Therapeutics
Review: Sumatriptan plus naproxen improves acute migraine more than placebo, sumatriptan, or naproxen
Law S, Derry S, Moore RA. Sumatriptan plus naproxen for acute migraine attacks in adults. Cochrane Database Syst Rev. 2013;(10): CD008541.
Clinical impact ratings: F ★★★★★★✩ E ★★★★★✩✩ N ★★★★★✩✩ Question
Main results
In adults with acute episodic migraine, what are the short-term efficacy and safety of sumatriptan plus naproxen?
The main results are in the Table.
Review scope
In adults with acute episodic migraine, sumatriptan plus naproxen improves pain and headache relief compared with placebo or sumatriptan or naproxen alone.
Included studies compared self-administered sumatriptan plus naproxen, as a fixed-dose combination (FDC) tablet or separate tablets, with placebo or other active control for treatment of episodic acute migraine attacks in adults ≥ 18 years of age; had ≥ 10 patients per group; had separate reporting of consecutive episodes; and included a washout period ≥ 48 hours for crossover trials. Exclusion criteria were chronic migraine or prophylactic studies. Primary outcomes were freedom from pain and headache relief (pain reduced from moderate or severe to none or mild) at 2 hours. Secondary outcomes included any adverse events.
Review methods MEDLINE, EMBASE/Excerpta Medica (both to Aug 2013), Cochrane Central Register of Controlled Trials (Issue 6, 2013), reference lists, and clinical trials databases were searched for doubleblind, randomized, controlled trials (RCTs); drug manufacturers were contacted. 12 RCTs (n = 9595, mean age range 40 to 43 y, 85% to 100% women) met selection criteria. All trials included a placebo group. 11 RCTs used an FDC tablet of sumatriptan, 85 mg, plus naproxen, 500 mg; and 1 RCT used separate tablets of sumatriptan, 50 mg, and naproxen, 500 mg. 3 RCTs also included groups treated with sumatriptan, 50 or 85 mg, or naproxen, 500 mg, alone; and 1 RCT included a group treated with a combination of acetaminophen, caffeine, and butalbital. 2 RCTs included only patients with menstrual migraine. Results were analyzed by mild (8 RCTs) or moderate or severe (4 RCTs) pain intensity at administration of treatment. None of the RCTs had high risk for bias.
Conclusion
Sources of funding: Global Campaign against Headache, UK and International Headache Society, UK. For correspondence: Dr. Sheena Derry, University of Oxford, Oxfordshire, England, UK. E-mail [email protected]. ■
Commentary The Cochrane review by Law and colleagues assessed the combination of the nonsteroidal antiinflammatory drug (NSAID) naproxen with sumatriptan for acute relief of episodic migraine. This combination modestly improved effectiveness, with no difference in adverse events for sumatriptan alone compared with combined treatment. Used alone, naproxen, compared with placebo, is not very effective for treatment of acute episodic migraine, with a number needed to treat (NNT) > 10 for short-term outcomes (1). On the other hand, sumatriptan alone is as effective as any single agent (2). Compared with sumatriptan alone, the combination of sumatriptan and naproxen had an NNT of 10. The 2 medications together seem to have additive effects, suggesting that they have different mechanisms of action.
Patients who are not enrolled in research studies probably use combinations of medications to abort migraine attacks. Previous reviews have examined the combination of acetaminophen (paracetamol) or an NSAID with an antiemetic (3). Reviews of naproxen (1), ibuprofen (4), and diclofenac (5) found no studies that examined the NSAID of interest Sumatriptan plus naproxen (sum + nap) vs placebo, sumatriptan (sum), or combined with an antiemetic. Aspirin (6) or acetanaproxen (nap) in adults with acute episodic migraine* minophen (3) plus an antiemetic provided improveOutcomes Pain Number of Weighted event rates At 2 h ments approaching the standard of oral sumatriptan, intensity† trials (n) 100 mg. Until newer agents are discovered, future Sum + nap Placebo RBI (95% CI) NNT (CI) research could examine combinations of an antiemetic, Pain-free‡ Mild 8 (3395) 49% 18% 176% (143 to 213) 4 (3 to 4) an NSAID, and/or a triptan in the hope that effects Mod/severe 4 (2596) 28% 7.7% 265% (197 to 349) 5 (5 to 6) might be additive or synergistic. Relief§
Mod/severe
4 (2596)
58%
27%
Sum + nap
Sum
116% (95 to 139)
4 (3 to 4)
Pain-free‡
Mod/severe
3 (1925)
32%
23%
42% (23 to 65)
10 (8 to 18)
Relief§
Mod/severe
3 (1925)
62%
52%
20% (11 to 29)
10 (7 to 17)
Sum + nap
Nap
Pain-free‡
Mod/severe
3 (1944)
33%
16%
103% (71 to 140)
7 (5 to 8)
Relief§
Mod/severe
3 (1925)
62%
44%
41% (30 to 54)
6 (5 to 8)
Sum + nap Placebo Adverse events
All
10 (5616)
17%
9.5%
RRI (CI)
NNH (CI)
76% (53 to 103)
14 (11 to 20)
*Abbreviations defined in Glossary. Weighted event rates, RBI, RRI, NNH, and CI calculated from control event rates and risk ratios in article using a fixed-effect model. NNTs are as reported in the article. †Pain intensity at administration of treatment classified as mild, or moderate or severe (mod/severe). ‡Freedom from pain without use of rescue medication. §Pain reduced from moderate or severe to none or mild without use of rescue medication.
JC8
© 2014 American College of Physicians
Downloaded From: http://annals.org/ by a University of York User on 11/21/2016
Alexander W. Chessman, MD Medical University of South Carolina Charleston, South Carolina, USA References 1. Law S, Derry S, Moore RA. Cochrane Database Syst Rev. 2013;10:CD009455. 2. Derry CJ, Derry S, Moore RA. Cochrane Database Syst Rev. 2012;2:CD008615. 3. Derry S, Moore RA. Cochrane Database Syst Rev. 2013; 4:CD008040. 4. Rabbie R, Derry S, Moore RA. Cochrane Database Syst Rev. 2013;4:CD008039. 5. Derry S, Rabbie R, Moore RA. Cochrane Database Syst Rev. 2013;4:CD008783. 6. Kirthi V, Derry S, Moore RA. Cochrane Database Syst Rev. 2013;4:CD008041.
18 February 2014 | ACP Journal Club | Volume 160 • Number 4
Review: Sumatriptan plus naproxen improves acute migraine more than placebo, sumatriptan, or naproxen
Law S, Derry S, Moore RA. Sumatriptan plus naproxen for acute migraine attacks in adults. Cochrane Database Syst Rev. 2013;(10): CD008541.
Clinical impact ratings: F ★★★★★★✩ E ★★★★★✩✩ N ★★★★★✩✩ Question
Main results
In adults with acute episodic migraine, what are the short-term efficacy and safety of sumatriptan plus naproxen?
The main results are in the Table.
Review scope
In adults with acute episodic migraine, sumatriptan plus naproxen improves pain and headache relief compared with placebo or sumatriptan or naproxen alone.
Included studies compared self-administered sumatriptan plus naproxen, as a fixed-dose combination (FDC) tablet or separate tablets, with placebo or other active control for treatment of episodic acute migraine attacks in adults ≥ 18 years of age; had ≥ 10 patients per group; had separate reporting of consecutive episodes; and included a washout period ≥ 48 hours for crossover trials. Exclusion criteria were chronic migraine or prophylactic studies. Primary outcomes were freedom from pain and headache relief (pain reduced from moderate or severe to none or mild) at 2 hours. Secondary outcomes included any adverse events.
Review methods MEDLINE, EMBASE/Excerpta Medica (both to Aug 2013), Cochrane Central Register of Controlled Trials (Issue 6, 2013), reference lists, and clinical trials databases were searched for doubleblind, randomized, controlled trials (RCTs); drug manufacturers were contacted. 12 RCTs (n = 9595, mean age range 40 to 43 y, 85% to 100% women) met selection criteria. All trials included a placebo group. 11 RCTs used an FDC tablet of sumatriptan, 85 mg, plus naproxen, 500 mg; and 1 RCT used separate tablets of sumatriptan, 50 mg, and naproxen, 500 mg. 3 RCTs also included groups treated with sumatriptan, 50 or 85 mg, or naproxen, 500 mg, alone; and 1 RCT included a group treated with a combination of acetaminophen, caffeine, and butalbital. 2 RCTs included only patients with menstrual migraine. Results were analyzed by mild (8 RCTs) or moderate or severe (4 RCTs) pain intensity at administration of treatment. None of the RCTs had high risk for bias.
Conclusion
Sources of funding: Global Campaign against Headache, UK and International Headache Society, UK. For correspondence: Dr. Sheena Derry, University of Oxford, Oxfordshire, England, UK. E-mail [email protected]. ■
Commentary The Cochrane review by Law and colleagues assessed the combination of the nonsteroidal antiinflammatory drug (NSAID) naproxen with sumatriptan for acute relief of episodic migraine. This combination modestly improved effectiveness, with no difference in adverse events for sumatriptan alone compared with combined treatment. Used alone, naproxen, compared with placebo, is not very effective for treatment of acute episodic migraine, with a number needed to treat (NNT) > 10 for short-term outcomes (1). On the other hand, sumatriptan alone is as effective as any single agent (2). Compared with sumatriptan alone, the combination of sumatriptan and naproxen had an NNT of 10. The 2 medications together seem to have additive effects, suggesting that they have different mechanisms of action.
Patients who are not enrolled in research studies probably use combinations of medications to abort migraine attacks. Previous reviews have examined the combination of acetaminophen (paracetamol) or an NSAID with an antiemetic (3). Reviews of naproxen (1), ibuprofen (4), and diclofenac (5) found no studies that examined the NSAID of interest Sumatriptan plus naproxen (sum + nap) vs placebo, sumatriptan (sum), or combined with an antiemetic. Aspirin (6) or acetanaproxen (nap) in adults with acute episodic migraine* minophen (3) plus an antiemetic provided improveOutcomes Pain Number of Weighted event rates At 2 h ments approaching the standard of oral sumatriptan, intensity† trials (n) 100 mg. Until newer agents are discovered, future Sum + nap Placebo RBI (95% CI) NNT (CI) research could examine combinations of an antiemetic, Pain-free‡ Mild 8 (3395) 49% 18% 176% (143 to 213) 4 (3 to 4) an NSAID, and/or a triptan in the hope that effects Mod/severe 4 (2596) 28% 7.7% 265% (197 to 349) 5 (5 to 6) might be additive or synergistic. Relief§
Mod/severe
4 (2596)
58%
27%
Sum + nap
Sum
116% (95 to 139)
4 (3 to 4)
Pain-free‡
Mod/severe
3 (1925)
32%
23%
42% (23 to 65)
10 (8 to 18)
Relief§
Mod/severe
3 (1925)
62%
52%
20% (11 to 29)
10 (7 to 17)
Sum + nap
Nap
Pain-free‡
Mod/severe
3 (1944)
33%
16%
103% (71 to 140)
7 (5 to 8)
Relief§
Mod/severe
3 (1925)
62%
44%
41% (30 to 54)
6 (5 to 8)
Sum + nap Placebo Adverse events
All
10 (5616)
17%
9.5%
RRI (CI)
NNH (CI)
76% (53 to 103)
14 (11 to 20)
*Abbreviations defined in Glossary. Weighted event rates, RBI, RRI, NNH, and CI calculated from control event rates and risk ratios in article using a fixed-effect model. NNTs are as reported in the article. †Pain intensity at administration of treatment classified as mild, or moderate or severe (mod/severe). ‡Freedom from pain without use of rescue medication. §Pain reduced from moderate or severe to none or mild without use of rescue medication.
JC8
© 2014 American College of Physicians
Downloaded From: http://annals.org/ by a University of York User on 11/21/2016
Alexander W. Chessman, MD Medical University of South Carolina Charleston, South Carolina, USA References 1. Law S, Derry S, Moore RA. Cochrane Database Syst Rev. 2013;10:CD009455. 2. Derry CJ, Derry S, Moore RA. Cochrane Database Syst Rev. 2012;2:CD008615. 3. Derry S, Moore RA. Cochrane Database Syst Rev. 2013; 4:CD008040. 4. Rabbie R, Derry S, Moore RA. Cochrane Database Syst Rev. 2013;4:CD008039. 5. Derry S, Rabbie R, Moore RA. Cochrane Database Syst Rev. 2013;4:CD008783. 6. Kirthi V, Derry S, Moore RA. Cochrane Database Syst Rev. 2013;4:CD008041.
18 February 2014 | ACP Journal Club | Volume 160 • Number 4
