A network meta-analysis of 61 trials and 20,680 patients found no high-certainty evidence favoring any one migraine preventive over another, though CGRP antibodies had significantly fewer discontinuations due to side effects than topiramate.
16.2% fewer dropouts with CGRP-mAbsCGRP monoclonal antibodies had 16.2% fewer treatment discontinuations due to adverse events compared to topiramate — the clearest advantage identified across all 16 treatments and 61 studies.
What the researchers found
Across 61 studies (20,680 patients) evaluating 16 pharmacologic treatments for episodic migraine prevention:
- No high-certainty evidence favored any one treatment over another for effectiveness
- CGRP monoclonal antibodies probably resulted in fewer treatment discontinuations due to adverse events compared to topiramate (risk difference -16.2%, 95% CI: -18.4% to -12.8%; moderate-certainty evidence)
- CGRP-mAbs may result in less migraine-related disability and improved quality of life compared to gepants (low-certainty evidence)
- For most other comparisons, evidence was of low certainty, uncertain, or absent
- Only 19 of 61 studies had low risk of bias
Why it matters
With over a dozen migraine prevention options available, clinicians and patients need guidance on which to choose first. This authoritative ACP-commissioned analysis reveals that the evidence doesn't strongly favor one drug over another for efficacy — making tolerability, cost, and patient preference more important in treatment selection. The better side-effect profile of CGRP antibodies compared to older drugs like topiramate is particularly relevant for shared decision-making.
How the study worked
This systematic review and network meta-analysis was commissioned by the American College of Physicians. Researchers searched MEDLINE, EMBASE, and Cochrane Central through April 2024 for randomized trials of pharmacologic migraine prevention in adults with episodic migraine. Only treatments previously shown to be superior to placebo were included. Data extraction was verified by a second reviewer. Risk of bias was assessed using the Cochrane tool, and evidence certainty was graded using GRADE methodology.
What this study cannot tell us
Head-to-head comparisons between specific treatments were very limited, requiring indirect comparisons through the network meta-analysis. Evidence certainty was mostly low or insufficient. Minimal important differences for outcome measures were not well-established. Only 19 of 61 studies had low risk of bias. The analysis was limited to episodic migraine — chronic migraine was not included. Cost-effectiveness was not assessed despite being a key clinical consideration.
How to read the evidence
This is a high-quality systematic review and network meta-analysis commissioned by the American College of Physicians, published in Annals of Internal Medicine. It represents the highest level of evidence synthesis available, though the underlying evidence for most comparisons was low or moderate certainty.
When this study was published
Published in 2025 with literature searched through April 2024, this is a very current and authoritative synthesis that reflects the latest available evidence for migraine prevention.
The bigger picture
This analysis from a major medical society essentially levels the playing field among migraine preventives. While CGRP-targeting therapies have been marketed as breakthroughs, this meta-analysis finds their efficacy isn't clearly superior to older, cheaper options. The advantage is tolerability, not effectiveness. This has significant implications for insurance coverage decisions, clinical guidelines, and cost-effectiveness discussions — particularly as CGRP antibodies are substantially more expensive than generic alternatives like topiramate or propranolol.
Questions still open
- If CGRP antibodies aren't clearly more effective than older drugs, should cost be a major factor in first-line treatment selection?
- Would similar network analyses for chronic migraine show different comparative effectiveness patterns?
- Are there patient subgroups where specific preventives are clearly superior, even if no overall advantage exists?
Common questions
Which migraine prevention medication works best?
Are expensive CGRP migraine drugs worth it compared to cheaper options?
Read the original research
Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians.
Annals of internal medicine, 178(3), 369-380
Citation
Damen, Johanna A A; Yang, Bada; Idema, Demy L; Vernooij, Robin W M; Huis In 't Veld, Linde; Kusters, Mike; Spijker, Rene; van der Braak, Kim; Heus, Pauline; Jenniskens, Kevin; Hooft, Lotty. (2025). Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians.. Annals of internal medicine, 178(3), 369-380. https://doi.org/10.7326/ANNALS-24-00315