A List of 50 Uncommon PREVENTIVE Migraine Medications
Posted on April 23 2023,

Below is a list of 50 PREVENTIVE migraine medications. This list is for chronic, refractory migraine patients that have not responded to first, second, or third-line preventive medications.
Many of these medications are not well-studied for migraine, may have serious adverse effects, and/or are not well-tolerated.
The ONLY purpose of this list is to start a conversation with your neurologist about the medications below. It is possible that some of these drugs will only be prescribed at a headache center specifically for chronic, refractory cases.
Every week, we will add a description to at least one medication with the available studies. Bookmark this page and come back to it on a semi-weekly basis. After every medication on this list is described with sources, we will move on to acute migraine medications that are less commonly used.
- Milnacipran (SNRI)
- Venlafaxine (SNRI) - considered a 2nd line preventive, but belongs with the other SNRIs
- Desvenlafaxine (SNRI)
- Duloxetine (SNRI)
- Telmisartan (ARB)
- Methylergonovine (ergot alkaloid)
- Lamotrigine (anticonvulsant)
- Depakote (anticonvulsant)
- Levetiracetam (anticonvulsant)
- Metformin (antidiabetic, biguanide)
- Clopidogrel (antiplatelet)
- Memantine (NMDA receptor antagonist, antidementia)
- Amantadine (NMDA receptor antagonist, antiviral)
- Ketamine (NMDA receptor antagonist, general anesthetic, analgesic)
- Mexiletine (antiarrhythmic)
- Lidocaine (anesthetic, antiarrhythmic)
- Bupivacaine (anesthetic)
- Acetazolamide (carbonic anhydrase inhibitor, diuretic)
- Haldol (1st gen antipsychotic)
- Haloperidol (1st gen antipsychotic)
- Droperidol (1st gen antipsychotic)
- Chlorpromazine (1st gen antipsychotic)
- Fluvoxamine (SSRI)
- Fluoxetine (SSRI)
- Buspirone (anxiolytic)
- Flunarizine (calcium channel blocker)
- Amlodipine (calcium channel blocker)
- Estrogen (hormone)
- Timolol (non-selective beta blocker)
- Nebivolol (selective beta blocker)
- Bisoprolol (selective beta blocker)
- Clonidine (central alpha agonist)
- Hydroxyzine (1st gen antihistamine)
- Cyproheptadine (1st gen antihistamine)
- Desipramine (tricyclic antidepressant)
- Doxepin (tricyclic antidepressant)
- Mirtazapine (tetracyclic antidepressant)
- Clonazepam (benzodiazepine, antidepressant)
- Phenelzine (MAOI, antidepressant)
- Cannabidiol (cannabinoids)
- Baclofen (muscle relaxant)
- Low dose naltrexone (opioid antagonist)
- Amiloride (K-sparing drug diuretic)
- Spironolactone (K-sparing diuretic, aldosterone receptor antagonist)
- Lisinopril (ACEi)
- Butterbur (No)
- ALA (No)
- THC (only some states)
- Psilocybin (hallucinogen, only some states)
- CBN with melatonin
Thu, Sep 04, 25
Understanding Migraine Prodrome
Discover the migraine prodrome phase: 36 warning symptoms that occur 1-6 hours before headache onset. Learn timing patterns, predictive confidence levels, and new treatment approaches based on groundbreaking 2025 research...
Read MoreThu, Aug 07, 25
Dizziness and Migraine: When is it Vestibular Migraine?
Dizziness and migraine: Learn when dizziness is vestibular migraine vs BPPV, Meniere's disease, or vascular causes. Guide covers symptoms, diagnosis, cutaneous allodynia, and treatment options for recurrent dizziness episodes.
Read MoreMon, Aug 04, 25
Evidence-Based Guide to Migraine Nutraceuticals and Herbal Options
Evidence-based guide to natural migraine treatments including riboflavin, magnesium, ginger, and CoQ10. Compare effectiveness, dosing, and safety of 15+ nutraceuticals and herbal remedies for migraine prevention and acute treatment with...
Read More