point
in one, of the eight SF-36 domain scores for
patients randomised to rizatriptan. Average mean
follow-up scores rose by 0.6 to 11.9% points for
three, and declined by 2.6 to 10.3% points for
five, of the SF-36 domains scores for patients
Headache Severity and Functional Disability
The percentage of headaches by treatment group
according to severity and functional disability is
shown in table II. The rizatriptan 10mg group had
more patients rating their baseline headache sever-
ity as severe (40.8%) compared with the standard
care group (33.7%). Functional disability at base-
line was roughly comparable between the two
groups.
2
1
5
9
3
Usual therapy
Rizatriptan
p = 0.05
p = 0.015
p < 0.01
p < 0.01
p < 0.001
1
Work
Functioning
Social
Functioning
Energy/
Vitality
Migraine
Symptoms
Feelings/
Concerns
Domain
Fig. 1. Migraine-specific quality of life, showing mean (standard error) scores for the 24-Hour Migraine-Specific Quality-of-Life
Questionnaire for 174 patients on rizatriptan and 35 on usual therapy. Domain scores range from 3 (worst possible functioning/
migraine symptoms all of the time) to 21 (best possible functioning/no symptoms).
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Clin Drug Invest 2001; 21 (12)

Quality of Life with Rizatriptan in Migraine
857
Table III. SF-36 domain and physical and mental component
scores
Discussion
The migraine-specific quality-of-life instru-
ment used in this study was used previously in
several of the randomised, placebo-controlled
SF-36 construct
Rizatriptan
n = 164)
Usual care
(n = 42)
p-Value
(
Physical functioning
Baseline a
Follow-up b
Role physical
Baseline
89.6 (1.2)
90.4 (1.1)
90.1 (2.1)
90.9 (1.9)
trials designed to test the efficacy and safety of
0.772
0.762
0.792
0.613
0.048
0.139
0.844
0.887
0.202
0.068
[6,9,16]
rizatriptan.
In a substudy of a triple-blinded,
[
17]
rizatriptan dose-ranging trial, patients receiving
rizatriptan 10mg showed a significantly better re-
sponse than those receiving placebo in three of five
domains of the 24-HrMQoLQ (Social Functioning,
62.6 (3.3)
69.8 (3.2)
59.5 (6.7)
71.4 (5.3)
Follow-up
Bodily pain
Baseline
59.7 (1.6)
62.3 (1.6)
62.4 (3.7)
63.0 (2.7)
[16]
Migraine Symptoms and Feelings/Concerns).
Follow-up
Social functioning
Baseline
(Note that patients randomised to placebo in that
trial were allowed a blinded dose of rizatriptan
10mg at 2 hours, which may have tended to dimin-
ish the difference in HR-QoL between the placebo
and rizatriptan arms.) In a multicentre, double-
blinded trial of rizatriptan 10mg versus placebo (in
which patients receiving placebo were not allowed
a blinded dose of rizatriptan at 2 hours), rizatriptan
improved patients’ HR-QoL across all five domains
75.2 (1.5)
77.5 (1.7)
78.3 (3.0)
76.0 (2.8)
Follow-up
Mental health
Baseline
74.2 (1.4)
75.8 (1.2)
77.7 (2.0)
72.0 (1.9)
Follow-up
Role emotional
Baseline
77.6 (2.8)
84.7 (2.7)
88.1 (3.6)
77.8 (4.4)
Follow-up
Vitality
[
6]
of the 24-HrMQoLQ. Randomised, controlled
trials comparing rizatriptan with sumatriptan have
shown that rizatriptan provides faster pain re-
Baseline
58.4 (1.6)
61.0 (1.3)
63.2 (2.2)
61.4 (2.2)
Follow-up
General health
Baseline
[
9,10]
[10]
77.3 (1.5)
76.2 (0.9)
79.7 (2.9)
76.0 (1.6)
lief.
In one of these trials, patients receiving
Follow-up
rizatriptan 10mg had statistically significantly
better 24-HrMQoLQ scores than patients receiving
placebo in all five domains, whereas scores with
sumatriptan 100mg were statistically significant
from placebo in only three domains (Migraine
Symptoms, Feelings/Concerns, and Energy/Vital-
Physical component scale
Baseline
47.8 (0.6)
48.4 (0.6)
47.2 (1.3)
49.7 (1.1)
Follow-up
Mental component scale
Baseline
48.8 (0.8)
50.3 (0.6)
52.0 (1.1)
48.0 (1.1)
Follow-up
[
10]
ity).
Assessment with the 24-HrMQoLQ in
a
b
Mean (standard error).
[
9]
another trial indicated that rizatriptan 10mg had
effects on HR-QoL similar to those of sumatriptan
Least-squares mean (standard error) adjusted for age, gender
and baseline value.
SF-36 = Short Form Health Survey.
5
0mg, except in the Work Functioning domain
where rizatriptan 10mg was superior to suma-
triptan 50mg. In the present study, rizatriptan 10mg
was compared with patients’ usual medication(s)
in a non-blinded, parallel group, randomised
randomised to standard care. The rizatriptan group
showed a trend towards significantly higher scores
on the Mental Component Scale (p = 0.068), but
there was no statistically significant between-
group difference in either the Mental Component
Scale or the Physical Component Scale (table III).
[11]
trial.
Patients randomised to rizatriptan had a
better HR-QoL during the 24-hour period follow-
ing initial drug administration for a migraine attack
than patients on their usual medication, as evi-
denced by statistically significantly higher scores
in all five domains of the 24-HrMQoLQ.
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Clin Drug Invest 2001; 21 (12)

8
58
Gerth et al.
The 24-HrMQoLQ[12,13] is episode-specific,
while other migraine-specific quality-of-life in-
patients randomised to rizatriptan. Conversely,
scores decreased from their baseline values for five
of the domains in the standard care group. The
Mental Component Scale increased from baseline
by 1.5% points for the rizatriptan group, but de-
creased by 4% points in the standard care group.
While not reaching statistical significance, the
SF-36 results are consistent with better mental
health with rizatriptan than with patients’ usual
medication.
The 24-HrMQoLQ measures HR-QoL across
five dimensions. The 24-HrMQoLQ domain scores
in this study were weakly negatively correlated
with changes in migraine severity and functional
disability as recorded by patients in their diaries
at 2 and 4 hours post administration. Correlations
between the 24-HrMQoLQ and the 0- to 2-hour
changes in migraine severity and functional dis-
ability were statistically significant (p < 0.01) for
all five domains, but were relatively modest,
ranging from −0.34 to −0.19 (Spearman’s correlation
coefficient). Correlations for the 0- to 4-hour
changes in diary measures were weaker (−0.10 to
−0.22) and in most cases were not statistically
significant. The 0- to 4-hour correlations might be
confounded by patients either re-taking rizatriptan
or using additional rescue medications 2 hours
after initial drug administration. These correlations
are similar in magnitude to the correlations be-
tween the five domains of the 24-HrMQoLQ,
[
18-20]
struments
were designed to measure HR-QoL
over a several-week period. The SF-36 is a generic
instrument that can be used to assess HR-QoL over
extended time periods punctuated by migraine
attacks and which, in conjunction with the 24-
HrMQoLQ, can provide a more complete picture
of the migraineur’s life experience. Compared with
US norms, individuals with migraine have reduced
scores in all eight SF-36 domains, but in particular
in the Social Functioning, Physical Functioning,
Role Physical and Bodily Pain domains, with the
magnitude of the reductions being proportional to
[
2,4]
migraine severity.
In several studies in which
the SF-36 was used to measure the effect of
sumatriptan on HR-QoL, Social Functioning
[
2]
scores improved most consistently. In an uncon-
trolled non-blinded study, treatment of migraine
with sumatriptan for up to 24 months was associ-
ated with improvements over baseline in the Social
Functioning, Bodily Pain and General Health
[21]
Perceptions domains. In the present randomised,
parallel-group trial comparing rizatriptan 10mg
with standard care, a statistically significant differ-
ence between treatment groups was seen only in the
Mental Health domain; however, rizatriptan recip-
ients showed a trend towards better scores in the
Mental Health Component Scale of the SF-36.
The scores on the individual SF-36 domains in
this study were within the range of values reported
elsewhere for migraine.[ Comparison with other
studies is, however, complicated by the fact that
baseline SF-36 values in this extension study re-
flected patients’ status at the end of a randomised,
blinded trial of rizatriptan for multiple migraine
which range from 0.08 to 0.38, indicating minimal
2]
[12]
overlap of the domains.
Thus, the effects of
rizatriptan measured by the 24-HrMQoLQ repre-
sent improvement in HR-QoL dimensions beyond
simply pain and disability, which are the most
obvious manifestations of a migraine attack.
[
7]
attacks. In that trial, 80% had their last migraine
attack treated with rizatriptan and 20% with pla-
cebo. Thus, most patients randomised to rizatriptan
in the extension trial would not be expected to ex-
perience any change in their SF-36 scores, whereas
scores might be expected to rise for a minority of
these patients. Consistent with this, mean scores
rose by 0.8% to 7.2% points from the baseline
values for seven of the eight SF-36 domains for
The rapid action of rizatriptan compared with
patients’usual therapy might explain the improved
HR-QoL during the period following an attack. In
the 025 extension trial, the odds ratios for pain
relief and freedom from pain at 2 hours were 3.64
and 2.61, respectively, for rizatriptan compared
[
11]
with standard care.
The improved migraine-
specific HR-QoL with rizatriptan might also be
related to better tolerability. Patients’ usual migraine
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Clin Drug Invest 2001; 21 (12)

Quality of Life with Rizatriptan in Migraine
859
therapy comprised a number of different drugs
tend to bias the 24-HrMQoLQ results against the
rizatriptan group.
(
most often sumatriptan, NSAIDs or barbiturates)
and several of these medications have well estab-
lished adverse effects. Several items of the 24-
HrMQoLQ might be sensitive to the adverse effects
of barbiturates and other drugs, e.g. the ability to
stay alert, operate machinery or sleep. The overall
incidence of adverse experiences in the extension
trials was similar in the rizatriptan 10mg (80%) and
the usual care (78%) groups.[ However, patient’s
fears or expectations of adverse drug effects might
influence their HR-QoL to a greater extent than
the adverse effects themselves. Such fears are
tested in the Feelings/Concerns domain of the 24-
HrMQoLQ, which queries whether respondents
feel ‘concern that your migraine medication will
not relieve migraine symptoms’. Other relevant
items in the Feelings/Concerns domain ask
whether respondents ‘feel physically uncomfort-
able’ and whether they ‘feel upset about having
migraine headaches’.
This study has several limitations. First, selec-
tion bias might plausibly have contributed to the
positive effects of rizatriptan on HR-QoL. Of the
migraineurs from the blinded, randomised trial that
preceded the extension study, 85% chose to enrol
in the extension phase. Some patients might have
chosen not to participate due to a lack of efficacy
of rizatriptan. Patients categorised as responders in
the previous blinded trial were more likely than
non-responders to enter the non-blinded extension
In the treatment of migraine, the clinical goals
are to alleviate headache pain and associated
symptoms rapidly and to restore normal function-
ing in the period following onset of a migraine
attack. In this study, these goals were met more
often for patients receiving rizatriptan than for
patients receiving usual care. Patients receiving
rizatriptan faired better in terms of their migraine
symptoms, their energy and vitality, their func-
tioning both socially and at work, and their con-
cerns about migraine and their migraine treatment.
Faster relief of headache pain and improved
quality of life are likely to result in better patient
satisfaction with the migraine therapy.
11]
Conclusion
Treatment with rizatrpitan resulted in a better
migraine-specific HR-QoL than did patients’ usual
medication, according to results from a validated
instrument measuring short-term migraine-specific
HR-QoL.
Acknowledgements
The authors gratefully acknowledge the assistance of
Alan Morrison in the preparation of this manuscript. This
study was supported by Merck & Co., Inc.
References
1
. Lobo BL, Cooke SC, Landy SH. Symptomatic pharmaco-
therapy of migraine. Clin Ther 1999; 21: 1118-30
. Solomon GD, Litaker DG. The impact of drug therapy on
quality of life in headache and migraine. Pharmacoeconomics
1997; 11: 334-42
2
(
68.5% versus 54.7%; ‘response’ defined as pain
relief in the last attack experienced). Patients re-
ceiving rizatriptan were more assiduous in record-
ing their headaches in their study diaries. A greater
proportion of rizatriptan patients completed the
3
4
5
. Dahlof CG, Dimenas E. Migraine patients experience poorer
subjective well-being/quality of life even between attacks.
Cephalalgia 1995; 15: 31-6
. Osterhaus JT, Townsend RJ, Gandek B, et al. Measuring the
functional status and well-being of patients with migraine
headache. Headache 1994; 34: 337-43
. Ahrens SP, Farmer MV, Williams DL, et al. Efficacy and safety
of rizatriptan wafer for the acute treatment of migraine.
Rizatriptan Wafer Protocol 049 Study Group. Cephalalgia
1999; 19: 525-30
2
4-HrMQoLQ (80.9% versus 70.0%). The signif-
icance of this is that HR-QoL improvements might
not be as good in an unselected population of
migraineurs as in the population in the current
study. Finally, since patients in the usual care
group reported a slightly lower incidence of severe
headaches, it is possible that they selectively
under-reported severe headaches, which would
6
7
. Teall J, Tuchman M, Cutler N, et al. Rizatriptan (MAXALT) for
the acute treatment of migraine and migraine recurrence. A
placebo-controlled, outpatient study. Rizatriptan 022 Study
Group. Headache 1998; 38: 281-7
. Kramer MS, Matzura-Wolfe D, Polis A, et al. A placebo-
controlled crossover study of rizatriptan in the treatment of
©
Adis International Limited. All rights reserved.
Clin Drug Invest 2001; 21 (12)

8
60
Gerth et al.
multiple migraine attacks. Rizatriptan Multiple Attack Study
Group. Neurology 1998; 51: 773-81
. Dooley M, Faulds D. Rizatriptan: a review of its efficacy in the
management of migraine. Drugs 1999; 58: 699-723
. Goldstein J, Ryan R, Jiang K, et al. Crossover comparison of
rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50
mg in migraine. Headache 1998; 38: 737-47
0. Tfelt-Hansen P, Teall J, Rodriguez F, et al. Oral rizatriptan
versus oral sumatriptan: a direct comparative study in the
acute treatment of migraine. Headache 1998; 38: 748-58
16. Santanello NC, Polis AB, Hartmaier SL, et al. Improvement in
migraine-specific quality of life in a clinical trial of
rizatriptan. Cephalalgia 1997; 17: 867-72
17. Gijsman H, Kramer MS, Sargent J, et al. Double-blind, placebo-
controlled, dose-finding study of rizatriptan (MK-462) in the
acute treatment of migraine. Cephalalgia 1997; 17: 647-51
18. Wagner TH, Patrick DL, Galer BS, et al. A new instrument to
assess the long-term quality of life effects from migraine:
development and psychometric testing of the MSQOL. Head-
ache 1996; 36: 484-92
8
9
1
1
2
2
9. Jhingran P, Osterhaus JT, Miller DW, et al. Development and
validation of the Migraine-Specific Quality of Life Question-
naire. Headache 1998; 38: 295-302
0. Jhingran P, Davis SM, LaVange LM, et al. MSQ: Migraine-
Specific Quality-of-Life Questionnaire. Further investigation
of the factor structure. Pharmacoeconomics 1998; 13: 707-17
1. Jhingran P, Cady RK, Rubino J, et al. Improvements in health-
related quality of life with sumatriptan treatment for migraine.
J Fam Pract 1996; 42: 36-42
1
1. Block GA, Goldstein J, Polis A, et al. , Rizatriptan Multicenter
Study Groups. Efficacy and safety of rizatriptan versus stand-
ard care during long-term treatment for migraine. Headache
1
998; 38: 764-71
1
1
1
1
2. Hartmaier SL, Santanello NC, Epstein RS, et al. Development
of a brief 24-hour migraine-specific quality of life question-
naire. Headache 1995; 35: 320-9
3. Santanello NC, Hartmaier SL, Epstein RS, et al. Validation of
a new quality of life questionnaire for acute migraine head-
ache. Headache 1995; 35: 330-7
4. Ware JE, Kosinski M, Keller SD. SF-36 Physical and Mental
Health Summary Scales: AUser’s Manual. Boston (MA): The
Health Institute, New England Medical Center, 1994
5. Littel RC, Milliken GA, Stroup WW, et al. SAS system for
mixed models. Cary (NC): SAS Institute, Inc., 1996
Correspondence and offprints: William C. Gerth, Outcomes
Research, Merck & Co., Inc., Whitehouse Station, One
Merck Drive, PO Box 100, NJ 08889, USA.
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Clin Drug Invest 2001; 21 (12)