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16th February 2011
A Cochrane review of 10 studies with over 2,700 patients, found that a single oral dose of paracetamol 1000mg was effective in relieving moderate to severe migraine symptoms, compared with placebo. While CKS recommend the use of paracetamol alone to treat acute migraine, other recent guidelines do not. However, this review provides new efficacy and tolerability data that support the first-line use of paracetamol 1000mg alone for people with migraine headaches that do not cause severe disability.
Level of evidence:
Level 2 (limited quality patient-oriented evidence) according to the SORT criteria.
Action
These new data support recommendations from CKS that paracetamol used alone is an appropriate first-line analgesic for the treatment of acute migraine headaches that are not very severe and disabling. Health professionals, particularly community pharmacists, advising people on over-the-counter (OTC) treatments for acute migraine should consider these new data in discussions with patients. As paracetamol has a good safety profile and is well tolerated, it may offer advantages over aspirin and other NSAIDs for some people, particularly those at high gastrointestinal (GI) or cardiovascular (CV) risk. If nausea/vomiting is a symptom, paracetamol plus metoclopramide is as effective as, but better tolerated than, sumatriptan. CKS recommends an individualised, stepwise approach, using the least expensive drugs with known efficacy first, before advancing up the treatment ladder to migraine-specific drugs (i.e. triptans).
What is the background to this?
Migraine is a common, disabling headache disorder that is characterised by episodic severe headaches, with associated symptoms such as photophobia, phonophobia, and nausea and vomiting. Many people suffering from an acute migraine episode self-manage their symptoms using OTC analgesics. There is currently no NICE guidance on the drug management of acute migraine, but CKS recommends the use of simple analgesics first-line (for the first three attacks, unless they are very severe and disabling). Paracetamol, aspirin, and ibuprofen are all suitable options and are available OTC. If nausea and vomiting are troublesome, an antiemetic (e.g. metoclopramide, domperidone) can be considered. Triptans (e.g. sumatriptan) can be considered if first-line treatment has been ineffective (e.g. on three independent episodes of migraine).
Some recent guidelines (BASH [British Association for the Study of Headache] 2010, EFNS [European Federation of Neurological Societies] 2009) have not recommended paracetamol for the treatment of acute migraine, either on grounds of lack of efficacy, or by expert consensus. The aim of this Cochrane review was to determine the efficacy and tolerability of paracetamol, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. No other systematic reviews appear to have assessed the efficacy of this intervention in adults.
What does this study claim?
This systematic review and meta-analysis of 10 double-blind RCTs in over 2,700 patients found that paracetamol 1000mg alone is an effective treatment for acute migraine headaches in adults. When taken for moderate to severe pain, paracetamol was superior to placebo for all efficacy outcomes including 2-hour pain-free (risk ratio [RR] 1.80, 95% confidence interval [95%CI] 1.24 to 2.62, NNT 12), and 2-hour headache relief (RR 1.55, 95%CI 1.32 to 1.83, NNT 5). Nausea, photophobia and phonophobia were also significantly reduced at 2 hours with paracetamol, compared with placebo (NNT range 7 to 11). Adverse events were poorly reported, but there were significantly more adverse events with placebo, compared with paracetamol (NNH 21).
Furthermore, the addition of metoclopramide 10mg to paracetamol provided short-term efficacy equivalent to oral sumatriptan 100mg alone. When taken for moderate to severe pain, there was no significant difference in headache relief at 2 hours between paracetamol plus metoclopramide vs. sumatriptan (RR 0.93, 95%CI 0.81 to 1.10). The proportion of patients experiencing adverse events were significantly lower with paracetamol plus metoclopramide, compared with sumatriptan (28% vs. 47%, RR 0.61, 95%CI 0.53 to 0.71, NNH 5).
So what?
This review included new studies, which supports the existing evidence that paracetamol as an appropriate first-line option for treating acute migraine headaches that do not cause severe disability. Due to small numbers of patients divided between many different comparators, there were only sufficient data to compare paracetamol with placebo. However, this is an important comparison as a strong placebo effect is observed during placebo-controlled trials of migraine. Head-to-head studies with other active comparators (e.g. aspirin, NSAIDs), particularly those available OTC, are required to compare the effectiveness of different treatments. Given that paracetamol has a good safety profile and is well tolerated, it may offer advantages over NSAIDs for some people, particularly those at high GI and/or CV risk. Guidelines that have excluded paracetamol as a first-line option for acute migraine may need to review their recommendations in light of these new data.
Data were previously lacking on paracetamol in the acute treatment of severe migraine, but this review considered the use of paracetamol when pain intensity had become moderate or severe (measured using a pain intensity scale). There were insufficient data to compare treating an attack at onset with treating once pain had become moderate or severe, or to compare single with multiple dosing regimens.
The only other comparison that provided adequate data was the combination of paracetamol plus metoclopramide (either single or combined products), compared with sumatriptan. Overall, there was no significant difference between the two treatments when baseline pain was moderate to severe, but sumatriptan was associated with more adverse events. Therefore, this review supports current recommendations that triptans should be reserved for those people who have not been controlled with simple analgesics on three independent episodes of migraine, or for those with very severe and disabling episodes.
Design
Systematic review and meta-analysis of 10 double-blind RCTs with at least 10 participants per treatment arm. Cross over studies were accepted if there was an adequate washout period (>48 hours).
Patients
2769 adults at least 18 years of age (4062 acute migraine attacks) with acute migraine (as defined by, or conforming with, the International Headache Society diagnostic criteria).
Intervention and comparison
Self-administered oral paracetamol 1000mg (alone, or in combination with an antiemetic) vs. placebo or other active comparator (usually sumatriptan 100mg) to treat an acute migraine headache episode. Prophylactic migraine medications were allowed.
Outcomes
Primary outcomes:
- pain free at 2 hours, without the use of rescue medication
- reduction in headache pain (’headache relief ’) at 1 and 2 hours (pain reduced from moderate or severe to none or mild without the use of rescue medication)
- sustained pain-free over 24 hours (pain-free within 2 hours, with no use of rescue medication or recurrence within 24 hours)
- sustained pain reduction over 24 hours (headache relief at 2 hours, sustained for 24 hours, with no use of rescue medication or a second dose of study medication).
Pain intensity measured by patients (not investigator or carer) using a pain intensity scale e.g. 4-point categorical scale, 100mm visual analogue scale (VAS).
Secondary outcomes — any adverse event over 24 hours post dose; particular adverse events over 24 hours post dose; withdrawals due to adverse events over 24 hours post dose; relief of headache associated symptoms; functional disability.
Results
Few data were available for meta-analysis.
| Paracetamol 1000mg vs. placebo | No. of patients in comparison | RR (95%CI) |
| Pain free at 2 hoursa | 717 | 1.80 (1.24 to 2.62) |
| Headache relief at 2 hoursa | 717 | 1.55 (1.32 to 1.83) |
| Nausea at 2 hours | 536 | 1.37 (1.17 to 1.61) |
| Photophobia at 2 hours | 985 | 1.40 (1.19 to 1.64) |
| Phonophobia at 2 hours | 944 | 1.42 (1.21 to 1.67) |
| Any adverse event | 1293 | 0.78 (0.64 to 0.95) |
| Paracetamol 1000mg/ metoclopramide 10mg vs. sumatriptan 100mg | No. of patients in comparison | RR (95%CI) |
| Headache relief at 2 hoursa | 1140 | 0.93 (0.81 to 1.07) |
| Relief of light/noise sensitivity at 2 hours | 1001 | 1.01 (0.85 to 1.21) |
| Use of rescue medication at 24 hours | 1243 | 1.17 (1.01 to 1.36) |
| Any adverse event | 1328 | 0.61 (0.53 to 0.71) |
| Major adverse event | 1328 | 0.50 (0.30 to 0.83) |
amoderate/severe pain
Sponsorship The review was conducted by Cochrane authors.
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