A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines

Benjamin W. Friedman, Michael Hochberg, David Esses, Polly E. Bijur, Jill Corbo, Joseph Paternoster, Clemencia Solorzano, Babak Baghizadeh Toosi, Richard B. Lipton, E. John Gallagher

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background. - Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs. Objective. - To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan. Methods. - This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached. Results. - The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group. Conclusions. - SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.

Original languageEnglish (US)
Pages (from-to)934-941
Number of pages8
JournalHeadache
Volume46
Issue number6
DOIs
StatePublished - Jun 2006

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Sumatriptan
Diphenhydramine
Migraine Disorders
Clinical Trials
Pain
Hospital Emergency Service
Clinical Trials Data Monitoring Committees
trimethobenzamide
Antiemetics
Emergency Treatment
Intramuscular Injections
Telephone
Headache
Therapeutics
Recurrence

Keywords

  • Diphenhydramine
  • Emergency department
  • Migraine
  • Sumatriptan
  • Trimethobenzamide

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines. / Friedman, Benjamin W.; Hochberg, Michael; Esses, David; Bijur, Polly E.; Corbo, Jill; Paternoster, Joseph; Solorzano, Clemencia; Toosi, Babak Baghizadeh; Lipton, Richard B.; Gallagher, E. John.

In: Headache, Vol. 46, No. 6, 06.2006, p. 934-941.

Research output: Contribution to journalArticle

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T1 - A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines

AU - Friedman, Benjamin W.

AU - Hochberg, Michael

AU - Esses, David

AU - Bijur, Polly E.

AU - Corbo, Jill

AU - Paternoster, Joseph

AU - Solorzano, Clemencia

AU - Toosi, Babak Baghizadeh

AU - Lipton, Richard B.

AU - Gallagher, E. John

PY - 2006/6

Y1 - 2006/6

N2 - Background. - Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs. Objective. - To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan. Methods. - This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached. Results. - The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group. Conclusions. - SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.

AB - Background. - Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs. Objective. - To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan. Methods. - This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached. Results. - The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group. Conclusions. - SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.

KW - Diphenhydramine

KW - Emergency department

KW - Migraine

KW - Sumatriptan

KW - Trimethobenzamide

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