Botox
J Headache Pain. 2007 Sep 24; [Epub ahead of print]
Botulinum toxin type-A therapy in cluster headache: an open study.
Sostak P, Krause P, Förderreuther S, Reinisch V, Straube A.
Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich, Germany, Petra.Sostak@med.uni-muenchen.de.
The objective of this open single-centre study was to evaluate the efficacy and tolerability of botulinum toxin type-A (BTX-A) as add-on in the prophylactic treatment of cluster headache (CH). Twelve male patients with episodic (n=3) or chronic (n=9) CH, unresponsive to common prophylactic medications, were treated with a cumulative dose of 50 International Units (IU) BTX-A according to a standardised injection scheme into the ipsilateral pericranial muscles. One patient with chronic CH experienced a total cessation of attacks and in 2 patients attack intensity and frequency improved. In another patient with chronic CH typical attacks were not influenced, but an ipsilateral continuous occipital headache significantly improved. Patients with episodic CH did not benefit from BTX-A treatment. Tolerability was excellent. These findings provide evidence that BTX-A may be beneficial as an add-on prophylactic therapy for a limited number of patients with chronic CH.
PMID: 17901920
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Cephalalgia. 2002 Nov;22(9):699-710. Related Articles, Links
Treatment of headache with botulinum toxin A--a review according to
evidence-based medicine criteria.
Evers S, Rahmann A, Vollmer-Haase J, Husstedt IW.
Department of Neurology, University of Munster, Munster, Germany. everss@uni-muenster.de
The aim of this review is to evaluate the studies available from reference
systems and published congress contributions on the prophylactic treatment of
idiopathic and cervicogenic headache with botulinum toxin A, and to classify
these studies according to evidence-based medicine (EBM) criteria. The studies
were analysed with respect to the study design, the number of patients enrolled,
the efficacy parameters, and the significance of results. We used the following
classification of EBM. I: randomized, controlled study with sufficient number of
patients; II: well-designed, controlled study (or randomized, controlled study
with insufficient number of patients, no exact diagnosis, missing data of
botulinum toxin A dose); III: well-designed, descriptive study; IV: case
reports, opinions of experts. For tension-type headache, two studies were found
with negative evidence of I with respect to the primary endpoint. There are
about as many positive as negative studies with evidence of II or III. For the
therapy of migraine, one study with both negative and positive evidence of I,
one in part positive study of II, and three positive studies classified as III
are available. Two studies on cervicogenic headache with evidence of II and III
are contradictory. In addition, we found several positive case reports. For
patients with cluster headache, there are positive and negative case reports. We
found one positive case report for the treatment of chronic paroxysmal
hemicrania. As a result of this analysis, we consider no sufficient positive
evidence for a general treatment of idiopathic and cervicogenic headaches with
botulinum toxin A to date. Further studies are needed for a definite evaluation
of subgroups with benefit from such treatment.
PMID: 12421155
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May 2002 http://www.headachedrugs.com/archives/botulinum_toxin_typeb.html
Lawrence Robbins, MD, Director, Robbins Headache Clinic
Excerpt relating to Cluster headache from:
Botulinum Toxin Type B for Refractory Cluster Headache
COMMENTS:
This small study demonstrates that, for some refractory cluster
sufferers, botulinum toxin may provide some benefit. While expensive, botulinum
toxin is a relatively safe therapy that, although expensive, is relatively easy
to administer. It is possible that larger doses than the low amounts utilized in
this study may prove to be more effective.
Numerous studies have been published on the use of botulinum toxin for migraine
and tension headache. Cluster headache and BTA / BTB has been the focus of
several small studies.
Cluster Headache: A limited number of studies have been performed regarding botulinum toxin in patients with cluster headache. One study with 2 patients yielded excellent results, where both patients had no further clusters after 1 week of treatment. The effects lasted 10-12 weeks11. A recent study12 on botulinum toxin for cluster headache (by Robbins) concluded that botulinum toxin was not very effective for most of the cluster patients in the study. However, several cluster sufferers did obtain excellent relief from the toxin. One other cluster study found that 2 of 4 patients improved, with doses ranging widely from 24 to 150 U.13.
For the complete article, please visit: http://www.headachedrugs.com/archives/botulinum_toxin_typeb.html
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Presented at the 10th Congress of the International Headache Society; New York, New York; June 29 - July 2, 2001.
Robbins, L.
Botulinum Toxin for Cluster Headache; 10 Patients
ABSTRACT -
Ten chronic cluster headache patients received botulinum toxin for refractory
clusters. The injections were done with low dose botulinum toxin; either 24 units of BTA
per patient, or the equivalent BTB (1200 units). These were patients who had
been refractory to the usual preventive and abortive medications for cluster
headache. Side effects were minimal in this study. For the 7 chronic cluster
patients, the injections were moderately effective in 3/7, and extremely
effective for one. The botulinum toxin was not effective for 3 of the chronic
cluster sufferers. Of the the 3 episodic cluster sufferers, 1 obtained complete
relief and 1 had moderate relief. The 3rd achieved complete relief with the
first set of injections, but only moderate improvement after a further set of
injections one year later.
INTRODUCTION -
Most patients with cluster headache receive some degree of relief from the usual
preventive medications. These include verapamil, lithium, cortisone, sodium
valproate, indomethacin, etc. In addition, many of the patients obtain relief
from the abortive medications. The abortives include oxygen, sumatriptan
injections, sumatriptan nasal spray, other forms of triptans, lidocaine nasal
spray, etc. Many patients with cluster headache do not achieve an adequate
response to the preventive or abortive medications. Botulinum toxin has shown
promise in the treatment of migraine headache. Many therapies that have been
useful for migraine headache also are somewhat beneficial for cluster headache.
This study evaluated 10 patients with refractory cluster headache who were given
botulinum toxin type A (BTA) or botulinum toxin type B (BTB) injections.
MATERIALS AND METHODS -
There were 8 male patients and 2 females, ages 28 to 63, in this study. Seven
patients had chronic cluster headache, and three suffered from episodic
clusters. They were refractory to the usual preventive medications. Each patient
kept a headache diary, using a visual analog scale, for four months
post-injection. Twelve injections of 2 units of BTA (or 100 units of BTB) were
utilized. Thus, the total was 24 units BTA, or 1200 units of BTB, per patient,
which is a low dose. Eight injections were given frontally and temporally
ipsilateral to the pain, and four in the contralateral frontal area. The case
summaries are as follows:
CASE SUMMARIES -
Chronic Cluster Patients (7):(1) 59 year old man with chronic clusters, in a
severe exacerbation (2 to 3 per day). BTA was not effective. (2) 63 year old man
with chronic clusters, in a severe exacerbation (4 to 5 per day). BTA was
moderately effective. The clusters decreased to one daily. This relief lasted 4
months. He had been scheduled to have a surgical procedure for the clusters, but
cancelled it due to the relief from the BTA. (3) 53 year old man with chronic
clusters, in a moderate exacerbation. No relief from the BTA. (4) 38 year old
man with chronic clusters in a severe exacerbation. There was dramatic,
immediate relief after the BTA injections, with no headache for 3 months. (5) 28
year old man with chronic clusters. BTB was moderately effective. The clusters
decreased from 4 to 5 per day down to 1 daily. The relief lasted 2 months. (6)
48 year old man with 2 cluster headaches per day. BTB was moderately effective.
Clusters decreased to 0 to 1 attack per day, and this relief lasted 2½ months.
(7) 52 year old female with chronic clusters; BTB was not effective.
Episodic Cluster Patients (3): (1) 62 year old man with episodic clusters, 2 per
day. Complete relief after BTA (the injections immediately stopped the cycle).
(2) 43 year old man with severe episodic clusters. He received 2 sets of
injections, one year apart. After the first BTA injections there was immediate,
complete relief. The second time, with BTB, there was only moderate improvement.
After the second set, the clusters diminished from 4 per day (lasting 1 to 2
hours each) down to 1 headache daily lasting less than 1 hour. (3) 47 year old
female with episodic cluster headache. The attacks occurred 3 times daily, and
she had moderate relief after the BTB. The attacks decreased to 0 or 1 per day.
The relief lasted for the remainder of the cycle.
ADVERSE EVENTS -
One patient experienced a mild ptosis for 12 days post-injection. One patient
described a burning sensation in both eyes that resolved after 6 days.
SUMMARY OF RESULTS -
There were 7 chronic cluster headache patients. Botulinum toxin was ineffective
for 3 of the patients. The injections were moderately effective for 3 of the
cluster sufferers. One patient had dramatic, immediate relief that lasted for 3
months. There were 3 episodic cluster headache patients. One had complete
relief, one experienced moderate relief, and the third achieved complete relief
with his first set of injections, but only moderate improvement one year later,
after the second set of injections.
COMMENTS -
Botulinum toxin is a safe therapy that, although expensive, is relatively easy
to administer. This small study demonstrated that, for some refractory cluster
patients, botulinum toxin may be a worthwhile treatment. It is possible that
larger doses (low doses were utilized in this study) would be more effective.
There have been a number of studies of botulinum toxin (primarily BTA, Botox)
for the treatment of migraine and tension headache. The initial retrospective
chart review of 106 patients revealed that 46% achieved complete relief from
their migraines. Another 30% had partial improvement. The mean dose in this
study was 35.5 units of BTA per patient. There have been several positive
prospective randomized trials in migraineurs since that time. In one of the key
studies, both the 25 unit (total) BTA patients and the 75 unit patients did
better than the patients who received placebo. However, the patients who had
received 75 units did have significantly more treatment-related adverse advents
(primarily forehead weakness) than placebo. In another study, 51% of patients
had complete relief for a mean of 4.1 months, and 38% reported a partial
response. This was an open label trial of 77 patients with migraine headache.
Another open-label study over a three year period did include a small number of
cluster headache patients. The doses were higher in this study, 80-150 units of
BTA. Fifty-eight percent of patients with chronic tension-type headache achieved
positive outcomes, 67% of migraine sufferers responded favorably, and 2 of the 4
patients with cluster headache had positive responses. In these cluster
patients, a positive response was determined by termination of the cluster
episode within 3 weeks of BTA injections. These same investigators went on to
conduct a double blind, placebo controlled, randomized study involving 40
patients with chronic tension-type headache. The number of headache-free days
was significantly increased in the BTA group at 3 months post treatment. Other
studies have not been as positive for tension-type headache, however. One study
that was double blind, placebo controlled and randomized revealed no significant
differences through 12 weeks for chronic tension-type headache. One further
report on 2 patients with episodic cluster headaches revealed complete relief
after 50 units of BTA. These injections were given ipsilateral to the pain.
Naturally, in the beginning years of treatment utilizing botulinum toxin for
cluster headache, only the more refractory patients will be injected. However,
if experience and studies dictate that botulinum toxin is an effective therapy,
and with some reduction in cost, this may become a standard treatment. The
question as to the dose of injection has not been adequately answered in the
studies. There are studies that indicate that low doses may be as effective as
high doses. Higher doses carry the risk of increased adverse events. Further
studies will be needed to determine the adequate dose. As to the location of the
injections, it makes sense intuitively to inject primarily on the ipsilateral
side of the cluster headache. However, a number of studies will be needed to
determine the most effective location for botulinum toxin injections.
There are relatively few disadvantages for the utilization of botulinum toxin
for cluster headache. Cost, pain during the injections, and the possibility of
ptosis are some of the considerations.
Botulinum toxin is a relatively safe treatment, particularly in the low doses
that have been utilized for migraine headache. If adequate efficacy for cluster
headache can be established, botulinum toxin may become a primary first line
therapy for the treatment of cluster headache.
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