After stopping anti-CGRP migraine therapy, patients experienced increased migraine frequency but maintained a net benefit of nearly 4 fewer monthly migraine days compared to their pre-treatment baseline.
-3.78 migraine days vs. baseline retainedEven after stopping anti-CGRP antibody treatment, patients still had nearly 4 fewer monthly migraine days compared to before they started — suggesting a residual or disease-modifying benefit.
What the researchers found
Monthly migraine days after discontinuation were still significantly lower than pre-treatment baseline (MD -3.78 days; 95% CI: -4.89 to -2.67), indicating a lasting residual benefit even after stopping therapy.
However, compared to the active treatment period, discontinuation led to a significant worsening: monthly migraine days increased by approximately 2.5 days and acute headache medication use rose by 3.22 days per month. The proportion of patients maintaining ≥50% reduction in migraines dropped substantially after cessation (RR 0.42; 95% CI: 0.33-0.53), meaning most patients who were responding well lost that level of benefit.
Why it matters
Insurance companies and clinical guidelines often require periodic treatment breaks or 'drug holidays' from anti-CGRP therapies. This meta-analysis provides the first pooled evidence of what patients can expect when treatment stops. The finding that some benefit persists beyond discontinuation is clinically important — it suggests these drugs may have partial disease-modifying effects rather than being purely symptomatic. However, the significant worsening also means discontinuation decisions should be carefully considered.
How the study worked
This systematic review and meta-analysis searched PubMed, Embase, and Cochrane databases through September 2024 for randomized or observational studies reporting outcomes after discontinuing anti-CGRP monoclonal antibodies or gepants for migraine prevention. Eight studies with 1,012 patients evaluating anti-CGRP antibody discontinuation met inclusion criteria. No gepant cessation studies were found. Random-effects models pooled mean differences and risk ratios. The study was pre-registered on PROSPERO (CRD42024595771).
What this study cannot tell us
Only eight studies with 1,012 total patients were available, limiting statistical power. No studies evaluating gepant (oral CGRP pathway blocker) discontinuation were found, so conclusions apply only to injectable anti-CGRP antibodies. Heterogeneity was moderate to high for several outcomes (I² = 57-86%). Follow-up periods after discontinuation varied, making it difficult to determine how long any residual benefit lasts. The mix of randomized and observational studies introduces potential bias.
How to read the evidence
This is a systematic review and meta-analysis pre-registered on PROSPERO, following rigorous methodology. It pooled data from 8 studies (1,012 patients) using random-effects models. However, the mix of study designs, moderate-to-high heterogeneity, and limited number of studies somewhat weaken the overall evidence quality. The findings are consistent and statistically significant but should be interpreted with these limitations in mind.
When this study was published
Published in 2026 with searches through September 2024, this is the most current meta-analysis on anti-CGRP therapy discontinuation outcomes. As more patients accumulate long-term experience with these drugs, additional evidence should become available.
The bigger picture
The question of whether anti-CGRP therapies modify the underlying disease or simply suppress symptoms is one of the most important open questions in headache medicine. This meta-analysis provides evidence for a partial disease-modifying effect — the residual benefit after discontinuation. If confirmed, this would distinguish anti-CGRP antibodies from most other preventive migraine therapies and could influence how long patients need to be treated and when treatment breaks are appropriate.
Questions still open
- How long does the residual migraine benefit persist after stopping anti-CGRP antibodies — weeks, months, or longer?
- Do patients who restart anti-CGRP therapy after a drug holiday respond as well as they did initially?
- What patient characteristics predict who will maintain benefit after discontinuation versus who will relapse quickly?
Common questions
Will my migraines come back if I stop my anti-CGRP medication?
Is it safe to take a break from anti-CGRP migraine therapy?
Read the original research
Estimating Changes in Clinical Outcomes after Discontinuation of Anti-CGRP Targeting Therapy for Migraine Prophylaxis: A Systematic Review and Meta-analysis.
CNS drugs, 40(1), 71-82
Citation
Makita, Luana Miyahira; Fagundes, Thales Pardini; Reginato, Pedro Henrique; Carpinelli, Lucca Passow; de Freitas Morais, Giovanna; Montanarin, Renata Trinkel; de Freitas Kleimmann, Rafael; Streit, Rafael Eduardo; Koppanatham, Aishwarya; Rodrigues, Andressa Christine Sales; Piovesan, Elcio Juliato. (2026). Estimating Changes in Clinical Outcomes after Discontinuation of Anti-CGRP Targeting Therapy for Migraine Prophylaxis: A Systematic Review and Meta-analysis.. CNS drugs, 40(1), 71-82. https://doi.org/10.1007/s40263-025-01233-0