Dipyrone for acute primary headaches
Abstract
Background
Dipyrone is used to treat headaches in many countries, but is not available in others (particularly the USA and UK) because of its association with potentially life‐threatening blood dyscrasias such as agranulocytosis.
Objectives
To determine the effectiveness and safety of dipyrone for acute primary headaches in adults and children.
Search methods
We searched the Cochrane Pain, Palliative & Supportive Care Group's Trials Register; the Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; LILACS, and the reference lists of included studies.
Selection criteria
Double‐blind randomised controlled trials of dipyrone for the symptomatic relief of acute primary headaches in adults and children.
Data collection and analysis
Three authors independently screened articles, extracted data, assessed trial quality and analysed results. Relative risks (RRs), risk differences (RDs), weighted mean differences (WMDs), and numbers‐needed‐to‐treat (NNTs) were calculated as appropriate.
Main results
Four trials involving a total of 636 adult subjects were included. Methodological quality was generally high. One study each evaluated oral and intravenous dipyrone for episodic tension‐type headache (ETTH); two trials evaluated intravenous dipyrone for migraine, but only one of these described pain outcomes. No pediatric trials were identified.
The largest trial (n = 356) evaluated two doses (0.5 g, 1 g) of oral dipyrone for ETTH, which were significantly better than placebo for pain relief. The 1 g dose was also significantly better than acetylsalicylic acid (ASA) 1 g . A smaller trial (n = 60) evaluated intravenous dipyrone 1 g versus placebo for ETTH. RRs were statistically significant favouring dipyrone for pain‐free and headache improvement outcomes. Finally, one trial (n = 134) evaluated intravenous dipyrone 1 g versus placebo for pain outcomes in patients with migraine. RRs were again statistically significant favouring dipyrone for pain‐free and headache improvement outcomes.
Two of the four trials assessed adverse events. No serious adverse events were reported, and no significant differences in adverse events were detected between dipyrone and comparators (placebo and ASA).
Authors' conclusions
Evidence from a small number of trials suggests that dipyrone is effective for ETTH and migraine. No serious adverse events were observed in the included trials, but agranulocytosis is rare and would probably not be observed in such a relatively small sample. A study now ongoing in Latin America may clarify the true risk of agranulocytosis associated with dipyrone use.
Plain language summary
Dipyrone for the treatment of headaches
Dipyrone is a popular medicine used to treat headaches in many countries, but it is not available in others (particularly the USA and UK) because of its association with potentially life‐threatening blood disorders such as agranulocytosis.
This review identified four trials of dipyrone for headache involving a total of 636 adult patients. The quality of the trials was generally high. Three of the four trials specifically evaluated dipyrone's effect on headache pain. The results suggest that dipyrone effectively relieves tension‐type ('muscle contraction') headache pain when taken by mouth (one trial) or given intravenously (one trial), and that dipyrone effectively relieves migraine headache pain when given intravenously (one trial). At a dose of 1 g, the oral form of dipyrone was more effective than a 1 g dose of aspirin for tension‐type headache pain.
Only two of the four included trials provided information on side effects. No serious side effects were reported. However, the most serious potential side effect related to dipyrone, agranulocytosis, is rare and would probably not be observed in such a relatively small sample. A study is now being conducted in Latin America which may help estimate more precisely the risk of agranulocytosis in patients taking dipyrone.
