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Metoclopramine with or without diphenhydrAMINE

In the pediatric patient diagnosed with refractory migraine, is metoclopramide an effective treatment?

Plain language summary from the office of evidence based practice: 
Based on very low quality evidence, the Migraine Therapy in the ED CPG team makes a conditional recommendation to use metoclopramide as the back-up medication for the treatment of refractory migraine during shortages of prochlorperazine. Of metoclopramide, valproic acid, or ketorolac, metoclopramide is more likely to relieve headache pain within two hours of administration. Rescue medications to relieve continued pain are less likely to be administered when metoclopramide is administered versus the other two potential back-up medications, and the number of adverse drug events is similar among the three medications. The comparison of metoclopramide versus valproic acid and ketorolac is from a single study performed by Friedman et al. (2014). Although the study is methodologically strong, as more evidence becomes of available, the estimates of effect may change. Further research, if performed will have an important influence on our confidence in the estimate of the effect.

Review of literature: Metoclopramide is significantly less likely to produce pain relief within two hours of administration than prochlorperazine (OR= 0.34, 95% CI [0.16, 0.71], and is more likely to require the administration of rescue medications than prochlorperazine (OR= 3.05, 95% CI [1.32, 7.02] (Coppola, Yealy, & Leibold, 1995; Friedman et al., 2008; Jones, Pack, & Chun, 1996) (see Figures 2-4). Friedman et al. (2014) reported that metoclopramide provided greater reduction in headache pain on an 11-point visual analog scale within 2 hours of dosing than either valproic acid or ketorolac OR = 1.90, 95% CI [1.21, 2.59] and 0.80, 95% CI [0.03, 1.57], respectively. Subjects who received metoclopramide received less rescue medication than those who received valproic acid (OR=0.22, 95% CI [0.12, 0.38] or ketorolac OR= 0.45, 95% CI [0.26, 0.78].

Friedman et al. (2008) performed a dose finding study, comparing a 10 mG IV dose to a 20 mG and 40 mG IV dose, and a 20 mG IV dose to a 40 mG IV dose. There was no difference in the number of subjects with pain relief within two hours, or need for rescue medication (see Figure 5).

The individual studies are strong studies; biases were not identified (see Figure 1) for the comparison of metoclopramide vs. prochlorperazine, the three included studies are inconsistent. Two studies use IV dosing, and the other uses IM dosing. Studies did not control for the concomitant use of diphenhydramine. These factors increase the inconsistency among the studies, decreasing confidence in the results. The studies are also downgraded for imprecision. There are small numbers of subjects in the included studies, with small number of events. Therefore, the precision of the outcome measurement is low. Finally, the evidence is indirect, as the subjects in all studies were primarily adults. However, we value pain relief with the least amount of rescue medication needed to be administered (see Table 1).

For the comparison of metoclopramide vs. valproic acid and ketorolac, only one study was identified, and meta-analysis could not be performed (Friedman et al., 2014). Further research is likely to have an important influence on our confidence in the estimate of effect and is likely to change the estimate. Since the desirable effects of effective pain reduction and less use of rescue medications are met with metoclopramide compared with valproic acid or ketorolac, it is our recommendation when a prochlorperazine shortage is in effect.

Dose: Metoclopramide -0.1 mG/kg (max 10 mG) IV, over 15 minutes

See Appendix H for the full Critically Appraised Topic (CAT).

These guidelines do not establish a standard of care to be followed in every case. It is recognized that each case is different and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare guidelines for each. Accordingly these guidelines should guide care with the understanding that departures from them may be required at times.