Dopamine Blockers in Migraine Headache

Timothy C. Hain, M.D. Chicago IL.• Page last modified: September 27, 2020

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Haloperidol (Haldol), Prochlorperazine (Compazine), Domperidone, Chlorpromazine, Flunarizine, Metoclopramide have all been reported helpful for migraine (Perotka, 1997) and there were more than 200 papers on dopamine and migraine in Pubmed as of Dec 16, 2016. Thus it would seem that migraine and dopamine must have something to do with each other. The extreme genetic heterogeneity of migraine (probably not one disease) also extends to dopamine metabolism (Sezer et al, 2016), implying that there may be some patients who are especially sensitive to blocking of dopamine. This is another justification for the "trial and error" method of migraine treatment. In all of these drugs there is the potential for short term extrapyramidal effects (think tremor, rigidity), dystonia (think oculogyric crisis or tongue protrusion), and long term movement disorders (tardive dyskinesia). The chance of a side effect is correlated with the strength of the effect.

In spite of the worry about side effects, dopamine blockers are somewhat popular as abortives in the emergency department, where they may be preferred to opiates. Sheridan et al (2016) notes that the three most common dopamine blocker drugs are prochlorperazine, metoclopramide, or promethazine. They studied the combination of one of these with ketorolac. Promethazine (phenergan) was the least effective. Prochlorperazine (Compazine) and metoclopramide (Reglan) were more effective. Rozen et al (2015) notes in adults, that "Dopamine receptor antagonists appear to have some of the highest medical evidence for efficacy."

Dopamine blockers are a little used treatment avenue for prevention of migraine. They are on the "secondary prevention" treatment category primarily. The general problem with these drugs are their side effects. If you block dopamine, you can induce parkinsonism, or movement disorders such as dystonia or dyskinesia. Persons on dopamine blockers generally do not move around as much, and usually gain weight. This usually restricts use of strong dopamine blockers to situations where all else has failed, and symptoms are very serious.

Interestingly, dopamine AGONISTS -- i.e. constant bromocriptine -- is used to treat menstrual migraine(Herzog, 1997). This is due to the interaction between dopamine agonists and circuitry involved in releasing sex hormones such as estrogen. So it would seem that manipulating dopamine can both decrease and increase migraine.

Antipsychotic drugs

Antipsychotic drugs often are very effective for acute migraine, but of course they have significant side effects. Of the lot, haldol (haloperidol) is probably the most useful as a last-resort abortive medication. Symptoms must be very severe to consider this drug, and patients must be informed about the potential adverse consequences.

Aripiprazole (Abilify).

There has been one anecdotal report concerning effectiveness of this atypical antipsychotic drug for migraine prevention (LaPorta, 2007). Aripiprazole is a partial agonist at both the dopamine D2 receptor and the serotonin 5-HT1A receptor. Dopamine agonism would be expected to worsen migraine and nausea, while 5-HT1A agonsm, treats migraine. Like the other atypical antipsychotics, aripiprazole displays an antagonist profile at the 5-HT2A receptor. Dose is 10 mg. Common side effects include akathisia (restlessness), headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, light-headedness, insomnia, sleepiness, shaking, and blurred vision. This is an expensive drug with significant side effects, and it is unclear whether or not it works for migraine. We would say best to avoid right now.

Chlorpromazine (thorazine) - Kanis and Timm (2014) reported that use in the pediatric setting was unimpressive.

Droperidol (not often used because of "black box" warning). This drug, like haloperidol is very effective for acute migraine, but it can rarely cause cardiac adverse effects. (Thomas et al, 2015)

Haloperidol (very effective for acute treatment). Haloperidol is reportedly more effective than metoclopramide (Galfigan et al, 2015). We have had patients do very well on intermittent haloperidol drops. This is mainly helpful in persons who have failed everything else and who have very serious migraines (such as those with fainting).

Olanzapine (Zyprexa) use has been reported in a study of 50 patients with chronic migraine. Silberstein et al (2002) reported a strong effect on headache severity, going from 8.7 to 2.2. 5-10 mg doses at night are used at bedtime.

Quetiapine (Seroquel) is an atypical antipsychotic, mainly used for bipolar affective disorder.

There is a small body of evidence that quitiapine is helpful to prevent migraine. (Krymchantowski, et al. (2010). Weight gain is a common side effect. The mechanism of action is attributed to D2 antagonism. This makes it similar to flunarizine (see below).

Antiemetics used for migraine.

These drugs are probably effective because they are dopamine blockers. They are occasionally used in the emergency department, in an attempt to avoid use of addictive pain medications. We think one should be especially cautious in using these in young women, who are prone to develop dystonic reactions. Thus using it in the pediatric department in girls, may be risky.

Kelly et al (2012) reported that "Dopamine antagonists, in general, appear to be equivalent for migraine pain relief to the migraine-"specific" medications sumatriptan and dihydroergotamine.." In other words, these are powerful drugs.

Flunarizine (Sibellium)

This drug is available in Europe. It is a mixed mechanism drug. We rarely prescribe it because of its side effects (i.e. think major tranquilizer) and long half-life

Flunarizine is at least as effective as propranolol. Flunarizine is likely more effective than verapamil because it combines calcium channel and dopamine blocking activity in a single preparation (Afran et al, 1998). Flunarizine has an 18 day half-life, meaning that good effects as well as adverse effects might take a long time to start and end. Flunarizine has been reported as effective in cyclic vomiting (Kothare et al, 2005), and in childhood migraine (Visudtibhan et al, 2004; Peer Mohamed et al, 2012). The usual dose is 5 to 10 mg at night.