A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches

Abstract

BackgroundPrimary 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.MethodsWe 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.ResultsThe 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).ConclusionHeadache 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.

Have the IHS Guidelines for controlled trials of acute treatment of migraine attacks been followed? Laying the ground for the 4th edition

“…It is also worth noting that the number of controlled trials published in the 2012–2018 period was much lower than in the previous analysis (2002–2008) (5), when 145 trials were eligible for review. Indeed, a recent review of studies on the acute treatment of headache showed that the number of publications decreased after 2010 (8). In the post-triptan era, there has been a progressive increase in clinical trials on preventive treatment in contrast to trials for the acute treatment of migraine attacks.…”

“…The current analysis of adherence to the 3rd edition of IHS Guidelines for the acute treatment of migraine shows that there has not been a substantial improvement in the compliance with the IHS Guidelines over the years, as we detected a reduction in the percentage of trials using a placebo-controlled design together with a slight increase in the percentage of trials that adopted the recommended primary outcome measure. This last observation is somewhat surprising considering that a recent review on the compliance with the primary endpoints for the acute treatment of headache recommended by subsequent editions of the IHS Guidelines over the period 1991–2013 showed that the adherence to the 2-hour headache-free endpoint progressively increased over time: 36.4% in 1991, 39.6% in 2000–2002, 83.3% in 2013 (8). It must be, however, noted that the figures reported in the above review also include studies targeting other primary headaches besides migraine; furthermore, headache freedom was assessed at timings different from 2 hours, which makes the findings difficult to compare with our analysis.…”

Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study (Preprint)

“…Attempts to analyze such recorded data are still too subjective and serve the purpose of general assumptions of patients' clinical pain complexity. Some studies have addressed the complexity of pain evaluation in the clinical setting [25][26][27][28]. For instance, one study indicated that the complexity of chronic pain in a biopsychosocial context includes not only physical but also mental and social outcomes [25].…”

Triptanophobia in migraine: A case-control study on the causes and consequences of the nonuse of triptans in chronic migraine patients

“…Symptomatic treatment aims to abort migraine episodes and restore patients' normal function, minimizing migraine morbidity and impact. To date, different symptomatic treatments have been used 1 , representing triptan discovery a new era with more robust studies and better clinical results 2 .…”