Ibuprofen for acute treatment of episodic tension‐type headache in adults
Tension‐type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults.
We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in‐house database to January 2015. We sought unpublished studies by asking personal contacts and searching on‐line clinical trial registers and manufacturers' websites.
We included randomised, placebo‐controlled studies (parallel‐group or cross‐over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm.
Data collection and analysis
Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).
We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast‐acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of treatment. Other participants were either in studies not reporting outcomes we could analyse, or were given one of several active comparators in single studies.
For the IHS‐preferred outcome of being pain free at 2 hours the NNT for ibuprofen 400 mg (all formulations) compared with placebo was 14 (95% confidence interval (CI), 8.4 to 47) in four studies, with no significant difference from placebo at 1 hour (moderate quality evidence). The NNT was 5.9 (4.2 to 9.5) for the global evaluation of 'very good' or 'excellent' in three studies (moderate quality evidence). No study reported the number of participants experiencing no worse than mild pain at 1 or 2 hours. The use of rescue medication was lower with ibuprofen 400 mg than with placebo, with the number needed to treat to prevent one event (NNTp) of 8.9 (5.6 to 21) in two studies (low quality evidence).
Adverse events were not different between ibuprofen 400 mg and placebo; RR 1.1 (0.64 to 1.7) (high‐quality evidence). No serious adverse events were reported.
Ibuprofen 400 mg provides an important benefit in terms of being pain free at 2 hours for a small number of people with frequent episodic tension‐type headache who have an acute headache with moderate or severe initial pain. There is no information about the lesser benefit of no worse than mild pain at 2 hours.
Sheena Derry, Philip J Wiffen, R Andrew Moore, Lars Bendtsen
Plain language summary
Oral ibuprofen for acute treatment of episodic tension‐type headache in adults
Frequent episodic tension‐type headache (TTH) means having between one and 14 headaches per month. The condition causes much disability, and stops people concentrating and working properly. When headaches occur the pain usually goes away over time.
Ibuprofen is a commonly‐used painkiller available without prescription in most parts of the world. The usual dose is 400 mg taken by mouth.
We searched the literature in January 2015 and found 12 studies involved 3094 participants. Of these, about 1800 were included in comparisons between ibuprofen 400 mg and placebo. Others involved lower doses of ibuprofen, or different types of ibuprofen, or were in comparisons with other active drugs.
The outcome preferred by the International Headache Society (IHS) is being pain free after two hours. This outcome was reported by 23 in 100 people taking ibuprofen 400 mg, and in 16 out of 100 taking placebo. The result was statistically significant, but only 7 people (23 minus 16) in 100 benefited specifically because of ibuprofen 400 mg.
The IHS also suggests a range of other outcomes, but few were reported consistently enough for them to be used. People with pain value an outcome of having no worse than mild pain, but this was not reported by any study.
About 4 in 100 people taking ibuprofen 400 mg had an adverse event with ibuprofen, the same as with placebo. There were no serious adverse events.
There are questions about how studies in this type of headache are conducted. These questions involve the type of people chosen for the studies, and the outcomes reported. This limits the usefulness of the results, especially for people who just have an occasional headache.
Sheena Derry, Philip J Wiffen, R Andrew Moore, Lars Bendtsen
Implications for practice
For people with episodic tension‐type headache
Ibuprofen 400 mg may relieve headache pain, but the chance of the pain being relieved entirely by 2 hours is low. We do not know how or if these results can be extrapolated to people with an occasional headache.
While ibuprofen 400 mg is one choice for treatment of episodic TTH, it may be that higher doses or different formulations might be better, but evidence on this is lacking. Ibuprofen 400 mg is probably not much different from any other treatment, based on what is known.
For policy makers
There is insufficient information on drugs, doses, formulations, or outcomes to be able to make strong recommendations.
There is insufficient information on drugs, doses, formulations, or outcomes to be able to make confident decisions on cost effectiveness.
Implications for research
Episodic TTH is common and debilitating. The amount and reporting of evidence was limited by reporting issues, particularly of outcomes; this is a general finding for all TTH studies, not just those involving ibuprofen. It is not sufficient just to call for more studies. What is needed is a better understanding of TTH studies, in terms of the outcomes that can be reported from clinical trials, and often is not, and the differential effects of treatments in people with different degrees of headache frequency. This can be done from individual participant‐level analyses. Given that a number of modern studies have been completed or are underway, this would appear to be the research priority before new studies are commissioned.
The design of studies was generally good, though some were small.
The measurement of pain is not a major issue, as most studies, especially modern studies, have used standard pain intensity and pain relief scales. What is at issue are the outcomes reported using those pain measurements. It is not clear that the IHS‐preferred outcome of being free of pain at 2 hours is entirely appropriate, and while it is reasonable by analogy with migraine, it requires substantiating.
Comparison between active treatments
No authoritative comparisons between active treatments is possible in the present state of knowledge.