Conventional Therapy


A Cochrane Review in 2010 by Derry et al found ten studies (2769 participants, 4062 attacks) comparing paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes, paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Adverse event rates were similar between paracetamol and placebo. The addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg.2


An updated Cochrane review by Kirthi in 2013. Thirteen studies (4222 participants) compared aspirin 900 mg or 1000 mg, alone or in combination with metoclopramide 10 mg, with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg. For all efficacy outcomes, all active treatments were superior to placebo, with NNTs of 8.1, 4.9 and 6.6 for 2-hour pain-free, 2-hour headache relief, and 24-hour headache relief with aspirin alone versus placebo, and 8.8, 3.3 and 6.2 with aspirin plus metoclopramide versus placebo Addition of metoclopramide 10 mg significantly improves relief of nausea(P < 0.00006) and vomiting(P = 0.002). Adverse events were mainly mild and transient, and were slightly more common with aspirin than placebo, but less common than with sumatriptan 100 mg.3


In a series of Cochrane reviews in 2012 were shown to efficacious in intravenous intranasal and subcutaneous routes however all routes are associated with increased adverse effects which are often mild and transient.4,5,6


A Metanalysis of Randomised controlled trials by Colman in BMJ 2004 found 13 eligible trials totalling 655 adults. In studies comparing metoclopramide with placebo, metoclopramide was more likely to provide significant reduction in migraine pain (odds ratio 2.84, 95% confidence interval 1.05 to 7.68). Used as the only agent, metoclopramide showed mixed effectiveness when compared with other single agents. Treatments that did include metoclopramide were as, or more, effective than comparison treatments for pain, nausea, and relapse outcomes reported in all studies.7


A Metanalysis of RCTs by Golikhatir et al in Headache in 2019 included 11 studies (n = 771) Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31).8