Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review.
We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline. The study population included patients participating in a controlled study about symptomatic treatment. The comparator could be placebo or the standard of care. The collected information was the primary outcome of the study and all secondary outcomes. We evaluated the studied drug, the year of publication and the type of journal. We performed a search and we screened all the potential papers and reviewed them considering inclusion/exclusion criteria.
The search showed 4288 clinical trials that were screened and 794 full articles were assessed for eligibility for a final inclusion of 495 papers. The studies were published in headache specific journals (58%), general journals (21.6%) and neuroscience journals (20.4%).
Migraine was the most studied headache, in 87.8% studies, followed by tension type headache in 4.7%. Regarding the most evaluated drug, triptans represented 68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only 4.6% of the papers evaluated ergots and 1.6% analyzed opioids.
The most frequent primary endpoint was the relief of the headache at a determinate moment, in 54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning other endpoints, tolerance was the most frequently addressed (83%), followed by headache relief (71.1%), improvement of other symptoms (62.5%) and presence of relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0) before 1991 to 6.39 after 2013 (p = 0.001).
Headache relief has been the most employed primary endpoint but headache disappearance starts to be firmly considered. The number of secondary endpoints increases over time and other outcomes such as disability, quality of life and patients’ preference are receiving attention.
Steiner TJ, Stovner LJ, Vos T et al (2018) Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain 19(1):17 CrossRef
Osumili B, McCrone P, Cousins S et al (2018) The economic cost of patients with migraine headache referred to specialist clinics. Headache 58:287–294 CrossRef
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2015;388:1545–602
Bloudek LM, Stokes M, Buse DC et al (2012) Cost of health care for patients with migraine in five European countries: results from the international burden of migraine study (IBMS). J Headache Pain 13(5):361–378 CrossRef
Committee on Clinical Trials in Migraine. Guidelines for Controlled Trials of Drugs in Migraine. First ed Cephalalgia 1991;11(1):1-12
Bendtsen L, Bigal M, Cerbo R, Diener H, Holroyd K, Lampl C et al (2009) Guidelines for controlled trials of drugs in tension-type headache: second edition. Cephalalgia 30(1):1–16 CrossRef
Tfelt-Hansen P, Pascual J, Ramadan N, Dahlöf C, Damico D, Diener H-C et al (2012) Guidelines for controlled trials of drugs in migraine: third edition. A guide for investigators. Cephalalgia 32(1):6–38 CrossRef
Macedo A, Farré M, Baños J-E (2006) A meta-analysis of the placebo response in acute migraine and how this response may be influenced by some of the characteristics of clinical trials. Eur J Clin Pharmacol 62(3):161–172 CrossRef
Hougaard A, Tfelt-Hansen P (2010) Are the current IHS guidelines for migraine drug trials being followed? J Headache Pain 11(6):457–468 CrossRef
Lipton RB, Hamelsky SW, Dayno JM (2002) What do patients with migraine want from acute migraine treatment? Headache 42(s1):3–9 CrossRef
Bigal M, Rapoport A, Aurora S, Sheftell F, Tepper S, Dahlof C (2007) Satisfaction with current migraine therapy: experience from 3 centers in US and Sweden. Headache 47(4):475–479 CrossRef
Patrick DL, Martin ML, Bushmell DM, Pesa J (2003) Measuring satisfaction with migraine treatment: expectations, importance, outcomes, and global ratings. Clin Ther 25(11):2920–2935 CrossRef
Díez FI, Straube A, Zanchin G (2007) Patient preference in migraine therapy. J Neurol 254(2):242–249 CrossRef
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700
Ferrari MD et al (2010) Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan – a randomised proof-of-concept trial. Cephalalgia 30(10):1170–1178 CrossRef
Connor KM, Shapiro RE, Diener HC et al (2009) Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 73:970–977 CrossRef
Diener HC, Limmroth V (2004) Medication-overuse headache: a worldwide problem. Lancet Neurol 3:475–483 CrossRef
Bigal ME, Lipton RB (2009) Excessive opioid use and the development of chronic migraine. Pain 142:179–182 CrossRef
Marshall S, Haywood K, Fitzpatrick R (2006) Impact of patient-reported outcome measures on routine practice: a structured review. J Eval Clin Pract 12(5):559–568 CrossRef
- A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches
L. M. Messina
M. L. Speranza
on behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)
- Springer Milan
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