ORIGINAL CONTRIBUTION migraine, therapy, chlorpromazine

Parenteral- Chlorpromazine Treatment of Migraine

A prospective, uncontrolled clinical trial was conducted to test the safety and efficacy of intramuscular chlorpromazine (1 mg/kg) in the acute, outpa- tient treatment of migraine. One hundred adult patients were included in the study. There was complete relief of both pain and nausea/emesis symp- toms in 96 patients within 55 minutes of the injection. Eighteen patients experienced orthostatic hypotension following injection. All but one re- sponded to noninvasive therapy. The results suggest that chlorpromazine is a safe, effective alternative medication in the outpatient treatment of acute migraine. [Iserson KV: Parenteral chlorpromazine treatment of migraine. Ann Emerg Med 12:756-758, December 1983.]

I N T R O D U C T I O N Migraine, in all its many forms, is a common presenting symptom com-

plex in emergency departments and outpatient clinics. Up to 15% of the population in the United States is afflicted with this disorder.1

The medications commonly used to abort a migraine once it begins in- clude tranquilizers, sedatives, vasodilators, antidepressants, serotonin an- tagonists, extracranial vasoconstrictors, MAO inhibitors, and beta block- ers. ~-4 Non-medical therapy has also been investigated. 3'5

Recent studies of the pathophysiolog7 of migraine, as well as sporadic re- ports of the usefulness of chlorpromazine (Thorazine) in the acute and chron- ic management of migraine, support this study of chlorpromazine's safety and efficacy in the t reatment of migraine. 3'6

MATERIALS A N D M E T H O D S One hundred seventeen consecutive patients with vascular-type cephalgia

and without exclusion criteria were identified on presentation to the emer- gency department. Diagnosis was made on the basis of the current history and physical examination, and the previous medical record when available. Diagnostic criteria included the presence of an aura, lateralizing cephalgia, typical 7 associated symptoms (Figure), a compatible personal or family his- tory, and the absence of other abnormal physical or laboratory findings.

Fifty-four patients were excluded from the study for one of the following reasons: 1) age less than 18 years or more than 60 years; 2) known in- tolerance to phenothiazines; 3) current therapy with phenothiazines; 4) no responsible person available to care for and transport the patient when de- parting the emergency department; 5) refusal to have chlorpromazine or any other parenteral medication administered; 6) complex neurological findings; 7) unstable vital signs, including orthostatic hypotension; or 8) pregnancy or nursing.

Chlorpromazine was administered intramuscularly in a dose of 1 mg/kg (total body weight) to a m a x i m u m of i00 mg.

Patients subsequently were kept in a darkened room and were monitored frequently for symptom relief. Vital signs were repeated prior to discharge, and more frequently if indicated.

RESULTS One hundred patients were treated a total of 104 times with intramuscular

chlorpromazine. Ages ranged from 18 to 60 years, with a preponderance

Kenneth V Iserson, MD, FACEP Tucson, Arizona

From the Section of Emergency Medicine, Arizona Health Sciences Center, University of Arizona, Tucson

Received for publication March 4, 1983. Revision received July 29, 1983. Accepted for publication August 5, 1983.

Address for reprints: Kenneth V Iserson, MD, FACEP, Section of Emergency Medicine, Arizona Health Sciences Center, 1501 North Campbell, Tucson, Arizona 85724.

12:12 December 1983 Annals of Emergency Medicine 756/41

MIGRAINE THERAPY Iserson

Fig. Migraine: associated symptoms.

(84%) below 42 years. There were 28 men and 72 women (1:2.6)~ Eighty-one patients were white and 19 were non- white.

In 96 of the 100 patients, symptoms of cephalgia, and nausea/vomiting if present, completely resolved with this treatment. Four obtained no signifi- cant relief of their headache, although the two with nausea/vomit ing did obtain relief for these symptoms. Pa- tients who obtained relief of all symp- toms did so on the average of 35 min- utes (range 20 to 55 minutes) post injection. Although not quantitated, it appeared that the majority of patients with nausea/vomiting obtained much more rapid relief of these symptoms than of the cephalgia.

Four patients who initially obtained relief with chlorpromazine returned with a recurrent headache within 48 hours of their initial visit. All were given chlorpromazine in the same dose as on their initial visit - - with relief of symptoms. One of these pa- tients was subsequently hospitalized with status migraine.

Eighteen pat ients were found to have orthostatic hypotension (a di- astolic blood pressure drop greater than 10 m m Hg or a pulse rate in- crease greater than 20/min) after medication administration. Eleven of the patients were symptomatic, but only one required parenteral fluids to correct symptoms. Five of these pa- tients had significant emesis prior to therapy, and 14 were obese. In the 17 patients not requiring parenteral fluid, vital signs returned to normal within two hours.

DISCUSSION Migraine is thought to be a familial,

not necessarily genetic, disorder of paroxysmal vasoregulative instabil- ity. ~'3 It is characterized by episodes of sequential or concurrent intracerebral arterial constriction and extracerebral arterial dilatation. Other events found to occur during migraine include the opening of cephalic ar ter iovenous shunts, release of platelet 5-hydrox- ytryptamine (5-HT), increased concen- t ra t ion of plasma free fat ty acids, platelet activation, decreased platelet m o n o a m i n e oxidase act ivi ty, de- creased plasma norepinephrine, and increased gamma-aminobutyrate, lac- tate and cyclic AMP in the cerebral spinal fluid. ~

Scintillations Visual scotomata Visual field defects III or IV (rare) nerve palsy with ptosis Ptosis and ipsilateral miosis (cluster) Conjunctival injection and ipsilateral Mood alterations Mild aphasia Minimal confusion Drowsiness Syncope or coma (rare) Hemiparesis Facial or extremity sensory disturbance Postural instability Abdominal pain (children) Nausea or emesis

Note: At most, a few of these symptoms occur in a single patient. Each patient tends to have recurrence of symptoms. Most neurological symptoms last less than 15 minutes.

While many drugs are used as ther- apy for migraine, it has been suggested that blocking 5-HT release may be a common mechanism of action, s

The commonly used medications for treating an acute migraine in the outpatient setting all have serious drawbacks.

Ergotamine, with or without caf- feine, is most effective at the time of an aura or beginning of the headache. Eighty percent of patients can be treat- ed successfully if the medication is used then, 3,s,9 but it may be ineffec- tive if there is a simultaneous muscle- contraction pain. It is ineffective in depressing, and may exacerbate, the symptoms of nausea and vomiting. In addition it should not be used in pa- tients with significant peripheral vas- cular disease, severe hypertension, or ischemic heart disease. Relative con- traindications include peptic ulcer, re- nal or hepatic disease, hyperthyroid- ism, and pregnancy. 9

The non-narcotic analgesics, with sedatives or caffeine, are also used fre- quent ly :to abort early migraines. However, by the time the patient ar- rives in the emergency department or outpatient clinic with the migraine fully developed, these drugs are no longer effective.

Steroids, while effective in pro- longed attacks, may take days to be- come effective, s

Narcotics, often with hydroxyzine or promethazine, are commonly used parenterally in the treatment of acute migraine. The episodic and sometimes transient nature of the emergency de- partment patient population, which includes a relatively large number of potential drug abusers, makes nar-

cotics dangerous and inappropriate t use for migraine in the emergency & partment setting. The fact that tw medications (frequently including phenothiazine) rather than one are bc ing used only compounds the pro~ lem. The final problem with narcotic is that in patients with severe, recu rent headaches, addiction is a maj; concem. 3,5

Chlorpromazine is an aliphatic ph~ nothiazine and is classified as a majc tranquilizer.t° It has also been used is termittently for both abortive and i~ terval t rea tment of migraine. 3's It multiple effects, potentially useful i the treatment of migraine, include marked sedation, a potent anti-emetJ effect, and strong anti-5-HT and MA( inhibitor activity. 8,1tA2

Chlorpromazine is also the bes known drug in the aliphatic class an, is used by many practitioners for it major tranquilizer effect.

The major benefit of using chlorprc mazine to abort acute migraine in th outpatient setting is that only on, non-addictive medication with a goo~ success rate arid relatively few, easil' controlled side effects would be used

Acute dystonia was not seen in thi series. It is a relatively common prob lem when using any of the phenc thiazines, especial ly those of th~ piperazine series, t° Diphenhydramin~ or benztropine easi.ly control thi= symptom.t°,13

Orthostat ic hypotension was th~ only medical complication seen. 'It i: reported to occur in approximatel, ' 15% of patients receiving parentera chlorpromazine for the first time: 1 The incidence might be lessened b! using ideal body weights i n dose cal

42/757 Annals of Emergency Medicine 12:12 December I98~

culations or us ing other phenothia- zines, such as those of the piperazine class, with less hypotens ive effect. Although chlorpromazine is known to lower the seizure threshold in some patients, ~2 no seizures were seen in this series. However, it would be pru- dent to avoid this therapy in patients with known seizure disorders.

Finally, it should be remembered that this s tudy design was a non- randomized, non -b l i nded tr ial of a single therapeutic agent, and the con- clusions drawn have all the l imita- tions inherent in such a design.

CONCLUSION One h u n d r e d emergency depart-

ment pa t ien ts were eva lua ted pro- spectively during acute treatment of migraine with parenteral chlorproma- zine. There was r e s o l u t i o n of all symptoms within 55 minutes in 96% of patients. Orthostat ic hypotension was seen in 18 pa t i en t s bu t spon-

taneously resolved in all but one. Par- enteral chlorpromazine was shown to be safe, rapid, and effective in the t r e a t m e n t of acute o u t p a t i e n t mi- graine.

REFERENCES 1. Ziegler DK: The epidemiology and ge- netics of migraine. Res Clin Stud Head- ache 5:21-33, 1978.

2. Raskin NH: Pharmacology of migraine. Annu Rev Pharmacol Toxicol 21:463-478, 1981. 3. Caviness VS, O'Brien P: Headache. N Engl J Med 302:446-450, 1980. 4. Raskin NH, Schwartz RK: Interval ther- apy of migraine: Long-term results. Head- ache 20:340-366, 1980.

5. Saper JR: Migraine. II. Treatment. JAMA 239:2480-2484, 1978.

6. Caviness VS, O'Brien P: Cluster head- ache: Response to chlorpromazine. Head- ache 20:128-131, 1980.

7. Cohen MJ, McArthur DL: Classification

of migraine and tension headaches from a survey of 10,000 headache diaries. Head- ache 21:25-29, 1981. 8. Fozard JR: Basic mechanisms of anti- migraine drugs. Adv Neurol 33:295-307, 1982. 9. Dalessio DJ: Use of ergot preparations in acute migraine attacks. Headache 21:75, 1975. 10. Iserson KV: Tranquilizer overdose, in Rosen P, Baker FJ, Braen GR, et al (eds): Emergency Medicine: Concepts in Clinical Practice. St Louis, CV Mosby, 1983, p 1508 - 1515.

11. Cooper M, Wyllie JH: Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharm 67:79- 85, 1979. 12. Gilman AG, Goodman LS, Gilman A (eds): The Pharmacological Basis of Ther- apeutics. New York, Macmillan, 1980. 13. Guzzardi L: Phenothiazines and the antipsychotic agents, in Haddad LM, Winchester JF (eds): Clinical Management of Poisoning and Drug Overdose. Phil- adelphia, WB Saunders, 1983, p 487-496.

Notice of Address Change The American College of Emergency Physicians has been notified by the United States Postal Service that its mailing address has been changed to PO Box 619911, Dallas, TX 75261-9911 as a result of the introduction of Zip + 4. Please note this new address and use it in future correspondence.

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