Review

Pharmacotherapy options for

cluster headache
Mark Obermann†, Dagny Holle, Steffen Naegel, Jan Burmeister &
1. Introduction Hans-Christoph Diener
University of Duisburg-Essen, Department of Neurology, Essen, Germany
2. Disease burden
3. Pharmacological treatment for Introduction: Cluster headache (CH) is a primary headache disorder and the
CH most common trigeminal autonomic cephalalgia. Patients suffer from very
4. Transitional treatment severe unilateral headache attacks accompanied by ipsilateral trigeminal
5. Prophylactic treatment autonomic symptoms. Previous studies described a high burden of disease
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15

due to its impact on social life as well as an increased suicide ideation rate.
6. Conclusion
The mean time to diagnosis in western industrialized countries is estimated
7. Expert opinion
at 4 years.
Areas covered: Many treatment options for CH exist, but due to the rarity of
the disease, controlled randomized clinical studies remain difficult to per-
form. This review summarizes the current knowledge about the treatment
of CH including internationally accepted treatment guidelines, and an
additional MEDLINE search (1 February 2015).
Expert opinion: International treatment recommendations and official guide-
lines give reassurance about specific pharmacotherapy options for CH, but
only few of these are backed by sufficient scientific evidence. The limited
For personal use only.

therapeutic efficacy in some patients leads to the use of alternative, comple-

mentary, but also illicit drugs to better cope with the disease. Many single
cases, case series and uncontrolled studies were performed with different
substances in an attempt to find a better way to treat or prevent the excruci-
atingly painful attacks associated with CH. Large-scale, randomized
controlled clinical trials are desperately needed in order to further increase
the quality of patient care for this outstanding but terrifying disease.

Keywords: cluster headache, current treatment, future treatment, pharmacotherapy, treatment

options

Expert Opin. Pharmacother. [Early Online]

1. Introduction

Cluster headache (CH) is a primary headache disorder and the most common tri-
geminal autonomic cephalalgia (TAC) [1]. CH has a lifetime prevalence of
124 per 100,000 persons [2]. It is characterized by unilateral, unbearable headache
attacks that are accompanied by ipsilateral trigeminal autonomic symptoms such
as rhinorrhea and lacrimation [1]. Pain attacks usually last between 15 and
180 min, attacks can occur from one every second day to 8 times per day. During
the headache attacks, the predominantly male patients are restless, which is an
important clinical feature to distinguish this headache from other headache
disorders such as migraine. Most patients have an episodic course of disease with
a circannual periodicity of symptoms that occur mainly in autumn and spring.
Pain attacks occur in clusters over periods of weeks or months (inside bout). In
between, patients are usually pain free (outside bout). Despite this episodic course
of disease, 10 -- 20% of patients develop chronic CH without longer attack-free
time periods [1]. The pharmacological management divides into: i) acute treatment
of the recurrent, single attack; ii) the discontinuation of the current bout (transient)
and iii) the prophylactic treatment to prevent recurrence of the bout (phase of

10.1517/14656566.2015.1040392 © 2015 Informa UK, Ltd. ISSN 1465-6566, e-ISSN 1744-7666 1

All rights reserved: reproduction in whole or in part not permitted
 M. Obermann et al.
Article highlights
. Pharmacological treatment options for cluster headache
(CH) are effective and sufficient in most patients.
. Pharmacological treatment is sometimes delayed, not
specific for CH or underdosed.
.
Sumatriptan, zolmitriptan and oxygen inhalation are
effective to treat the acute CH attack.
. Corticosteroids and occipital nerve block are
recommended for short-term prophylaxis to abort the
current cluster bout.
. Verapamil and lithium should be initiated as soon as
possible as long-term prophylaxis to reduce attack
frequency and prevent the development of chronic CH.
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15
This box summarizes key points contained in the article.
repeated cluster attacks). Several guidelines that address treat-
ment recommendations for CH were published over the past
years, including the European Federation of Neurological
Societies from 2006 [3]. Other countries produced their own
specific guideline (Germany [4], Taiwan [5]) or included
recommendations in broader guidelines on the treatment of
headache in general (Scotland [6], Croatia [7], Italy [8]).
This review will summarize current knowledge about the
established treatment options of CH. An additional MED-
For personal use only.
LINE search (1 February 2015) for articles containing ‘cluster
headache’ AND treatment was performed. The search
returned 1643 articles of which 497 were marked as review
articles. One hundred and fifty articles were labelled as clinical
trial and 62 actually were clinical trials on visual confirmation
written in English. Seventeen out of these trials were random-
ized controlled trials according to current evidence-based
medicine standards. Even though CH is the most common
TAC, the condition is still rare, which makes studies on this
topic challenging.
2. Disease burden
Little is known about the burden of disease caused by CH.
Jensen et al. showed that 78% of CH patients complain of
restrictions of daily living during cluster periods, 13% even
outside bout [9]. A quarter of CH patients report extensive
limitations in their every day life, regarding participation in
social life activities, family life and housework. Every fifth
patient has lost his job secondary to CH as shown in the larg-
est survey on CH patients in the USA including 1134 subjects
[10]. In the past, CH was even nicknamed ‘suicide headache’,
which was already mentioned by Horton in 1939, who
described the headache to be that severe that patients had to
be ‘constantly watched for fear of suicide’. Today, despite
having far better treatment options still 55% of CH patients
report suicidal ideation [10]. Patient satisfaction with treat-
ment for CH was evaluated recently in Norway. The general
satisfaction with general practitioners (63%) was well as
neurologists (71%) was good [11]. However, the main problem
2 Expert Opin. Pharmacother. (2015) 16(8)
of patient care was the mean time to diagnosis (4 years) and
the additional use of alternative and complementary medi-
cine [11]. This clearly shows that patient management in CH
needs improvement and therapy is not efficient enough, yet.
Besides lacking efficacy, often side effects or drug intolerance
are the main problem, why patients discontinue therapy.
Therefore, occipital nerve injection and neurostimulation
techniques have come more and more into focus over the
last couple of years.
3. Pharmacological treatment for CH
Treatment of CH can be difficult and requires a dual strategy
including acute and prophylactic drug treatment. Acute ther-
apy (i.e., oxygen, triptans, nasal lidocaine) is used for attack
abortion or suppression, but does not influence the duration
of the cluster episode. In contrast, transitional and prophylac-
tic medication is initiated to terminate the cluster episode
(transient) and prevent further cluster attacks (prophylactic).
Prophylactic compounds are given daily until the CH episode
subsides and are then tapered down.
3.1 Acute treatment
Several substances have proven efficacy to abort the acute CH
attack in randomized controlled clinical trials (RCTs).
3.1.1Oxygen
Inhalation of 100% oxygen is one of the most frequently used
acute therapies, as it has no adverse events. There are two
RCTs with 6 l/min for up to 15 min and 12 l/min for
15 min versus regular air inhalation. Fifty-six percent of
patients reported substantial headache relief in the first
study [12], while in the second study 78% were pain-free after
15 min compared with 20% that breathed regular air (pla-
cebo; p < 0.001) [13]. A high-concentration, non-rebreather
mask should be recommended for optimal oxygen efficacy.
One hundred percent oxygen should be offered to treat acute
CH attacks.
3.1.2 Triptans
Triptans are also very effective to treat the CH attack. A recent
Cochrane review found six RCTs for the acute treatment of
CH episodes [14]. Sumatriptan (subcutaneous/nasal spray)
and zolmitriptan (nasal spray/oral) were tested in multiple
RCTs. For many patients, subcutaneous sumatriptan 6 mg
is the preferred choice as it is generally considered to work
the fastest [14]. In one of the RCTs, 36% of patients were
pain free within 10 min and 48% (63/131; range
46 -- 49%) within 15 min post-injection [15]. Numbers needed
to treat (NNTs) for subcutaneous sumatriptan 6 mg were
3.3 (95% CI 2.4 -- 5.0) [15] in one study and 2.4 (95% CI
1.9 -- 3.2) in the other [16]. Alternatively, intranasal zolmitrip-
tan 5 or 10 mg can be a good option for those patients who do
not like to inject themselves [17,18]. Pain-free response was
reached in 38.5% within 30 min for 5 mg and 46.9% for

the 10 mg. The 10 mg dose is more effective and works faster
with 12% of patients pain free, and 28% with no or mild pain
after 15 min. NNTs for intranasal zolmitriptan 10 mg
were 11 (6.4 -- 49) and 4.9 (3.3 -- 9.2), respectively [18].
Unfortunately, 10 mg zolmitriptan is not generally available.
Sumatriptan 20 mg nasal spray was also effective in one
RCT [19]. Oral zolmitriptan 10 mg was also effective but
required a longer time to work [20]. Therefore, this may not
be an option for many patients in everyday clinical practice.
Adverse events associated with triptans are nausea, vomiting,
dizziness, fatigue, paresthesias, feeling of heaviness, non-chest
tightness and unpleasant or bitter taste. The main problem
with triptans is that it is generally recommended not to use
Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15
more than two applications per day, so that patients with
CH tend to overuse triptans in their acute phase. Kallweit
and Sandor reported a 15-year follow-up of one patient who
took sumatriptan in excessive doses between 12 and 222 mg
(average of 150 mg during 1 year). The patient had a good
treatment effect and no adverse events. In this case, the thera-
peutic safety margin was probably much wider than generally
recommended [21].
3.1.3 Intranasal lidocaine
One randomized crossover clinical trial, one non-randomized
For personal use only.
trial and two case series describe the efficacy of lidocaine for
the treatment of the acute CH attack [22-25]. Either 4 or
10% lidocaine (1 ml) was used. The controlled, crossover trial
included nine patients with nitroglycerin-induced CH
attacks [25]. The pain stopped on average 37 (± 7.8) min after
lidocaine application to the ipsilateral nostril. Intranasal
cocaine 10% were equally effective in this study. Major points
of critique that prevent a clear-cut recommendation for
lidocaine were the experimental model of CH without spon-
taneous attacks, the low patient numbers and the application
via anterior rhinoscopy, which is not applicable in everyday
clinical practice [26]. Therefore, intranasal lidocaine remains
second-line therapy for CH attacks, but should be considered
if standard treatment fails.
3.1.4 Ergotamine
Dihydroergotamine (DHE) is an injectable alternative to
triptans, but not generally available, with more side effects
and little formal scientific evidence for efficacy. It has a long
half-life and is therefore also used as transitional therapy to
stop the cluster episode. In a retrospective study, most
patients were headache free within 2 days with 1 mg DHE
2 -- 3 times daily [27]. Sixteen percent became headache free
after the first dose and it may protect patients with frequent
attacks from further attacks for up to 12 h (i.e., overnight).
Its onset is slower compared with that experienced with trip-
tans (e.g., sumatriptan subcutaneously). Intranasal DHE
showed insufficient evidence in improving CH response in
one RCT [28]. The Committee for Medicinal Products for
Human Use of the European Medical Agency prohibited
the use of DHE containing medications in 2014 due to safety
Expert Opin. Pharmacother. (2015) 16(8)
Cluster headache pharmacotherapy
concerns (mainly fibrosis and intoxication). It remains
available in other countries (i.e., Canada).
3.1.5 Octreotide
Subcutaneous octreotide 100 µg was compared with placebo
in 57 patients with CH. Headache relief (mild to no pain)
was achieved in 57% of patients after 30 min with ocreotide
versus 36% with placebo (p < 0.01). Adverse events were diar-
rhea, abdominal bloating, nausea, dull background headache
and injection-site reactions. Octreotide may be useful as
second-line agent to treat acute CH attacks, but evidence is
thin.
4. Transitional treatment
The lack of randomized, placebo-controlled trials results in
uncertainty towards appropriate CH therapy, especially
regarding prophylactic compounds. Therefore, many patients
experience insufficient treatment, resulting in unnecessary
prolongation of cluster episodes and suffering.
4.1 Corticosteroids
Mainly clinical experience and small, uncontrolled clinical trials
suggest bridging therapy with corticosteroids until prophylactic
treatment reaches sufficient efficacy to control the attacks [29].
Verapamil, for example, becomes efficient usually not before
10 -- 14 days after treatment initiation [3]. By estimation, about
one-third of patients receive corticosteroids for bout abortion,
but documentation of efficacy in the literature is limited.
Some small open studies reported a negative outcome [30-32],
others suggested effectiveness of corticosteroids [33-35]. Only
one placebo-controlled trial was conducted including 19 CH
patients [36]. Fourteen of them were reported to be free of
pain after one single dose of corticosteroid. However, the study
had some methodological limitations that make interpretation
of results difficult. Two non-randomized studies treated CH
patients with high-dose intravenous methylprednisone
(250 -- 500 mg). After treatment, the CH attacks were signifi-
cantly less frequent compared with previous episodes and dif-
ferent treatments [34,35]. A large, multicenter, randomized,
placebo-controlled study is currently running that aims to clar-
ify the efficacy of corticosteroids for the treatment of cluster
headache (PredCH-Study) [37].
4.2 Occipital nerve block
Greater occipital nerve block is one emerging alternative to
corticosteroids as bridging therapy. Efficacy and safety of
occipital injections were documented by two randomized con-
trolled trials [38,39], even though the optimal technique and
substance to be injected are still subject to discussion [40].
Cortivazol (3.75 mg in 1.5 ml saline), or a mixture containing
a long-acting salt of betamethasone (dipropionate 12.46 mg),
a rapid-acting salt of betamethasone (disodium phosphate
5.26 mg) mixed with 0.5 ml xylocaine 2%, respectively, was
used in these studies [38,39]. In many centers, slow-release
3
 M. Obermann et al.
methylprednisolone 40 -- 80 mg (or equivalent) is used in
combination with lidocaine in repeated injections.
4.3 Ergotamine
Another alternative is subcutaneous or intramuscular DHE
that is often used 2 or 3 times a day for a week and may be
continued once or twice a day for another week if tolerated.
Contraindications are vasocontriction-related side effects,
and its availability is limited in some countries (see above).
Methysergide is probably effective, even though there are no
controlled trials available. It is not available in many countries
and concerns with concomitant triptan use as well as potential
fibrotic complications over longer treatment periods limits its
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use [41].
4.4 Triptans
Sometimes long-acting triptans are used as short-term prophy-
lactic therapy before verapamil or lithium start to work, even
though RCTs are still missing. Frovatriptan 2.5 mg was tested
in nine patients with episodic CH and eight of these patients
reported to have complete pain relief after 48 h. Patients
received frovatriptan for up to 3 weeks once or twice daily until
their verapamil dosage was considered sufficient. They were
not permitted to use other triptans, but were allowed other res-
For personal use only.
cue medication such as oxygen [42]. One attempted RCT with
frovatriptan discontinued prematurely due to insufficient
recruitment and other problems during the trial [43]. Naratrip-
tan 2.5 mg once or twice daily improved headaches in seven
out of nine CH patients and eletriptan 40 mg was also tested
successfully in one patient [44]. Oral sumatriptan was not
effective as short-term prophylactic [45].
5. Prophylactic treatment
Prophylactic therapy should be started in parallel to the
transitional therapies stated above. Most prophylactic drugs
require some time for dosage escalation until the sufficient
dosage is reached and the drug’s efficacy starts. RCTs about
the efficacy of currently used prophylactic drugs are sparse.
European treatment guidelines (European Federation of the
Neurological Societies [EFNS]) suggest the use of the calcium
channel blocker verapamil at a dose of at least 240 mg daily as
first-line therapy [3].
5.1 Verapamil
Verapamil 360 mg/day is the only prophylactic treatment
available that has proven efficacy in a randomized, placebo-
controlled, double-blind clinical trial [46]. Starting dose should
be 40 -- 80 mg 3 times a day, with an increase in dose by
80 mg every week until 3 times 120 mg are reached. Many
patients will require a dosage of 480 mg/day and some
patients use as much as 720 mg/day and more. Lanteri-
Minet et al. investigated cardiac safety in 29 CH patients
who were on 877 ± 227 mg verapamil per day. Incidence of
total ECG changes was 38% (11/29), seven patients showed
4 Expert Opin. Pharmacother. (2015) 16(8)
clinically not relevant bradycardia, four (14%) presented
with arrhythmia (right bundle branch block, complete heart
block with junctional rhythms) that was considered serious.
Those patients with detected ECG changes had a higher
dose (1003 ± 295 mg/day) compared with those with normal
ECG (800 ± 143 mg/day). This study emphasizes carful ECG
monitoring of patients with verapamil, but also reassures a
wide therapeutic margin for this drug [47]. Titration of verap-
amil should always be a compromise between cardiac safety
and fast amelioration of painful attacks. Patients who take
verapamil should be advised to be cautious with grapefruit
as it contains furanocoumarins that inactivate CYP3A4,
which can result in increased verapamil levels leading to
cardiac side effects [48].
5.2 Lithium
Lithium is generally considered the first treatment alternative
to verapamil, even though the only placebo-controlled, clinical
trial investigating lithium for CH was negative. This trial used
a relatively low dose (800 mg) and observed a short period of
only 1 week [49]. A comparison study with verapamil showed
a comparable efficacy with slower onset of action and more
side effects [50]. Lithium may also be used as add-on to verap-
amil when sufficient pain relief cannot be achieved by mono-
therapy alone. Lithium can be started at 300 mg twice a day
and may be increased to 3 times a day after 1 week. Before
increasing the dose any further, lithium levels need to be
checked. The serum levels should remain below 1.2 mEq/l to
avoid toxicity, the therapeutic response is usually achieved
with serum levels between 0.4 and 0.8 mEq/l [51]. Some
patients may require an increased dose of 1200 mg/day. Thy-
roid and renal function should be monitored. Typical side
effects are nausea, diarrhea, polyuria, tremor, confusion, leth-
argy and ataxia. There is some drug interaction with verapamil
at higher doses (> 560 mg/day) that have to be considered.
Lithium should be reduced in these cases (Table 1).
5.3 Antiepileptic drugs
Topiramate was recommended by the EFNS guidelines as
‘probably effective’, as some earlier studies suggested effi-
cacy [3]. In a more recent open-label study, only 7 out of
33 patients experienced a headache reduction of 50% or
more so that this positive efficacy could not be confirmed [52].
Sodium valproate 500 mg/day was not superior to placebo in
pain control and cannot be recommended for the treatment of
CH [53]. Two patients were treated with levetiracetam
500 -- 1000 mg twice daily with complete cessation of head-
ache attacks within 1 week with only transient mild somno-
lence as documented side effect [54]. This will have to be
reconfirmed in RCT.
5.4 Melatonin, prostaglandin and testosterone
There is evidence from one RCT with 20 CH patients that
10 mg melatonin is effective in reducing the daily headache
frequency considerably compared with placebo (p < 0.03).
 Cluster headache pharmacotherapy

Table 1. Recommended pharmacotherapy for cluster headache.

Acute Dosage Side effects/comments Level of

medications evidence

Oxygen 100% oxygen 12 l/15 min None reported Level A

Sumatriptan Subcutaneous 6 mg Application 2/day; injection site reactions, nausea, Level A
vomiting, dizziness, fatigue, paresthesias
Intranasal 20 mg Application 2/day; bitter taste Level B
Zolmitriptan Intranasal 5 -- 10 mg Application 2/day; unpleasant taste, nasal cavity Level A
discomfort, somnolence, dizziness, nausea, throat/neck
tightness
Dihydroergotamine 1 mg nasal spray, subcutaneous, Application 3/day; long acting (up to 12 h), Level U
intramuscular vasocontriction-related side effects
Transitional medications
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Prednisone 60 -- 100 mg oral 100 mg/day over 5 days then slow tapering; many different Level C
treatment regimens, not longer than 18 days to avoid
steroid-related side effects
Occipital nerve Methylprednisolone slow-release, Different treatment regimen, with and without local Level B
block cortivazol (3.75 mg in 1.5 ml saline), anesthetic, injection-related side effects
plus lidocaine
Dihydroergotamine 1 mg subcutaneous, intramuscular Application 3/day; long acting (up to 12 h), Level C
vasocontriction-related side effects
Prophylactic medications
Verapamil 360 -- 480 mg/day Starting at 40 -- 80 mg 3/day, increasing by 80 mg/week, Level B
ECG initially and periodically to monitor potential cardiac side
effects; constipation, reduced blood pressure and heart rate
Lithium 900 mg/day Starting with 300 mg 2/day or 400 or 450 mg (where Level C
available) 1/day increase after 4 to 7 days; monitor lithium
For personal use only.

blood level (0.4 -- 0.8 mEq/l; not over 1.2 mEq/l)

Level of evidence A: data derived from multiple randomized clinical trials or meta-analyses.
Level of evidence B: data derived from a single randomized clinical trial or large non-randomized studies.
Level of evidence C: consensus of opinion of the experts and/or small studies, retrospective studies, registries.

No adverse events were reported [55]. However, a study using a
2 mg slow-release tablet melatonin failed to show a relevant
clinical benefit compared with placebo [56]. Prostaglandin E
(misoprostol) 600 µg was not effective in chronic CH over a
treatment period of 2 weeks [57]. Testosterone replacement
therapy in chronic, therapy refractory cluster patients who
had low testosterone serum levels resulted in cessation of
cluster attacks in five of seven patients and led to remission
in four patients [58]. All these investigations will have to be
reconfirmed in larger samples under controlled conditions.
5.5 Civamide (zucapsaicin)
Twenty-eight patients with episodic CH were investigated in
a placebo-controlled clinical trial with 100 µl of 0.025%
civamide (zucapsaicin) sprayed into each nostril for 7 days.
Civamide intranasally led to a marked reduction in the
number of headaches within 7 days (--55 vs --25.9% with
placebo; p = 0.03). Common adverse events were nasal
burning (78%), lacrimation (50%), pharyngitis (44%) and
rhinorrhea (33%) [59].
5.6 Warfarin, candesartan and baclofen
Warfarin at low anticoagulating intensity showed efficacy in
refractory, chronic CH. Thirty-four patients received warfarin
or placebo for 12 weeks in a crossover design with a washout
period of 2 weeks. International normalized ratio was held
between 1.5 and 1.9. Seventeen (50%) patients went into
remission for over 4 weeks during warfarin treatment versus
4 (11.8%) patients with placebo. NNT was 2.6 (95% CI
1.7 -- 5.5). Warfarin could be an interesting treatment alterna-
tive for CH, when these results could be confirmed in larger
RCTs [60]. The angiotensin II receptor blocker candesartan
16 mg did not have significant effect on CH attacks within
3 weeks compared with placebo [54]. A pilot study with
baclofen 15 -- 30 mg/day showed a promising efficacy in
12 patients with pain cessation within 1 week that may justify
further clinical testing [61].
6. Conclusion
CH is a rare primary headache disorder and its treatment can
be complex, even though conventional and currently available
pharmacotherapy is efficient in most cases (Figure 1). Chronic
cluster patients may require neuromodulation techniques or
even surgical intervention (occipital nerve stimulation,
sphenopalatine ganglion stimulation, etc.). Experience and
therapeutic expertise are required for treatment success.
Acute, transitional and prophylactic treatment should be
applied quickly, determined and appropriate for the individ-
ual patient. More evidence-based studies are urgently needed

Expert Opin. Pharmacother. (2015) 16(8) 5

 M. Obermann et al.
Actual therapy
First line Oxygen
Sumatriptan
Zolmitriptan
Second line Lidocaine (intrnasal)
Octreotide
Alternative Dihydroergotamine
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Figure 1. Guide to the pharmacological treatment of cluster headache.
to strengthen the scientific foundation of CH treatment
recommendations.
7. Expert opinion
Even though many pharmacotherapy options exist for the treat-
ment of CH, the scientific evidence for most of these treatments
For personal use only.
remains scarce. Future research should focus on conducting
RCTs in order to find out which treatment regime works best
in most patients rather than trial and error with every patient
anew. In a rare disease like CH this will be quite challenging
in the coming years, but may lead the way to new treatment
options and an increased quality of life for such patients. It
would be nice to see medications in development that are specif-
ically directed at CH treatment, as the available medications
now are without exception borrowed from other indications.
More pathophysiological insight may lead the path to new
and more specific therapies in this regard. Neurostimulation
and invasive techniques that came more and more into focus
over the past couple of year as the classical pharmacotherapy
seems to fail in some patients. However, these non-
pharmacological treatments will have to undergo the same evi-
dence-based procedures to test their efficacy as the drugs do. It
will be quite interesting to see which of the new and established
treatments will survive these high requirements demanded by
patient safety and quality of standard medical care.
6 Expert Opin. Pharmacother. (2015) 16(8)
Transitional therapy Prophylactic therapy
Corticosteroids Verapamil
Occipital nerve blockade Lithium
Triptans (long acting) Topiramate
Dihydrogergotamine Melatonin
Civamid
Warfarin
Baclofen
Levetiracetam
Declaration of interest
M Obermann has received scientific support, travel support
and/or honoraria from Biogen Idec, Novartis, Sanofi-Aventis,
Genzyme, Pfizer, Teva and Heel. He received research grants
from Allergan, Electrocore, Heel and the German Ministry
for Education and Research (BMBF). D Holle has received
a scientific grant from Gruenenthal. H-C Diener has received
honoraria for participation in clinical trials, contribution to
advisory boards or lectures from Addex Pharma, Allergan,
Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Coherex
Medical, CoLucid, B€ohringer Ingelheim, Bristol-Myers
Squibb, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Lilly,
La Roche, 3M Medica, Minster, MSD, Novartis, Johnson
& Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer,
Sanofi-Aventis, and Weber & Weber; received research sup-
port from Allergan, Almirall, AstraZeneca, Bayer, Galaxo-
SmithKline, Janssen-Cilag and Pfizer. Research at the
Department of Neurology in Essen is supported by the
German Research Council (DFG), the German Ministry of
Education and Research (BMBF) and the European Union.
The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those
disclosed.

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Affiliation
Mark Obermann† MD, Dagny Holle,
Steffen Naegel, Jan Burmeister &
Hans-Christoph Diener
†
Author for correspondence
University of Duisburg-Essen, Department of
Neurology, Hufelandstr. 55, 45122 Essen,
Germany
Tel: +49 201 723 84385;
Fax: +49 201 723 5542;
E-mail: mark.obermann@uni-due.de