Is there any literature to support the efficacy metoprolol vs propranolol for migraine prevention?

Comment by InpharmD Researcher

Both metoprolol and propranolol are supported by clinical guidelines as effective options for migraine prevention, although direct comparative evidence between the two agents is limited. The 2025 ACP guideline recommends either metoprolol or propranolol as first-line beta-blocker options for preventive therapy in nonpregnant adults with episodic migraine, and the 2012 AAN/AHS guideline considers both agents established as effective (Level A recommendation) for reducing migraine frequency and severity. A systematic review and meta-analysis further found that both metoprolol and propranolol were more effective than placebo for migraine prevention and improved multiple migraine-related outcomes, while network meta-analysis did not identify significant differences in efficacy between the two agents or other evaluated beta-blockers, suggesting a potential class effect. Limited head-to-head comparative data have likewise demonstrated similar reductions in migraine frequency and severity with metoprolol and propranolol, with no significant differences in efficacy or tolerability observed between the agents.

Background

The 2025 Clinical Guideline from the American College of Physicians (ACP) and the 2012 American Academy of Neurology (AAN)/American Headache Society (AHS) Guideline on Pharmacologic Treatment for Episodic Migraine Prevention in Adults both support the use of metoprolol and propranolol for migraine prevention. The ACP guideline recommends either metoprolol or propranolol as first-line beta-blocker options for preventive therapy in nonpregnant adults with episodic migraine and places them among the preferred oral agents to be considered before CGRP-targeted therapies, citing considerations related to cost and patient preference for oral treatments. Similarly, the AAN/AHS guideline concluded that both metoprolol and propranolol are established as effective for migraine prevention (Level A recommendation) and should be offered to reduce migraine attack frequency and severity. While the AAN/AHS guideline reviewed evidence supporting the efficacy of each agent individually, it did not identify direct comparative evidence demonstrating superiority of metoprolol over propranolol or vice versa. [1], [2]

A 2019 systematic review and meta-analysis examined the efficacy of beta-blockers for migraine and tension-type headache prevention in adults. The selection criteria focused on studies comparing beta-blockers with placebo or other interventions for headache prevention, particularly migraine and tension-type headaches. Out of 3,513 initial studies screened, 108 trials met the inclusion criteria, with 50 being placebo-controlled and 58 comparing beta-blockers with other interventions. The analysis highlighted the effectiveness of propranolol, showing a significant reduction in migraine frequency compared to placebo, with results indicating fewer headaches per month. Specifically, propranolol reduced episodic migraine frequency by approximately 1.5 headaches per month at 8 weeks and 1.2 headaches per month at 12 weeks compared with placebo, with both outcomes supported by high-quality evidence. Propranolol also increased the likelihood of achieving at least a 50% reduction in headache frequency and was associated with reductions in analgesic medication use, headache severity, headache duration, and headache index. Additionally, propranolol demonstrated efficacy comparable to other established migraine preventive therapies, including flunarizine, topiramate, and valproate, although comparative-effectiveness data were generally limited by small, underpowered studies. [3]

Metoprolol was also more effective than placebo for episodic migraine prevention, demonstrating a reduction in headache frequency at 8 weeks, with the evidence rated as moderate quality. Metoprolol additionally increased the likelihood of achieving at least a 50% reduction in headache frequency and was associated with reductions in analgesic medication use, headache severity, headache duration, and headache index. Furthermore, network meta-analysis did not identify significant differences in efficacy between propranolol, metoprolol, and other evaluated beta-blockers, suggesting that the benefit observed in migraine prevention may represent a class effect. In contrast, other beta-blockers like atenolol, bisoprolol, and timolol demonstrated some efficacy, though the evidence was generally weaker due to fewer and smaller studies. Adverse events associated with beta-blockers included increased incidence of dizziness and fatigue. Despite these side effects, withdrawal rates did not significantly differ from those observed in placebo groups, suggesting a favorable benefit-risk profile for beta-blocker therapy in migraine prophylaxis. [3]

References: [1] Qaseem A, Cooney TG, Etxeandia-Ikobaltzeta I, et al; Clinical Guidelines Committee of the American College of Physicians. Prevention of episodic migraine headache using pharmacologic treatments in outpatient settings: a clinical guideline from the American College of Physicians. Ann Intern Med. Published online February 4, 2025. doi:10.7326/ANNALS-24-01052.
[2] Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-1345.
[3] Jackson JL, Kuriyama A, Kuwatsuka Y, et al. Beta-blockers for the prevention of headache in adults, a systematic review and meta-analysis. PLoS One. 2019;14(3):e0212785. doi:10.1371/journal.pone.0212785.
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any literature to support the efficacy metoprolol vs propranolol for migraine prevention?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-2 for your response.

Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study
Design

Double-blind, cross-over multicentre trial

N= 56
Objective To evaluate the prophylactic antimigraine effect of the beta1-selective beta-blocker metoprolol and compare it with the non-selective beta-blocker propranolol
Study Groups

Metoprolol (n= 56)

Propranolol (n= 56)
Inclusion Criteria Out-patients aged 18-60 years with classical or common migraine, fulfilling at least 4 out of 6 specific criteria, and having 3-10 migraine attacks monthly confirmed during a 1-month run-in period
Exclusion Criteria Other types of vascular headache, chronic daily headache, non-separable tension and migraine headaches, diet as primary trigger, change of psychopharmaceutical treatment, contraindications for beta-blockers, pregnancy, change in oral contraceptive therapy, severe somatic disease
Methods Patients received placebo during a 4-week run-in period, followed by random allocation to metoprolol 50 mg b.i.d. or propranolol 40 mg b.i.d. for 8 weeks. A 4-week wash-out period with placebo was followed by crossover to the other beta-blocker for 8 weeks. Acute migraine medication was allowed and recorded. Efficacy was assessed using diary cards for attack frequency, intensity, and medication consumption. Heart rate and blood pressure were measured, and side-effects were recorded.
Duration 24 weeks total: 4-week run-in, 8-week treatment, 4-week wash-out, 8-week crossover treatment
Outcome Measures Primary: Reduction in attack frequency, migraine days, and severity score, consumption of ergotamine and analgesics
Baseline Characteristics   All patients (n= 56)
Age, years 39.6 (18-59)
Females 41
Classical migraine 22
Common migraine 34
% heredity 80
Duration of migraine, years 20.7 (5-43)
% earlier prophylactic treatment 16
% earlier acute treatment 93
Results   Run-in Propranolol Wash-out Metoprolol
Number of migraine attacks per 4 weeks 5.4 4.2 5.6 4.2
Number of migraine days per 4 weeks  6.7 4.5 6.0 5.0
Sum of severity score per 4 weeks  12.4 8.7 10.9 9.7
Number of ergotamine tablets consumed per 4 weeks  5.1 2.9 2.8 2.7
Number of analgesic tablets consumed per 4 weeks  9.1 5.7 9.0 7.6
Adverse Events The number and type of side-effects were similar during active treatment and the run-in period (placebo). No statistically significant difference between metoprolol and propranolol. Both drugs were generally well-tolerated.
Study Author Conclusions Metoprolol 50 mg twice daily and propranolol 40 mg twice daily are equally effective in the prophylactic treatment of migraine and are generally well-tolerated. 
Critique The study's strengths include its double-blind, cross-over design and the use of standardized criteria for migraine diagnosis. However, the study may be limited by the relatively low dosages used, which are considered starting dosages, and the inclusion of patients with severe, long-lasting migraines who were refractory to treatment, potentially affecting the response rate. Additionally, the study did not explore higher dosages that might have yielded better responses in some patients. 
References:
[1] [1] Olsson JE, Behring HC, Forssman B, et al. Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study. Acta Neurol Scand. 1984;70(3):160-168. doi:10.1111/j.1600-0404.1984.tb00815.x

Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study
Design

Double-blind, cross-over study

N= 36
Objective To compare the well-established migraine prophylactic effect of the non-selective beta-blocker propranolol with that of the beta1-selective beta-blocker metoprolol
Study Groups

Metoprolol (n= 33)

Propranolol (n= 33)
Inclusion Criteria Outpatients diagnosed with classical or common migraine, with well-defined intermittent migraine attacks, fulfilling at least four criteria: heredity, pulsating headache, prodromas, hemicrania, phono- and/or photophobia, gastrointestinal disturbances; history of migraine of at least three years, attack duration of at least one hour, and 3-10 migraine attacks monthly documented during the run-in period
Exclusion Criteria Other types of vascular headache, chronic daily headache, contraindications for beta-blockers, treatment with neuroleptics and anti-depressives, coronary or peripheral vascular occlusive disease, severe renal or hepatic disease, change in oral contraceptive medication, pregnancy
Methods Patients received placebo during a four-week run-in period, then were randomly allocated to metoprolol 200 mg once daily or propranolol 80 mg twice daily for eight weeks, followed by a four-week placebo wash-out period, and then switched to the alternate therapy for another eight weeks. Efficacy was assessed using diary cards for attack frequency, intensity, duration, and acute medication consumption. Heart rate, blood pressure, and side-effects were monitored
Duration 24 weeks total: 4-week run-in, 8-week treatment, 4-week wash-out, 8-week alternate treatment
Outcome Measures Severity score
Baseline Characteristics   All patients (n= 36)
Mean age, years 33.8 (18-51)
Females 32
Classical 6
Common 30
% heredity 94
Mean duration of migraine, years 15.6
% earlier prophylactic treatment 28
Mean weight, kg 63.0
Results   Propranolol Metoprolol
Reduction in sum of severity score ≥50% 15 17
Reduction in sum of severity score 1-50% 10 10
Negative response 6 5

There were no statistically significant differences between metoprolol and propranolol in their effects on attack frequency, number of migraine days, overall migraine severity (measured as severity score [intensity × migraine days]), or use of acute migraine medications (all data presented as figures).

An assessment of patient improvement indicated that 76% of participants reported marked or moderate improvement with metoprolol, compared to 63% with propranolol.
Adverse Events No statistically significant difference in side-effects between the two drugs. Two patients withdrew due to side-effects during propranolol treatment. No abnormal laboratory values were found.
Study Author Conclusions Metoprolol has a prophylactic anti-migraine effect comparable to propranolol. Both treatments are generally well tolerated.
Critique The study's double-blind, cross-over design is a strength, ensuring that each patient serves as their own control. However, the small sample size and short duration of active treatment may limit the generalizability of the findings. The study did not explore the long-term effects of propranolol, which could provide additional insights into its efficacy over time.
References:
[1] [1] Kangasniemi P, Hedman C. Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study. Cephalalgia. 1984;4:91-96.