Migraine secondary prevention

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The sections that follow describe our method for selecting migraine preventative therapy.

Selecting pharmacological treatment

First-line agents

We recommend amitriptyline, venlafaxine, one of the beta blockers propranolol or metoprolol, topiramate, or one of the calcitonin gene-related peptide (CGRP) antagonists as initial treatments for the majority of patients with episodic migraine (≤14 headache days per month) who meet the criteria for preventive therapy (see 'Indications' above).

As to the American Headache Society's 2024 position statement, we list CGRP antagonists erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, and atogepant as first-line alternatives.[1]. Numerous clinical trials, meta-analyses, and postapproval open-label cohort studies have demonstrated the effectiveness, safety, and tolerability of these medications.[2][3]

Second-line medications

In patients who do not respond well to two or more first-line medications, or who do not respond well enough to them after at least eight weeks at a therapeutic dose, we recommend using second-line medications to prevent episodic migraine. Among these are additional antihypertensives including gabapentin, venlafaxine, candesartan, lisinopril, verapamil, and valproate.

Treatment failure

For patients who do not improve after a sufficient trial of first pharmacologic therapy, we recommend switching to a migraine preventive medicine from a different class. Clinical trials have demonstrated that for those who have not responded to previous migraine preventive medications, switching to another preventive drug may be beneficial.[4]

Lifestyle measures

Therapeutic lifestyle measures may be beneficial for controlling migraine, including good sleep hygiene, routine meal schedules, regular exercise, limiting caffeine intake, and managing migraine triggers.


  1. Charles AC I. "Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update year=2024". PMID 38466028 Check |pmid= value (help). Text " doi: 10.1111/head.14692. Epub 2024 Mar 11 " ignored (help)
  2. Murray AM I. "Real-World Patient Experience of CGRP-Targeting Therapy for Migraine: a Narrative Review". PMID 38466028 Check |pmid= value (help). Text " doi: 10.1007/s11916-022-01077-z. Epub 2022 Sep 5." ignored (help)
  3. Haghdoost F I. "Evaluating the efficacy of CGRP mAbs and gepants for the preventive treatment of migraine: A systematic review and network meta-analysis of phase 3 randomised controlled trials". PMID 36855951 Check |pmid= value (help). Text " doi: 10.1177/03331024231159366." ignored (help); Vancouver style error: name (help)
  4. Pringsheim T I. "Canadian Headache Society guideline for migraine prophylaxis". PMID 22683887. Check |pmid= value (help). Vancouver style error: name (help)