Atypical Migraine Headache Symptoms Acute Therapy

This is an article about drugs that work for non-mainstream, difficult to treat patients who usually have medication overuse headache or episodic migraine who don't respond to usual acute migraine treatment with triptans or dihydroergotamine (DHE).  This list of drugs may be used for patients who have a contraindication for using triptans or dihydroergotamine (DHE), such as patients with stroke, coronary artery disease, or out of control hypertension.  These patients are difficult to treat.  Sometimes they don't have insurance or their insurance doesn't cover dihydroergotamine or the triptans well and the doctor has a dilemna finding something useful to use.

The dopamine antagonist group consists of drugs usually indicated for psychiatric disorders such as schizophrenia or bipolar disease.  They may be used "off-label" for treatment of  headache.  "Off label" means the drugs work for another indication than the usual illness the medication treats.  An  "off label" example would be that chlorpromazine is indicated for bipolar disorder but also helps treat migraine.  They work in migraine patients because dopamine is a major brain neurochemical released during the migraine process and increasing dopamine may help headache.  This group of drug may have a side effect of drowsiness.

Dopamine antagonists

Dopamine modulates processes involved in migraine such as nociception, autonomic response, and vasodilatation.  Dopamine also helps with many of the symptoms of migraine including nausea, vomiting, mood changes and fatigue.  Dopamine antagonists are appropriate for patients who do not respond to triptans.  They should be limited to using only 10 days per month.

Prochlorperazine (Compazine) can be given 5/10 mg oral or rectal 25 mg repeat q 6-8 hours PRN for status migrainosus

Chlorpromazine (Thorazine) 25 mg orally every 6 hours to a total dose of 100 milligrams for cluster headache or refractory migraine.

Droperidol (Inapsine) intramuscularly 2.7 mg, highly effective for intractable migraine, can prolong QT not to use with patients with heart disease.

Haldol (Haloperidol) 5 mg IV gives significant relief or 2 mg/5 mg oral haloperidol outpatient treatment to abort headache.

Prokinetic Agents

The prokinetic drugs listed below are usually indicated for treating nausea or vomiting.

Oral metoclopramide (Reglan) can be used 10 mg three times a day (TID). 

Promethazine (Phenergan) can be given 12.5, 25, 50 mg every 4-6 hours

Atypical Antipsychotics

Olanzapine (Zyprexa) can be used orally as 2.5-5 also 7.5, 10, 15, 20 ODT mg nightly for 5 to 10 nights to break status migrainosus.

Quetiapine (Seroquel) at 25 to 75 mg orally, reduces headache frequency and severity, can be used as rescue medicine.  Quetiapine may help with sleep and headache for treating medication overuse headache also.

The most beneficial oral medication is olanzapine followed by chlorpromazine.


Ketrolac 60 mg IM every 6 hours.  An NSAID (nonsteroidal antiinflammatory drug) which may be given intramuscularly as an injection 60 mg as single dose or 30 mg every 6hr, not to exceed 120 mg/day.

Local anaesthetic

Lidocaine spray 4 %, generic (lidoderm, xylocaine)  is available over the counter at drugstores.  For one sided frontal headache the spray should be injected on the involved side; use both right and left nostrils for bilateral headache.  Spray toward the back of the nose about 3 inches and medially toward the hard cartilage part of the nose.  Dose is one spray at onset, may repeat in 10 minutes if needed and then every 6 hours.

Betablocker eye drop

Timolol (Timoptic) eye drops 0.5 % solution 1-2 drops in each eye every 2-4 hours.  Betablockers work orally for migraine prevention but don't work for acute therapy, yet some patients respond well to Timolol given as an eyedrop and there is no rebound problem.  See my article on Timolol eye drops under acute treatment of migraine.


Headache. 1999 Sep;39(8):543-51.

Intranasal lidocaine for migraine: a randomized trial and open-label follow-up.

Maizels M1, Geiger AM.


To study the efficacy of intranasal lidocaine for the treatment of migraine when administered by subjects in a nonclinic setting.


A 1-month, randomized, controlled, double-blind trial, followed by a 6-month open-label follow-up.


Ambulatory subjects treating themselves outside of a medical setting.


One hundred thirty-one adult subjects with migraine, diagnosed according to International Headache Society criteria, were enrolled in the study: 113 treated at least one headache in the controlled trial, and 74 treated at least one headache in the open-label phase. All subjects were members of the Kaiser Permanente Southern California Medical Care Program and were recruited at two urban medical centers.


Intranasal lidocaine 4% or saline placebo 0.5 mL was dropped into the nostril on the side of the headache, or bilaterally for bilateral headache, according to study protocol.


Trial: percent of headaches relieved to mild or none at 15 minutes and relapse of headache within 24 hours. Open-label: percent of headaches relieved to mild or none at 15 and 30 minutes and relapse within 24 hours.


In the controlled trial, headache was relieved within 15 minutes in 34 (35.8%) of 95 subjects treated with 4% intranasal lidocaine compared with 8 (7.4%) of 108 subjects receiving placebo (P < .001). Headaches relapsed in 7 (20.6%) of 34 subjects treated with 4% intranasal lidocaine compared to 0 of 8 placebo subjects (P = .312). In the open-label follow-up, headaches were relieved in 129 (41.2%) of 313 episodes within 15 minutes and in 141 (57.6%) of 245 episodes after 30 minutes. Headaches relapsed in 28 (19.9%) of 140. The response did not diminish over time: 32 (62.8%) of 51 first headaches were relieved at 30 minutes and 10 (71.4%) of 14 seventh headaches were relieved. Relapse occurred in 28 (20%) [corrected] of 129 headaches at a mean time (+/- SD) of 7.4 (+/- 6.6) hours.


Intranasal lidocaine 4% provides rapid relief of migraine symptoms. For those subjects who do respond, the effect does not diminish over 6-month follow-up.