Many of treat migraines in the ED. I even discussed the use of Depakote recently. I figured for installment #2 of the WWDWWD series I’d take a step back and discuss the first line IV treatment for refractory migraines in the ED. Before I do that I wanted to make sure that I elaborated on the main goals of ED migraine therapy. In order it is important to:
  • Make the symptoms go away
  • Restore normal function
  • Align the patient for outpatient follow up
It turns out that the antiemetics Prochlorperazine and Metoclopramide are quite effective at accomplishing these 3 goals. Let’s explore the evidence in a stepwise fashion, asking some key questions along the way, beginning with Prochlorperazine as it was the first drug studied.

Why do these antiemetics work anyway and are there any worrisome side effects?

Great question. The answer is elusive, but it may have to do with how these agents affect dopamine in the brain. That’s enough of an explanation for me.

There are some side effects to watch out for as well:
  • Prochlorperazine – can cause restlessness, agitation, and in rare instances a dystonic reaction – treat this with benadryl. The exact incidence of side effects is not precisely known.
  • Metoclopramide – can also cause extrapyramidal reactions, and it appears that these may be more likely in patients under the age of 25 years.

Does it work, and is it safe to give to kids?

Largely yes. In a 2001 retrospective review on the use of prochlorperazine in 20 consecutive children with migraine headaches in the ED, Kabbouche et al noted that at 1 hour 75 % of patients had improvement with 50% headache free. At 3 hours 95% were improved with 60% headache free. The authors correctly noted that larger, randomized studies were needed. They also noted that there were no significant complications.

Why not just give toradol since it is a pain medicine and headaches are painful?

Brousseau et al investigated this exact question in 2004. they performed a double blinded RCT and noted the following at 1 hour:
  • 84.8% response to prochloroperazine
  • 55.2% response to Ketorolac
  • 93% response when treatments were combined
They also noted a 30% recurrence in 24 hours. This study is one of the main reasons why the common practice where I work is the administration of both an entiemetic and ketorolac.

I’ve seen Reglan used instead. Is it any better than Compazine?

A 1996 study from Coppola et al suggested that it wasn’t. They conducted a double blinded placebo RCT in adults with migraines comparing IV prochlorperazine versus metoclopramide. They noted that 82% of patients that received 10mg of prochlorperazine had pain improvement versus on 46% and 29% for 10mg of IV metoclopramide and IV placebo respectively. Friedman et al in 2008 disagreed, noting that in their double blind RCT comparing 10mg IV prochlorperzine + diphenhydramine versus 20mg IV metoclopramide + diphenhydramine that there was essentially no significant difference in the pain score of the two agents. The trent in pain seemed to favor prochlorperazine, but metoclopramide has less side effects. These differences would have been better elucidated had the study been larger – but still it seemed to be adequately powered to detect the outcomes it did.
The differences between these two studies include the addition of benadryl, and more importantly the higher dose of Reglan. It seems that the larger dose of the dopaminergic agent did not cause more side effects as had been feared, and was not inferior to Compazine. Of course, both of these studies were in adults. Where you draw the line between adult and child physiologically is challenging, but I feel comfortable giving both agents to kids and teens with migraines based on this evidence and my growing body of personal anecdotal evidence.


  • Ketorolac 0.5 mg/kg IV or IM (max 30mg)
  • Prochlorperazine (Compazine) 0.1-0.15 mg/kg IV (max 10mg)
  • Metoclopramide (Reglan) 0.5-2 mg/kg IV (max 20mg)

PEMBlog Overall Recommendations

  • If you’re going to pick one agent go with Compazine or Reglan
  • If you’re going to use two then add Toradol Reglan is a good alternative, especially if the patient had side effects to Compazine that Benadryl didn’t help
  • If the first line doesn’t work, then try Depakote
  • If Depakote doesn’t work admit (likely for DHE)