Efficacy of Diclofenac Sodium Softgel 100 mg with or without Caffeine 100 mg in Migraine without Aura: A Randomized, Double-blind, Crossover Study

Stephen J. Peroutka, James A. Lyon, James Swarbrick, Richard B. Lipton, Ken Kolodner, Jerome Goldstein

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objective.-A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. Background.-Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). Methods.-The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (χ 22 = 11.56, P = .003). Both the diclofenac plus caffeine (P < .03) and diclofenac only (P < .03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. Conclusions.-The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.

Original languageEnglish (US)
Pages (from-to)136-141
Number of pages6
JournalHeadache
Volume44
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

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Migraine without Aura
Diclofenac
Caffeine
Double-Blind Method
Cross-Over Studies
Placebos
Migraine Disorders
Headache
Analgesics
Sample Size
Ergotamine
Ibuprofen
Acute Pain
Acetaminophen

Keywords

  • Caffeine
  • Diclofenac
  • Migraine
  • ProSorb technology

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Efficacy of Diclofenac Sodium Softgel 100 mg with or without Caffeine 100 mg in Migraine without Aura : A Randomized, Double-blind, Crossover Study. / Peroutka, Stephen J.; Lyon, James A.; Swarbrick, James; Lipton, Richard B.; Kolodner, Ken; Goldstein, Jerome.

In: Headache, Vol. 44, No. 2, 02.2004, p. 136-141.

Research output: Contribution to journalArticle

Peroutka, Stephen J. ; Lyon, James A. ; Swarbrick, James ; Lipton, Richard B. ; Kolodner, Ken ; Goldstein, Jerome. / Efficacy of Diclofenac Sodium Softgel 100 mg with or without Caffeine 100 mg in Migraine without Aura : A Randomized, Double-blind, Crossover Study. In: Headache. 2004 ; Vol. 44, No. 2. pp. 136-141.
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abstract = "Objective.-A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. Background.-Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). Methods.-The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14{\%}) of 43 subjects reported headache relief at 60 minutes versus 12 (27{\%}) of 45 subjects in the diclofenac softgel group, and 19 (41{\%}) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95{\%} confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63{\%}) of 43 subjects treated with placebo, 15 (33{\%}) of 45 subjects treated with diclofenac softgel, and 14 (30{\%}) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (χ 22 = 11.56, P = .003). Both the diclofenac plus caffeine (P < .03) and diclofenac only (P < .03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. Conclusions.-The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.",
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T2 - A Randomized, Double-blind, Crossover Study

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AU - Lyon, James A.

AU - Swarbrick, James

AU - Lipton, Richard B.

AU - Kolodner, Ken

AU - Goldstein, Jerome

PY - 2004/2

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N2 - Objective.-A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. Background.-Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). Methods.-The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (χ 22 = 11.56, P = .003). Both the diclofenac plus caffeine (P < .03) and diclofenac only (P < .03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. Conclusions.-The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.

AB - Objective.-A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. Background.-Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). Methods.-The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (χ 22 = 11.56, P = .003). Both the diclofenac plus caffeine (P < .03) and diclofenac only (P < .03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. Conclusions.-The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.

KW - Caffeine

KW - Diclofenac

KW - Migraine

KW - ProSorb technology

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