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Agentes antiinflamatorios no esteroides para el resfriado común

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Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

Goto 2007 {published data only}

Goto M, Kawamura T, Shimbo T, Takahashi O, Ando M, Miyaki K, et al. Influence of loxoprofen use on recovery from naturally acquired upper respiratory tract infections: a randomized controlled trial. Internal Medicine 2006;46(15):1179‐86.

Graham 1990 {published data only}

Graham NM, Burrell CJ, Douglas RM, Debelle P, Davies L. Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus‐infected volunteers. Journal of Infectious Diseases 1990;162(6):1277‐82.

Itoh 1980 {published data only}

Itoh K, Nagaoka S, Hamada A, Noguchi E, Suzuki H, Taniai T, et al. A double‐blind clinical study of ketoprofen on acute upper respiratory infection ‐ comparison with aspirin. Clinical Evaluation 1980;8(2):457‐79.

Katsu 1993 {published data only}

Katsu M, Oishi A, Nakamura H, Matsuoka Y, Irimajiri S, Kobayashi H, et al. Clinical evaluation of loxoprofen sodium (CS‐600E) on upper respiratory tract inflammation: a double blind controlled study in comparison with ibuprofen. Journal of Clinical Therapeutics and Medicines 1993;9(10):2299‐320.

Nagaoka 1980 {published data only}

Nagaoka S, Nagahama F, Kunno K, Haga T, Ito K, Ito F, et al. Therapeutic effects of fentiazac on common cold ‐ a double‐blind clinical study. Clinical Evaluation 1980;8(3):757‐88.

Ryan 1987 {published data only}

Ryan PB, Rush DR, Nicholas TA, Graham DG. A double‐blind comparison of fenoprofen calcium, acetaminophen, and placebo in the palliative treatment of common nonbacterial upper respiratory infections. Current Therapeutic Research, Clinical and Experimental 1987;41(1):17‐23.

Sperber 1989 {published data only}

Sperber SJ, Sorrentino JV, Riker DK, Hayden FG. Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds. Bulletin of the New York Academy of Medicine 1989;65(1):145‐60.

Sperber 1992 {published data only}

Sperber SJ, Hendley JO, Hayden FG, Riker DK, Sorrentino JV, Gwaltney JM. Effects of naproxen on experimental rhinovirus colds. A randomized, double‐blind, controlled trial. Annals of Internal Medicine 1992;117(1):37‐41.

Winther 2001 {published data only}

Winther B, Mygind N. The therapeutic effectiveness of ibuprofen on the symptoms of naturally acquired common colds. American Journal of Rhinology 2001;15(4):239‐42.

Referencias de los estudios excluidos de esta revisión

Ir a:

Aggarwal 1997 {published data only}

Aggarwal P, Ambrose C, Kumar M, Bhavani V, Bose E, Bose S, et al. Piroxicam versus ibuprofen as adjuncts to antibiotic therapy for symptomatic relief in upper respiratory infections: a perspective, randomized, comparative, multicentre study. Indian Practitioner 1997;50(11):939‐47.

Azuma 2010 {published data only}

Azuma A, Kudoh S, Nakashima M, Nagatake T. A double‐blind study of zaltoprofen for the treatment of upper respiratory tract infection. Pharmacology 2010;85(1):41‐7.

Azuma 2011 {published data only}

Azuma A, Kudoh S, Nakashima M, Nagatake T. Antipyretic and analgesic effects of zaltoprofen for the treatment of acute upper respiratory tract infection: verification of a non‐inferiority hypothesis using loxoprofen sodium. Pharmacology 2011;87(3‐4):204‐13.

Bachert 2005 {published data only}

Bachert C, Chuchalin AG, Eisebitt R, Netayzhenko VZ, Voelker M. Aspirin compared with acetaminophen in the treatment of fever and other symptoms of upper respiratory tract infection in adults; a multicenter, randomized, double‐blind, double‐dummy, placebo‐controlled, parallel‐group, single‐dose, 6‐hour dose‐ranging study. Clinical Therapeutics 2005;27(7):993‐1003.

Banchini 1993 {published data only}

Banchini G, Scaricabarozzi I, Montecorboli U, Ceccarelli A, Chiesa F, Ditri L, et al. Double‐blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat. Drugs 1993;46(Suppl 1):100‐2.

Batista 1985 {published data only}

Batista NA, Zago MC, Schincarioli SM, Nader MC, Almeida J. Clinical evaluation of diclofenac resinate drops, associated to antibiotics, in the treatment of upper respiratory tract infections. Comparative study in pediatrics. Arquivos Brasileiros de Medicina 1985;59(6):479‐84.

Bellussi 1993 {published data only}

Bellussi L, Passali D. Treatment of upper airways inflammation with nimesulide. Drugs 1993;46(Suppl 1):107‐10.

Bellussi 1996 {published data only}

Bellussi L, Biagini C, Calearo C, Cenacchi V, De Campora E, Di Girolamo A, et al. Antiphlogistic therapy with ketoprofen lysine salt vs nimesulide in secretive otitis media, rhinitis/rhinosinusitis, pharyngitis/tonsillitis/tracheitis. Otorinolaringologia 1996;46(1):49‐57.

Benrimoj 2001 {published data only}

Benrimoj SI, Langford JH, Christian J, Charlesworth A, Steans A. Efficacy and tolerability of the anti‐inflammatory throat lozenge flurbiprofen 8.75mg in the treatment of sore throat: a randomised, double‐blind, placebo‐controlled study. Clinical Drug Investigation 2001;21(3):183‐93.

Bernstein 1974 {published data only}

Bernstein JE, Nelson FK. A double blind evaluation of an aspirin containing gum tablet for relief of the pain of common sore throat. Journal of International Medical Research 1974;2(1):76‐80.

Blagden 2002 {published data only}

Blagden M, Christian J, Miller K, Charlesworth A. Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double‐blind, placebo‐controlled study in UK general practice centres. International Journal of Clinical Practice 2002;56(2):95‐100.

Bonifaci 1977 {published data only}

Bonifaci E, Giorgi CM, Vibelli C. Symptomatic management of acute inflammation of the upper airways in paediatric patients. Minerva Pediatrica 1977;29(5):285‐96.

Cappella 1993 {published data only}

Cappella L, Guerra A, Laudizi L, Cavazzuti GB. Efficacy and tolerability of nimesulide and lysine‐acetylsalicylate in the treatment of paediatric acute upper respiratory tract inflammation. Drugs 1993;46(Suppl 1):222‐5.

Chachtel 2011 {published data only}

Chachtel BP, McCabe D, Berger M, Zhang R, Sanner KM, Savino L, et al. Efficacy of low‐dose celecoxib in patients with acute pain. Journal of Pain 2011;12(7):756.

Ebel 1985 {published data only}

Ebel DL, Shih WJ, Rhymer AR. A multi‐centre, double‐blind randomized study to assess the efficacy and tolerance of sulindac versus placebo in the symptomatic treatment of patients with upper respiratory tract infection. Current Medical Research and Opinion 1985;9(10):666‐75.

Eccles 2003 {published data only}

Eccles R, Loose I, Jawad M, Nyman L. Effects of acetylsalicylic acid on sore throat pain and other pain symptoms associated with acute upper respiratory tract infection. Pain Medicine 2003;4(2):118‐24.

Fujimori 1982 {published data only}

Fujimori I, Kono M, Takeda Y, Sekita K, Katsu M, Adachi M, et al. Clinical evaluation of Clinoril tablets in acute upper respiratory tract infections. Kansenshogaku Zasshi 1982;56(12):1186‐95.

Fujimori 1983 {published data only}

Fujimori I, Kono M, Sekita T, Takeda Y, Ogihara K, Nakagawa H, et al. A double‐blind clinical evaluation of suprofen on acute upper respiratory infection. Comparison with aspirin. Kansenshogaku Zasshi 1983;57(1):62‐81.

Gehanno 2003 {published data only}

Gehanno P, Dreiser RL, Ionescu E, Gold M, Liu JM. Lowest effective single dose of diclofenac for antipyretic and analgesic effects in acute febrile sore throat. Clinical Drug Investigation 2003;23(4):263‐71.

Gruber 1977 {published data only}

Gruber CM, Collins T. Dose response to fenoprofen in an antipyretic study of fenoprofen and propoxyphene. Journal of Medicine 1977;8(1):27‐34.

Kandoth 1984 {published data only}

Kandoth PW, Joshi MK, Joshi VR, Satoskar RS. Comparative evaluation of antipyretic activity of ibuprofen and aspirin in children with pyrexia of varied aetiology. Journal of International Medical Research 1984;12(5):292‐7.

Katsu 1977 {published data only}

Katsu M, Mashita H, Fujimori I, Shimada S, Fujii T. Therapeutic effects of fenbufen in common cold: multi‐clinic double‐blind study. Kansenshogaku Zasshi 1977;51(4):184‐96.

Katsu 1978 {published data only}

Katsu M, Fujii T, Fujimori I, Katayama T, Harada K, Koizumi H, et al. Therapeutic utility of naproxen on acute upper respiratory infection: multi‐clinical double‐blind study. Kansenshogaku Zasshi 1978;52(5):148‐63.

Katsu 1982 {published data only}

Katsu M, Hayakawa M, Kawai M, Fujimori I, Kohno M, Takeda Y, et al. Double blind controlled study of miroprofen in acute upper respiratory tract infections ‐ comparison with ibuprofen. Kansenshogaku Zasshi 1982;56(5):434‐53.

Katsu 1983 {published data only}

Katsu M, Adachi M, Hayakawa M, Fujimori I, Kohno M, Takeda Y, et al. Clinical evaluation of sulindac (CLINORIL) in the treatment of acute upper respiratory tract infection: double‐blind comparison with ibuprofen. Kansenshogaku Zasshi 1983;57(3):260‐72.

Kierszenbaum 1991 {published data only}

Kierszenbaum J, Vitral BG, Kierszenbaum AML, De Sousa PR. Evaluation of nimesulid oral suspension versus diclofenac resinate in upper respiratory tract infections in the pediatrics. Pediatria Moderna 1991;27(7):560‐2.

Lopes 1991 {published data only}

Lopes FO. Amoxicillin versus amoxicillin + nimesulide in otolaryngologic infections ‐ a randomized study. Folha Medica 1991;102(3):81‐5.

Martinez Gallardo 1994 {published data only}

Martinez Gallardo F, Lopez Fiesco A, Zamora G. Symptomatic treatment of common cold in children with a new combination of naproxen sodium plus pseudoephedrine hydrochloride: a comparative trial against pseudoephedrine syrup. Proceedings of the Western Pharmacology Society 1994;37:157‐8.

Matsumoto 1984 {published data only}

Matsumoto K, Fujimori I, Tsubura E, Sakuma A, Hayashi M, Kudo K, et al. Clinical evaluation of oxaprozin in the treatment of acute upper respiratory tract inflammations: a double‐blind comparative study using ibuprofen as the control drug. Kansenshogaku Zasshi 1984;58(7):628‐46.

Moore 2002 {published data only}

Moore N, Le Parc JM, Van Ganse E, Wall R, Schneid H, Cairns R. Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and flu symptoms and sore throat pain. International Journal of Clinical Practice 2002;56(10):732‐4.

Nagaoka 1985 {published data only}

Nagaoka S, Fumio N, Ohito O,  Hideyo N, Morise M, Osamu T, et al. Clinical effect of floctafenine in acute upper respiratory infection: a double blind test in comparison with aspirin. Japanese Pharmacology and Therapeutics 1985;13(2):981‐1010.

Nagaoka 1986a {published data only}

Nagaoka S, Hiraga H, Ohito O, Hideyo N,  Suetsugu S, Osamu T, et al. Clinical effect of emorfazone in acute upper respiratory infection: a double‐blind test in comparison with aspirin. Japanese Pharmacology and Therapeutics 1986;14(9):5883‐900.

Nagaoka 1986b {published data only}

Nagaoka S, Nakamura S, Umehara Y, Nagahama F, Okayasu M, Noguchi E, et al. Clinical evaluation of tolfenamic acid on acute upper respiratory tract inflammation: multi‐center double‐blind study with ibuprofen. Journal of Clinical Therapeutics and Medicines 1986;2(2):221‐50.

Nouri 1984 {published data only}

Nouri ME. Nimesulide for treatment of acute inflammation of the upper respiratory tract. Clinical Therapeutics 1984;6(2):142‐50.

Nouri 1993 {published data only}

Nouri E, Monti T. Nimesulide granules for the treatment of acute inflammation of the ear, nose or throat. Drugs 1993;46(Suppl 1):103‐6.

Pagella 2001 {published data only}

Pagella F, Rossi V, Zanoletti E, Benazzo M, Mira E. Efficacy and tolerability of a mouthwash based on diclofenac in the treatment of disorders of the upper respiratory tract. Double blind study versus flurbiprofen mouthwash. Otorinolaringologia 2001;51(2):77‐81.

Passali 1989 {published data only}

Passali D, Bellussi L, Ciferri G, Scaricabarozzi I. Use of nimesulide in inflammations of the upper respiratory tract. Clinica Terapeutica 1989;128(2):105‐11.

Passali 1997 {published data only}

Passali D, Gorga A, Ferri R, Bellussi L. Controlled clinical study on the efficacy and tolerability of methoxibutropate versus nimesulide in otorhinolaryngology. Otorinolaringologia 1997;47(3):145‐50.

Reiner 1983 {published data only}

Reiner M. Nimesulide and antibiotics in the treatment of acute infections of the respiratory tract. Current Medical Research and Opinion 1983;8(7):487‐92.

Ruperto 2011 {published data only}

Ruperto N, Carozzino L, Jamone R, Freschi F, Picollo G, Zera M, et al. A randomized, double‐blind, placebo‐controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians. Italian Journal of Pediatrics 2011;37:1.

Russo 2013 {published data only}

Russo M, Bloch M, Looze FD, Morris C, Shephard A. Flurbiprofen microgranules for relief of sore throat: a randomised, double‐blind trial. British Journal of General Practice 2013;63:607.

Salmon 1993 {published data only}

Salmon Rodriguez LE, Arista Viveros HA, Lopez E, Trujillo C, Maciel R, Lujan M. Evaluation of the efficacy and safety of nimesulide and naproxen in the symptomatic treatment of upper respiratory tract infections in children. A comparative blind study. Investigacion Medica Internacional 1993;20(2):43‐54.

Salzberg 1993 {published data only}

Salzberg R, Giambonini S, Maurizio M, Roulet D, Zahn J, Monti T. A double‐blind comparison of nimesulide and mefenamic acid in the treatment of acute upper respiratory tract infections in children. Drugs 1993;46(Suppl 1):208‐11.

Sanchez 1999 {published data only}

Sanchez Gonzalez A, Gonzalez Galindo T, Santana Hurtado O. Efficacy and safety assessment of tolmetin sodium (400 mg tid) vs naproxen sodium (275 mg tid) for the treatment of acute upper respiratory tract infection symptoms. Investigacion Medica Internacional 1999;26(1):3‐8.

Schachtel 1993 {published data only}

Schachtel BP, Thoden WR. A placebo‐controlled model for assaying systemic analgesics in children. Clinical Pharmacology and Therapeutics 1993;53(5):593‐601.

Schachtel 2002 {published data only}

Schachtel BP, Homan HD, Gibb IA, Christian J. Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Clinical Pharmacology and Therapeutics 2002;71(5):375‐80.

Stanley 1975 {published data only}

Stanley ED, Jackson GG, Panusarn C, Rubenis M, Dirda V. Increased virus shedding with aspirin treatment of rhinovirus infection. JAMA 1975;231(12):1248‐51.

Tamura 1984 {published data only}

Tamura M, Ito T, Sudo M, Tazawa M, Sayama T, Yoshida M, et al. A double‐blind clinical evaluation of flurbiprofen on acute upper respiratory tract inflammation‐comparative study with ibuprofen. Kansenshogaku Zasshi 1984;58(12):1289‐303.

Ulukol 1999 {published data only}

Ulukol B, Koksal Y, Cin S. Assessment of the efficacy and safety of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections. European Journal of Clinical Pharmacology 1999;55(9):615‐8.

Vauzelle 1996 {published data only}

Vauzelle‐Kervroedan F, Revzani Y, Pons G, Consten L, Pariente‐Khayat A, D'Athis P, et al. Antipyretic efficacy of tiaprofenic acid in febrile children. Fundamental Clinical Pharmacology 1996;10(1):56‐9.

Watson 2000 {published data only}

Watson N, Nimmo WS, Christian J, Charlesworth A, Speight J, Miller K. Relief of sore throat with the anti‐inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double‐blind, placebo‐controlled study of efficacy and safety. International Journal of Clinical Practice 2000;54(8):490‐6.

AlBalawi 2013

AlBalawi ZH, Othman SS, AlFaleh K. Intranasal ipratropium bromide for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD008231.pub3]

De Sutter 2012

De Sutter A, Van Driel M, Kenyon L. Oral antihistamine‐decongestant‐analgesic combinations for the common cold. Cochrane Database of Systematic Reviews 2012, Issue 2. [DOI: 10.1002/14651858.CD004976.pub2]

Eccles 2005

Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infectious Diseases 2005;5(11):718‐25.

Gwaltney 2002

Gwaltney JM. Viral respiratory infection therapy: historical perspectives and current trials. American Journal of Medicine 2002;112(Suppl 6A):33‐41.

Heikkinen 2003

Heikkinen T, Jarvinen A. The common cold. Lancet 2003;361(9351):51‐9.

Hernández‐Díaz 2000

Hernández‐Díaz S, Rodriguez LA. Association between nonsteroidal anti‐inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Archives of Internal Medicine 2000;160(14):2093‐9.

Higgins 2011

Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Irwin 2000

Irwin RS, Madison JM. The diagnosis and treatment of cough. New England Journal of Medicine 2000;343(23):1715‐21.

Lefebvre 2011

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Li 2013

Li S, Yue J, Dong BR, Yang M, Lin X, Wu T. Acetaminophen (paracetamol) for the common cold in adults. Cochrane Database of Systematic Reviews 2013, Issue 7. [DOI: 10.1002/14651858.CD008800.pub2]

Matchaba 2004

Matchaba P, Gitton X, Krammer G, Ehrsam E, Sloan VS, Olson M, et al. Risk of cardiovascular events and rofecoxib: cumulative meta‐analysis. Lancet 2004;364(9450):2021‐9.

Ofman 2002

Ofman JJ, MacLean CH, Straus WL, Morton SC, Berger ML, Roth EA, et al. A meta‐analysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. Journal of Rheumatology 2002;29(4):804‐12.

Ostberg 1997

Ostberg B, Winther B, Borum P, Mygind N. Common cold and high‐dose ipratropium bromide: use of anticholinergic medication as an indicator of reflex‐mediated hypersecretion. Rhinology 1997;35(2):58‐62.

Pratter 2006

Pratter MR. Cough and the common cold: ACCP evidence‐based clinical practice guidelines. Chest 2006;129(Suppl 1):72‐4.

Saraswat 2011

Saraswat A, van Driel ML, De Sutter AIM. Antihistamines for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 10. [DOI: 10.1002/14651858.CD009345]

Smith 2014

Smith SM, Schroeder K, Fahey T. Over‐the‐counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database of Systematic Reviews 2014, Issue 11. [DOI: 10.1002/14651858.CD001831.pub5]

Ta'i 2012

Ta'i SH, Ferguson KAM, Singh HK, Sharma AN, Kumar S, van Driel ML, et al. Nasal decongestants for the common cold. Cochrane Database of Systematic Reviews 2012, Issue 2. [DOI: 10.1002/14651858.CD009612]

Referencias de otras versiones publicadas de esta revisión

Ir a:

Kim 2007

Kim SY, Chang YJ, Cho HM, Hwang YW, Moon YS. Non‐steroidal anti‐inflammatory drugs for the common cold. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD006362]

Kim 2009

Kim Sy, Chang Y‐J, Cho HM, Hwang Y‐w, Moon YS. Non‐steroidal anti‐inflammatory drugs for the common cold. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD006362.pub2]

Kim 2011

Kim Sy, Chang Y‐J, Cho HM, Hwang Y‐w, Moon YS. Non‐steroidal anti‐inflammatory drugs for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 10. [DOI: 10.1002/14651858.CD006362.pub2]

Kim 2013

Kim SY, Chang YJ, Cho HM, Hwang YW, Moon YS. Non‐steroidal anti‐inflammatory drugs for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD006362.pub3]

Characteristics of studies

Characteristics of included studies [author‐defined order]

Ir a:

Graham 1990

Methods

Double‐blind, placebo‐controlled, experimental colds

Participants

59 inoculated; 42 colds. Mean age 20.1 years, 43.3% women, university students

Interventions

2 groups: aspirin 4 g/day and ibuprofen 1.2 g/day for 7 days

Outcomes

The proportion of nasal obstruction score > 5 in the aspirin group (6/15) significantly differed from that in the placebo group (0/14, P value < 0.05)
Mean mucus weight, mean tissue count, mean overall symptom score and mean overall side effect score were reported but any other statistical parameters such as SD, SE, 95% CI and P value for each group or the difference between these groups were not reported

Notes

—

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"... a randomised double‐blind, placebo‐controlled clinical trial"

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes

Low risk

"... identical capsules containing aspirin (500 mg), ibuprofen (200 mg) or placebo"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"... 4 volunteers who were considered uninfected and were excluded from further analyses"

Comment: probably done

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Goto 2007

Methods

Double‐blind, placebo‐controlled, natural colds

Participants

174 adults, age 18 to 65 years, 35% women, 23 outpatients facilities, URTI onset 2 days or less

Interventions

Loxoprofen 60 mg 2 times for 7 days

Outcomes

Duration of illness; the number of days with limited daily activities was not significantly different between groups

Notes

The primary outcome was duration of illness in days

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomisation was based on simple computer‐generated random digits"

Comment: probably done

Allocation concealment (selection bias)

Low risk

"... self‐drawing a sealed opaque envelope in the physician's sight....the correspondence between the digits and the group assignment was held in the central, secured location by a third party independent of the investigators until data collection was completed. Thus, allocation was concealed and masked from both patients and physicians"

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

"A double‐blind, randomised, placebo‐controlled trial"; "those in the control group were to take a placebo which was quite similar to active loxoprofen in shape and taste"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"... six (two in loxoprofen group and four in placebo group) withdrew from the study, because two patients (one in loxoprofen and another in placebo) did not complete the diary; three patients (one in loxoprofen and the others in placebo) did not return the diary; and one patient (placebo) decided not to continue the study after the allocation. We excluded nine more participants (two in loxoprofen and seven in placebo) from analyses"

Comment: probably done (missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups)

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Itoh 1980

Methods

Double‐blind, head‐to‐head comparison, natural colds

Participants

184 adults, mean age, sex not reported for the subgroup of colds, 29 centres, outpatient departments of hospitals and clinics, URTI onset ≤ 3 days

Interventions

2 groups: ketoprofen 50 mg 3 times and aspirin 500 mg 3 times for 3 days

Outcomes

No significant difference in FGIR between 2 groups

Notes

No available data on adverse effects for the subgroup of common colds

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)

Low risk

"... randomisation process was done by two controllers and key codes were kept by controllers (in Japanese)"

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

"... double‐blind method...active drug capsule and aspirin capsule were quite similar in shape (in Japanese)"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"91/93 cases in ketoprofen group and 89/91 cases in aspirin group were finally analyzed"

Number of withdrawals was too small to make any important difference to the estimated intervention effect

Comment: probably done

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Katsu 1993

Methods

Double‐blind, double‐dummy, head‐to‐head comparison, natural colds

Participants

167 adults, mean age, sex not reported for the subgroup of colds, 32 centres, outpatient departments of hospitals and clinics, moderate to severe URTI, not requiring antibiotics

Interventions

2 groups: loxoprofen 180 mg/day and ibuprofen 600 mg for 3 days

Outcomes

No significant difference in FGIR between 2 groups

Notes

No available data on adverse effects for the subgroup of common colds

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"... were randomly assigned to receive"

Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)

Unclear risk

Comment: insufficient information about the allocation concealment

Blinding (performance bias and detection bias)
All outcomes

Low risk

"... double‐blind, double‐dummy method...active drug and placebo were quite similar in shape (in Japanese)"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

"112/130 of the CS‐600 group and 113/132 group were evaluated in the assessment improvement ratings"

Comment: there are no reasons for missing participants. Insufficient reporting of attrition/exclusions to permit judgement

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Nagaoka 1980

Methods

Double‐blind, head‐to‐head comparison, natural colds

Participants

222 adults, sex not reported for the subgroup of colds, 51 centres, outpatient departments of hospitals and clinics, URTI onset ≤ 2 days and fever ≤ 39 °C

Interventions

2 groups: fentiazac 300 mg/day and ibuprofen 600 mg/day for 3 days

Outcomes

Moderate to marked improvement of FGIR was more frequent in the fenoprofen group than the placebo (P value < 0.05)

Notes

No available data on adverse effects for the subgroup of common colds

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)

Low risk

"... randomisation process was done by two controllers and key codes were kept by controllers (in Japanese)"

Blinding (performance bias and detection bias)
All outcomes

Low risk

"... double‐blind, double‐dummy method...active drug and placebo were quite similar in shape (in Japanese)"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"243 out of 244 patients were analyzed after the elimination of 1 drop‐out case"

Comment: number of withdrawals was too small to make any important difference to the estimated intervention effect

Comment: probably done

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Ryan 1987

Methods

Double‐blind, placebo‐controlled, natural colds

Participants

64 adults, age range 18 to 60 years, 75% women, single family centre, fever ≤ 37.8 °C with moderate pain due to malaise/aches

Interventions

Fenoprofen 200 mg single dose

Outcomes

No available data on efficacy

Notes

Only 2 adverse effects (1 stomach discomfort and 1 drowsiness), both in the fenoprofen group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"... assigned to one of three treatment groups via a computer‐generated random table"

Allocation concealment (selection bias)

Low risk

"Each dose of medication was dispensed in identically appearing capsules"

Single oral dose was given

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

"Each dose of medication was dispensed in identically appearing capsules in double‐blind method"

Single oral dose was given

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants who entered the study completed treatment and were included in the assessment of effectiveness and side effects

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Sperber 1989

Methods

Double‐blind, placebo‐controlled, experimental colds

Participants

40 inoculated, 31 colds, mean age 21 years, 39.1% women, setting not reported, fever ≤ 37.7 °C

Interventions

Ibuprofen 200 mg, 2 doses for the first day and 4 doses for the subsequent 4 days

Outcomes

4‐point scale. Moderate to marked severity (2‐ to 3‐point) was reduced in the ibuprofen group (18% versus 29%) but statistical significance was not reported

Notes

Adverse effects were slightly more frequent in the ibuprofen group (6/23) than in the control group (4/23)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"... were randomly assigned to receive"

Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)

Unclear risk

Comment: insufficient information about the allocation concealment

Blinding (performance bias and detection bias)
All outcomes

Low risk

"... two identically appearing capsules"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Among 58 inoculated participants, 8 were excluded (7 not infected, 1 infected with wild type virus), 1 was withdrawn

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Sperber 1992

Methods

Double‐blind, placebo‐controlled, experimental colds

Participants

79 inoculated (first cohort 34, second cohort 24 and third cohort 21); 56 colds. Mean age 21.4 years, 52% women. Setting not reported

Interventions

For first cohort, naproxen loading dose of 400 mg followed by 200 mg 3 times daily, and for second and third cohort, naproxen loading dose of 500 mg followed by 500 mg 3 times daily for 5 days

Outcomes

5‐point symptom score. Total cumulative 5‐day score for headache was lower in the naproxen group (0.5 versus 2.5, P value < 0.001)

Notes

1 in the naproxen group and 2 in the placebo group experienced gastrointestinal complaints

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"Participants were randomly assigned to receive..."

Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)

Unclear risk

Comment: insufficient information about the allocation concealment

Blinding (performance bias and detection bias)
All outcomes

Low risk

"The study drug and placebo were supplied in identically appearing capsules"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"Among 87 volunteers completed, 79 were considered evaluable"

The reason for exclusion (infected with wild type rhinovirus, not infected, missed dose of study drug) is unlikely to be related to the outcome of the trial (symptomatic improvement of common cold symptoms)

Comment: probably done

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Low risk

The study appears to be free of other sources of bias
Winther 2001

Methods

Double‐blind, placebo‐controlled, natural colds

Participants

80 adults, mean age 30.1 years, 60% women, single centre, medical students and members of the staff at the university

Interventions

Ibuprofen 400 mg 3 times for 3 days

Outcomes

4‐point symptom score by patients. Sneezing, earache, headache, and pain in muscles and joints were significantly reduced in the ibuprofen group compared with the placebo group. Number of sneezing episodes was also reduced (21.33 ± 3.3 and 12.44 ± 1.5, P value = 0.02)

Notes

No adverse effects in either group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"... randomised study of two parallel groups"

Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)

Unclear risk

Comment: insufficient information about the allocation concealment

Blinding (performance bias and detection bias)
All outcomes

Low risk

"Coded vials with ibuprofen and placebo tablets were provided by Benzon Pharma"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"All patients who entered the study completed treatment and were included in the assessment of effectiveness and side effects"

Comment: probably done

Selective reporting (reporting bias)

Unclear risk

No protocol, no convincing text

Other bias

Unclear risk

No data on baseline imbalance

CI: confidence interval
FGIR: final global improvement rating
SD: standard deviation
SE: standard error
URTI: upper respiratory tract infection

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Aggarwal 1997

Not common cold

Azuma 2010

Not common cold

Azuma 2011

Not common cold

Bachert 2005

Febrile URTI

Banchini 1993

Not common cold

Batista 1985

Not common cold

Bellussi 1993

Not common cold

Bellussi 1996

Not common cold

Benrimoj 2001

Not common cold

Bernstein 1974

Not common cold

Blagden 2002

Not common cold

Bonifaci 1977

Not common cold

Cappella 1993

Not common cold

Chachtel 2011

Not common cold

Ebel 1985

Not common cold

Eccles 2003

Not common cold

Fujimori 1982

Not randomised

Fujimori 1983

Not common cold

Gehanno 2003

Not common cold

Gruber 1977

Not common cold

Kandoth 1984

Not common cold

Katsu 1977

Not common cold

Katsu 1978

Not common cold

Katsu 1982

Randomisation is not clear

Katsu 1983

Not common cold

Kierszenbaum 1991

Not common cold

Lopes 1991

Not common cold

Martinez Gallardo 1994

Randomisation is not clear

Matsumoto 1984

Not common cold

Moore 2002

Not common cold

Nagaoka 1985

Not common cold

Nagaoka 1986a

Not common cold

Nagaoka 1986b

Not common cold

Nouri 1984

Not common cold

Nouri 1993

Not common cold

Pagella 2001

Not common cold

Passali 1989

Not common cold

Passali 1997

Not common cold

Reiner 1983

Not common cold

Ruperto 2011

Not common cold

Russo 2013

Not common cold

Salmon 1993

Not common cold

Salzberg 1993

Not common cold

Sanchez 1999

Not common cold

Schachtel 1993

Not common cold

Schachtel 2002

Not common cold

Stanley 1975

Randomisation is not clear

Tamura 1984

Not common cold

Ulukol 1999

Not common cold

Vauzelle 1996

Not common cold

Watson 2000

Not common cold

URTI: upper respiratory tract infection

Data and analyses

Open in table viewer
Comparison 1. NSAIDs versus placebo, global effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Sum of overall symptom score (random‐effects model) Show forest plot

3

293

Std. Mean Difference (IV, Random, 95% CI)

‐0.40 [‐1.03, 0.24]
Analysis 1.1
Comparison 1 NSAIDs versus placebo, global effect, Outcome 1 Sum of overall symptom score (random‐effects model).

Comparison 1 NSAIDs versus placebo, global effect, Outcome 1 Sum of overall symptom score (random‐effects model).

2 Moderate to marked severity Show forest plot

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.18, 2.11]
Analysis 1.2
Comparison 1 NSAIDs versus placebo, global effect, Outcome 2 Moderate to marked severity.

Comparison 1 NSAIDs versus placebo, global effect, Outcome 2 Moderate to marked severity.

3 Duration of colds (random‐effects model) Show forest plot

2

214

Mean Difference (IV, Random, 95% CI)

‐0.23 [‐1.75, 1.29]
Analysis 1.3
Comparison 1 NSAIDs versus placebo, global effect, Outcome 3 Duration of colds (random‐effects model).

Comparison 1 NSAIDs versus placebo, global effect, Outcome 3 Duration of colds (random‐effects model).

4 Duration of restriction of daily activities Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

‐0.56 [‐1.24, 0.12]
Analysis 1.4
Comparison 1 NSAIDs versus placebo, global effect, Outcome 4 Duration of restriction of daily activities.

Comparison 1 NSAIDs versus placebo, global effect, Outcome 4 Duration of restriction of daily activities.

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Comparison 2. NSAIDs versus placebo, analgesic effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Throat irritation score (fixed‐effect model) Show forest plot

2

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.33, 0.30]
Analysis 2.1
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 1 Throat irritation score (fixed‐effect model).

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 1 Throat irritation score (fixed‐effect model).

2 Headache score (random‐effects model) Show forest plot

2

159

Std. Mean Difference (IV, Random, 95% CI)

‐0.65 [‐1.11, ‐0.19]
Analysis 2.2
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 2 Headache score (random‐effects model).

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 2 Headache score (random‐effects model).

3 Score of pain in muscles/joints score (fixed‐effect model) Show forest plot

2

114

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐0.77, ‐0.03]
Analysis 2.3
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 3 Score of pain in muscles/joints score (fixed‐effect model).

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 3 Score of pain in muscles/joints score (fixed‐effect model).

4 Malaise score (fixed‐effect model) Show forest plot

2

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.29 [‐0.60, 0.03]
Analysis 2.4
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 4 Malaise score (fixed‐effect model).

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 4 Malaise score (fixed‐effect model).

5 Chilliness score (random‐effects model) Show forest plot

2

159

Std. Mean Difference (IV, Random, 95% CI)

‐0.03 [‐1.12, 1.06]
Analysis 2.5
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 5 Chilliness score (random‐effects model).

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 5 Chilliness score (random‐effects model).

6 Nose irritation score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.48, 0.40]
Analysis 2.6
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 6 Nose irritation score.

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 6 Nose irritation score.

7 Score of pain on swallowing Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.51, 0.37]
Analysis 2.7
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 7 Score of pain on swallowing.

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 7 Score of pain on swallowing.

8 Eye itching score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.58, 0.30]
Analysis 2.8
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 8 Eye itching score.

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 8 Eye itching score.

9 Earache score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.59 [‐1.04, ‐0.14]
Analysis 2.9
Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 9 Earache score.

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 9 Earache score.
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Comparison 3. NSAIDs versus placebo, non‐analgesic effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cough score (random‐effects model) Show forest plot

2

159

Std. Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.66, 0.56]
Analysis 3.1
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 1 Cough score (random‐effects model).

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 1 Cough score (random‐effects model).

2 Sneezing score (fixed‐effect model) Show forest plot

2

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.44 [‐0.75, ‐0.12]
Analysis 3.2
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 2 Sneezing score (fixed‐effect model).

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 2 Sneezing score (fixed‐effect model).

3 Total number of sneezes Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.51 [‐0.95, ‐0.06]
Analysis 3.3
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 3 Total number of sneezes.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 3 Total number of sneezes.

4 Rhinorrhoea score (fixed‐effect model) Show forest plot

3

199

Std. Mean Difference (IV, Fixed, 95% CI)

0.03 [‐0.25, 0.30]
Analysis 3.4
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 4 Rhinorrhoea score (fixed‐effect model).

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 4 Rhinorrhoea score (fixed‐effect model).

5 Nasal obstruction score (fixed‐effect model) Show forest plot

3

199

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐0.43, 0.13]
Analysis 3.5
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 5 Nasal obstruction score (fixed‐effect model).

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 5 Nasal obstruction score (fixed‐effect model).

6 Nasal obstruction score > 5 Show forest plot

1

27

Risk Ratio (M‐H, Fixed, 95% CI)

5.36 [0.28, 102.12]
Analysis 3.6
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 6 Nasal obstruction score > 5.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 6 Nasal obstruction score > 5.

7 Total number of nose blows Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.17 [‐0.27, 0.61]
Analysis 3.7
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 7 Total number of nose blows.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 7 Total number of nose blows.

8 Total mucus weight Show forest plot

1

40

Std. Mean Difference (IV, Fixed, 95% CI)

0.13 [‐0.49, 0.76]
Analysis 3.8
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 8 Total mucus weight.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 8 Total mucus weight.

9 Total tissue number count Show forest plot

1

40

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.83, 0.42]
Analysis 3.9
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 9 Total tissue number count.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 9 Total tissue number count.

10 Score of dryness in the nose Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.04 [‐0.40, 0.48]
Analysis 3.10
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 10 Score of dryness in the nose.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 10 Score of dryness in the nose.

11 Score of reduced sense of smell Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.08 [‐0.36, 0.51]
Analysis 3.11
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 11 Score of reduced sense of smell.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 11 Score of reduced sense of smell.

12 Hoarseness score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.32 [‐0.12, 0.76]
Analysis 3.12
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 12 Hoarseness score.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 12 Hoarseness score.

13 Fatigue score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.26, 0.62]
Analysis 3.13
Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 13 Fatigue score.

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 13 Fatigue score.
Open in table viewer
Comparison 4. NSAIDs versus placebo, adverse effects

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall side effects (random‐effects model) Show forest plot

2

220

Risk Ratio (M‐H, Random, 95% CI)

2.94 [0.51, 17.03]
Analysis 4.1
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 1 Overall side effects (random‐effects model).

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 1 Overall side effects (random‐effects model).

2 GI complaint (fixed‐effect model) Show forest plot

3

189

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.17, 3.32]
Analysis 4.2
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 2 GI complaint (fixed‐effect model).

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 2 GI complaint (fixed‐effect model).

3 Lethargy/drowsiness (fixed‐effect model) Show forest plot

2

110

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.14, 6.91]
Analysis 4.3
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 3 Lethargy/drowsiness (fixed‐effect model).

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 3 Lethargy/drowsiness (fixed‐effect model).

4 Feeling hyperactive Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]
Analysis 4.4
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 4 Feeling hyperactive.

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 4 Feeling hyperactive.

5 Feeling more awake Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]
Analysis 4.5
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 5 Feeling more awake.

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 5 Feeling more awake.

6 Flushed face Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]
Analysis 4.6
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 6 Flushed face.

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 6 Flushed face.

7 Difficulty sleeping Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.78]
Analysis 4.7
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 7 Difficulty sleeping.

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 7 Difficulty sleeping.

8 Light‐headedness Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.15, 6.51]
Analysis 4.8
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 8 Light‐headedness.

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 8 Light‐headedness.

9 Dry mouth Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]
Analysis 4.9
Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 9 Dry mouth.

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 9 Dry mouth.
Open in table viewer
Comparison 5. Head to head comparison, global effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global improvement rating, marked improvement (fixed‐effect model) Show forest plot

2

365

Risk Ratio (M‐H, Fixed, 95% CI)

1.52 [0.99, 2.34]
Analysis 5.1
Comparison 5 Head to head comparison, global effect, Outcome 1 Global improvement rating, marked improvement (fixed‐effect model).

Comparison 5 Head to head comparison, global effect, Outcome 1 Global improvement rating, marked improvement (fixed‐effect model).

2 Global improvement rating, moderate to marked improvement (fixed‐effect model) Show forest plot

2

365

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [1.02, 1.41]
Analysis 5.2
Comparison 5 Head to head comparison, global effect, Outcome 2 Global improvement rating, moderate to marked improvement (fixed‐effect model).

Comparison 5 Head to head comparison, global effect, Outcome 2 Global improvement rating, moderate to marked improvement (fixed‐effect model).

'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies
Figuras y tablas -
Figure 1

'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies

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'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study
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Figure 2

'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study

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Comparison 1 NSAIDs versus placebo, global effect, Outcome 1 Sum of overall symptom score (random‐effects model).
Figuras y tablas -
Analysis 1.1

Comparison 1 NSAIDs versus placebo, global effect, Outcome 1 Sum of overall symptom score (random‐effects model).

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Comparison 1 NSAIDs versus placebo, global effect, Outcome 2 Moderate to marked severity.
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Analysis 1.2

Comparison 1 NSAIDs versus placebo, global effect, Outcome 2 Moderate to marked severity.

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Comparison 1 NSAIDs versus placebo, global effect, Outcome 3 Duration of colds (random‐effects model).
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Analysis 1.3

Comparison 1 NSAIDs versus placebo, global effect, Outcome 3 Duration of colds (random‐effects model).

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Comparison 1 NSAIDs versus placebo, global effect, Outcome 4 Duration of restriction of daily activities.
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Analysis 1.4

Comparison 1 NSAIDs versus placebo, global effect, Outcome 4 Duration of restriction of daily activities.

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 1 Throat irritation score (fixed‐effect model).
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Analysis 2.1

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 1 Throat irritation score (fixed‐effect model).

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 2 Headache score (random‐effects model).
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Analysis 2.2

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 2 Headache score (random‐effects model).

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 3 Score of pain in muscles/joints score (fixed‐effect model).
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Analysis 2.3

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 3 Score of pain in muscles/joints score (fixed‐effect model).

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 4 Malaise score (fixed‐effect model).
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Analysis 2.4

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 4 Malaise score (fixed‐effect model).

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 5 Chilliness score (random‐effects model).
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Analysis 2.5

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 5 Chilliness score (random‐effects model).

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 6 Nose irritation score.
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Analysis 2.6

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 6 Nose irritation score.

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 7 Score of pain on swallowing.
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Analysis 2.7

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 7 Score of pain on swallowing.

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 8 Eye itching score.
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Analysis 2.8

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 8 Eye itching score.

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Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 9 Earache score.
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Analysis 2.9

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 9 Earache score.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 1 Cough score (random‐effects model).
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Analysis 3.1

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 1 Cough score (random‐effects model).

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 2 Sneezing score (fixed‐effect model).
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Analysis 3.2

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 2 Sneezing score (fixed‐effect model).

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 3 Total number of sneezes.
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Analysis 3.3

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 3 Total number of sneezes.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 4 Rhinorrhoea score (fixed‐effect model).
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Analysis 3.4

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 4 Rhinorrhoea score (fixed‐effect model).

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 5 Nasal obstruction score (fixed‐effect model).
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Analysis 3.5

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 5 Nasal obstruction score (fixed‐effect model).

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 6 Nasal obstruction score > 5.
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Analysis 3.6

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 6 Nasal obstruction score > 5.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 7 Total number of nose blows.
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Analysis 3.7

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 7 Total number of nose blows.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 8 Total mucus weight.
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Analysis 3.8

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 8 Total mucus weight.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 9 Total tissue number count.
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Analysis 3.9

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 9 Total tissue number count.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 10 Score of dryness in the nose.
Figuras y tablas -
Analysis 3.10

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 10 Score of dryness in the nose.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 11 Score of reduced sense of smell.
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Analysis 3.11

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 11 Score of reduced sense of smell.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 12 Hoarseness score.
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Analysis 3.12

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 12 Hoarseness score.

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Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 13 Fatigue score.
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Analysis 3.13

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 13 Fatigue score.

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 1 Overall side effects (random‐effects model).
Figuras y tablas -
Analysis 4.1

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 1 Overall side effects (random‐effects model).

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 2 GI complaint (fixed‐effect model).
Figuras y tablas -
Analysis 4.2

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 2 GI complaint (fixed‐effect model).

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 3 Lethargy/drowsiness (fixed‐effect model).
Figuras y tablas -
Analysis 4.3

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 3 Lethargy/drowsiness (fixed‐effect model).

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 4 Feeling hyperactive.
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Analysis 4.4

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 4 Feeling hyperactive.

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 5 Feeling more awake.
Figuras y tablas -
Analysis 4.5

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 5 Feeling more awake.

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 6 Flushed face.
Figuras y tablas -
Analysis 4.6

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 6 Flushed face.

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 7 Difficulty sleeping.
Figuras y tablas -
Analysis 4.7

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 7 Difficulty sleeping.

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 8 Light‐headedness.
Figuras y tablas -
Analysis 4.8

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 8 Light‐headedness.

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Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 9 Dry mouth.
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Analysis 4.9

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 9 Dry mouth.

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Comparison 5 Head to head comparison, global effect, Outcome 1 Global improvement rating, marked improvement (fixed‐effect model).
Figuras y tablas -
Analysis 5.1

Comparison 5 Head to head comparison, global effect, Outcome 1 Global improvement rating, marked improvement (fixed‐effect model).

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Comparison 5 Head to head comparison, global effect, Outcome 2 Global improvement rating, moderate to marked improvement (fixed‐effect model).
Figuras y tablas -
Analysis 5.2

Comparison 5 Head to head comparison, global effect, Outcome 2 Global improvement rating, moderate to marked improvement (fixed‐effect model).

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Summary of findings for the main comparison. Non‐steroidal anti‐inflammatory drugs for the common cold

Non‐steroidal anti‐inflammatory drugs for the common cold

Patient or population: patients with common cold
Settings: community or care facilities or hospital
Intervention: non‐steroidal anti‐inflammatory drugs

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Non‐steroidal anti‐inflammatory drugs

Sum of overall symptom score

—

The mean sum of overall symptom score in the intervention groups was
0.4 standard deviations lower
(1.03 lower to 0.24 higher)

—

293
(3 studies)

⊕⊕⊕⊝
moderate1

—

Duration of colds

—

The mean duration of colds in the intervention groups was
0.23 lower
(0 to 0 higher)

—

214
(2 studies)

⊕⊕⊕⊝
moderate2

—

Throat irritation score

—

The mean throat irritation score in the intervention groups was
0.01 standard deviations lower
(0.33 lower to 0.3 higher)

—

159
(2 studies)

⊕⊕⊕⊝
moderate2

—

Headache score

—

The mean headache score in the intervention groups was
0.65 standard deviations lower
(1.11 to 0.19 lower)

—

159
(2 studies)

⊕⊕⊕⊝
moderate2

—

Score of pain in muscles/joints score

—

The mean pain in muscles/joints score in the intervention groups was
0.40 standard deviations lower
(0.77 to 0.03 lower)

—

0
(2 studies)

See comment

—

Cough score

—

The mean cough score in the intervention groups was
0.05 standard deviations lower
(0.66 lower to 0.56 higher)

—

159
(2 studies)

⊕⊕⊕⊝
moderate2

—

Rhinorrhoea score

—

The mean rhinorrhoea score in the intervention groups was
0.03 standard deviations higher
(0.25 lower to 0.3 higher)

—

199
(3 studies)

⊕⊕⊕⊝
moderate2

—

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

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# NSAIDs group 141, placebo group 152.
2Too small sample size.

Figuras y tablas -
Summary of findings for the main comparison. Non‐steroidal anti‐inflammatory drugs for the common cold
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Comparison 1. NSAIDs versus placebo, global effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Sum of overall symptom score (random‐effects model) Show forest plot

3

293

Std. Mean Difference (IV, Random, 95% CI)

‐0.40 [‐1.03, 0.24]

2 Moderate to marked severity Show forest plot

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.18, 2.11]

3 Duration of colds (random‐effects model) Show forest plot

2

214

Mean Difference (IV, Random, 95% CI)

‐0.23 [‐1.75, 1.29]

4 Duration of restriction of daily activities Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

‐0.56 [‐1.24, 0.12]
Figuras y tablas -
Comparison 1. NSAIDs versus placebo, global effect
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Comparison 2. NSAIDs versus placebo, analgesic effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Throat irritation score (fixed‐effect model) Show forest plot

2

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.33, 0.30]

2 Headache score (random‐effects model) Show forest plot

2

159

Std. Mean Difference (IV, Random, 95% CI)

‐0.65 [‐1.11, ‐0.19]

3 Score of pain in muscles/joints score (fixed‐effect model) Show forest plot

2

114

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐0.77, ‐0.03]

4 Malaise score (fixed‐effect model) Show forest plot

2

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.29 [‐0.60, 0.03]

5 Chilliness score (random‐effects model) Show forest plot

2

159

Std. Mean Difference (IV, Random, 95% CI)

‐0.03 [‐1.12, 1.06]

6 Nose irritation score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.48, 0.40]

7 Score of pain on swallowing Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.51, 0.37]

8 Eye itching score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.58, 0.30]

9 Earache score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.59 [‐1.04, ‐0.14]
Figuras y tablas -
Comparison 2. NSAIDs versus placebo, analgesic effect
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Comparison 3. NSAIDs versus placebo, non‐analgesic effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cough score (random‐effects model) Show forest plot

2

159

Std. Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.66, 0.56]

2 Sneezing score (fixed‐effect model) Show forest plot

2

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.44 [‐0.75, ‐0.12]

3 Total number of sneezes Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.51 [‐0.95, ‐0.06]

4 Rhinorrhoea score (fixed‐effect model) Show forest plot

3

199

Std. Mean Difference (IV, Fixed, 95% CI)

0.03 [‐0.25, 0.30]

5 Nasal obstruction score (fixed‐effect model) Show forest plot

3

199

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐0.43, 0.13]

6 Nasal obstruction score > 5 Show forest plot

1

27

Risk Ratio (M‐H, Fixed, 95% CI)

5.36 [0.28, 102.12]

7 Total number of nose blows Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.17 [‐0.27, 0.61]

8 Total mucus weight Show forest plot

1

40

Std. Mean Difference (IV, Fixed, 95% CI)

0.13 [‐0.49, 0.76]

9 Total tissue number count Show forest plot

1

40

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.83, 0.42]

10 Score of dryness in the nose Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.04 [‐0.40, 0.48]

11 Score of reduced sense of smell Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.08 [‐0.36, 0.51]

12 Hoarseness score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.32 [‐0.12, 0.76]

13 Fatigue score Show forest plot

1

80

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.26, 0.62]
Figuras y tablas -
Comparison 3. NSAIDs versus placebo, non‐analgesic effect
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Comparison 4. NSAIDs versus placebo, adverse effects

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall side effects (random‐effects model) Show forest plot

2

220

Risk Ratio (M‐H, Random, 95% CI)

2.94 [0.51, 17.03]

2 GI complaint (fixed‐effect model) Show forest plot

3

189

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.17, 3.32]

3 Lethargy/drowsiness (fixed‐effect model) Show forest plot

2

110

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.14, 6.91]

4 Feeling hyperactive Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]

5 Feeling more awake Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]

6 Flushed face Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]

7 Difficulty sleeping Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.78]

8 Light‐headedness Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.15, 6.51]

9 Dry mouth Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.02]
Figuras y tablas -
Comparison 4. NSAIDs versus placebo, adverse effects
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Comparison 5. Head to head comparison, global effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global improvement rating, marked improvement (fixed‐effect model) Show forest plot

2

365

Risk Ratio (M‐H, Fixed, 95% CI)

1.52 [0.99, 2.34]

2 Global improvement rating, moderate to marked improvement (fixed‐effect model) Show forest plot

2

365

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [1.02, 1.41]
Figuras y tablas -
Comparison 5. Head to head comparison, global effect
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