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Vol. 161 No. 21, November 26, 2001 |
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Review Article |
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Patient Treatment Preferences and the 5-HT1B/1D Agonists
Robert E. Ryan, Jr, MD
Arch Intern Med. 2001;161:2545-2553.
ABSTRACT
Migraineurs have specific preferences with regard to migraine therapy.
In surveys, they consistently cite several attributes they seek in a migraine
medication: rapid pain relief, complete pain relief, ability to return to
normal functioning, relief of migraine-associated symptoms, reduction in headache
recurrence, and minimal adverse effects. When prescribing medication for patients
with migraine, physicians should respect patients' treatment preferences and
select drugs that most closely meet patients' needs. As a class, the 5-HT1B/1D agonists, or triptans, have many of these attributes, including
effectively relieving pain and associated symptoms and allowing patients to
return fairly quickly to their normal activities. However, differences have
emerged in the ability of specific triptans to satisfy patient preferences.
Physicians should consider these differences when prescribing triptans for
their patients with migraine.
INTRODUCTION
The pounding, throbbing, unilateral pain that is the hallmark of migraine
is often so severe that patients cannot function normally, or at least find
it difficult to do so. This pain, combined with the other common symptoms
of migraine—nausea, vomiting, photophobia, and phonophobia—may
incapacitate patients for hours, a day, or longer. In one study, 71% of patients
reported they could not think or concentrate at all when symptoms were severe,
and 83% could not perform daily activities such as shopping or housework during
a severe migraine attack.1
Logic dictates that patients with migraine, particularly those with
severe or frequent migraine attacks, would seek medical help. However, for
various reasons, between 40% and 66% of migraineurs do not seek help from
a physician,2 and among those who do, many
do not continue regular physician visits.3
This may be because of patients' perceived lack of empathy from the physician
and a belief that physicians cannot effectively treat migraine. In a 1999
British survey, 17% of 9770 migraineurs had not consulted a physician because
they believed their condition would not be taken seriously, and 8% had not
seen a physician because they believed existing migraine medications were
ineffective.2 By far, the most common reason
(cited by 76% of patients) for not seeking a physician's advice was the patients'
belief that they did not need a physician's opinion to treat their migraine
attacks.2 Interestingly, the severity of the
migraine attack did not correlate with a patient's tendency to seek medical
help: patients with severe migraine pain were no more likely to consult a
physician than were those with milder symptoms.2
What does this mean for primary care physicians? Clearly, when patients
do consult physicians for migraine, physicians must take the problem seriously.
Migraine is not just a headache; it is a disabling, chronic condition that
considerably affects patients' everyday lives. To help patients most effectively,
physicians need to accurately diagnose the condition, excluding other types
of severe headache and pathologic conditions such as tumor. Once the diagnosis
is confirmed, physicians need to maintain open lines of communication with
their patients and respect patient preferences for migraine treatment and
prevention.
IDENTIFYING PATIENT PREFERENCES
Pain is a subjective experience that can be assessed only by questioning
patients about its type and severity. Likewise, questioning patients about
a drug's effects is the only way to determine response to a pain-relieving
medication. Patients with migraine have several choices of pain-relieving
medications, ranging from over-the-counter analgesics and older migraine medications
(eg, ergotamine and dihydroergotamine) to the newer 5-HT1B/1D agonists,
including sumatriptan, zolmitriptan, rizatriptan, naratriptan, and almotriptan.
Determining how well these newer agents meet patients' needs requires an understanding
of patients' desires in a migraine medication. Headache specialists and researchers
are recognizing the importance of respecting patient preferences for and satisfaction
with migraine drugs. Consequently, formal measurement of patient priorities
and satisfaction with medication are receiving greater emphasis as part of
the overall assessment of a migraine drug.
To determine the treatment priorities of patients with migraine, investigators
have relied on 2 methods: patient surveys and use of "patient satisfaction"
as an end point in clinical trials of migraine drugs. In both of these methods,
the treatment priorities identified by patients tend to be fairly consistent1, 4-5 (Table 1). Not surprisingly, the most desired attribute by far for
a migraine medication is rapid and complete pain relief.
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Table 1. Treatment Priorities of Patients With Migraine*
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In 1995, Silberstein4 published the results
of a telephone survey of 500 self-reported migraineurs. Almost all the survey
respondents were women (443 women and 57 men), which is consistent with the
greater prevalence of migraine in women than men. Most of the respondents
(60%) had 3 or fewer migraine attacks per month; 15% reported 4 attacks per
month, and 25% had 5 or more attacks per month. When describing their most
recent migraine attack, 93% of patients reported moderate or severe headache
pain, 76% had moderate or severe nausea, and 92% had moderate or severe visual
problems. When asked to rate the importance of specific attributes of a migraine
medication on a 10-point scale (with 1 indicating not at all important and
10, extremely important), survey respondents gave the highest ratings to "provides
quick headache relief" (mean rating, 9.91) and "decreases headache pain" (mean
rating, 9.87). Other migraine medication features considered important by
the participants in this survey were "decreases likelihood of recurrence,"
"does not cause nausea," "decreases nausea," "decreases vomiting," "decreases
sensitivity to light," "orally administered," "decreases visual problems,"
and "does not cause drowsiness."
In a 1999 telephone survey of 688 migraineurs by Lipton and Stewart,5 patients expressed a strong preference for a migraine
medication that could provide complete pain relief. When asked to rate the
importance of various drug attributes, complete pain relief was considered
important or very important by 87% of the participants, followed by no recurrence
(86%), rapid onset (83%), no adverse effects (79%), relief of migraine-associated
symptoms (76%), and route of administration (56%).
With knowledge of patients' preferences for migraine medication, the
challenge for the physician is to select the drug that best meets patients'
expressed needs. Although many different drugs are available to treat migraine
and its associated symptoms, this review focuses on the 5-HT1B/1D
agonists, commonly called triptans. This new class of migraine medication
can provide considerable relief for patients with moderate to severe migraine,
while causing few adverse effects. However, for many patients with mild migraine,
nontriptan medications, including over-the-counter analgesics and prescription-strength
nonsteroidal anti-inflammatory drugs, provide adequate pain relief and may
be preferred by these patients because of the drugs' lower cost and ease of
availability. Also, nonpharmacologic approaches to migraine treatment (eg,
avoiding migraine triggers and biofeedback) remain important even with the
advent of effective migraine-specific therapy and should be incorporated into
the overall treatment plan.
HOW WELL DO THE TRIPTANS MEET PATIENT NEEDS?
Because patients have specific needs with regard to acute migraine medications,
they tend to be dissatisfied with medications that do not meet these needs.
Lipton and Stewart5 found that the most common
reason migraineurs were dissatisfied with their current medication was that
pain relief took too long (Figure 1). Patients also were dissatisfied if pain was not completely relieved, the medication
was not consistently effective, the headache recurred, or they experienced
too many adverse effects.
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Most common reasons migraineurs are dissatisfied with their current
migraine medication.5
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Patients with moderate to severe migraine who have been treated with
older acute migraine medications such as ergotamine and dihydroergotamine
and who have obtained relief with these drugs without undue adverse effects
may prefer to continue using these drugs. However, for patients newly diagnosed
with migraine and for those in whom older migraine medications are ineffective,
the triptans offer a suitable alternative and are becoming the drugs of choice
for moderate to severe migraine.
There is now a fair amount of data on the efficacy and safety of the
triptans, along with some information on patient satisfaction with these drugs.
A review of these data can help determine how well the profiles of the various
triptans correspond with patient treatment preferences6-30
(Table 2). As previously stated,
one of the most important attributes patients seek in a migraine medication
is complete relief of pain. Most triptan studies have used pain relief (ie,
a reduction in pain from moderate/severe to mild/none) at 2 hours as the primary
efficacy end point, although in several studies data on complete pain relief
(ie, a reduction in pain from moderate/severe to none) are also presented.
For some clinicians, the distinction between pain relief and complete pain
relief (ie, pain free) may be unclear, and the International Headache Society
Clinical Trials Committee31 now recommends
that the primary efficacy end point in migraine drug trials be pain free at
2 hours.
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Table 2. Ability of the Triptans to Satisfy Selected Patient Treatment
Preferences
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Sumatriptan
Sumatriptan was the first 5-HT1B/1D agonist approved for
use in the United States. Introduced in 1993 as a subcutaneous formulation,
sumatriptan is also available in oral and intranasal formulations.
Sumatriptan seems to meet several patient treatment priorities. When
administered subcutaneously at the recommended dose of 6 mg, sumatriptan relieves
pain within 30 minutes in 63% of patients and within 2 hours in 81% of patients.6 Between 54% and 61% of patients treated with 50 mg
of oral sumatriptan experience pain relief within 2 hours,9
and in some patients response occurs within 30 minutes after dosing.21 Both the subcutaneous and oral formulations are significantly
more effective than placebo in relieving migraine-associated symptoms (eg,
nausea, vomiting, photophobia).8 With the oral
50-mg dose, between 54% and 84% of patients experience no or mild clinical
disability within 4 hours after taking the drug; results for the percentage
of patients with no or mild clinical disability at the more commonly measured
2-hour time point are not available.10-11
Adverse effects are few with the 50-mg oral dose, most commonly atypical
sensations (eg, paresthesia) and pain and other pressure sensations.9 For the 6-mg injectable dose, about 60% of patients
in clinical trials experienced an injection site reaction, and 42% reported
atypical sensations.6 Dizziness or vertigo
was another common adverse effect of subcutaneous sumatriptan, occurring in
12% of patients.6 Accurate assessment of headache
recurrence is difficult, but studies indicate that 21% to 57% of patients
taking oral or subcutaneous sumatriptan experience recurrence 24 to 48 hours
after initial dosing.8 In clinical practice,
most physicians agree that the recurrence rate is about 30%. Most patients
in whom headache recurs respond to a second dose of sumatriptan.8
Most migraineurs prefer oral medication. However, when given a choice
between traditional migraine therapy and subcutaneous sumatriptan, many patients
prefer the injectable drug, primarily because it offers more rapid relief
of pain. In a study published in 1995, not long after subcutaneous sumatriptan
became available, patients with migraine expressed a strong preference for
sumatriptan over their usual migraine therapy, which included meperidine hydrochloride,
acetaminophen with or without codeine, butalbital with or without codeine,
ergotamine, and aspirin.32 Nearly all the 648
patients in this study considered "how well it works" the most important attribute
for an acute migraine medication, followed by safety and speed of onset of
effect. Patients rated subcutaneous sumatriptan more highly than their customary
migraine medications, indicating that sumatriptan better met their needs.
Similar findings were reported by Bouchard et al,33
who assessed patient satisfaction with subcutaneous sumatriptan as part of
an open-label, prospective, multinational study. In this study, 433 patients
who had treated at least one migraine attack with subcutaneous sumatriptan
completed a patient satisfaction questionnaire. Each of these patients had
used their customary prescription migraine medication to treat an unlimited
number of attacks over a 12-week period. Patients were then enrolled in a
24-week treatment phase during which they could treat an unlimited number
of migraine attacks with 6 mg of subcutaneous sumatriptan. To determine patients'
level of satisfaction with sumatriptan compared with their usual therapy,
the investigators asked them to rate the medications' performance in 5 areas:
speed of onset of action, duration of effect, dependability, ease of use,
and speed of return to normal activities. Except for ease of use, patients
rated sumatriptan higher than their customary medication on each of these
attributes.
Different formulations of sumatriptan seem to meet specific patient
needs: convenience and ease of use for the oral drug, and rapid pain relief
for the subcutaneous formulation.34 Nevertheless,
some patients fear self-injecting a drug, and others experience a burning
sensation at the injection site.35 Therefore,
subcutaneous sumatriptan, despite its high ranking in patient surveys, may
not be an ideal first choice for acute migraine therapy. However, for patients
who need quick relief, such as those who awake with an incapacitating migraine,
and for those whose nausea or vomiting prevents use of an oral drug, the subcutaneous
route is preferred.
An alternative to the subcutaneous and oral formulations of sumatriptan
is the intranasal spray. This formulation is useful for patients who want
to avoid an injectable drug and for those who cannot take oral medication
because of nausea or vomiting. Intranasal sumatriptan is rapidly absorbed
after administration, and some patients report pain relief as soon as 15 minutes
after taking the 20-mg dose.14 In controlled
clinical trials, between 55% and 64% of patients treated with 20 mg of intranasal
sumatriptan reported no or mild pain within 2 hours after administration.12 In a dose-ranging study, 42% of patients taking 20
mg of intranasal sumatriptan were pain free within 2 hours.13
Intranasal sumatriptan is also effective in relieving functional disability:
between 70% and 74% of patients taking 20 mg of intranasal sumatriptan reported
no or mild clinical disability 2 hours after administration.14-15
One drawback to intranasal administration of sumatriptan is that about 25%
of patients experience a bitter or bad taste after using this formulation.12
Zolmitriptan
Zolmitriptan is available in 2.5-mg and 5-mg conventional tablets and
in an orally disintegrating formulation that patients can take without water
(the wafer disintegrates on the tongue). The orally disintegrating formulation
of zolmitriptan is available in a 2.5-mg dose only. Although both doses are
effective, the optimal dose is 2.5 mg36; the
5-mg dose offers little added benefit over the 2.5-mg dose and has an increased
risk of adverse effects.16
Between 62% and 65% of patients treated with the 2.5-mg dose of zolmitriptan
experience pain relief within 2 hours.18 For
some patients treated with 2.5- or 5-mg zolmitriptan, pain relief begins as
soon as 45 minutes after dosing.37 Zolmitriptan
is also effective for relieving migraine-associated symptoms. In a study by
Solomon et al,18 compared with patients given
placebo, a greater percentage of patients taking 2.5 mg of zolmitriptan reported
relief of photophobia, phonophobia, and nausea 2 hours after taking the drug.
In the study by Solomon et al,18 63%
of patients with moderate or severe activity impairment before treatment with
2.5-mg zolmitriptan reported improvement in function within 2 hours after
initial dosing. However, no information was available on whether functional
impairment was completely eliminated by this point. Nevertheless, patients
taking zolmitriptan lost slightly less time from work than did those given
placebo. Patients taking zolmitriptan also had a lower rate of headache recurrence
than those given placebo (22% for 2.5-mg zolmitriptan vs 30% for placebo).
In other studies, the recurrence rate with zolmitriptan ranged from 21% to
27%.38
The most common adverse effects of 2.5-mg zolmitriptan are atypical
sensations (reported by 12% of patients in clinical trials), pain and pressure
sensations (14%), digestive problems (eg, dry mouth, dyspepsia, dysphagia,
and nausea) (16%), and neurologic problems (eg, dizziness, somnolence, vertigo)
(17%).16
No published studies have specifically assessed patient satisfaction
with zolmitriptan or whether patients prefer zolmitriptan to their usual migraine
therapy. The results of double-blind, placebo-controlled trials suggest that
patients might prefer zolmitriptan to conventional migraine drugs because
of its good efficacy and ability to relieve migraine-associated symptoms and
functional disability.18, 38
Zolmitriptan apparently can be given later in the headache phase than
other triptans with equally good results. However, this treatment strategy
is not ideal; all patients, no matter what triptan they are taking, should
be encouraged to take the medication as early in the migraine attack as possible
to obtain the greatest and most rapid benefit.
Rizatriptan
Rizatriptan is available as a conventional tablet and in an orally disintegrating
formulation (wafer). Rizatriptan is available in 5-mg and 10-mg doses; for
most patients, the 10-mg dose provides the greatest response. In clinical
trials, between 67% and 77% of patients treated with 10-mg rizatriptan reported
pain relief within 2 hours.19 Notably, compared
with patients given placebo, significantly more patients taking 10-mg rizatriptan
experience pain relief within 30 minutes after drug administration.21 Between 42% and 48% of patients treated with 10-mg
rizatriptan are able to function normally within 2 hours after taking the
drug, based on a stringent measure of functional disability (the absence of
any disability whatsoever).20 Return to normal
functioning is aided by the ability of rizatriptan to relieve migraine-associated
symptoms. Within 2 hours after dosing, nausea, photophobia, and phonophobia
are alleviated in 60% to 77% of patients given 10 mg of rizatriptan.20
Adverse effects associated with rizatriptan are similar to those of
other triptans. The most common adverse effects reported by patients treated
with 10-mg rizatriptan in clinical trials included pain and other pressure
sensations (reported by 9% of patients), dizziness (9%), somnolence (8%),
and asthenia or fatigue (7%).19 Headache recurrence
rates with rizatriptan are also similar to those reported for other triptans.
More than 80% of patients obtain relief from headache recurrence with a second
rizatriptan dose.39
Many patients have a better response to rizatriptan than to standard
acute migraine therapy. In a study by Block et al,40
613 patients were randomly assigned to treatment with 5-mg rizatriptan, 825
patients to 10-mg rizatriptan, and 329 patients to standard migraine therapy
prescribed by the investigators (including sumatriptan, nonsteroidal anti-inflammatory
drugs, acetaminophen, and barbiturates). At the end of the 12-month study
period, patients taking 10-mg rizatriptan reported pain relief within 2 hours
for a median of 90% of their migraine attacks, compared with 70% of attacks
for patients treated with standard therapy. The median percentage of migraine
attacks for which patients reported being pain free within 2 hours was 50%
for 10-mg rizatriptan and 29% for standard therapy.
In a prospective study by Solomon et al,41
194 patients who had never taken any triptan prior to the study and who used
10-mg rizatriptan in the study to treat 2 migraine attacks reported better
responses to rizatriptan than to the nontriptan medications they had been
using. Thirteen percent of patients taking the rizatriptan tablet and 19%
of those taking the rizatriptan orally disintegrating tablet (wafer) reported
pain relief within 30 minutes of dosing; when taking their nontriptan medication,
only 7% of patients had pain relief within 30 minutes. Significantly more
patients treated with rizatriptan were able to return to normal activities
within 2 hours and had no or only mild pain within 2 hours as opposed to those
taking nontriptan medications. With these improved treatment outcomes, patients
were significantly more satisfied (very or somewhat satisfied) with rizatriptan
than with their usual therapy (73% for rizatriptan tablets and 76% for rizatriptan
wafers vs 34% for nontriptan medications).
Naratriptan
Based on clinical trial results, naratriptan seems less likely than
other available triptans to satisfy patients' clear desire for rapid pain
relief. In clinical trials of naratriptan, the primary end point was pain
relief at 4 hours (the primary end point in trials of other triptans was pain
relief at 2 hours). Although 60% to 66% of patients treated with 2.5-mg naratriptan
reported pain relief within 4 hours,25 only
an estimated 48% of patients taking naratriptan experienced pain relief at
2 hours (a more widely used and accepted end point).26
Naratriptan at the 2.5-mg dose is effective for migraine-associated symptoms
(relieves nausea within 2 hours in 55%-60% of patients, photophobia in 37%-42%,
and phonophobia in 43%-47%).27-28
At 4 hours, 71% to 75% of patients taking 2.5 mg of naratriptan had no nausea,
57% to 61% had no photophobia, and 57% to 65% had no phonophobia.27-28 Return to normal functioning was
specifically assessed in only 1 clinical trial. In this study, within 4 hours
of dosing, 70% of patients treated with 2.5-mg naratriptan were able to function
normally or had only a mild impairment in ability to function.27
A recently published report of an open-label trial found that patients
preferred naratriptan to conventional migraine therapy.42
In this study, patients were asked to treat 3 migraine attacks with 2.5-mg
naratriptan and record their responses in a diary. Of the 143 patients participating
in this study, 62% had previously used a triptan (lack of prescribing was
the primary reason these patients did not continue to use a triptan). Among
the nontriptan agents used to treat migraine, 59% of patients took simple
analgesic agents, 46% used combination products, and 13% used narcotic agents.
At the end of the study, patient satisfaction with migraine therapy increased
from 47% to 75%. Also, 63% of patients preferred naratriptan to their previous
nontriptan medication, while 27% preferred their nontriptan medication, and
10% had no preference. The principal reasons patients preferred naratriptan
was that it effectively relieved their pain and allowed them to return to
normal functioning.
The percentage of patients experiencing adverse effects with naratriptan
is low. In clinical trials of 2.5-mg naratriptan, atypical sensations were
reported by 4% of patients, nausea by 7%, neurologic problems (dizziness,
drowsiness, malaise, or fatigue) by 7%, and pain and other pressure sensations
by 4%.25 Two studies found headache recurrence
in 27%,27 and 28%28
of patients, respectively; another found a 45% recurrence rate.26
Nonetheless, naratriptan may be appropriate for patients whose migraines frequently
recur and for those with a tendency toward triptan rebound.
Almotriptan
Almotriptan is the newest triptan to become available in the United
States. Almotriptan is available in 6.25-mg and 12.5-mg tablets; in clinical
trials, the 12.5-mg dose proved more effective than the 6.25-mg dose for most
patients.29 Betweeen 57% and 65% of patients
treated with 12.5-mg almotriptan reported pain relief within 2 hours after
taking the drug.29 The incidence of adverse
effects with almotriptan is low. The most common adverse effects reported
in clinical trials of 12.5-mg almotriptan were nausea in 2% of patients, dry
mouth in 1%, and paresthesia in 1%.29
The low incidence of adverse effects with almotriptan is a positive
attribute for patients. In a comparison of treatment satisfaction, functional
status, and health-related quality of life in 1173 patients treated with 12.5-mg
almotriptan or 50-mg sumatriptan, no significant differences in treatment
satisfaction were seen between the 2 groups in terms of pain relief.43 However, when treatment satisfaction was based on
adverse events, patients were significantly more satisfied with almotriptan
than with sumatriptan (P = .02). Improvement in functional
disability, however, did not differ between groups.
COMPARISON STUDIES
Although none of the triptans meets all the criteria established by
patients for an ideal migraine drug, some may be better than others in meeting
patients' needs. Data from comparison trials therefore are useful21-22,24, 30, 44-46(Table 3).
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Table 3. Comparison of the Ability of Triptans to Satisfy Selected
Patient Treatment Preferences
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Rizatriptan vs Sumatriptan
Ten-milligram rizatriptan seems to have some advantages over 50- and
100-mg sumatriptan in satisfying patient treatment preferences. In a study
by Goldstein et al,21 10-mg rizatriptan provided
faster and greater pain relief as well as greater improvement in functional
disability than did 50-mg sumatriptan. In this trial of 1329 patients, 10-mg
rizatriptan and 50-mg sumatriptan were similarly effective in relieving pain
within 2 hours, but rizatriptan was significantly more effective than sumatriptan
in providing complete pain relief within 1 hour. Significant differences favoring
rizatriptan also emerged between the 2 groups in relief of nausea, ability
to return to normal functioning, and overall satisfaction with the medication.
In a study comparing 10-mg rizatriptan with 100-mg sumatriptan, rizatriptan
was superior to sumatriptan on several efficacy measures, including pain relief
at 1 hour, pain free at 1.5 and 2 hours, return to normal functioning at 2
hours, and complete relief of nausea at 2 hours.22
Rizatriptan doses of 10 mg also caused significantly fewer drug-related adverse
effects than did 100-mg sumatriptan.22
The ability of rizatriptan to rapidly relieve migraine pain clearly
is important to patients. In a study of 386 migraineurs, significantly more
patients preferred 10-mg rizatriptan (wafer formulation) to 50-mg sumatriptan
(oral tablet) (57% preferred rizatriptan and 43% preferred sumatriptan; P = .01). The principal reason (50%) for preferring one
drug to the other was speed of pain relief.47
The convenience of the rizatriptan wafer (the drug can be taken anywhere,
without water) also was important for patients preferring rizatriptan.47
Zolmitriptan vs Sumatriptan
A recently published report suggests that 2.5-mg zolmitriptan might
be somewhat more effective than 50-mg sumatriptan. In this study of 1445 patients
with migraine, 2.5-mg zolmitriptan was significantly more likely than 50-mg
sumatriptan to relieve pain at 2 hours and 4 hours; at 2 hours, 67% of patients
taking 2.5-mg zolmitriptan and 64% of those given 50-mg sumatriptan reported
pain relief (P = .02).44
The investigators in this study also concluded that patients taking zolmitriptan
were significantly more likely to have pain relief over 24 hours than were
those given sumatriptan.
In a patient preference study by Pascual et al,48
more rapid pain relief was the most important reason cited by patients for
preferring 2.5-mg zolmitriptan to 50-mg sumatriptan. In this study, 100 migraineurs
treated 3 migraine attacks with zolmitriptan or sumatriptan. Among the 94
patients who completed the study, 44% preferred zolmitriptan, 29% preferred
sumatriptan, and 27% had no preference. In addition to speed of pain relief,
patients preferred zolmitriptan because of its duration of effect, fewer adverse
effects, and lower price.
Rizatriptan vs Zolmitriptan
Compared with zolmitriptan, rizatriptan seems to offer several advantages.
In a randomized, double-blind, placebo-controlled trial of 766 patients, 10-mg
rizatriptan was more effective than 2.5-mg zolmitriptan in speed of pain relief,
complete pain relief, relief of functional disability, and relief of nausea
and photophobia.45 In this trial, significantly
more patients taking rizatriptan were completely pain free at 2 hours than
were those treated with zolmitriptan (43% vs 36%; P
= .04). Patients taking rizatriptan also were more likely than those given
zolmitriptan to experience sustained complete pain relief (ie, no recurrence
of pain or need for additional medication within 24 hours after dosing among
patients who initially reported being pain free within 2 hours after dosing).
Significantly more patients in the rizatriptan group than in the zolmitriptan
group reported pain relief within 1 hour (43% vs 35%; P = .03). Moreover, compared with patients taking zolmitriptan, patients
given rizatriptan were more likely to be able to function normally within
1.5 hours and afterward; at 2 hours, 45% of patients in the rizatriptan group
and 37% of those in the zolmitriptan group had no functional disability (P = .03).
An open-label study comparing 10-mg rizatriptan with 5-mg zolmitriptan
in patients who had not responded to sumatriptan further suggests that rizatriptan
might be a better choice in this patient population.45
In this trial, rizatriptan had a more rapid onset of effect (mean ±
SD time to onset, 35 ± 10 minutes vs 45 ± 9 minutes), relieving
pain in 81% of patients within 2 hours, compared with 73% of patients taking
zolmitriptan. At 1 hour, 29% of patients treated with rizatriptan and 21%
of those given zolmitriptan were pain free. Rizatriptan also was rated higher
than zolmitriptan on a patient satisfaction index. This study also supports
the clinical observation that failure to respond to one triptan does not mean
a patient will not respond to another, as evidenced by the high response rate
to rizatriptan and zolmitriptan among patients who had not responded to sumatriptan
when using that drug to treat 5 migraine attacks.
Rizatriptan vs Naratriptan
In a study of 522 migraineurs, 10-mg rizatriptan relieved pain and provided
complete pain relief more quickly than did 2.5-mg naratriptan; rizatriptan
also provided faster relief of migraine-associated symptoms and allowed patients
to return to normal activities sooner.24 Overall,
rizatriptan seemed to better meet patients' needs, as reflected in scores
on a 7-point medication satisfaction scale in which lower scores indicated
greater satisfaction (ie, 1 indicated completely satisfied and 7, completely
dissatisfied). At 2 hours, the mean score was 3.55 for rizatriptan vs 4.21
for naratriptan (P<.001).
Almotriptan vs Sumatriptan
In a double-blind, randomized trial of 1255 patients, 12-mg almotriptan
and 50-mg sumatriptan proved equally effective in relieving migraine pain.30 At 2 hours, 58% of patients taking almotriptan and
57% of those given sumatriptan reported pain relief. However, compared with
the almotriptan group, significantly more patients in the sumatriptan group
reported being pain free at 2 hours (25% vs 18%; P
= .005). Although no significant differences in complete pain relief between
groups were seen at 0.5 hour or 1 hour, this finding suggests that almotriptan
might be less likely than sumatriptan to meet patients' preference for complete
relief of pain.
In this study, almotriptan and sumotriptan were comparable in their
ability to relieve migraine-associated symptoms, and no significant differences
were seen in the percentage of patients reporting recurrence (headache recurred
within 24 hours in 27% of patients in the almotriptan group and 24% of those
in the sumatriptan group). Significant differences were seen in the incidence
of adverse effects, with treatment-related events being lower in the almotriptan
group (9% vs 16%; P = .001). Based on the results
from this comparative trial, almotriptan causes few adverse effects, a desirable
attribute, but is less likely than sumatriptan to completely relieve pain
within 2 hours.
CONCLUSIONS
Patients with migraine have clear treatment preferences in migraine
medication. They generally want a drug that provides rapid, complete relief
of pain and migraine-associated symptoms, allows them to quickly return to
their normal activities, prevents the headache from recurring, and causes
few adverse effects. Individual patients may have specific preferences; for
example, some may prefer the convenience of oral administration while others
seek the rapid onset of effect provided by a subcutaneous drug. In all cases,
physicians need to recognize the needs of their patients with migraine and
seek out the medications that will best meet these needs.
The triptan class of migraine drugs provides many of the attributes
patients seek in a migraine medication. With all the drugs in this class,
most patients experience relief of pain and relief of associated symptoms
(eg, nausea, photophobia, phonophobia) within 2 hours after dosing. In comparison
trials, some differences among the triptans emerge, although further studies
are necessary to confirm whether one triptan relieves pain better or more
rapidly than another. Until clear distinctions among the drugs in this class
emerge, physicians can be confident that each of the currently available triptans
satisfies many of the treatment preferences expressed by patients with migraine.
AUTHOR INFORMATION
Accepted for publication April 9, 2001.
Corresponding author and reprints: Robert E. Ryan, Jr, MD, 1585 Woodlake
Dr, Suite 200, St Louis, MO 63017 (e-mail: drrerjr{at}aol.com).
From the Ryan Headache Center and Unity Health Research and the Department
of Otolaryngology, St Louis University School of Medicine, St Louis, Mo.
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