RANDOMIZED, PLACEBO-CONTROLLED EVALUATION OF PROCHLORPERAZINE VERSUS METOCLOPRAMIDE FOR EMERGENCY DEPARTMENT TREATMENT OF MIGRAINE HEADACHE.

Coppola M, Yealy DM, Leibold RA. Ann Emerg Med 1995 Nov;26(5):541-6.

STUDY OBJECTIVE: To determine the comparative efficacy of i.v. metoclopramide and prochlorperazine for the initial emergency department treatment of migraine headache.

DESIGN: Prospective, randomized, double-blind, placebo-controlled trial.

SETTING: Military community hospital ED with an annual census of 75,000.

PARTICIPANTS: Seventy consenting adults from a convenience sample of patients presenting with migraine headache similar to that experienced in at least one prior episode. Exclusion criteria were pregnancy, fever, signs of meningismus, altered sensorium, drug or alcohol use, oxygen saturation less than 90%, recent trauma or seizure, "worst headache," abnormal blood pressure, recent (within 48 hours) use of metoclopramide or prochlorperazine, and allergy to metoclopramide or prochlorperazine.

INTERVENTIONS: In a random manner, each subject received a 2-mL i.v. injection of identical-appearing fluid containing metoclopramide (10 mg), prochlorperazine (10 mg), or saline solution (placebo). No other analgesics or medications were administered during the initial study period; rescue agents were administered by the choice of the treating physician after all data were collected.

MEASUREMENTS: Patients scored their nausea, pain, and sedation before receiving the 2-mL injections and at 30 minutes after injection. Ten-centimeter nonhatched visual analog scales were used for these measurements, with distance from the left end (zero) calculated for each use. Clinically important successful treatment was defined a priori as achievement of the following criteria: patient satisfaction and either a decrease of 50% or more in the 30-minute pain score (compared with the initial score) or an absolute pain score of 2.5 cm or less. Failure to achieve these criteria constituted treatment failure. Differences between groups were analyzed with the Kruskal-Wallis ANOVA and chi 2 tests. Data are reported as frequency percentages and median values, with a two-tailed P value of .05 or less considered significant.

RESULTS: Nausea, pain, and sedation scores were similar in all three groups before therapy. Thirty minutes after treatment, pain scores differed among those treated with prochlorperazine (1.1 cm), with metoclopramide (3.9 cm), and with placebo (6.1 cm, P = .003). Clinical success occurred more commonly after treatment with prochlorperazine (82%) than after metoclopramide (46%) or placebo (29%, P = .03). However, metoclopramide and placebo scores did not differ (P = .14). Nausea tended to be improved after prochlorperazine, compared with metoclopramide or placebo, at 30 minutes (P = .64). Four patients (6%) returned to the ED for relapse of migraine headache within 24 hours (three in the placebo group and one in the metoclopramide group).

CONCLUSION: i.v. prochlorperazine relieves the headache and tends to improve nausea better than metoclopramide in ED patients with acute migraine headache.

REPETITIVE INTRAVENOUS PROCHLORPERAZINE TREATMENT OF PATIENTS WITH REFRACTORY CHRONIC DAILY HEADACHE.

Lu SR, et al. Headache 2000 Oct;40(9):724-9.

OBJECTIVES: To investigate the efficacy and long-term outcome of intravenous prochlorperazine for the treatment of refractory chronic daily headache.

BACKGROUND: Unlike dihydroergotamine, the treatment results of intravenous neuroleptics as first-line agents for refractory chronic daily headache have rarely been reported.

METHODS: We retrospectively analyzed the data of inpatients with refractory chronic daily headache who received intravenous repetitive prochlorperazine treatment from November 1996 to March 1999. A semistructured telephone follow-up interview was done in September 1999.

RESULTS: A total of 135 patients (44 men, 91 women) were recruited, including 95 (70%) with analgesic overuse. After intravenous prochlorperazine treatment, 121 (90%) achieved a 50% or greater reduction of headache intensity, including 85 (63%) who became headache-free. The mean hospital stay was 6.2 +/- 2.7 days, and mean total prochlorperazine used was 98 +/- 48 mg. Acute extrapyramidal symptoms occurred in 21 patients (16%). One hundred twenty-four patients (92%) were successfully followed up, with a mean duration of 14.3 +/- 7.5 months. Compared with pretreatment status, 93 patients (75%) considered their headache intensity decreased, and 86 patients (69%) considered their headache frequency decreased, although 40 (32%) still had a daily headache. Of the 87 patients with analgesic overuse who could be followed, 61 (70%) no longer overused analgesics. Poor response to prochlorperazine treatment (relative risk, 1.8) and presence of major depression (relative risk, 1.8) were predictors of persistent chronic daily headache at follow-up.

CONCLUSIONS: Prochlorperazine was effective and safe in the treatment of patients with refractory chronic daily headache with or without analgesic overuse. Compared with dihydroergotamine, prochlorperazine seemed less effective at achieving "freedom from headache" during hospitalization, but had a similar outcome at follow-up.

TOLERABILITY AND EFFECTIVENESS OF PROCHLORPERAZINE FOR INTRACTABLE MIGRAINE IN CHILDREN.

Kabbouche MA, et al. Pediatrics 2001 Apr;107(4):E62.

OBJECTIVE: To study the effectiveness of prochlorperazine in aborting severe, intractable migraines in children.

STUDY DESIGN: Patients for this study were drawn from the population seen and evaluated in the Headache Center at Cincinnati Children's Hospital Medical Center. All patients were diagnosed with migraine headache by both clinical and International Headache Society criteria. The effectiveness of intravenous prochlorperazine in 20 consecutive patients referred to the emergency department for severe, prolonged migraines was retrospectively reviewed.

RESULTS: Patients evaluated in this study presented with a mean headache severity of 8.4 on a 0- to 10-point scale and an average duration of 54 hours. At 1 hour, 90% of the patients reported feeling better with 50% becoming pain-free. A 50% or greater reduction in severity occurred in 75% of patients at 1 hour and in 95% at 3 hours. At 3 hours, 95% of the patients reported feeling better, and 60% were pain-free. Only 1 patient failed to respond to prochlorperazine.

CONCLUSION: Prochlorperzaine was shown to be highly effective in aborting intractable migraines in children. It was well tolerated with no significant side effects. Additional large, double-blinded, randomized, placebo-controlled studies are needed to further investigate its effectiveness.

A RANDOMIZED CLINICAL TRIAL TO ASSESS THE EFFICACY OF INTRAMUSCULAR DROPERIDOL FOR THE TREATMENT OF ACUTE MIGRAINE HEADACHE.

Richman PB, et al. Am J Emerg Med 2002 Jan;20(1):39-42.

BACKGROUND: In a recent case series, we reported that intramuscular droperidol appeared to be an effective therapy for the treatment of acute migraine headache. The objective of the study was to further assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache.

DESIGN: The study design was a randomized, clinical trial set in a community-based ED. The population was a convenience sample of ED patients who met International Headache Society acute migraine criteria. Exclusions included pregnancy, use of narcotic or phenothiazine medications within 24 hours. For the protocol, patients were randomized to 1 of 2 treatment groups. Patients and physicians were blinded as to the treatment provided. Patients recorded their initial pain on a 100mm Visual Analog Scale (VAS) Patients were randomized to receive either 2.5 mg droperidol intramuscularly; the other group received 1.5 mg/kg meperidine intramuscularly. After 30 minutes patients recorded their pain on the VAS and recorded their preference for the medication on a Likert Scale. Physicians recorded the incidence of any side effects and the need for rescue medication. Statistical analysis consisted of categorical variables that were analyzed by chi-square, continuous interval data by t-tests and ordinal data by Mann-Whitney U test. The primary outcome parameters were mean VAS score change and the percentage of patients who wanted to go home without rescue medication. The study had an 80% power to detect a 26 mm difference in the mean change in VAS between groups.

RESULTS: Of the 29 patients who were enrolled, 15 received droperidol. Both groups were similar with respect to age (30.7 +/- 8.9 years droperdol v 32.7 +/- 9.9 years meperidine; P =.59), female sex (73% v 71%; P =.91), mean headache duration (24.7 +/- 28.3 v 18.3 +/- 25.8 hours; P =.55). The droperidol group had a higher mean initial VAS score (88 v 76 mm; P =.03). The 2 groups were similar with regard to outcome, including: mean change in VAS score (47 v 37 mm; P =.33), average Likert score (1.1 v 1.9; P =.85), and the percentage of patients who did not want rescue medication (67% v 57%; P =.61). The incidence of sedation was 6.7 v 14.3%. Akathisia occurred in 13.3% of pts who received droperidol.

CONCLUSION: We found that intramuscular droperidol was similar in efficacy to meperidine with a low incidence of side effects.

DROPERIDOL VS. PROCHLORPERAZINE FOR BENIGN HEADACHES IN THE EMERGENCY DEPARTMENT.

Miner JR, et al. Acad Emerg Med 2001 Sep;8(9):873-9.

OBJECTIVE: To compare the efficacy of droperidol with that of prochlorperazine for the treatment of benign headaches in emergency department (ED) patients.

METHODS: Prospective, randomized clinical trial in an urban ED. Patients were given either droperidol, 5 mg intramuscular (IM) or 2.5 mg intravenous (IV), or prochlorperazine, 10 mg IM or 10 mg IV. Measurements included side effects and the patient's pain perception as measured on a 100-mm visual analog scale (VAS) at baseline, 30, and 60 minutes after the medication was given. Data were analyzed using chi-square, two-tailed t-tests, and two-way analysis of variance (ANOVA) when appropriate.

RESULTS: During an eight-month period, 168 patients were enrolled. Eighty-two (48.8%) of the patients received droperidol; 86 (51.2%) received prochlorperazine. In the droperidol group, 49 (59.6%) received IM administration and 33 (40.4%) IV. In the prochlorperazine group, 57 (66.3%) received IM administration and 29 (33.7%) IV. Sixty minutes after the medication, the mean decrease in the VAS scores was 81.4% for droperidol and 66.9% for prochlorperazine (p = 0.001). At 30 minutes, 60.9% of the patients receiving droperidol and 44.2% of the patients receiving prochlorperazine had obtained at least a 50% reduction in their VAS scores (p = 0.09). At 60 minutes, 90.2% of the patients receiving droperidol and 68.6% of the patients receiving prochlorperazine had at least a 50% reduction in their VAS scores (p = 0.017). No difference between IM dosing and IV dosing was detected. Side effects, including dystonia, akathisia, and decreased level of consciousness, were seen in 15.2% of the patients receiving droperidol and 9.61% of the patients receiving prochlorperazine. No significant or persisting morbidity was detected.

CONCLUSIONS: Droperidol was more effective than prochlorperazine in relieving pain associated with benign headaches.

COMPARATIVE EFFICACY OF CHLORPROMAZINE AND MEPERIDINE WITH DIMENHYDRINATE IN MIGRAINE HEADACHE.

Lane PL, McLellan BA, Baggoley CJ. Ann Emerg Med 1989 Apr;18(4):360-5.

BACKGROUND: Approximately 20% of the population suffers from migraine headache, and a significant number develop "fixed" migraines, refractory to oral medications. Of this group, many become habitual narcotic users. A previously published case series using IV chlorpromazine suggested efficacy, so a randomized, double-blind, controlled trial was conducted. The study compared IV chlorpromazine against IV meperidine with dimenhydrinate.

SETTING: Entry criteria were emergency department patients from 18 to 60 years of age with a clinical diagnosis of common or classic migraine headache. After informed consent was obtained, an IV line with normal saline was established, and a bolus of 5 mL/kg was administered. Patients were randomized into two groups: chlorpromazine and meperidine with dimenhydrinate. The chlorpromazine group received a bolus injection of 5 mL normal saline placebo followed by 0.4 mL/kg chlorpromazine solution (0.1 mg/kg). The chlorpromazine was repeated every 15 minutes as needed up to a total of three doses. The meperidine with dimenhydrinate group received 5 mL dimenhydrinate solution (25 mg) followed by 0.04 mL/kg meperidine (0.4 mg/kg). Again, the meperidine solution was repeated in the same dosage every 15 minutes as needed up to a total of three doses. If response was inadequate 15 minutes after the third dose, the sequence was broken, and the other medication given. Rescue medication was given to 8% of the patients treated with chlorpromazine compared to 45% of those receiving meperidine (p<0.01). Blood pressure and response were assessed at 15-minute intervals for one hour. Pain was assessed by both visual and verbal analogue scales every 15 minutes.

RESULTS: In all, 46 patients were entered in the study (24 chlorpromazine and 22 meperidine with dimenhydrinate). Patients receiving chlorpromazine reported a significantly greater decrease in pain intensity, assessed on a visual analogue scale, than those treated with meperidine (p<0.001). The prevalence of side effects (most commonly drowsiness) was 46% in patients receiving chlorpromazine and 27% in those receiving meperidine. The authors point out the difficulty of determining if certain side effects were due to the migraine headache or to the treatment regimens. There were no cases of significant hypotension or dystonia.

CONCLUSION: These findings suggest that IV chlorpromazine is an effective agent for use in patients presenting to the ED with migraine, permitting avoidance of narcotics.