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
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