J Headache Pain (2011) 12:235 238
DOI 10.1007/s10194-011-0294-8
RAPID COMMUNICATION
Experience with onabotulinumtoxinA (BOTOX) in chronic
refractory migraine: focus on severe attacks
" "
A. Oterino C. Ram贸n J. Pascual
Received: 8 December 2010 / Accepted: 9 January 2011 / Published online: 5 February 2011
脫 The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract The objective of this study is to analyse our consumption of triptans and the need of visits to Emer-
experience in the treatment of refractory chronic migraine gency, which makes this treatment a profitable option both
(CM) with onabotulinumtoxinA (BTA) and specifically in clinically and pharmacoeconomically.
its effects over disabling attacks. Patients with CM and
inadequate response or intolerance to oral preventatives Keywords Chronic migraine Chronic refractory
were treated with pericranial injections of 100 U of TBA migraine OnabotulinumtoxinA
every 3 months. The dose was increased up to 200 U in case
of no response. The patients kept a headache diary. In
addition, we specifically asked on the effect of BTA on the Introduction
frequency of disabling attacks, consumption of triptans and
visits to Emergency for the treatment of severe attacks. This Chronic migraine, understood as the presence of headache
series comprises a total of 35 patients (3 males), aged during 15 or more days in a month in patients with
24 68 years. All except three met IHS criteria for analgesic migraine history, is an important health problem [1]. It is
overuse. The number of sessions with BTA ranged from 2 to estimated that about 2% of general population meets the
15 (median 4) and nine (26%) responded (reduction of criteria for chronic migraine with or without analgesic
[50% in headache days). However, the frequency of severe overuse [2, 3]. Prevalence in women around 40 50 years of
attacks was reduced to an average of 46%. Oral triptan age reaches 5%, thus justifying that almost 5% of consul-
consumption (29 patients) was reduced by 50% (from an tations to Neurology Services in Spain are caused by this
average of 22 to 11 tablets/month). Those six patients who condition [4].
used subcutaneous sumatriptan reduced its consumption to Chronic migraine is important not only on account of its
a mean of 69% (from 4.5 to 1.5 injections per month). great frequency, but also because it significantly reduces
Emergency visits went from an average of 3 to 0.4 per the quality of life of the patients affected and it determines
trimester (-83%). Six patients complained of mild adverse an unquestionable morbidity [5]. On one hand, these
events, transient local cervical pain being the most com- patients often develop complications connected with
mon. Although our data must be taken with caution as this is analgesic consumption, such as upper digestive haemor-
an open trial, in clinical practice treatment of refractory CM rhage or analgesic nephropathy [6]. On the other hand, they
with BTA reduces the frequency of disabling attacks, the usually associate chronic depression, partly due to the
increased frequency of disabling pain [3, 5]. Lastly, recent
data suggest the increased frequency of severe attacks
A. Oterino
related to chronic migraine is a stroke risk factor [7].
Service of Neurology, University Hospital Marqu閟 de
Valdecilla, Santander, Spain Migraine treatment is a complex issue. If analgesic
overuse is present, especially opiates or ergotics, with-
C. Ram贸n J. Pascual (&)
drawal becomes compulsory. Most patients are in need of a
Neuroscience Area, Service of Neurology,
preventive treatment. Even though with the exception of
University Hospital Central de Asturias, Oviedo, Spain
e-mail: juliopascual@telefonica.net topiramate [8, 9], there are no controlled trials in chronic
123
236 J Headache Pain (2011) 12:235 238
migraine for the majority of the preventative treatments Results
used in episodic migraine, clinical practice suggests that
beta-blockers, amitryptiline, flunarizine and some neuro- Our series covers 35 patients (3 males) aged between 24
modulators can be useful when treating these patients. and 68. Only three of them did not meet the criteria for
However, a relevant subgroup of these patients does not analgesic overuse. The average of headache days per
respond effectively to any of the preventative treatments. month before treatment with BTA was 24.7, while that of
These patients met the criteria for chronic refractory days with severe, disabling headaches was 8.2 per month.
migraine [10]. Aggressive options such as bilateral sub- A total of 29 patients were taking oral triptans regularly
occipital stimulation have been tried lately in these patients (an average of 22 pills/month before the study) and 6
with poor results. Recently, effectiveness of onabotuli- were also using subcutaneous sumatriptan (an average of
numtoxinA (BTA), BOTOX to be precise, has been proven 4.5 injections/month before the study). Only one patient
for preventive treatment of patients with chronic migraine was not undergoing oral preventative treatment. At the
[11 13]. Our goal was to assess our experience in treating time of the evaluation 16 patients were taking one oral
those patients with chronic refractory migraine with BTA preventative, 15 were taking two and 3 patients were
in daily clinical practice, focusing on its effect on disabling undergoing medical tritherapy. Drugs used were in the
attacks and taking into account various parameters that had order: topiramate, 15 patients; amitriptyline, 12; zonisa-
not been specifically studied in clinical trials. mide, 7; beta-blockers, 5; valproic acid, 4; candesartan 4
and flunarizine, 4.
The number of treatments ranged between a minimum
Patients and methods of 2 and a maximum of 16 (median 4). Response
(reduction of headache days per month at least by 50%)
Subjects involved in this study were patients from our was observed in 9 patients (26%) and excellent
refractory headache clinic and had to satisfy the following response ([75% reduction) in only 2 of them (6%). The
requirements: (1) meet the criteria for chronic migraine average number of days with severe, disabling headache
with or without analgesic overuse; (2) show insufficient after treatment was 3.8 per month (mean reduction 46%,
response (over a minimum of 6 weeks) or absence of tol- limits 0 905). Consumption of oral triptans in 29 patients
erability of beta-blockers, flunarizine, topiramate, valproic who took them regularly halved (from 22 to 11 oral
acid and amitryptiline; and (3) give their informed consent triptans/month). The 6 patients using subcutaneous suma-
to pericranial treatment with BTA. All patients with criteria triptan went from 4.5 injections/month to 1.5 injections/
for analgesic abuse had failed in at least one withdrawal month (69% reduction). Finally, the average number of
attempt. Both patients with fibromyalgia and active visits to casualty department for parenteral treatment went
depression as well as those overusing ergotics or opiates from 3 in the pretreatment quarter to 0.4 (87% reduction)
were excluded. Patients were allowed to continue with (Fig. 1).
preventative oral medication during the treatment with Only six patients (18%) experienced adverse effects,
BTA. always mildly and temporarily, consisting of cervical pain
Patients were treated with BTA every 3 months. All in four cases and eyebrow asymmetry in two of them.
patients received a minimum of two treatments. The first of
them consisted of injecting 100 U into 20 sites (5 units per
site) distributed among the muscles of each hemicranium
as follows: one site into corrugator, two into frontalis, three
Reduction in Emergency
87
into temporalis, two into suboccipitalis, one into semispi-
visits
nalis and one into splenius. In case of insufficient response,
Decrease in consumption
the dose was increased up to a maximum of 200 U and 40 50
of oral triptans
sites in accordance with the protocol for phase III trials.
Patients kept a conventional headache diary regularly.
Adverse events 18
Under this study we took into consideration the diary noted
in the second month of the last quarter of the treatment and
Reduction in severe
46
attacks
compared it to the one written during the pretreatment.
Consequently, we compiled specific information about the
Response 26
%
effect of BTA on disabling attacks and on consumption of
triptans as well as about the visits to Emergency, whether it
0 25 50 75 100
be a health centre or the hospital, for parenteral treatment
of attacks refractory to domiciliary management. Fig. 1 Summary of the main results of this study
123
J Headache Pain (2011) 12:235 238 237
Discussion dose, as against the daily clinical practice that tries to
optimize the dose and comfort of the patient.
Our experience in clinical practice conditions brings To conclude, we would like to highlight that BTA has
effectiveness and excellent tolerability to pericranial been useful in our experience with patients with chronic
injections of BTA for the treatment of chronic refractory refractory migraine who showed analgesic overuse in most
migraine along the lines of published clinical trials [11 cases. Although we excluded patients abusing of ergotics
13]. Like in those trials, response rate, i.e., the reduction and opiates from the study, these results indicate, along the
of headache days at least by 50%, was not outstanding. lines of phase II results [18 20], that patients with chronic
Only one-fourth of the patients met the criteria of response migraine and analgesic overuse can improve specifically
laid down by the International Headache Society and less with preventative treatment, in this instance BTA.
than 10% fulfilled the criteria for excellent response [14]. If
Acknowledgments This study was conducted independently with-
we analyze, however, what occurred in disabling attacks,
out any kind of support from the pharmaceutical industry. We thank
BTA s effectiveness was very clear: their frequency halved
Paula Pascual for her stylistic review of the manuscript.
and the number of visits to Emergency was reduced by
almost 90%. These data explain what seems a discrepancy Conflict of interest None.
in the results (in terms of response) of the clinical trials,
Open Access This article is distributed under the terms of the
which are not spectacular over placebo, and what happens
Creative Commons Attribution License which permits any use, dis-
in clinical practice, where the patient declares to feel
tribution and reproduction in any medium, provided the original
clearly better although the number of headache days in the
author(s) and source are credited.
diary has not dropped dramatically. However, even taking
into consideration that during our series patients had been
refractory to various treatments, we cannot rule out a pla-
cebo effect; these data suggest that the effect of BTA in
References
chronic migraine lies in a downward modulation of severe
1. Olesen J, Bousser MG, Diener HC et al (2006) New appendix
pain attacks, which would then be less invalidating and
criteria open for a broader concept of chronic migraine. Cepha-
easier to deal with. This is endorsed by two of our results:
lalgia 26:742 746
both the halved consumption of triptans, drugs these
2. Castillo J, Mu艅oz P, Guitera V, Pascual J (1999) Epidemiology of
patients only take for their most disabling attacks, and the
chronic daily headache in the general population. Headache
39:190 196
dramatic decrease in the number of visits to Emergency for
3. Jensen R, Stovner LJ (2008) Epidemiology and comorbidity of
parenteral treatment. Again, however, we would like to
headache. Lancet Neurol 7:354 361
emphasize that these data must be taken with caution as no
4. Pascual J, S醤chez del R韔 M, Jim閚ez-Hern醤dez MD et al
placebo arm was included in this trial. This is not a formal
(2010) La migra艅a cr贸nica vista por el neur贸logo y el paciente.
pharmacoeconomic study, but its results can help to illus- Rev Neurol 50:705 710
5. Col醩 R, Mu艅oz P, Temprano R, G贸mez C, Pascual J (2004)
trate the potential cost advantages of this new treatment
Chronic daily headache with analgesic overuse: epidemiology
approach. Consider the following examples: an easy cal-
and impact on quality of life. Neurology 62:1338 1342
culation taking into consideration the local average price of
6. Giopponi S, Venturelli E, Rao R, Liberini P, Padovani A (2010)
oral triptans indicates that the savings only in oral trip- Hypertension is a factor associated with chronic daily headache.
Neurol Sci 31(Suppl 1):S171 S173
tans per patient and month would be of 殴 101. Savings in
7. Kruit MC, van Buchem MA, Launer LJ, Terwindt GM, Ferrari
casualty department visits, taking into account the official
MD (2010) Migraine is associated with an increased risj of deep
price in our country of 殴 138 per visit without further
white matter lesions, subclinical posterior circulation infacts and
brain iron accumulation: the population-based MRI CAMERA
studies, is even higher.
study. Cephalalgia 30:129 136
Our treatment protocol differs in some aspects from the
8. Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S,
one carried out in phase III of the clinical trials. In this
Goadsby PJ (2007) Topiramate reduces headache days in chronic
study we administered an initial dose of 100 U and we only
migraine: a randomized, double-blind, placebo-controlled study.
Cephalalgia 27:814 823
raised it to 150 200 U in those patients whose response
9. Silberstein SD, Lipton RB, Dodick DW (2007) Efficacy and
was insufficient. The same happened with the number of
safety of topiramate for the treatment of chronic migraine. A
points injected, which was lower (20 compared to a min-
randomized, double-blind, placebo-controlled trial. Headache
imum of 31). Same muscular groups were injected, except
47:170 180
10. Schulman EA, Lake AE III, Goadsby PJ et al (2008) Defining
for the trapezius, which was left with no treatment. Positive
refractory migraine and refractory chronic migraine: proposed
open results for BTA with the same dose and lower than
criteria from the refractory headache special interest section of
ours exist [15 17]. Therefore, these differences are logical
the American Headache Society. Headache 48:778 782
since the protocol of the clinical trial tries to guarantee that
11. Diener HC, Dodick DW, Aurora SK et al (2010) Onabotuli-
numtoxinA for treatment of chronic migraine: results from the
a potential lack of effectiveness is not due to an insufficient
123
238 J Headache Pain (2011) 12:235 238
double-blind, randomized, placebo-controlled phase of the daily headache: a five-year long experience. J Headache Pain
PREEMPT 2 trial. Cephalalgia 30:804 814 7:407 412
12. Aurora SK, Dodick DW, Turkel CC et al (2010) Onabotuli- 17. Freitag FG, Diamond S, Diamond M, Urban G (2008) Botulinum
numtoxinA for treatment of chronic migraine: results from the toxin type A in the treatement of chronic migraine without
double-blind, randomized, placebo-controlled phase of the medication overuse. Headache 48:201 209
PREEMPT 1 trial. Cephalalgia 30:793 803 18. Mathew NT, Frishberg BM, Gawel M, Dimitrova R, Gibson J,
13. Dodick DW, Turkel CC, DeGryse RE et al (2010) Onabotuli- Turkel C, the BOTOC CDH Study Group (2005) Botulinum toxin
numtoxinA for the treatment of chronic migraine: pooled results type A for the prophylaxis of chronic daily headache: a randomized,
from the double-blind, randomized, placebo-controlled phases of double-blind, placebo-controlled trial. Headache 45:293 307
the PREEMPT clinical program. Headache 50:921 936 19. Silberstein SD, Stark SR, Lucas SM, Christie SN, DeGryse ER,
14. Silberstein S, Tfelt-Hansen P, Dodick DW et al (2008) Guidelines Turkel CC, BoNTA-039 Group (2005) Botulinum toxin type A
for controlled trials of prophylactic treatment of chronic migraine for the prophylactic treatment of chronic daily headache: a ran-
in adults. Cephalalgia 28:484 495 domized, double-blind, placebo-controlled trial. Mayo Clin Proc
15. Silberstein S, Mathew N, Saper J, Jenkins S, Group for the 80:1126 1137
BOTOX Migraine Clinical Research Group (2000) Botulinum 20. Dodick DW, Mauskop A, Elkind AH, DeGryse R, Brin MF,
toxin type A as a migraine preventive treatment. Headache Silberstein SD (2005) Botulinum toxin type A for the prophylaxis
40:445 450 of patients not receiving other prophylactic medications: a ran-
16. Farinelli I, Coloprisco G, De Filippis S, Marteletti P (2006) Long- domized double-blind, placebo-controlled study. Headache
term benefits of botulinum toxin type A (BOTOX) in chronic 45:315 324
123
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