Knee Surgery, Sports Traumatology, Arthroscopy

, Volume 23, Issue 8, pp 2390–2399 | Cite as

Non-steroidal anti-inflammatory drugs (NSAIDs) for treating acute ankle sprains in adults: benefits outweigh adverse events

  • Michel P. J. van den BekeromEmail author
  • Arnout Sjer
  • Matthijs P. Somford
  • Gythe H. Bulstra
  • Peter A. A. Struijs
  • Gino M. M. J. Kerkhoffs



In the recent clinical guideline for acute lateral ankle sprain, the current best evidence for diagnosis, treatment and prevention strategies was evaluated. Key findings for treatment included the use of ice and compression in the initial phase of treatment, in combination with rest and elevation. A short period of taking non-steroidal anti-inflammatory drugs (NSAIDs) may facilitate a rapid decrease in pain and swelling can also be helpful in the acute phase. The objective was to assess the effectiveness and safety of oral and topical NSAID in the treatment for acute ankle sprains.


Randomised controlled trials comparing oral or topic NSAID treatment with placebo or each other were included. Primary outcome measures were pain at rest or at mobilisation and adverse events. Trials were assessed using the Cochrane risk of bias tool.


Twenty-eight studies were included, and 22 were available for meta-analysis. Superior results were reported for oral NSAIDs when compared with placebo, concerning pain on weight bearing on short term, pain at rest on the short term, and less swelling on short- and intermediate term. For topical NSAIDs, superior results compared with placebo were found for pain at rest (short term), persistent pain (intermediate term), pain on weight bearing (short- and intermediate term) and for swelling (short and intermediate term). No trials were included comparing oral with topic NSAIDs, so conclusions regarding this comparison are not realistic.


The current evidence is limited due to the low number of studies, lack of methodological quality of the included studies as well as the small sample size of the included studies. Nevertheless, the findings from this review support the use of NSAIDs for the initial treatment for acute ankle sprains.

Level of evidence

Meta-analysis of RCTs, Level I.


Ankle sprain NSAID Injury Efficacy Adverse events Systematic review 


  1. 1.
    Almekinders LC, Baynes AJ, Bracey LW (1995) An in vitro investigation into the effects of repetitive motion and nonsteroidal antiinflammatory medication on human tendon fibroblasts. Am J Sports Med 23:119–123PubMedCrossRefGoogle Scholar
  2. 2.
    Andersson S, Fredin H, Lindberg H, Sanzén L, Westlin N (1983) Ibuprofen and compression bandage in the treatment of ankle sprains. Acta Orthop Scand 54:322–325 PubMedCrossRefGoogle Scholar
  3. 3.
    Ascherl R, Schlemmer H, Blümel G, Lechner F (1982) The effectiveness of etofenamate in minor sports injuries of the knee and ankle joint. A double-blind study. Fortschr Med 100:1729–1734PubMedGoogle Scholar
  4. 4.
    Bahamonde LA, Saavedra H (1990) Comparison of the analgesic and anti-inflammatory effects of diclofenac potassium versus piroxicam versus placebo in ankle sprain patients. J Int Med Res 18:104–111PubMedGoogle Scholar
  5. 5.
    Billigmann P (1996) Treatment of ankle sprains with ibuprofen microgel. Therapiewoche 21:1187–1192Google Scholar
  6. 6.
    Billigmann P, Vogtle-Junkert U (1993) Results from a placebo-controlled double-blind study with ibuprofen 600 mg tablets. Injuries of the upper ankle joint. Ther Osterr 8:227–230Google Scholar
  7. 7.
    Campbell J, Dunn T (1994) Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains. J Accid Emerg Med 11:178–182PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Costantino C, Kwarecki J, Samokhin AV, Mautone G, Rovati S (2011) Diclofenac epolamine plus heparin plaster versus diclofenac epolamine plaster in mild to moderate ankle sprain: a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase III trial. Clin Drug Investig 31:15–26PubMedCrossRefGoogle Scholar
  9. 9.
    Coudreuse J-M, de Vathaire F (2010) Effect of a plaster containing DHEP and heparin in acute ankle sprains with oedema: a randomized, double-blind, placebo-controlled, clinical study. Curr Med Res Opin 26:2221–2228PubMedCrossRefGoogle Scholar
  10. 10.
    De Nies F, Lagrand WK, Patka P (1989) The effect of flurbiprofen in acute ankle distortions. Ned Tijdschr Geneeskd 133:449–451PubMedGoogle Scholar
  11. 11.
    Diebschlag W (1986) Volumetric monitoring of swollen ankle. Joints treated with diclofenac emulgel. Fortschr Med 104:437–451PubMedGoogle Scholar
  12. 12.
    Diebschlag W, Nocker W, Bullingham R (1990) A double-blind study of the efficacy of topical ketorolac tromethamine gel in the treatment of ankle sprain, in comparison to placebo and etofenamate. J Clin Pharmacol 30:82–89PubMedCrossRefGoogle Scholar
  13. 13.
    Dreiser RL, Riebenfeld D (1993) A double-blind study of the efficacy of nimesulide in the treatment of ankle sprain in comparison with placebo. Drugs 46(Suppl 1):183–186PubMedCrossRefGoogle Scholar
  14. 14.
    Dreiser RE, Charlot J, Lopez A, Ditisheim A (1990) Clinical evaluation of niflumic acid gel in the treatment of uncomplicated ankle sprains. Curr Med Res Opin 12:93–99PubMedCrossRefGoogle Scholar
  15. 15.
    Dreiser RL, Roche R, De Sahb R, Thomas F, Leutenegger E (1994) Flurbiprofen local action transcutaneous (LAT): clinical evaluation in the treatment of acute ankle sprains. Eur J Rheumatol Inflamm 14:9–13PubMedGoogle Scholar
  16. 16.
    Dupont M, Béliveau P, Thériault G (1987) The efficacy of antiinflammatory medication in the treatment of the acutely sprained ankle. Am J Sports Med 15:41–45PubMedCrossRefGoogle Scholar
  17. 17.
    Ekman EF, Fiechtner JJ, Levy S, Fort JG (2002) Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain. Am J Orthop (Belle Mead NJ) 31:445–451Google Scholar
  18. 18.
    Ekman EF, Ruoff G, Kuehl K, Ralph L, Hormbrey P, Fiechtner J, Berger MF (2006) The COX-2 specific inhibitor Valdecoxib versus tramadol in acute ankle sprain: a multicenter randomized, controlled trial. Am J Sports Med 34:945–955PubMedCrossRefGoogle Scholar
  19. 19.
    Elswood R, MacLeod DA (1985) Treatment of ankle sprains with benzydamine. Practitioner 229:70–71PubMedGoogle Scholar
  20. 20.
    Ferry ST, Dahners LE, Afshari HM, Weinhold PS (2007) The effects of common anti-inflammatory drugs on the healing rat patellar tendon. Am J Sports Med 35:1326–1333PubMedCrossRefGoogle Scholar
  21. 21.
    Fredberg U, Hansen PA, Skinhøj A (1989) Ibuprofen in the treatment of acute ankle joint injuries. A double-blind study. Am J Sports Med 17:564–566PubMedCrossRefGoogle Scholar
  22. 22.
    Goldie IF, Gunterberg B, Jacobson C (1974) Foot volumetry as an objective test of the effect of antiphlogistic drugs in ankle sprains. A preliminary study. Rheumatol Rehabil 13:204–207PubMedCrossRefGoogle Scholar
  23. 23.
    Higgins J, Green S (Eds) (2008) Cochrane Handbook for systematic reviews of interventions version 5.0.2. The Cochrane CollaborationGoogle Scholar
  24. 24.
    Jones P, Lamdin R (2010) Oral cyclo-oxygenase 2 inhibitors versus other oral analgesics for acute soft tissue injury: systematic review and meta-analysis. Clin Drug Investig 30:419–437PubMedCrossRefGoogle Scholar
  25. 25.
    Joussellin E (2003) Flector Tissugel in the treatment of painful ankle sprains [Flector Tissugel dans le traitement des entorses douloureuses de la cheville]. J Traumatol Sport 20:15–19Google Scholar
  26. 26.
    Kerkhoffs GMMJ, Tol JL (2012) A twist on the athlete’s ankle twist: some ankles are more equal than others. Br J Sports Med 46:835–836PubMedCrossRefGoogle Scholar
  27. 27.
    Kerkhoffs GMMJ, Rowe BH, Assendelft WJJ, Kelly K, Struijs PAA, van Dijk CN (2002) Immobilisation and functional treatment for acute lateral ankle ligament injuries in adults. Cochrane database Syst Rev (3):CD003762Google Scholar
  28. 28.
    Kerkhoffs GMMJ, Struijs PAA, Marti RK, Assendelft WJJ, Blankevoort L, van Dijk CN (2002) Different functional treatment strategies for acute lateral ankle ligament injuries in adults. Cochrane Database Syst Rev (3):CD002938Google Scholar
  29. 29.
    Kerkhoffs GM, van den Bekerom M, Elders LAM, van Beek PA, Hullegie WAM, Bloemers GMFM, de Heus EM, Loogman MCM, Rosenbrand KCJGM, Kuipers T, Hoogstraten JWAP, Dekker R, Ten Duis H-J, van Dijk CN, van Tulder MW, van der Wees PJ, de Bie RA (2012) Diagnosis, treatment and prevention of ankle sprains: an evidence-based clinical guideline. Br J Sports Med 46:854–860PubMedCrossRefGoogle Scholar
  30. 30.
    Lester AA (1981) Management of sprained ankles. A double-blind study. Practitioner 225:935–936PubMedGoogle Scholar
  31. 31.
    Lin C-WC, Uegaki K, Coupé VMH, Kerkhoffs GM, van Tulder MW (2013) Economic evaluations of diagnostic tests, treatment and prevention for lateral ankle sprains: a systematic review. Br J Sports Med 47(18):1144–1149Google Scholar
  32. 32.
    Linde F, Hvass I, Jürgensen U, Madsen F (1985) Treatment of sprained ankles with 5 % benzydamine creme. A double-blind study. Ugeskr Laeger 148:12–13PubMedGoogle Scholar
  33. 33.
    Lionberger DR, Joussellin E, Lanzarotti A, Yanchick J, Magelli M (2011) Diclofenac epolamine topical patch relieves pain associated with ankle sprain. J Pain Res 4:47–53PubMedCentralPubMedGoogle Scholar
  34. 34.
    Lopez Vera H (1984) Valoracion de ketoprofen sodico versus placebo en el tratamiento del esguince de tobillo. Investig Med Int 11:102–104Google Scholar
  35. 35.
    Mazières B, Rouanet S, Velicy J, Scarsi C, Reiner V (2005) Topical ketoprofen patch (100 mg) for the treatment of ankle sprain: a randomized, double-blind, placebo-controlled study. Am J Sports Med 33:515–523PubMedCrossRefGoogle Scholar
  36. 36.
    McLatchie GR, Allister C, MacEwen C, Hamilton G, McGregor H, Colquhuon I, Pickvance NJ (1985) Variable schedules of ibuprofen for ankle sprains. Br J Sports Med 19:203–206PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Morán M (1990) An observer-blind comparison of diclofenac potassium, piroxicam and placebo in the treatment of ankle sprains. Curr Med Res Opin 12:268–274PubMedCrossRefGoogle Scholar
  38. 38.
    Morán M (1991) Double-blind comparison of diclofenac potassium, ibuprofen and placebo in the treatment of ankle sprains. J Int Med Res 19:121–130PubMedGoogle Scholar
  39. 39.
    Oakland C, Rapier C (1993) A comparison of the efficacy of thetopical NSAID felbinac and ultrasound in the treatment of acute ankle injuries. British J Clin Res 4:89–96Google Scholar
  40. 40.
    Oian P, Kleive I, Lereim P (1981) [Indomethacin in acute ankle torsion]. Tidsskr. den Nor. lægeforening Tidsskr Prakt Med ny række 101:91–2Google Scholar
  41. 41.
    Predel H-G, Hamelsky S, Gold M, Giannetti B (2012) Efficacy and safety of diclofenac diethylamine 2.32 % gel in acute ankle sprain. Med Sci Sports Exerc 44:1629–1636PubMedCrossRefGoogle Scholar
  42. 42.
    Schmidt M, Pedersen L, Maeng M, Lassen JF, Lash TL, Nielsen TT, Sørensen HT (2011) Nonsteroidal antiinflammatory drug use and cardiovascular risks after coronary stent implantation. Pharmacotherapy 31:458–468PubMedCrossRefGoogle Scholar
  43. 43.
    Slatyer MA, Hensley MJ, Lopert R (1997) A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study. Am J Sports Med 25:544–553PubMedCrossRefGoogle Scholar
  44. 44.
    van den Bekerom MPJ, Kerkhoffs GMMJ, McCollum GA, Calder JDF, van Dijk CN (2013) Management of acute lateral ankle ligament injury in the athlete. Knee Surg Sports Traumatol Arthrosc 21:1390–1395PubMedCrossRefGoogle Scholar
  45. 45.
    Viljakka T, Rokkanen P (1983) The treatment of ankle sprain by bandaging and antiphlogistic drugs. Ann Chir Gynaecol 72:66–70PubMedGoogle Scholar
  46. 46.
    Slimmon D, Brukner P (2010) Sports ankle injuries—assessment and management. Aust Fam Physician 39:18–22Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Michel P. J. van den Bekerom
    • 1
    Email author
  • Arnout Sjer
    • 2
  • Matthijs P. Somford
    • 3
  • Gythe H. Bulstra
    • 1
  • Peter A. A. Struijs
    • 4
  • Gino M. M. J. Kerkhoffs
    • 4
  1. 1.OLVGAmsterdamThe Netherlands
  2. 2.MCAAlkmaarThe Netherlands
  3. 3.Amphia hospitalBredaThe Netherlands
  4. 4.AMCAmsterdamThe Netherlands

Personalised recommendations