Evidence-Based Reviews

Antipsychotics for migraines, cluster headaches, and nausea

Current Psychiatry. 2013 February;12(2):E1-E4

References

1. Dusitanond P, Young WB. Neuroleptics and migraine. Cent Nerv Syst Agents Med Chem. 2009;9(1):63-70.

2. McEwen JI, O’Connor HM, Dinsdale HB. Treatment of migraine with intramuscular chlorpromazine. Ann Emerg Med. 1987;16(7):758-763.

3. Bigal M, Bordini CA, Speciali JG. Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial. J Emerg Med. 2002;23(2):141-148.

4. Bell R, Montoya D, Shuaib A, et al. A comparative trial of three agents in the treatment of acute migraine headache. Ann Emerg Med. 1990;19(10):1079-1082.

5. Shrestha M, Singh R, Moreden J, et al. Ketorolac vs chlorpromazine in the treatment of acute migraine without aura. A prospective, randomized, double-blind trial. Arch Intern Med. 1996;156(15):1725-1728.

6. Wang SJ, Silberstein SD, Young WB. Droperidol treatment of status migrainosus and refractory migraine. Headache. 1997;37(6):377-382.

7. Miner JR, Fish SJ, Smith SW, et al. Droperidol vs. prochlorperazine for benign headaches in the emergency department. Acad Emerg Med. 2001;8(9):873-879.

8. Richman PB, Allegra J, Eskin B, et al. A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache. Am J Emerg Med. 2002;20(1):39-42.

9. Jones J, Sklar D, Dougherty J, et al. Randomized double blind trial of intravenous prochlorperazine for the treatment of acute headache. JAMA. 1989;261(8):1174-1176.

10. Lu SR, Fuh JL, Juang KD, et al. Repetitive intravenous prochlorperazine treatment of patients with refractory chronic daily headache. Headache. 2000;40(9):724-729.

11. Sharma S, Prasad A, Nehru R, et al. Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine. Headache. 2002;42(9):896-902.

12. Seim MB, March JA, Dunn KA. Intravenous ketorolac vs intravenous prochlorperazine for the treatment of migraine headaches. Acad Emerg Med. 1998;5(6):573-576.

13. Honkaniemi J, Liimatainen S, Rainesalo S, et al. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache. 2006;46(5):781-787.

14. Fisher H. A new approach to emergency department therapy of migraine headache with intravenous haloperidol: a case series. J Emerg Med. 1995;13(1):119-122.

15. LaPorta LD. Relief from migraine headache with aripiprazole treatment. Headache. 2007;47(6):922-926.

16. Silberstein SD, Peres MF, Hopkins MM, et al. Olanzapine in the treatment of refractory migraine and chronic daily headache. Headache. 2002;42(6):515-518.

17. Schreiber S, Getslev V, Backer MM, et al. The atypical neuroleptics clozapine and olanzapine differ regarding their antinociceptive mechanisms and potency. Pharmacol Biochem Behav. 1999;64(1):75-80.

18. Krymchantowski AV, Jevoux C. Quetiapine for the prevention of migraine refractory to the combination of atenolol + nortriptyline + flunarizine: an open pilot study. Arq Neuropsiquiatr. 2008;66(3B):615-618.

19. Cahill CM, Hardiman O, Murphy KC. Treatment of refractory chronic daily headache with the atypical antipsychotic ziprasidone-a case series. Cephalalgia. 2005;25(10):822-826.

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22. Rozen TD. Olanzapine as an abortive agent for cluster headache. Headache. 2001;41(8):813-816.

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Cluster headaches

Subcutaneous sumatriptan and inhaled oxygen are first-line treatments for cluster headaches.³¹ A single, small study²⁰ reported that chlorpromazine may prevent cluster headaches, which suggests that D2 receptor blockade may treat such headaches. However, limited supporting evidence relegates its use to a second- or third-line therapy.

Clinical Point

A small study reports that chlorpromazine may prevent cluster headaches, which suggests D2 receptor blockade may treat such headaches

In an open-label study (N = 5), olanzapine provided some relief of pain associated with cluster headache within 20 minutes of administration.²² In another study, patients with schizophrenia and comorbid cluster headaches improved with olanzapine.²¹

Because evidence is limited to small prospective studies, antipsychotic treatment of cluster headache is not well established.^20-22 However, olanzapine may benefit patients with comorbid cluster headaches and schizophrenia.

Nausea

The signaling pathways that mediate emesis involve 5-HT3, D2, muscarinic, and histamine receptors.³² Before 5-HT3 antagonists were available, the FGAs metoclopramide, droperidol, prochlorperazine, and promethazine were used to manage acute emesis in emergency departments.²³ A double-blind, placebo-controlled trial found IV droperidol, 1.25 mg, was more effective than metoclopramide, 10 mg, or prochlorperazine, 10 mg, for relieving moderate to severe nausea in adult patients.²³ However, droperidol and prochlorperazine were associated with akathisia. In addition, this trial did not find a clinically significant difference between groups—including placebo—in anxiety, sedation, or need for rescue medications.²³ Use of droperidol to treat nausea decreased after the drug received a “black-box” warning for QT prolongation and torsades de pointes.

Metoclopramide is effective for treating acute migraine and associated nausea²⁴ and has been used to treat gastroparesis because of its effect on upper GI motility. Phenothiazines have been used to treat nausea and studies have shown prochlorperazine to be more effective than promethazine.²⁵ Some studies of prochlorperazine have reported a 44% incidence of akathisia, which limits the drug’s use in patients who may be sensitive to such effects.³³ Promethazine can cause sedation and risk of tissue necrosis at the injection site.³⁴

Clinical Point

Metoclopramide effectively treats acute migraine and associated nausea and has been used for gastroparesis

Among SGAs, olanzapine effectively prevented acute and delayed chemotherapy-induced nausea and vomiting in a proof-of-concept study of patients receiving high and moderate emetogenic therapies.^26,27 National Comprehensive Cancer Network guidelines cite olanzapine as a potential option for treating refractory and breakthrough emesis.³⁵ In a small study (N = 50), olanzapine showed comparable anti-nausea effect to aprepitant—a neurokinin 1 receptor antagonist—and effectively prevented chemotherapy-induced nausea and vomiting in highly emetogenic chemotherapy.³⁶

Related Resources

Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache. 2012;52(2):292-306.
Dusitanond P, Young WB. Neuroleptics and migraine. Cent Nerv Syst Agents Med Chem. 2009;9(1):63-70.

Drug Brand Names

Aprepitant • Emend
Aripiprazole • Abilify
Chlorpromazine • Thorazine
Dihydroergotamine • D.H.E 45
Droperidol • Inapsine
Ergotamine tartrate • Ergostat
Haloperidol • Haldol
Ketorolac • Toradol
Lidocaine • Xylocaine, Lidoderm
Meperidine • Demerol
Metoclopramide • Reglan
Olanzapine • Zyprexa
Prochlorperazine • Compazine
Promethazine • Phenergan
Quetiapine • Seroquel
Risperidone • Risperdal
Sumatriptan • Imitrex
Valproate • Depakote

Disclosures

Dr. Macaluso has received grant or research support from EnVivo Pharmaceuticals, Janssen L.P., and Pfizer, Inc.

Dr. Tripathi reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.