1. Introduction
Cluster headache is a devastating primary headache, characterized by attacks of severe, strictly
unilateral pain which is orbital, supraorbital and/or temporal, lasting between 15 to 180 minutes
when untreated. The attacks occur almost every other day, up to 8 times a day. Chronic cluster
headache (CCH) is a type of cluster headache in which attacks occur for more than a year without
remission or with remission periods lasting less than 1 month (1). The clinical characteristics of
CCH suggest a substantial disease burden, both to patients as well as society. We aim to provide
an overview of the disease burden of CCH and outcomes of treatments recommended by the
European Federation of Neurological Societies (EFNS) for CCH (2).
Two research questions were designed:
1) What evidence is reported in the literature with regard to epidemiological, economic, and
humanistic burden and comorbidities for CCH?
2) What evidence is reported in the literature with regard to economic burden, complications and
outcomes for treatments recommended in the EFNS guidelines?
Methods
A predefined search strategy was used to search Medline, Embase, Econlit, Cochrane and NHS EED
databases for citations published from the year 2000 and onwards. The search was performed on
May 27th
2014. Identification of relevant citations was based on PICOS criteria (Table 1). Data was
extracted using data extraction forms; one researcher extracted the data and a second independent
researcher checked each extraction. Details on study design (e.g. study objective, case finding
method, inclusion criteria); patient characteristics (e.g. age, gender, number of CCH patients) and
outcomes (e.g. prevalence, humanistic burden, treatment efficacy) were extracted.
Table 1 PICOS criteria
Question 1 Question 2
Population Inclusion
criteria
Adult patients (≥18 years)
Chronic Cluster headache according to ICHD-III beta criteria:
A. At least five attacks fulfilling criteria B–D
B. Severe or very severe unilateral orbital, supraorbital and/or
temporal pain lasting 15–180 minutes (when untreated)
C. Either or both of the following:
• At least one of the following symptoms or signs, ipsilateral to
the headache:
- conjunctival injection and/or lacrimation
- nasal congestion and/or rhinorrhoea
- eyelid edema
- forehead and facial sweating
- forehead and facial flushing
- sensation of fullness in the ear
- miosis and/or ptosis
• A sense of restlessness or agitation
D. Attacks have a frequency between one every other day and
eight per day for more than half of the time when the disorder
is active
E. Not attributed to another ICHD-3 diagnosis
F. Occurring without a remission period, or with remissions lasting
<1 month, for at least 1 year.
Exclusion
criteria
Healthy patients without CCH
Studies including only patients with headache or migraine
Mixed populations (migraine and CCH), but not reported separately
Inter­
vention
Inclusion
criteria
Not applicable
Oxygen inhalation therapy
Sumatriptan 6 mg s.c
Sumatriptan 20 mg nasal
Zolmitriptan 5 mg nasal
Zolmitriptan 10 mg oral
Lidocaine nasal
Octreotide
Verapamil
Steroids
Lithium
Methysergide
Topiramate
Ergotamine tartrate
Valproic acid
Melatonin
Baclofen
Exclusion
criteria
All other treatments not listed
under inclusion criteria
Comparison Inclusion
criteria
Not applicable Studies comparing interventions
of interest listed above to each
other or to placebo
Exclusion
criteria
Outcomes Inclusion
criteria
All outcomes related to:
• Epidemiological burden
• Economic burden
• Humanistic burden
• Comorbidities
All outcomes related to:
• Economic consequences
• Treatment outcomes
• Treatment complications
Exclusion
criteria
Humanistic and economic
burden and comorbidities are
reported linked to the treat-
ments and not to disease itself
Study
design
Inclusion
criteria
Observational studies
Registries
Randomized controlled trials
Exclusion
criteria
Methodology papers/protocols
Case reports/ small studies (n<5 patients per arm)
Editorials/ letters
Conference reviews or proceedings
Biomarker studies
In vitro studies
Non-systematic reviews
Systematic literature reviews
Meta-analysis
Results
Database searches identified 3364 records, of which 74 were duplicates between databases. A
total of 3290 citations were screened using the PICOS criteria. Figure 1 presents the flowchart of
the study selection process for research questions 1 and 2. Ultimately, 10 publications covering 7
unique studies were included for data-extraction to assess the disease burden of CCH and 7
publications covering 5 unique studies were included to assess outcomes associated with treatment
for CCH.
Figure 1 Flowchart of study selection process
Question 1: Disease burden
Of the seven included studies, five were observational, one study followed a cohort of patients and
one was retrospective in design. Two multicenter studies, both observational, and four single center
studies were identified. Six studies were based in Europe and one in the USA. All studies included
patients diagnosed with CCH based on ICHD-2 criteria. See Table 2 for more details on the design
of identified studies.
Patient characteristics are presented in Table 3. The number of CCH patients included in the studies
ranged from 19 to 113 (21% to 100%). Mean age ranged between 42.1 to 46.3 years and 54% to
82% of patients were male. The number of attacks in 24 hours was rarely reported; one study
reported an average of 3.3 attacks in 24 hours. Four studies provided information on illness duration
of included patients, which was at least 10 years in each of the studies.
Data reported on outcomes of interest is available in Table 4. Little information was available on
the epidemiology of CCH. Four studies reported information on the male-to-female ratio of CCH,
suggesting between 3 to 4 times as many men suffer from CCH than women (3-9). Comorbidities
were reported in 3 studies in heterogeneous ways. One study reported different types of headaches
accompanying CCH (10), one study reported the number of patients suffering from sleep apnea
syndrome (11) and the final study reported comorbid psychological issues patients suffered from
(7-9). The effect of CCH on work productivity was reported in 3 studies, each suggesting a substantial
impact (3, 4, 6-9). Ranging from 26% of patients reporting complete inability to work to 36% of
patients reporting any work loss. Health related quality of life using the SF-36 questionnaire was
reported in one study (3, 4). Patients with CCH reported scores between 40.9 and 59.3 for all
subscales of the SF-36, except physical functioning, on which patients scored relatively high, i.e.
80.7. (Note: a lower score equals more disability). Details on the economic burden of CCH are
scarce. One study provided information on health care resource use by CCH patients, showing
patients visited neurologists 4.4 times, neurosurgeons 1.8 times and pain specialists 7.3 times per
per 6 months (6). Lastly, one study reported health care costs associated with CCH. Direct per
capita costs were €9,073 and indirect per capita costs were €1,912 (expressed in 2010 Euros) (6).
Question 2: Treatment outcomes
Five unique clinical trials were identified during the review process. Three studies were randomized,
double-blind, placebo-controlled by design; one study was non-randomized, single-blind and one
study did not provide details on study design. Study centers were based in Europe and North
America. All trials included patients with CCH diagnosis according to ICHD criteria and reported
efficacy outcomes. Two studies provided details on the safety of interventions (Table 5).
Table 6 presents the patients characteristics for the identified clinical trials. Two trials compared
oral or nasal spray zolmitriptan (5mg and 10mg) to placebo, one study compared cortivazol injection
to placebo, one study compared melatonin to placebo and one study compared triptans to oxygen
treatment. The size of the trials ranged from very small (9 patients) to large (366 patients). The
average age of included patients ranged from 40 to 55 years and the percentage of males from
50% to 100%. The number of attacks per 24 hours was reported in one study and averaged
between 4.0 and 3.6 attacks per day.
Oral zolmitriptan 5 and 10mg achieved lower response rates compared to placebo (16% and 25%
versus 31% respectively) (12), however zolmitriptan 5 and 10mg nasal spray performed better
than placebo (28% and 36% versus 14% respectively) (13, 14). These results were confirmed by
other outcomes, such as need for rescue medication, pain free at 30 minutes and headache relief
at 30 minutes. Efficacy of melatonin was measured as the number of attacks per day, however no
statistically significant difference compared to placebo was observed (15). When comparing triptans
and oxygen treatment the percentage of responders and non-responders was similar (16). No
efficacy outcomes of interested were reported for cortivazol injection (17, 18). See Table 7 for
more details on efficacy outcomes of CCH treatment.
Safety of treatments in CCH was reported in only two studies, no (serious) adverse events or
withdrawals due to adverse events occurred. Details on other safety endpoints, such as nausea and
tension type headache were not reported.
None of the identified trials reported economic outcomes of interest, such as health care resource
use and direct or indirect costs.
Conclusion
Little evidence was found for both research questions in CCH patients. However, economic and
humanistic burden and comorbidities of CCH patients have a considerable impact on both patients
and the society. CCH is a disease with a few available treatment options. Efficacy outcomes of
specific treatments were, however, also non-consistently reported. Better understanding of the
disorder and the efficacy of treatments will lead to better identification, diagnosis and treatment of
CCH. Our review showed an evidence gap in a systematic way. More well-controlled, randomized
trials should be conducted with CCH patients to reduce heterogeneity in reporting and increase
evidence base.
References
1. Levin M. The international classification of headache disorders, 3rd Edition (ICHD III) - Changes and challenges. Headache. 2013; 53: 1383-95.
2. Evers S AJ, Frese A, Goadsby PJ, Linde M, May A, Sandor PS. Cluster headache and other trigemino-autonomic cephalgias. In: Gilhus NE BM,
Brainin M,, ed., European handbook of neurological management. 2nd ed. Oxford (UK): Wiley-Blackwell, 2011.
3. D’Amico D, Rigamonti A, Solari A, et al. Health-related quality of life in patients with cluster headache during active periods. Cephalalgia. 2002;
22: 818-21.
4. D’Amico D, Usai S, Grazzi L, et al. Quality of life and disability in primary chronic daily headaches. Neurological Sciences. 2003; 24: S97-S100.
5. Donnet A, Lanteri-Minet M, Guegan-Massardier E, et al. Chronic cluster headache: A French clinical descriptive study. Journal of Neurology,
Neurosurgery and Psychiatry. 2007; 78: 1354-58.
6. Gaul C, Finken J, Biermann J, et al. Treatment costs and indirect costs of cluster headache: A health economics analysis. Cephalalgia. 2011; 31:
1664-72.
7. Jurgens TP, Gaul C, Lindwurm A, et al. Burden of disease in cluster headache. Journal of Headache and Pain. 2010; 11: S138-S39.
8. Jurgens TP, Gaul C, Lindwurm A, et al. Impairment in episodic and chronic cluster headache. Cephalalgia. 2011; 31: 671-82.
9. Luerding R, Henkel K, Gaul C, et al. Aggressiveness in different presentations of cluster headache: Results from a controlled multicentric study.
Cephalalgia. 2012; 32: 528-36.
10. Gaul C, Christmann N, Schroder D, et al. Differences in clinical characteristics and frequency of accompanying migraine features in episodic and
chronic cluster headache. Cephalalgia. 2012; 32: 571-77.
11. Hornyak M, Kiemen A, Kaube H. Sleep apnea syndrome in chronic cluster headache. European Journal of Pain Supplements. 2011; 5: 137.
12. Bahra A, Gawel MJ, Hardebo J-E, et al. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000; 54: 1832-39.
13. Cittadini E, Goadsby PJ. Intranasal zolmitriptan is effective and well tolerated in acute cluster headache: A randomized placebo-controlled
double-blind crossover study. Progress in Neurotherapeutics and Neuropsychopharmacology. 2008; 3: 127-35.
14. Cittadini E, May A, Straube A, et al. Effectiveness of intranasal zolmitriptan in acute cluster headache: A randomized, placebo-controlled,
double-blind crossover study. Archives of Neurology. 2006; 63: 1537-42.
15. Pringsheim T, Magnoux E, Dobson CF, et al. Melatonin as adjunctive therapy in the prophylaxis of cluster headache: a pilot study. Headache. 2002;
42: 787-92.
16. Schurks M, Rosskopf D, de Jesus J, et al. Predictors of acute treatment response among patients with cluster headache. Headache. 2007; 47:
1079-84.
17. Leroux E, Ducros A, Vicaut E, et al. Greater occipital nerve infiltration with cortivazol for cluster headache (CHCI): A double blind randomized
controlled trial. Journal of Headache and Pain. 2010; 11: S81.
18. Leroux E, Valade D, Taifas I, et al. Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache
attacks per day: A randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2011; 10: 891-97.
19. Marmura MJ, Abbas M, Ashkenazi A. Dynamic mechanical (brush) allodynia in cluster headache: A prevalence study in a tertiary headache clinic.
Journal of Headache and Pain. 2009; 10: 255-58.
Systematic Literature Review of Treatments
of Chronic Cluster Headache
Medic G.1
, Thavaneswaran S.2
, Papadimitropoulou K.1
, Stauble F.2
, Karabis A.1
1
Mapi - HEOR & Strategic Market Access, Houten, Netherlands, 2
Medtronic International, Tolochenaz, Switzerland
Search strategy: OVID + Cochrane Library + NHS EED
3364 abstracts retrieved - 74 duplicates from Cochrane = 3290 abstracts
Abstracts excluded Question 1: 3119
Patient pop. not of interest (1077)
Intervention not of interest (0)
Comparator not of interest (0)
Outcomes not of interest (376)
Study design not of interest (1647)
Duplicate (19)
Abstracts excluded Q2: 3169
Patient pop. not of interest (1030)
Intervention not of interest (466)
Comparator not of interest (3)
Outcomes not of interest (7)
Study design not of interest (1644)
Duplicate (19)
Full-texts excluded Q1: 161
Patient pop. not of interest (45)
Intervention not of interest (0)
Comparator not of interest (0)
Outcomes not of interest (60)
Study design not of interest (55)
Not retrievable (1)
Duplicate (0)
Full-texts excluded Q2: 114
Patient pop. not of interest (16)
Intervention not of interest (10)
Comparator not of interest (22)
Outcomes not of interest (4)
Study design not of interest (62)
Duplicate (0)
3290 publications for abstract screening
Question 1: 171 publications for full text screening
Question 2: 121 publications for full text screening
Question 1: 10 publications retrieved for data extraction
Question 2: 7 publications retrieved for data extraction
Table 2 Study design; Research Question 1
Author & Year Objective/ Statement of decision problem Study type Study Design Country Inclusion criteria Outcomes reported
D’Amico 2002
D’Amico 2003
To assess functional disability and HRQOL in Italian patients
suffering from CCH most often diagnosed in tertiary care
units.
Observational
study
SC Italy
Diagnosis based on IHS
Had not started prophylactic treatment
when recruited or had started but were
still having daily headaches
Humanistic burden
Donnet 2007
To present the data collected between 2002 and 2005 that
concern specifically the clinical characteristics of CCH patients.
Observational
study
MC France
Diagnosis based on IHS
Only CCH patients
Humanistic burden
Gaul 2012
To address:
• Frequency and lateralization of accompanying autonomous
symptoms typically occurring in ECH and CCH attacks.
• Frequency of accompanying migrainous symptoms.
• Association between comorbid migraine diagnosis and
occurrence of accompanying migrainous symptoms in CH
attacks.
• Differences in pain intensity and pain localization between
ECH and CCH.
• Association between pain intensity and number and
­lateralization of reported autonomic symptoms.
• Comparison of circadian and circannual rhythmicity in ECH
and CCH
Cohort study SC Germany Diagnosis based on ICHD-II Comorbidities
Gaul 2011
To estimate the expenses of treatment of ECH and CCH over
6-month period; relationship between costs, burden of disease
and attack frequency within the 6-month period.
Retrospective
study
SC Germany
Diagnosis based on ICHD-II
Age ≥18 years
Adequate knowledge of German
Humanistic burden
Economic
Hornyak 2011
To investigate the frequency of SAS in CCH by means of a
validated diagnosis screening questionnaire for SAS and diary
in a multicenter study
Observational
study
NR Germany NR Comorbidities
Jurgens 2010
Jurgens 2011
Luerding 2012
To determine the extent of disability in CH patients and its
subtypes in comparison to migraine patients and healthy
controls, concerning epidemiological factors, disability and
concomitant psychiatric symptoms.
Observational
study
MC,
prospective
Germany
Diagnosis based on ICHD-II for
migraine without and with aura for ECH
and CCH
Epidemiology
Humanistic burden
Comorbidities
Marmura 2009
To evaluate the prevalence of dynamic mechanical (brush)
allodynia (BA) in CH patients attending a tertiary headache
clinic, and to assess its relation to disease characteristics.
Observational
study
SC USA
Age ≥18 years
Diagnosis based on ICHD-II criteria for
ECH or CCH
Epidemiology
BA: Brush Allodynia; CCH: Chronic cluster headache; CH: Cluster headache; ECH: Episodic cluster headache; HAD: Hospital Anxiety and Depression; HIT-6: Headache Impact Test-6; HRQOL: Health Related Quality of Life; ICHD-II: International Classification of
Headache Disorders 2; IHS: International Headache Society; MC: Multi center; MIDAS: Migraine Disability Assessment Test; NR: Not reported; SAS: Sleep Apnea Syndrome; SC: Single center; SF-36: Short-Form 36; USA: United States of America
Table 3 Patient characteristics; Research Question 2
Author & Year Sample
size
CCH (n) ECH (n) Setting Males (%) Age mean (SD) Age of onset mean (SD) Number of attacks in
24 hours mean (SD)
Illness duration
mean years (SD)
D’Amico 2002
D’Amico 2003
22 22 0 Hospital 82% 46.2 (11.0) NR NR 11.5 (9.9)
Donnet 2007 113 113 0 Hospital 82% NR
<20 years: 7 pts
20-29 years: 30 pts
30-39 years: 28 pts
40-49 years: 23 pts
50-59 years: 16 pts
60-75 years: 3 pts
NR NR
Gaul 2012 209 65 144 Outpatient NR 46.3 (11.3) 33.8 (13.9) 3.3 (3) NR
Gaul 2011 179 72 107 Outpatient 75% 45.0 (11.8) NR NR 11.3 (9.2)
Hornyak 2011 26 26 NR NR NR NR NR NR NR
Jurgens 2010
Jurgens 2011
Luerding 2012
130 27 48 NR 82% 42,1 30,6 NR 11,4
Marmura 2009 41 19 22 Outpatient 54% 44.9 (10.5) NR NR 12.3 (9.6)
CCH: Chronic cluster headache; CH: Cluster headache; ICHD-II: International Classification of Headache Disorders 2; IHS: International Headache Society; NR: Not reported; Pts: Patients; SAS: Sleep Apnea Syndrome; SD: Standard Deviation
Table 4 Outcomes; Research Question 1
Author & Year Male-to-female
ratio
Co-morbidities N (%) Disability status Work productivity/
Decreased ability to work
Number of visits to GP
per patient mean (SD)
Number of visits to the
specialist per patient
mean (SD)
D’Amico 2002
D’Amico 2003
4.5:1 NR NR
Work loss: 8/22 (36.4%)
Work reduced by >50%:
11/22 (50.0%)
NR NR
Donnet 2007 4.65:1 NR NR NR NR NR
Gaul 2012 NR
Migraine: 21 (10.0%)
Tension-type-headache: 35 (16.7%)
Medication overuse headache: 1 (0.5%)
Trigeminal neuralgia: 1 (0.5%)
NR NR NR NR
Gaul 2011 3.0:1 NR
Officially classified
as severely handi-
capped: 30/72
Daily loss: €95
Absent from work: 8.5 days
12.4 (17.3)
Neurologist: 4.4 (6.7)
Neurosurgeon: 1.8 (1.0)
Pain specialist: 7.3 (5.2)
Hornyak 2011 NR SAS: 16 (61.5%) NR NR NR NR
Jurgens 2010
Jurgens 2011
Luerding 2012
4.4:1
Panic syndrome: 4 (15.0%)
Agoraphobia: 9 (33.0%)
Social phobia: 5 (19.0%)
Specific phobia: 2 (7.0%)
Generalized anxiety disorder: 5 (19.0%)
Obsessive-compulsive disorder: 1 (4.0%)
Depressive syndrome: 15 (56.0%)
Dysthymia: 3 (11%)
Suicidal tendencies: 6 (22.0%)
NR Unable to work: 26% NR NR
Marmura 2009 NR NR NR NR NR NR
GP: General Practitioner; NR: Not Reported; SD: Standard Deviation; SAS: Sleep Apnea Syndrome
Table 5 Study design; Research Question 2
Author & year Study Design Country Study period Primary study outcome Inclusion criteria Outcomes
reported
Leroux 2011
Leroux 2011
RCT, DB, PC,
SC
France
November 2008 -
July 2009
Reduction in the mean number of
attacks per day to 2 or fewer during the
2nd, 3rd and 4th day after the 3rd
injection
Age 18–65
Diagnosis based on ICHD-II
Had a mean of >2 attacks per 24 h in the 3 days preceding
the day of inclusion
ECH patients also needed to have been in their present
phase of attacks for no more than 1 month, on the basis of
reports from patients and medical records, if available
Efficacy
Adverse events
Bahra 2000
RCT, DB, PC,
MC, cross-over
Canada, UK,
Sweden
NR
Headache response defined as a
two-point or greater improvement from
pretreatment headache intensity on the
five-point cluster headache rating scale
at 30 minutes
Age 18–65
Diagnosis based on IHS 2 criteria
Had CH for at least 3 months before the start of the study
Experienced CH usually lasting more than 45 min in duration
Was able to distinguish CH from other episodic headaches
Had tolerated previous treatment with a 5-HT1B/1D receptor
agonist, such as sumatriptan or ergotamine
Women had to practice adequate contraception
Efficacy
Adverse events
Cittadini 2008
Cittadini 2006
RCT, DB, PC,
cross-over
Germany, Italy,
UK
12 June 2003 -
24 May 2005
Headache relief at 30 min: reduction in
headache from moderate, severe or
very severe pain to mild or no pain
Age 18-65
Diagnosis based on IHS criteria
Untreated attacks lasting at least 45 min
Patients that used zolmitriptan in the past and zolmitriptan-
naïve patients were included if, in the opinion of the
investigator, it was safe to do so
Efficacy
Pringsheim 2002
PC, SB,
cross-over
Canada
November 2000 -
April 2001
Number of headaches per day Diagnosis based on IHS criteria Efficacy
Schurks 2007 NR Germany
April 2002 -
March 2004
Predictors for triptan and oxygen
response
Caucasian CH patients
Diagnosis based on IHS criteria
Efficacy
CCH: Chronic cluster headache; CH: Cluster headache; DB: Double blind; ECH: Episodic cluster headache; ICHD-II: International Classification of Headache Disorders 2; IHS: International Headache Society; MC: Multi center; NR: Not reported; PC: Placebo
controlled; RCT: Randomized Controlled Trial; SB: Single blind; SC: Single center; UK: United Kingdom
Table 6 Patient characteristics; Research Question 2
Author & year Setting Treatment and dosage Male (%) ITT (n) CCH
patients
(n)
ECH
patients
(n)
Age mean
(SD)
Age of
onset
mean (SD)
Number of
attacks in 24h
mean (SD)
Illness duration
mean (SD)
(years)
Leroux 2011
Leroux 2011
Hospital
Cortivazol 3.75 mg suboccipial injection 85% 21 7 14 41 (13)
NR
4.0 (1.4)
NR
Placebo 100% 22 8 14 43 (12) 3.6 (1.4)
Bahra 2000 Outpatients
Zolmitriptan 10 mg (oral)
NR
111 32 79
NR NR NR NRZolmitriptan 5 mg (oral) 114 31 83
Placebo 115 32 83
Cittadini 2008
Cittadini 2006
NR
Zolmitriptan 5 mg (nasal spray)
87% 69 29 40 40 (10) NR NR 12 (7)Zolmitriptan 10 mg (nasal spray)
Placebo
Pringsheim 2002 Outpatient
Melatonin 2mg 50%
9 6 3 55 (NR) NR NR 10 (NR)
Placebo 50%
Schurks 2007
Hospital and
outpatient
Triptans 79% 191
41 184
44 (11)
37 (12) NR NR
Oxygen 83% 175 45 (11)
CCH: Chronic cluster headache; ECH: Episodic cluster headache; ITT: Intention-to-treat; NR: Not reported; SD: Standard deviation
Table 7 Outcomes; Research Question 2
Author & year Treatment and dosage N
[efficacy
analysis]
Overall response
to treatment n
(%)
Complete
pain relief
n (%)
Need for
rescue
medications
n (%)
# of
attacks
treated
n/N (%)
# of attacks
per day
mean (SD)
Pain free
at 15 min
n (%)
Pain free
at 30 min
n (%)
Headache
relief
at 30 min
n (%)
Leroux 2011
Leroux 2011
Cortivazol 3.75 mg suboccipial
injection
7
NR NR NR NR NR NR NR NR
Placebo 8
Bahra 2000
Zolmitriptan 10 mg (oral) 32 NR (25%) 14 (44%) 12 (37%)
NR NR NR
12 (37%) 15 (47%)
Zolmitriptan 5 mg (oral) 31 NR (16%) 12 (39%) 12 (39%) 15 (48%) 16 (52%)
Placebo 32 NR (31%) 14 (28%) 9 (28%) 15 (47%) 16 (50%)
Cittadini 2008
Cittadini 2006
Zolmitriptan 5 mg (nasal spray)
29
8 (28%)
NR
CH: 23 (35%)
85 NR
CH: 1 (1%) CH: 31 (50%) CH: 27 (42%)
Zolmitriptan 10 mg (nasal spray) 10 (36%) CH: 17 (27%) CH: 2 (3%) CH: 18 (28%) CH: 38 (61%)
Placebo 4 (14%) CH: 30 (50%) CH: 0 (0%) CH: 10 (16%) CH: 12 (23%)
Pringsheim 2002
Melatonin 2 mg
6 NR NR NR NR
1.07 (0.61)
NR NR NR
Placebo 1.02 (0.65)
Schurks 2007
Triptans 191
Responders: 21%
NR NR NR NR NR NR NR
Nonresponders: 19%
Oxygen 175
Responders: 21%
Nonresponders: 24%
CH: Cluster headache; NR: Not reported; SD: Standard deviation
Presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR),
Philadelphia, PA, USA, May 16–20, 2015.
Corresponding author:
Goran Medic, MSc. Pharm.
Research Consultant – HEOR & Strategic Market Access
Mapi, De Molen 84, 3995 AX Houten, The Netherlands
Tel.: +31 (0)30 63 697 63
Email: gmedic@mapigroup.com
www.mapigroup.com