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

Abstract

Migraine is the most common cause of vascular headache and a highly prevalent illness. In the last 20 years, the discovery of new agents has increased clinical research on migraine. In most of clinical trials that have been conducted, the efficacy was established using a placebo as a control treatment. The objective of the study reported here was to analyse the response rate in patients who received a placebo as well as to determine how a number of the methodological factors may affect the effect of the placebo in clinical trials of acute migraine. Computer-based information searches were conducted on the Medline database. Data analysis included the outcomes 'pain relief', 'pain-free', 'associated symptoms', 'recurrence', 'patients' opinion' about pain relief and 'adverse events'. Administration route, study design and country in which the study was carried out were the methodological factors that were analyzed. Meta-analysis was computed using Mantel-Haenszel, and a total of 98 papers were considered in the final analysis. After 2 h, 28.6% of the patients of the placebo group improved and 8.8% were pain-free. The percentage of pain-free patients was the highest in the placebo and active drug groups in which the placebo or drug had been administered subcutaneously, in parallel design studies (vs. cross-over trials) and in studies performed in Europe (vs. North America). Adverse events in the placebo group were significantly higher in studies performed in North America. These data reinforce the need for knowing the magnitude of the placebo response in each specific situation during the planning of clinical trials on acute migraine.

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

“…Requiring a 50% symptom improvement to qualify as a treatment responder resulted in 26% placebo responders in diabetic neuropathic pain (Arakawa et al, 2015) but this was lower in other pain conditions (e.g., dental pain: 16%; Averbuch and Katzper, 2001). Similar response rates were reported in migraine (29%; Macedo et al, 2006), fibromyalgia (45%; Hauser et al, 2011), and pancreatic pain (20%; Capurso et al, 2012) investigations.…”

Author’s response to the Letter to the Editor of Tfelt-Hansen

“…He states the need of accepting that headache relief should be defined as the decrease in its intensity from moderate (2) or severe (3) to none (0) or mild (1). In fact, in our article we wrote that 'pain relief means a pain reduction higher than 50%".…”

“…We have read with attention the letter of Dr. Tfelt-Hansen regarding our article published in the journal which considered the placebo effect in migraine using meta-analytic techniques 1 . We consider that his comments will help to clarify some of the topics included in our paper.…”

“…We fully agree with that point of view. In fact, in all tables of our article 1 we showed pain free and pain relief variables to give the readers the possibility of comparing both of them. The first can be considered as a hard outcome and the second as a soft outcome.…”

Safety of opioid patch initiation in Australian residential aged care

“…A significant placebo effect was observed in migraine trials, particularly if the treatment was administered by injection (Macedo et al, 2006 Level I) and it may be more common in children and adolescents (Evers et al, 2009 Level I).…”