J Headache Pain (2004) 5:S112S116
DOI 10.1007/s10194-004-0123-4Michele Feleppa
Fred D. Sheftell
Luciana Ciannella
Amedeo DAlessio
Giancarlo Apice
Nino N. Capobianco
Donato M.T. Saracino
Walter Di Iorio
Marcelo E. BigalA new questionnaire for assessment of adverse
events associated with triptans: methods of
assessment influence the results.
Preliminary resultsReceived: Accepted in revised form: M. Feleppa () L. CiannellaA. DAlessio G. Apice N.N. CapobiancoW. Di IorioDepartment of Neuroscience,
Hospital G. Rummo,
Via dellAngelo, I-82100 Benevento, Italy
e-mail: [email protected]
Tel.: +39-0824-57492/57465
Fax: +39-0824-57465F.D. SheftellDepartment of Psychiatry,
New York Medical College, NY, USAF.D. Sheftell M.E. BigalThe New England Center for Headache,
Stamford, CT, USAD.M.T. SaracinoDepartment of Medical Up-Grading,
Hospital G. Rummo, Benevento, ItalyM.E. BigalDepartment of Neurology,
Albert Einstein College of Medicine,
NY, USAAbstract Triptans are the treatment
of choice for migraine sufferers
with disabling attacks. However,
the proportion of patients reporting
side effects after any acute treatment may vary in regard to the
method of assessment. This study
was conducted in a neurology
office focusing on headache in
Italy. We prospectively surveyed
adult headache sufferers who had
been using the same triptan for at
least 3 months (from March 2001 to
May 2003). Participants were asked
about their headache and treatment
history. Subjects then completed a
standardized questionnaire, assessing adverse events in two different
ways. First, subjects were asked if
they had any adverse events when
using the triptan. If they answered
yes, they were asked to list them
and grade their severity as mild,
moderate, or severe. After returning
the first part of the questionnaire,
subjects received a second form,
where 49 possible adverse events
were listed. Most of them were
known triptan side effects; some
confounders (side effects not
expected to be related with triptan
use) were added. We contrasted and
correlated both sets of answers. We
surveyed 108 subjects, (87.1%
female, mean age 39.5 years). Most
patients (65.5%) reported no side
effects in the unprompted questionnaire. However, most of them(54.1%) reported at least one side
effect in the prompted questionnaire. The majority of patients that
reported side effects in the
unprompted questionnaire said they
had only one adverse event, while
most reported two or more side
effects in the prompted questionnaire. Both in the unprompted and
in the prompted questionnaires,
most side effects were rated as mild
or moderate. Two (1.9%) subjects
graded their adverse events as
severe in the prompted questionnaire, but had not self-reported
them. We conclude that when
assessing the adverse events of triptans (or any class of medication),
the method of data collection may
dramatically influence the results.Key words Triptans Adverse
events Methods of assessmentS113IntroductionTriptans are the treatment of choice for migraine sufferers
with disabling attacks [1]. Six oral triptans, in different
doses and formulations, are available in Italy [2, 3].
Tolerability is the second most important attribute of an
acute treatment for nave migraine sufferers [4]. Triptans
have different tolerability profiles [5]. Sheftell et al. recently conducted a study showing that from 7% to 39% (depending on the triptan and the formulation) of migraine sufferers
switching triptans did so because of side effects [6].Major methodological issues involve the assessment of
tolerability. Safety and tolerability have different definitions
and different methods of assessment [7]. In addition, the
proportion of patients reporting side effects after any acute
treatment may vary in regard to the method of assessment.
This issue is also of major significance regarding triptans.
Because we consider that the methods of assessing tolerability may dramatically influence the results, in this study
we prospectively contrasted two methods of assessing
adverse events (prompted and unprompted) in headache sufferers using triptans.Patients and methodsWe prospectively surveyed adult headache sufferers from March
2001 to May 2003 fulfilling the following inclusion criteria:1. Diagnosis of migraine made according to the first edition of the
International Headache Society (1988) criteria [8], or diagnosis
of transformed migraine without medication overuse according
to the criteria proposed by Silberstein and Lipton [9]2. Patients had been using the same triptan for at least 3 months.3. Patients had been followed up at the center for at least 1 year
At the time this study was performed, frovatriptan and naratriptan were not available.Participants were first asked about their headache and treatment
history. After being included, all subjects completed a standardized
questionnaire, assessing adverse events in two different ways. First,
subjects were asked if they had any adverse events when using the
triptan (unprompted questionnaire) (Fig. 1). If they answered yes,
they were asked to list them and grade their severity as mild, moderate, or severe and their time relief in minutes.After returning the first part of the questionnaire, subjects
received a second form. The second form was answered on the
same day, but the subjects did not have the opportunity to check
their answers in the first questionnaire. In the second questionnaire (prompted questionnaire), 49 possible adverse events wereFig. 1 Questionnaire (simplified) for
unprompted and prompted side effectsS114listed (Table 1). Most of them were known triptan side effects,
chosen from the PDR and from the pivotal clinical trials; some
confounders (side effects not expected to be related with triptan
use) were added.The main objective of this study was to contrast and correlate both sets of answers (prompted and unprompted). Data were
analyzed using Stata (Intercooled Stata 6.0 for Windows,
College Station, TX). The chi-square test was used to determine
statistical significance unless otherwise indicated. The number
and severity of side effects in both methods were assessed using
the chi-square test for trends.n (%) ResultsWe surveyed 108 subjects (87.1% female, mean age 39.5
years) (Table 1). The vast majority of the participants had
migraine (94.6%). Most patients were using rizatriptan(39.8%), followed by almotriptan (21.3%) (Table 2). The
majority of patients (65.5%) reported no side effects in the
unprompted questionnaire. However, most of them(54.1%) reported at least one side effect in the prompted
questionnaire (Fig. 2). Most patients who reported side
effects in the unprompted questionnaire said they had only
one adverse event, while most reported two or more side
effects in the prompted questionnaire. Both in the
unprompted and in the prompted questionnaires, most side
effects were rated as mild or moderate (Table 3).Table 1 Demographic characterizationDiagnosisMigraine 102 (94.6)
Transformed migraine 6 1(5.4)
Male 14 (12.9)
Female 94 (87.1)
Age, mean (SD) 39.5 (12.2)Table 2 Triptan being used when patients were enrolled in the
study. Surveyed patients n=108n (%)Sumatritptan 11 (10.2)Tablet 100 mg 7 1(4.7)
Tablet 50 mg 11 1(7.4)
Nasal spray 20 mg 0 (12.9)
Injection (6 mg) 0 (12.9)
Zolmitriptan 14 (12.9)Tablet 5 mg 2 1(1.4)
Tablet 2.5 mg 12 1(8.1)
Dissolving tablet 5 1(3.4)
Rizatriptan 43 (39.8)Tablet 10 mg 26 (17.6)
Tablet 5 mg 1 1(6.7)
Dissolving tablet 30 (20.7)
Eletriptan 17 (15.8)
Almotriptan 23 (21.3)*Subjects (%)* *Fig. 2 Proportion of subjects reporting side effects in the unprompted
and prompted questionnaires.
*p<0.001; **p<0.0001S115Table 3 Number and intensity of side effects assessed by the
unprompted and prompted methodsUnprompted Prompted pNumber of different
adverse events, n (%)1 23 (56) 26 (40.6) 0.01
2 14 (34.1) 22 (34.3)3 or more 4 (9.7) 16 (25)
Intensity ofadverse events, %Mild 37.2 37.5 NS
Moderate 39.2 42.5Severe 23.6 20.0Table 4 Common side effects in the unprompted and prompted
questionnairesSide effects Unprompted Prompted pPalpitation 7 (6.7%) 18 (17.3%) <0.001
Sleep disturbances 8 (7.6%) 18 (17.3%) <0.001
Sweating 7 (6.7%) 18 (17.3%) <0.001
Difficulty of concentration 4 (3.8%) 14 (13.4%) <0.0001
Weakness 4 (3.8%) 4 1(3.8%) NS
Abdominal pain 2 (1.9%) 3 1(2.8%) NS
Chest tightness 2 (1.9%) 6 1(5.7%) <0.01
Chest pain 2 (1.9%) 9 1(8.6%) <0.01
Tremor 1 (0.9%) 5 1(4.8%) <0.0001Interestingly, two (1.9%) subjects graded their adverse
events as severe in the prompted questionnaire, but had
not self-reported them. Most side effects were significantly more frequently reported in the prompted method.
While only 1.9% of the subjects reported chest tightness
and chest pain in the unprompted method, 5.7% and 8.6%
of them (p<0.01), respectively, reported these symptoms
in the prompted method. Palpitations were self-reported
by 6.7% of the subjects, and actively reported by 17.3% of
them (p<0.001); sleep disturbances were self-reported by7.6% of the subjects, and actively reported by 17.3%
(p<0.001); sweating was self-reported by 6.7% of the subjects, and actively reported by 17.3% (p<0.001); difficulty
concentrating was self-reported by 3.8% of the subjects,
and actively reported by 13.4% (p<0.0001) (Table 4).DiscussionThe triptans are generally very well tolerated, with less
than half of patients reporting adverse events, mostly
mild in intensity and transient [2, 1012]. The methods
used to assess tolerability often are not described in detail
in randomized clinical trials on triptans. It is difficult to
assess, for a particular trial, how information on side
effects was collected and whether lists of side effects
were presented. While some trials do not report the methods used to collect side effects [14], others used what
seems to be an unprompted method [15]. There are
methodological differences even when the unprompted
method is used. In some trials, patients record the side
effects in a headache diary [15], while in others the collection is also complemented by communication with the
study coordinator [16]. Finally, some studies actively
searched for the incidence and nature of all serious
adverse events (at any time before or after administration) [17]. In our preliminary data, we showed that when
assessing triptan adverse events, the method of data collection may dramatically influence the results. We also
showed that from those subjects who did not self-report
adverse events after using a triptan, most checked one or
more of these events when presented with a list of possible adverse events. Even the rates of more dramatic side
effects (like palpitations, chest pain, or chest tightness)
may dramatically differ according to the methodology of
data collection used. At first sight, it seems that prompted methods are more sensitive in assessing side effects,
but on the other hand, it is important to note, as some
authors argue, that patients given considerable information about the side effects of drugs substantially overestimate their personal risk. For example, the European
Union guidelines recommend use of qualitative descriptions for five bands of risk, ranging from very rare
(affecting <0.01% of the population) to very common
(>10%) [17]. A study assessed 360 adults who were given
either qualitative descriptions of drug side effects (common and rare) or corresponding quantitative descriptions (2% and 0.02%). Participants given the term common rated their personal risk of having a side effect as
50%, whereas those given the equivalent numerical value
of 2% rated their risk as 9.5%; people who were told their
chances of side effects were rare estimated their risk as
21%, compared with 7% for patients who were given a
quantitative risk of 0.02% [18]. Triptans are the drug of
choice for most migraine sufferers who seek care [1, 2].
Even though there are more similarities than differences
among triptans, they do have important clinical differences. Our data support the following conclusions: (1)
when assessing triptan (or any class of medication)
adverse events, the method of data collection may dramatically influence the results; (2) some patients who do
not self-report adverse events after using a triptan do in
fact have side effects (44.3%); (3) care should be taken
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Copyright Springer-Verlag 2004
Abstract
Triptans are the treatment of choice for migraine sufferers with disabling attacks. However, the proportion of patients reporting side effects after any acute treatment may vary in regard to the method of assessment. This study was conducted in a neurology office focusing on headache in Italy. We prospectively surveyed adult headache sufferers who had been using the same triptan for at least 3 months (from March 2001 to May 2003). Participants were asked about their headache and treatment history. Subjects then completed a standardized questionnaire, assessing adverse events in two different ways. First, subjects were asked if they had any adverse events when using the triptan. If they answered yes, they were asked to list them and grade their severity as mild, moderate, or severe. After returning the first part of the questionnaire, subjects received a second form, where 49 possible adverse events were listed. Most of them were known triptan side effects; some confounders (side effects not expected to be related with triptan use) were added. We contrasted and correlated both sets of answers. We surveyed 108 subjects, (87.1% female, mean age 39.5 years). Most patients (65.5%) reported no side effects in the unprompted questionnaire. However, most of them (54.1%) reported at least one side effect in the prompted questionnaire. The majority of patients that reported side effects in the unprompted questionnaire said they had only one adverse event, while most reported two or more side effects in the prompted questionnaire. Both in the unprompted and in the prompted questionnaires, most side effects were rated as mild or moderate. Two (1.9%) subjects graded their adverse events as severe in the prompted questionnaire, but had not self-reported them. We conclude that when assessing the adverse events of triptans (or any class of medication), the method of data collection may dramatically influence the results.[PUBLICATION ABSTRACT]
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer