Randomised controlled trial of butterbur and cetirizine
for treating seasonal allergic rhinitis
Andreas Schapowal on behalf of Petasites Study Group
Objectives To compare the efficacy and tolerability of
butterbur (Petasites hybridus) with cetirizine in patients
with seasonal allergic rhinitis (hay fever).
Design Randomised, double blind, parallel group
Setting Four outpatient general medicine and allergy
clinics in Switzerland and Germany.
Participants 131 patients were screened for seasonal
allergic rhinitis and 125 patients were randomised
(butterbur 61; cetirizine 64).
Interventions Butterbur (carbon dioxide extract
tablets, ZE 339) one tablet, four times daily, or
cetirizine, one tablet in the evening, both given for two
Main outcome measures Scores on SF-36
questionnaire and clinical global impression scale.
Results Improvement in SF-36 score was similar in
the two treatment groups for all items tested
hierarchically. Butterbur and cetirizine were also
similarly effective with regard to global improvement
scores on the clinical global impression scale (median
score 3 in both groups). Both treatments were well
tolerated. In the cetirizine group, two thirds (8/12) of
reported adverse events were associated with sedative
effects (drowsiness and fatigue) despite the drug being
considered a non-sedating antihistamine.
Conclusions The effects of butterbur are similar to
those of cetirizine in patients with seasonal allergic
rhinitis when evaluated blindly by patients and
doctors. Butterbur should be considered for treating
seasonal allergic rhinitis when the sedative effects of
antihistamines need to be avoided.
Allergic rhinitis,whether seasonal or perennial,is char-
acterised by sneezing, rhinorrhoea, obstruction of the
nasal passages, conjunctival and pharyngeal itching,
and lacrimation. Allergic rhinitis, often inappropriately
called hay fever, is caused by the deposition of
membranes, resulting in a type I hypersensitivity
Butterbur (Petasites hybridus; butter dock, bog rhu-
barb, exwort) is an Asteraceae herbaceous plant native
to Europe, northern Africa, and south western Asia.3
The leaves and roots of butterbur contain a mixture of
eremophilan type sesquiterpenes (petasines). Extracts
of butterbur have been used in bronchial asthma,
smooth muscle spasms, and headache.4Petasines
inhibit the biosynthesis of leukotrienes, which may be
associated with antispasmodic activity and anti-
inflammatory action in type I hypersensitivity.5–7
The usual treatment for seasonal allergic rhinitis is
antihistamines. These reduce rhinorrhoea and sneez-
ing but are less effective for nasal congestion and may
cause sedation and drowsiness. Antihistamines can be
obtained over the counter for treatment of hay fever,
and all may interact with alcohol and decrease driving
ability.8We conducted a randomised controlled trial of
butterbur extract tablets (ZE 339) and a commonly
used non-sedating antihistamine (cetirizine) to com-
pare the effectiveness of these two treatments.
Participants and methods
All participants were outpatients attending four general
medicine and allergy clinics between June 1999 and
June 2000. Study medication consisted of butterbur
(petasites carbon dioxide extract ZE 339 standardised to
8.0mg of total petasine per tablet; one tablet, four times
daily) or cetirizine (one 10 mg tablet daily), as
recommended by the manufacturers. Each day, partici-
pants took five tablets, four of which contained either
or placebo, depending on the treatment group. The
study was approved by the relevant ethics committees in
Germany and Switzerland.
All participants were aged >18 years, had a history of
seasonal allergic rhinitis for at least two consecutive
years, and fulfilled the seasonal allergic rhinitis diagnos-
tic criteria. Baseline assessment was made at the referral
consultation, when the inclusion and exclusion criteria
were checked. All participants had skin allergy tests, and
all but one were allergic to pollen. They also had a full
medical examination, after which they were given treat-
ment for two weeks. Participants could return after one
week if they experienced adverse events or deteriora-
tion. At the visit at the end of week 2, participants had a
full medical examination and we checked compliance
and adverse events. Exposure to pollen was confirmed
for each participant through crosschecking the treat-
ment period with the online regional pollen count
Statistics, assignment, and analysis
Randomisation was provided centrally in blocks of
four.Analysis was on an intention to treat basis,defined
as all randomised patients who had at least one
baseline and one follow up value and took any
medication. The planned sample size was a minimum
of 120 patients, based on previous studies of allergic
rhinitis,9 10with a 10% expected withdrawal rate and an
assumed effect size of 0.5.
The main outcome variable was change from base-
line to end point in the score of each item on the medi-
cal outcome health survey questionnaire (SF-36).10The
secondary outcome variables were the physicians’clini-
cal global impression score and the SF-36 score for
Between treatment comparisons were tested by the
Mann-Whitney test (two sided). The exploratory
secondary variables were evaluated by inference statis-
tics with a shifted null hypothesis adjustment to
The full version of
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consultant in ear,
BMJ VOLUME 32419 JANUARY 2002bmj.com
baseline according to the method of Abt,12with means,
standard deviation, medians, 95% confidence intervals,
and absolute and relative frequencies. For participants
who withdrew we carried forward the last observation.
The mean of both treatment groups was used to
substitute missing values.
Patients’ characteristics and flow through study
A total of 131 patients were initially screened; six did
not give consent, and 125 were randomised. Partici-
pants’ characteristics at entry were similar in the two
groups (table 1). The population was representative of
patients with seasonal allergic rhinitis who seek
treatment in the primary care sector
At the end of the treatment period none of the scores
in the butterbur group was more than 10% worse than
in the cetirizine group (table 2). The secondary
outcome measures were also comparable in the two
The overall incidence of adverse events was similar for
the two treatments: 16% in the butterbur group
(10/61) and 17% in the cetirizine group (11/64). No
event could be considered to be typically associated
with butterbur, all having been reported once or twice
only. Conversely, two thirds of events in the cetirizine
group were typical of antihistamines—that is, drowsi-
ness and fatigue.One patient was withdrawn (butterbur
group) because she required corticosteroids for previ-
ously existing asthma.
conduct, not least because of the easy access to
anti-allergic treatments by patients. These treatments
include a large number of antihistamines and cortico-
steroid nasal sprays available without prescription. To
overcome the possible contamination of results by the
use of other treatments, we monitored patients closely
and allowed them to visit the clinics whenever they felt
enhance patient compliance, and bearing in mind the
acutely debilitating symptoms of hay fever,we also kept
the treatment period as short as possible (two weeks).
In our experience, patients with this condition do not
tolerate ineffective treatments for longer periods.
The number of randomised controlled trials with
recently.13–15Herbal treatments are being used more
often by doctors and, in our experience, are often
requested by patients.
further intervention. To
Table 1 Patients’ characteristics at entry to study
Mean (SD) age (years)
Mean (SD) height (m)
Mean (SD) weight (kg)
No (%) of women
No (%) of smokers
Sneezing (No (%) moderate or worse)
Rhinorrhoea (No (%) moderate or worse)
Itchy nose or eyes (No (%) moderate or worse)
Nasal congestion (No (%) moderate or worse)
Mean (SD) SF-36 item score (main outcome measures):
Secondary outcome measures:
Mean (SD) clinical global impression score (severity of
SF-36 score for overall status (No (%) worse or much worse
than 1 year ago)
Butterbur (n=61) Cetirizine (n=64)
5.6 (0.8)5.6 (0.8)
27 (44)32 (50)
Table 2 Results of primary and secondary outcome measures after two weeks’ treatment
Median score (minimum-maximum)
P value for
medians*Butterbur (n=61)Cetirizine (n=64)
Primary outcome measures (SF-36 score)
Secondary outcome measures
Clinical global impression score:
Severity of condition‡
Risk to benefit§
SF-36 score for overall status (No (%) worse or much worse
than 1 year ago)§
*Mann-Whitney test (two sided). Significant values mean the treatment effects are different.
†Mann-Whitney rank sum test (one sided). Significant values mean butterbur is not inferior.
‡Negative values represent improvement in scores.
§Results for these items are medians at endpoint not adjusted for baseline.
Note: Data are non-normally distributed for all items (Shapiro-Wilk: P<0.01).
BMJ VOLUME 32419 JANUARY 2002bmj.com
Value of butterbur Download full-text
Although the effects of butterbur have been linked to its
constituents,5–7we set out to test whether its clinical
effects in seasonal allergic rhinitis were comparable to
those of antihistamines as judged separately and blindly
by patients and their doctors. The results showed that
the effects of the two treatments are similar. The trends
in favour of butterbur in some measures need to be con-
firmed in future prospective trials. With regard to safety,
butterbur was well tolerated and did not have the
sedative effects associated with antihistamines. We
believe butterbur should be considered for treating sea-
sonal allergic rhinitis, particularly in cases where the
sedative effects of antihistamines need to be avoided.
Contributors: see bmj.com
Funding: Zeller AG (Switzerland) supplied study medication
and sponsored the study through the Clinical Research Organ-
Germany. The interpretation of the results was the prerogative
of the principal investigator and the study group.
Competing interests: None declared.
Praxis Klinische Arzneimittelforschung, Pohlheim,
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(Accepted 13 September 2001)
Analysis of adherence to peak flow monitoring when
recording of data is electronic
Helen K Reddel, Brett G Toelle, Guy B Marks, Sandra I Ware, Christine R Jenkins, Ann J Woolcock
Peak flow monitoring is widely recommended in
international asthma guidelines. However, suspicions
about the accuracy of conventional pen and paper
records were confirmed when studies with electronic
spirometers showed poor adherence and falsification of
data.1There seems to be a prevailing nihilistic attitude to
peak flow monitoring, largely based on the perception
that satisfactory adherence cannot be achieved. We
aimed to measure long term adherence to electronic
peak flow monitoring when participants were aware that
data were being stored and used to guide treatment.
Participants, methods, and results
We obtained data from a 72 week randomised study
comparing two starting doses of budesonide in
patients aged 18-75 with poorly controlled asthma.
The design and outcomes of the study are reported
elsewhere.2The study incorporated two novel features:
twice daily monitoring with electronic diary spiro-
Rochester, UK) and titration of dose of budesonide
(weeks 17-72) by using a clinical algorithm based on
peak flow and diary data. A cumulative chart of peak
flow and forced expiratory volume in one second was
discussed with each participant at each eight weekly
visit. We assessed adherence to monitoring as the
percentage of scheduled sessions recorded.
Median overall adherence to monitoring over
weeks 1-72 or until withdrawal was 89% (interquartile
range 69-97). Adherence declined gradually from 96%
in weeks 1-8 to 89% in weeks 64-72 (Spearman’s
R = − 0.20, P < 0.0001 for correlation between eight
week period and adherence) (figure).Eight participants
were withdrawn because of problems with adherence.
With appropriate use of electronic devices it is possible
to achieve high levels of adherence to monitoring,
What is already known on this topic
Seasonal allergic rhinitis (hay fever) is common in countries with
Most patients have their symptoms treated for short periods,
particularly during peaks in atmospheric pollen count
What this study adds
After two weeks, the effects of butterbur and cetirizine were
comparable in patients with hay fever
Butterbur produced fewer sedating effects than cetirizine
Butterbur should be considered when the sedating effects of
antihistamines must be avoided
This article is part
of the BMJ’s
controlled trial of
open peer review.
relating to the
making process is
available on the
H K Reddel
BMJ VOLUME 324 19 JANUARY 2002bmj.com