++
Clinicians began using BTX with the prospect of reducing pericranial
muscular tension and contractions that are thought to contribute
to headaches. BTX may reduce muscle spindle activity, and this,
in turn, may decrease the sensory feedback. BTX may also directly
affect sensory nerves by possibly inhibiting the neuropeptide-containing
fibers. Although large multi-center, double-blind, randomized data
are lacking, the evidence so far shows that BTX is an effective
anti-headache medication when certain criteria are met.
++
Although there are numerous case studies focusing on use of BTX-A
for treating migraines,1,3 chronic daily headaches
with migraine features,11 and chronic tension-type
headache,4–6,8,9,15 there is no uniformity
with the injection techniques or dosages. The studies use two general
injection paradigms for treating headaches. In the fixed-site paradigm
(Fig. 23-1), BTX is injected in sites that are predetermined and
the same for everyone in the study. In the follow-the-pain paradigm,
BTX is injected into or around the tender points that are reported
by the patients and confirmed on physical examination.
++
Recent double-blind, placebo-controlled studies have shown consistency
and homogeny with injection technique and dosage, allowing better
comparative data analysis. An upcoming wave of large multi-center,
double-blind, randomized placebo-controlled trials will further
clarify the role of BTX in the prophylactic treatment of a variety
of headache disorders.
++
Silberstein and colleagues, in 2000,1 reported
a double-blind, placebo-controlled study in which 123 patients were
randomly assigned into three groups, as follows: placebo (n = 42),
BTX-A, 25 units (n = 42), and
BTX-A, 75 units (n = 40). Patients
who had two to eight moderate to severe, IHS-defined migraine attacks
per months were enrolled. BTX-A injection sites were fixed-site
and included frontalis, glabellar, and bilateral temporalis muscles.
BTX-A decreased the frequency of moderate to severe migraines per month
but failed to reach statistical significance. This study also showed
a decrease in the number of days of acute medication usage. All
treatment-related adverse events were transient, and more commonly
associated with the 75-unit dose.
++
Binder, also in 2000,2 reported an open-label
study that included 77 patients with migraine. Results confirmed
the efficacy of BTX-A in reducing the number and severity of acute
attacks per month.
++
In 1998, Binder and colleagues3 performed a
retrospective review of 96 patients who had chronic migraines but
were treated with BTX-A for their movement disorder or were seen
in the cosmetic surgery clinics. This study evaluated patients who
received BTX-A injections into glabellar, temporalis, and occipitalis
regions. The mean total dosage of BTX-A was 26 ± 14
units. This study reported that 51% of the 96 patients
had complete elimination of their headaches, while 28% of the
subjects had more than 50% reduction in the frequency or
severity of their headaches. The remaining 21% of the 96
patients either had less than 50% response in headache
frequency and severity, or were lost to follow-up. The duration
of benefit in the complete responders group was 3.6 ± 2.4
months. The partial responders group (≥ 50% decrease
in headache frequency or severity) was 2.9 ± 1.6
months. Adverse effects reported were ecchymosis and transient,
local pain at the injection site.
+++
Tension-Type
Headaches
++
The first reported study, by Zwart and colleagues in 1994,10 showed
no effect in six patients with tension-type headache, not using
the IHS criteria. This study was carried out using the follow-the-pain
paradigm, with BTX-A injected unilaterally into the temporal muscle.
++
Since then, Rollnik and colleagues,4 in 2000,
conducted a double-blind placebo-controlled study involving 21 patients
with CTTH or ETTH. The injection sites were specified as follows: “pericranial
muscles around the head (2 injections into the fronto-occipital
muscle and 3 into the temporal muscles bilaterally).” This study
used BTX-A (Dysport) from Ipsen. The total dose used was 200 units.
These investigators found no significant difference (P > .5)
between the BTX-A and saline-treated groups. The study evaluated
the pain intensity (visual analog scale), clinical global impression,
headache frequency, and consumption of analgesics. Both groups tended
to improve on several measures; however, the pain intensity (P = .051)
and clinical global impression (probability not given) at 4 weeks.
The authors of this study suggest that given that Dysport is freeze
dried and susceptible to breakdown, in contrast to the Botox (an
American BTX-A) that is vacuum dried, a higher dose of Dysport may
be needed to obtain a successful outcome.
++
Smuts and colleagues,6 in 1999, reported a double-blind,
placebo-controlled study in which 37 patients with CTTH were randomized
into one of two groups: placebo (n= 15) or BTX-A
(n = 22). Of the 37 patients, 38% also
had history of migraines. The BTX-A injection sites were fixed and
included 100 units into bilateral trapezius, splenius capitis, and
temporalis muscles. At 3 months, 59% of the patients in the
BTX-A group had ≥ 25% improvement
in their headache severity score and number of headache-free days,
whereas only 13% of the placebo had the same response.
++
Schulte-Mattler and colleagues,7 also in 1999,
in an open-label prospective study, injected nine patients who had
ETTH and CTTH with BTX-A. They reported that eight of the nine patients
showed improvement of their headache symptoms.
++
Wheeler,8 in 1998, reported four case studies
of patients with CTTH for whom previous multiple therapies had been
unsuccessful. BTX-A was injected in a follow-the-pain paradigm,
using variable doses (20 units to 100 units) at the tender sites.
All four patients had subjective pain relief.
++
Relja,9 in 1997, did a preliminary open-label
study in which 10 patients with CTTH were injected with 15 to 35
units of BTX-A in up to six sites based on local tenderness. All
of the patients were refractory to previous pain medications, and
all reported elimination or reduction in severity and duration of
headaches at 2 weeks.
++
Relja and Korsic,5 in 1999, enrolled 16 CTTH
patients in a double-blind, placebo-controlled, crossover study.
The 35 to 80 units of BTX-A or placebo were injected in up to six
sites into bilateral frontalis, trapezius, or sternocleidomastoid
muscles based on local tenderness. The patients were followed 1,
2, 4, and 8 weeks post-injection. BTX-A significantly decreased
tenderness scores, as recorded in patient diaries, and also decreased
severity and duration of attacks (probability values not listed). Adverse
events included local pain at the injection site, which occurred
in some patients (number not specified) following BTX-A and saline.
+++
Chronic Daily
Headaches
++
Klapper and Klapper,11 in 1999, reported five
case studies of patients who had chronic daily headache with migrainous features.
All five received 75 units of BTX-A at 11 fixed injection sites
into the frontalis, glabellar, and temporalis muscles. Three of
the five patients showed more than 75% subjective improvement.
One patient had no response, and one showed only 35% subjective
improvement.
++
Freund and Schwartz,12 in 2000, reported a double-blind,
placebo-controlled study in which 26 patients (n = 14
BTX-A, n = 12 placebo) with daily
headaches secondary to cervical whiplash injuries were randomly
assigned to one of two groups. The inclusion criteria included neck
pain with musculoskeletal signs for more than 6 months. All of the
patients were 2 years post-injury and had failed conservative therapy.
BTX-A injection involved fixed doses of 100 units and the follow-the-pain
paradigm. After 4 weeks, 11 of 14 patients showed a significant
decrease in pain, and there was significant improvement in neck
pain and range of motion. No adverse effects were reported.