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Sumatriptan plus naproxen for acute migraine attacks in adults

  1. Simon Law1,
  2. Sheena Derry2,*,
  3. R Andrew Moore2

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 21 OCT 2013

Assessed as up-to-date: 3 OCT 2013

DOI: 10.1002/14651858.CD008541.pub2


How to Cite

Law S, Derry S, Moore RA. Sumatriptan plus naproxen for acute migraine attacks in adults. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD008541. DOI: 10.1002/14651858.CD008541.pub2.

Author Information

  1. 1

    Gloucester Hospitals NHS Foundation Trust, Department of Anaesthetics, Gloucestershire, UK

  2. 2

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

*Sheena Derry, Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. sheena.derry@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 21 OCT 2013

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This is not the most recent version of the article. View current version (20 APR 2016)

 
Characteristics of included studies [ordered by study ID]
Brandes 2007 Study 1

MethodsMulticentre, R, DB, PC, parallel group. Single dose to treat single attack

Medication taken when PI ≥ moderate

Assessments at 0, 0.5, 1, 1.5, 2, then hourly to 24 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years. History: > 6 months with frequency of 2-6 per month and untreated severity ≥ moderate

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease, using MAOI, ergot, SJW, or NSAID

n = 1461

F = 86%

Mean age 40 years

72% without aura


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 370 (364 analysed for efficacy)

Sumatriptan 85 mg, n = 365 (361 for efficacy)

Naproxen 500 mg, n = 361 (365 for efficacy)

Placebo, n = 365 (360 for efficacy)

Rescue medication allowed after 2 h if necessary (as prescribed by physician but not ergot-containing, serotonin agonist, or NSAID-containing medications)


OutcomesHeadache relief at 2 h

Pain-free at 2 h

24-h sustained headache relief

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Presence and relief of functional disability at 2 h (from Landy 2007)

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB1, W1. Total = 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeLow risk> 200 participants per treatment arm

Brandes 2007 Study 2

MethodsMulticentre, R, DB, PC, parallel group. Single dose to treat single attack

Medication taken when PI ≥ moderate

Assessments at 0, 0.5, 1, 1.5, 2, then hourly to 24 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years. History: > 6 months with frequency of 2-6 per month and untreated severity ≥ moderate

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease, using MAOI, ergot, SJW, or NSAID

n = 1495

F = 88%

Mean age 40 years

76% without aura


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 367 (362 for efficacy)

Sumatriptan 85 mg, n = 370 (362 for efficacy)

Naproxen 500 mg, n = 371 (364 for efficacy)

Placebo, n = 387 (382 for efficacy)

Rescue medication allowed after 2 h if necessary (as prescribed by physician but not ergot-containing, serotonin agonist, or NSAID-containing medications)


OutcomesHeadache relief at 2 h

Pain-free at 2 h

24-h sustained headache relief

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Presence and relief of functional disability at 2 h (from Landy 2007)

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB1, W1. Total = 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeLow risk> 200 participants per treatment arm

Lipton 2009 Study 1

MethodsMulticentre, R, DB, PC, cross-over. Single dose/attack. 4 attacks treated: all with active or 3 active and 1 placebo (in random order). Washout between attacks not specified, but all headache medications prohibited within 24 h of a treated attack, and AE data collected for 72 h after treatment

Medication taken within 1 h of onset when PI was mild

Assessments at 0, 2, 4, 24 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years. History ≥ 6 months with frequency of 2-6 attacks per month and untreated severity ≥ moderate and identifiable mild phase

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease

n = 570 (568 for efficacy)

F = 89%

Mean age 42 years


InterventionsSumatriptan/naproxen 85/500 mg (1693 attacks treated)

Placebo (424 attacks treated)

5 treatment groups with different medication sequences (N: naproxen; P: placebo; S: sumatriptan)

P, S/N, S/N, S/N; S/N, P, S/N, S/N; S/N, S/N, P, S/N; S/N, S/N, S/N, P; S/N, S/N, S/N, S/N

Rescue medication allowed after 2 h if necessary (recommended 2 x 220 mg naproxen sodium with additional 1 x 220 mg 6 h later if needed)


OutcomesPain-free at 2 h

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB1, W1. Total = 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeUnclear risk50-200 participants per treatment arm

Lipton 2009 Study 2

MethodsMulticentre, R, DB, PC, cross-over. Single dose/attack. 4 attacks treated: all with active or 3 active and 1 placebo (in random order). Washout between attacks not specified, but all headache medications prohibited within 24 h of a treated attack, and AE data collected for 72 h after treatment

Medication taken within 1 h of onset when PI was mild

Assessments at 0, 2, 4, 24 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years. History ≥ 6 months with frequency of 2-6 attacks per month and untreated severity ≥ moderate and identifiable mild phase

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease

n = 565 (563 for efficacy)

F = 90%

Mean age 41 years


InterventionsSumatriptan/naproxen 85/500 mg (1678 attacks treated)

Placebo (422 attacks treated)

5 treatment groups with different medication sequences (N: naproxen; P: placebo; S: sumatriptan)

P, S/N, S/N, S/N; S/N, P, S/N, S/N; S/N, S/N, P, S/N; S/N, S/N, S/N, P; S/N, S/N, S/N, S/N

Rescue medication allowed after 2 h if necessary (recommended 2 x 220 mg naproxen sodium with additional 1 x 220 mg 6 h later if needed)


OutcomesPain-free at 2 h

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB1, W1. Total = 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeUnclear risk50-200 participants per treatment arm

Mannix 2009 Study 1

MethodsMulticentre, R, DB, PC, parallel group. Single dose to treat single attack

Medication taken when PI mild and within 1 h of onset

Assessments at 0, 0.5, 1, 1.5, 2, 4, 24, 48 h


ParticipantsMigraine ± aura (IHS 2004), aged ≥ 18 years. History: frequency of migraines 1-6 per month with menstrual migraine in 2/3 previous cycles and dysmenorrhoea in 2/3 cycles. Untreated severity ≥ moderate, with identifiable mild phase

n = 312 (311 for efficacy)

F = 100%

Mean age 37 years

Aura: 26%; primary dysmenorrhoea: 77%


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 152

Placebo, n = 160

Rescue medication allowed after 2 h if necessary (including second dose, sumatriptan or naproxen sodium)


OutcomesPain-free at 2 h

24-h sustained pain-free

Use of rescue medication up to 48 h

AEs

Withdrawals


NotesOxford Quality Score: R2, DB1, W1. Total = 4


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomly assigned by a computer generated code"

Allocation concealment (selection bias)Low riskRemote allocation (computerised registration and ordering system)

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeUnclear risk50-200 participants per treatment arm

Mannix 2009 Study 2

MethodsMulticentre, R, DB, PC, parallel group. Single dose to treat single attack

Medication taken when PI mild and within 1 h of onset

Assessments at 0, 0.5, 1, 1.5, 2, 4, 24, 48 h


ParticipantsMigraine ± aura (IHS 2004), aged ≥ 18 years. History: frequency of migraines 1-6 per month with menstrual migraine in 2/3 previous cycles and dysmenorrhoea in 2/3 cycles. Untreated severity ≥ moderate, with identifiable mild phase

n = 311 (310 for efficacy)

F = 100%

Mean age 37 years

Aura: 40%; primary dysmenorrhoea: 92%


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 151

Placebo, n = 160

Rescue medication allowed after 2 h if necessary (including second dose, sumatriptan or naproxen sodium)


OutcomesPain-free at 2 h

24-h sustained pain-free

Use of rescue medication up to 48 h

AEs

Withdrawals


NotesOxford Quality Score: R2, DB1, W1. Total = 4


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomly assigned by a computer generated code"

Allocation concealment (selection bias)Low riskRemote allocation (computerised registration and ordering system)

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeUnclear risk50-200 participants per treatment arm

Mathew 2009 Study 1

MethodsMulticentre, R, DB, PC, cross-over. Single dose to treat single attack. Washout between attacks ≥1 week

Medication taken when PI mild and within 1 h of onset

Assessments at 0, 0.5, 1, 1.5, 2, 4 24, 48 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years, poor response to triptans with short half-life. History: frequency of 1-8 per month, < 15 headache days monthly. Untreated severity ≥ mild

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease

n = 144 (139 for efficacy)

F = 85%

Mean age 41 years

Aura: 32%


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 136

Placebo, n = 134

Rescue medication allowed after 2 h if necessary (not specified)


OutcomesPain-free at 2 h

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB1, W1 Total = 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeUnclear risk50-200 participants per treatment arm

Mathew 2009 Study 2

MethodsMulticentre, R, DB, PC, cross-over. Single dose to treat single attack. Washout between attacks ≥ 1 week

Medication taken when PI mild and within 1 h of onset

Assessments at 0, 0.5, 1, 1.5, 2, 4 24, 48 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years, poor response to triptans with short half-life. History: frequency of 1-8 per month, < 15 headache days monthly. Untreated severity ≥ mild

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease

n = 137 (131 for efficacy)

F = 93%

Mean age 40 years

27% without aura


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 134

Placebo, n = 133

Rescue medication allowed after 2 h if necessary (not specified)


OutcomesPain-free at 2 h

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB1, W1 Total = 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeUnclear risk50-200 participants per treatment arm

Silberstein 2008 Study 1

MethodsMulticentre, R, DB, PC, parallel group. Single dose to treat single attack

Medication taken when PI mild and within 1 h of onset

Assessments at 0, 0.5, 1, 2, 4, 24 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years. History: ≥ 6 months with frequency of 2-6 attacks per month, and ≤ 15 per month. Untreated severity ≥ moderate, with identifiable mild pain phase

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease, gastrointestinal history

n = 580 (576 for efficacy)

F = 87.5%

Mean age 40 years

Aura: 20%


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 283

Placebo, n = 297

Rescue medication allowed after 2 h if necessary (not triptans, NSAID-containing, ergot-containing or ergot-like medication)


OutcomesPain-free at 2 h

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Presence and relief of functional disability at 2 h (from Taylor 2007)

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R2, DB2, W1. Total = 5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Computer-generated randomization schedule"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low risk"Matching placebo"

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeLow risk> 200 participants per treatment arm

Silberstein 2008 Study 2

MethodsMulticentre, R, DB, PC, parallel group. Single dose to treat single attack

Medication taken when PI mild and within 1 h of onset

Assessments at 0, 0.5, 1, 2, 4, 24 h


ParticipantsMigraine ± aura (IHS 2004), aged 18-65 years. History: ≥ 6 months with frequency of 2-6 attacks per month, and ≤ 15 per month. Untreated severity ≥ moderate, with identifiable mild pain phase

Excluded: uncontrolled hypertension, cardio- or cerebrovascular disease, gastrointestinal history

n = 542 (535 for efficacy)

F = 90.5%

Mean age 41 years

66% without aura


InterventionsSumatriptan 85 mg/naproxen 500 mg, n = 278

Placebo, n = 264

Rescue medication allowed after 2 h if necessary (not triptans, NSAID-containing, ergot-containing or ergot-like medication)


OutcomesPain-free at 2 h

24-h sustained pain-free

Presence and relief of associated symptoms at 2 h

Presence and relief of functional disability at 2 h (from Taylor 2007)

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R2, DB2, W1. Total = 5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Computer-generated randomization schedule"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low risk"Matching placebo"

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeLow risk> 200 participants per treatment arm

Smith 2005

MethodsMulticentre, R, DB, DD, parallel group. Single dose to treat single attack

Medication taken when pain ≥ moderate

Assessments at 0, 15 min intervals to 2 h, 30 min to 4 h, hourly to 24 h


ParticipantsMigraine ± aura (IHS 2004), aged ≥18 years. History ≥ 1 year with 2-6 attacks per month, and able to tolerate oral triptan or ergot derivative

n = 972

F = 91%

Mean age 42 years

Without aura: > 70%


InterventionsSumatriptan 50 mg/naproxen 500 mg, n = 251

Sumatriptan 50 mg, n = 229

Naproxen 500 mg, n = 250

Placebo, n = 242

Rescue medication allowed after 2 h if necessary (not specified)


OutcomesHeadache relief at 1 and 2 h

Pain-free at 2 h

24-h sustained headache relief

24-h sustained pain-free

Presence and relief of functional disability at 2 h

Presence and relief of associated symptoms at 2 h

Use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low riskDD method, with sumatriptan encapsulated

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeLow risk> 200 participants per treatment arm

TRX109011/13

MethodsMulticentre, R, DB, DD, 3 phase cross-over. Single dose of each medication to treat single attack. Washout between attacks ≥ 72 h

Medication taken when pain ≥ moderate

Assessments at 0, 2, 4, 6, 8, 24, 48 h


ParticipantsMigraine ± aura (IHS 2004), aged ≥18 years. History of 2-8 attacks per month in previous 3 months

n = 375 attacks (ITT; 442 attacks for safety)

F = 88%

Mean age 43 years


InterventionsSumatriptan 50 mg/naproxen 500 mg, n = 406 (317 for efficacy)

Paracetamol (acetaminophen) 325 mg + caffeine 40 mg + butalbital 50 mg, n = 392 (304 for efficacy)

Placebo, n = 405 (320 for efficacy)


OutcomesHeadache relief at 2 h

Pain-free at 2 h

24-h sustained headache relief

24-h sustained pain-free

Presence and relief of functional disability at 2 h

Use of rescue medication

Mean time to first use of rescue medication

AEs

Withdrawals


NotesOxford Quality Score: R2, DB2, W1. Total = 5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low riskDD method

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-outs described

Study sizeLow risk> 200 participants per treatment arm

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Krymchantowski 2000Enriched enrolment study

Landy 2009Post hoc analysis of Landy 2007 (secondary publication under Brandes 2007 Study 1; Brandes 2007 Study 2)

Smith 2007Data pertains to quality of life and satisfaction outcomes only and not outcomes specified here

TRX107563No IHS definition of migraine for inclusion; participants had 'probable migraine without aura'

White 2011No single episode data for efficacy or adverse events

Winner 2007Open-label safety study

 
Comparison 1. Sumatriptan/naproxen versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain-free at 2 h12Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Mild baseline pain
83395Risk Ratio (M-H, Fixed, 95% CI)2.76 [2.43, 3.13]

    1.2 Moderate/severe baseline pain
42596Risk Ratio (M-H, Fixed, 95% CI)3.65 [2.97, 4.49]

 2 Headache relief at 2 h4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Moderate/severe baseline pain
42596Risk Ratio (M-H, Fixed, 95% CI)2.16 [1.95, 2.39]

 3 24-h sustained pain-free12Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Mild baseline pain
83396Risk Ratio (M-H, Fixed, 95% CI)3.04 [2.59, 3.56]

    3.2 Moderate/severe baseline pain
42596Risk Ratio (M-H, Fixed, 95% CI)3.43 [2.69, 4.36]

 4 24-h sustained headache relief4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Moderate/severe baseline pain
42596Risk Ratio (M-H, Fixed, 95% CI)2.61 [2.27, 2.99]

 5 Any adverse event105616Risk Ratio (M-H, Fixed, 95% CI)1.76 [1.53, 2.03]

    5.1 Mild baseline pain
62823Risk Ratio (M-H, Fixed, 95% CI)1.47 [1.16, 1.86]

    5.2 Moderate/severe baseline pain
42793Risk Ratio (M-H, Fixed, 95% CI)1.97 [1.64, 2.37]

 6 Rescue medication125565Risk Ratio (M-H, Fixed, 95% CI)0.45 [0.41, 0.48]

    6.1 Mild baseline pain
83396Risk Ratio (M-H, Fixed, 95% CI)0.42 [0.38, 0.47]

    6.2 Moderate/severe baseline pain
42169Risk Ratio (M-H, Fixed, 95% CI)0.47 [0.42, 0.53]

 7 Relief of associated symptoms at 2 h8Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    7.1 Nausea
81705Risk Ratio (M-H, Fixed, 95% CI)3.47 [2.79, 4.32]

    7.2 Photophobia
83127Risk Ratio (M-H, Fixed, 95% CI)2.77 [2.44, 3.13]

    7.3 Phonophobia
82856Risk Ratio (M-H, Fixed, 95% CI)2.63 [2.33, 2.97]

 8 Relief of functional disability at 2 h5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    8.1 Mild baseline pain
2981Risk Ratio (M-H, Fixed, 95% CI)2.91 [2.29, 3.72]

    8.2 Moderate/severe baseline pain
31984Risk Ratio (M-H, Fixed, 95% CI)3.36 [2.63, 4.29]

 
Comparison 2. Sumatriptan/naproxen versus sumatriptan alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain-free at 2 h31925Risk Ratio (M-H, Fixed, 95% CI)1.42 [1.23, 1.65]

 2 Headache relief at 2 h31925Risk Ratio (M-H, Fixed, 95% CI)1.20 [1.11, 1.29]

 3 24-h sustained pain-free31925Risk Ratio (M-H, Fixed, 95% CI)1.70 [1.41, 2.06]

 4 24-h sustained headache relief31925Risk Ratio (M-H, Fixed, 95% CI)1.39 [1.24, 1.55]

 5 Any adverse event31952Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.86, 1.16]

 6 Rescue medication31925Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.58, 0.76]

 7 Relief of associated symptoms at 2 h2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    7.1 Nausea
2718Risk Ratio (M-H, Fixed, 95% CI)1.51 [1.21, 1.87]

    7.2 Photophobia
21186Risk Ratio (M-H, Fixed, 95% CI)1.20 [1.04, 1.39]

    7.3 Phonophobia
21146Risk Ratio (M-H, Fixed, 95% CI)1.26 [1.10, 1.45]

 8 Relief of functional disability at 2 h21354Risk Ratio (M-H, Fixed, 95% CI)1.41 [1.18, 1.69]

 
Comparison 3. Sumatriptan/naproxen versus naproxen alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain-free at 2 h31944Risk Ratio (M-H, Fixed, 95% CI)2.03 [1.71, 2.40]

 2 Headache relief at 2 h31944Risk Ratio (M-H, Fixed, 95% CI)1.41 [1.30, 1.54]

 3 24-h sustained pain-free31944Risk Ratio (M-H, Fixed, 95% CI)2.25 [1.82, 2.78]

 4 24-h sustained headache relief31944Risk Ratio (M-H, Fixed, 95% CI)1.64 [1.45, 1.85]

 5 Any adverse event31970Risk Ratio (M-H, Fixed, 95% CI)1.77 [1.47, 2.13]

 6 Rescue medication31944Risk Ratio (M-H, Fixed, 95% CI)0.61 [0.54, 0.70]

 7 Relief of associated symptoms at 2 h2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    7.1 Nausea
2726Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.90, 1.32]

    7.2 Photophobia
21176Risk Ratio (M-H, Fixed, 95% CI)1.39 [1.19, 1.62]

    7.3 Phonophobia
21135Risk Ratio (M-H, Fixed, 95% CI)1.48 [1.28, 1.72]

 8 Relief of functional disability at 2 h21352Risk Ratio (M-H, Fixed, 95% CI)1.63 [1.35, 1.97]

 
Summary of findings for the main comparison. Sumatriptan 50 mg or 85 mg plus naproxen 500 mg compared with placebo for migraine headache

Sumatriptan 50 mg or 85 mg plus naproxen 500 mg compared with placebo for migraine headache

Patient or population: adults with migraine headache - moderate or severe and mild baseline pain

Settings: community

Intervention: sumatriptan 50 mg or 85 mg plus naproxen 500 mg

Comparison: placebo

OutcomesProbable outcome with
comparator
Probable outcome with
intervention
NNT or NNH
(95% CI)
No. of studies, attacks, eventsQuality of the evidence
(GRADE)
Comments

Pain-free response at 2 h for moderate to severe baseline pain77 in 1000280 in 1000NNT 4.9 (4.3 to 5.7)4 studies, 2596 attacks, 462 eventsHighLower NNTs are better than higher NNTs

Pain-free response at 2 h for mild baseline pain180 in 1000500 in 1000NNT 3.1 (2.9 to 3.5)8 studies, 3395 attacks, 1252 evevtsHighLower NNTs are better than higher NNTs

Headache relief at 2 h for moderate to severe baseline pain270 in 1000580 in 1000NNT 3.2 (2.9 to 3.6)4 studies, 2596 attacks, 1107 eventsHighLower NNTs are better than higher NNTs

Sustained pain-free during the 24 h post dose for moderate to severe baseline pain60 in 1000200 in 1000NNT 7.9 (5.9 to 8.5)4 studies, 2596 attacks, 339 eventsModerate1Lower NNTs are better than higher NNTs

Sustained pain-free during the 24 h post dose for mild baseline pain120 in 1000370 in 1000NNT 4.1 (3.7 to 4.6)8 studies, 3396 attacks, 907 eventsHighLower NNTs are better than higher NNTs

Sustained headache relief during the 24 h post dose for moderate or severe baseline pain160 in 1000430 in 1000NNT 3.8 (3.4 to 4.3)4 studies, 2596 attacks, 768 eventsHighLower NNTs are better than higher NNTs

At least 1 AE during treatment for moderate to severe baseline pain120 in 1000210 in 1000NNH 11 (8.3 to 15)4 studies, 2793 attacks, 465 eventsModerate1Higher NNHs are better than lower NNHs

At least 1 AE during treatment for mild baseline pain82 in 1000140 in 1000NNH 18 (13 to 30)6 studies, 2823 attacks, 329 eventsModerate1Higher NNHs are better than lower NNHs

Serious AE (all levels of baseline pain)No events1 event possibly related to intervention----

AE: adverse event; CI: confidence interval; NNT: number needed to treat; NNH: number needed to harm.

Note: NNT or NNH is reported when an outcome is statistically different from placebo or comparator. Where the result is not statistically different, a risk ratio or similar outcome is reported.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Quality of evidence downgraded from high because of threat from potential publication bias with modest effect size and modest number of events.