Is metoclopramide (Reglan) or Compazine (prochlorperazine) more effective for treating migraines?

Metoclopramide and Prochlorperazine Are Equally Effective for Acute Migraine Treatment

Both metoclopramide 10 mg IV and prochlorperazine 10 mg IV demonstrate equivalent efficacy for acute migraine relief, with approximately 75% of patients wanting the same medication for future attacks. 1 The choice between them should be based on route of administration preference, side effect profile, and clinical context rather than superior efficacy of one over the other.

Evidence for Equivalent Efficacy

Head-to-Head Comparison

• A randomized controlled trial directly comparing prochlorperazine 10 mg IV versus metoclopramide 20 mg IV (note: double the metoclopramide dose) found no significant difference in pain reduction at 1 hour (mean change 5.5 vs 5.2 on numeric rating scale, difference 0.3 points, 95% CI -1.0 to 1.6). 1
• Both medications showed similar efficacy at 2 hours and 24 hours post-treatment. 1
• Patient satisfaction was nearly identical: 77% of prochlorperazine patients and 73% of metoclopramide patients wanted the same medication for future ED visits (difference 4%, 95% CI -16% to 24%). 1

Metoclopramide Dose Considerations

• A dose-finding study demonstrated that 10 mg IV metoclopramide is as effective as higher doses (20 mg or 40 mg), with no additional benefit from dose escalation. 2
• All three doses (10,20,40 mg) produced similar pain reduction at 1 hour (4.7,4.9, and 5.3 points respectively) and similar rates of sustained pain freedom at 48 hours (16%, 20%, 21%). 2
• This means the comparison showing equivalence used twice the necessary metoclopramide dose, further supporting equal efficacy at standard dosing. 2, 1

Guideline Recommendations

Current Treatment Hierarchy

• The most recent 2021 Nature Reviews Neurology guidelines recommend prokinetic antiemetics (domperidone or metoclopramide) as adjunct oral medications for nausea and vomiting during migraine attacks, not as primary monotherapy. 3
• The 2025 Praxis guidelines specifically recommend IV metoclopramide (10 mg) as effective not only for nausea but also for providing synergistic analgesia for migraine pain. 4
• Prochlorperazine (10 mg IV) is noted to effectively relieve headache pain and be comparable to metoclopramide in efficacy. 4

Efficacy Ratings from Older Guidelines

• The 2002 American Family Physician guideline rated prochlorperazine with an efficacy score of 4 (most effective) versus metoclopramide with a score of 2, but this was based on clinical impression rather than head-to-head trials. 3
• This older rating system is contradicted by the 2008 direct comparison trial showing equivalent efficacy. 1

Practical Clinical Algorithm

When to Choose Metoclopramide (10 mg IV)

• First-line choice when rapid onset is needed (metoclopramide showed more rapid improvement at 15 and 30 minutes compared to paracetamol). 5
• Preferred when combining with NSAIDs (ketorolac 30 mg IV + metoclopramide 10 mg IV is recommended as first-line combination therapy). 4
• Better option when oral route is feasible and cost is a concern (oral metoclopramide plus analgesic is less expensive than triptans, though less effective). 6
• When used as adjunct to enhance analgesic absorption and provide antiemetic coverage. 3, 4

When to Choose Prochlorperazine (10 mg IV or 25 mg suppository)

• Alternative when metoclopramide is unavailable or contraindicated. 1
• When rectal route is preferred (prochlorperazine available as 25 mg suppository, maximum three doses per 24 hours). 3
• Patient has had previous success with prochlorperazine. 1

Route and Timing Considerations

• IV route is most studied and preferred for both medications in acute severe migraine. 4, 2, 1
• Administer early in the attack for maximum efficacy. 3, 4
• Both should be given with diphenhydramine 25 mg IV to prevent extrapyramidal side effects. 2, 1

Side Effect Profile

Common Adverse Effects

• Drowsiness is the most common side effect, impairing function in 17% of patients receiving metoclopramide (evenly distributed across all doses). 2
• Prochlorperazine showed 46% adverse event rate versus 32% for metoclopramide (difference 15%, 95% CI -6% to 36%), though not statistically significant. 1
• Akathisia occurred in approximately 10-15% of metoclopramide patients despite prophylactic diphenhydramine. 2

Serious Adverse Effects

• Both medications carry risk of extrapyramidal symptoms (dystonia, akathisia, pseudo-parkinsonism). 3, 2
• Prochlorperazine has additional risks of tardive dyskinesia, hypotension, tachycardia, and arrhythmias. 3
• No cases of tardive dyskinesia were reported at one-month follow-up in the metoclopramide dose-finding study. 2

Contraindications

• Metoclopramide: pheochromocytoma, seizure disorder, GI bleeding, GI obstruction. 3
• Prochlorperazine: CNS depression, use of adrenergic blockers. 3

Network Meta-Analysis Findings

• A 2023 systematic review and network meta-analysis found metoclopramide's effect on headache change was only significantly lower than granisetron, while being significantly better than placebo and sumatriptan. 7
• For headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide, which showed significantly higher effects than placebo. 7
• This supports the equivalence of these two medications in clinical practice. 7

Critical Pitfalls to Avoid

• Do not exceed 10 mg IV metoclopramide - higher doses provide no additional benefit and increase side effect burden. 2
• Always co-administer diphenhydramine 25 mg IV to reduce extrapyramidal symptoms. 2, 1
• Avoid frequent use (limit to no more than twice weekly) to prevent medication-overuse headache. 3, 4
• Do not use oral metoclopramide as monotherapy expecting triptan-level efficacy - it is inferior to oral triptans for primary treatment. 6
• Recognize that both medications work best when combined with NSAIDs rather than as monotherapy. 4, 5