Cochrane Database of Systematic Reviews Oral antihistamine-decongestant-analgesic combinations for the common cold (Review) De Sutter AIM, van Driel ML, Kumar AA, Lesslar O, Skrt A De Sutter AIM, van Driel ML, Kumar AA, Lesslar O, Skrt A. Oral antihistamine-decongestant-analgesic combinations for the common cold. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD004976. DOI: 10.1002/14651858.CD004976.pub3. www.cochranelibrary.com Oral antihistamine-decongestant-analgesic combinations for the common cold (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 3 OBJECTIVES ..................................... 3 METHODS ...................................... 4 RESULTS....................................... 5 Figure1. ..................................... 7 Figure2. ..................................... 8 DISCUSSION ..................................... 19 AUTHORS’CONCLUSIONS . 20 ACKNOWLEDGEMENTS . 20 REFERENCES ..................................... 21 CHARACTERISTICSOFSTUDIES . 24 DATAANDANALYSES. 64 Analysis 1.1. Comparison 1 Combination 1: Antihistamine-decongestant, Outcome 1 Global evaluation. 66 Analysis 1.2. Comparison 1 Combination 1: Antihistamine-decongestant, Outcome 2 Side effects: all - Combination 1: Antihistamine-decongestant. 67 Analysis 1.3. Comparison 1 Combination 1: Antihistamine-decongestant, Outcome 3 Side effects: drowsiness, hypersomnia and excessive sleepiness - Combination 1: Antihistamine-decongestant. 68 Analysis 1.4. Comparison 1 Combination 1: Antihistamine-decongestant, Outcome 4 Side effects: dry mouth - Combination 1: Antihistamine-decongestant. .......... 69 Analysis 1.5. Comparison 1 Combination 1: Antihistamine-decongestant, Outcome 5 Side effects: insomnia. 70 Analysis 1.6. Comparison 1 Combination 1: Antihistamine-decongestant, Outcome 6 Side effects: gastro-intestinal upset - Combination 1: Antihistamine + analgesic. ......... 70 Analysis 2.1. Comparison 2 Combination 2: Antihistamine-analgesic, Outcome 1 Global evaluation: Koychev 2003. 71 Analysis 2.2. Comparison 2 Combination 2: Antihistamine-analgesic, Outcome 2 Global evaluation: Middleton 1981 night. .................................... 72 Analysis 2.3. Comparison 2 Combination 2: Antihistamine-analgesic, Outcome 3 Side effects: drowsiness, hypersomnia and excessive sleepiness - Combination 2 : Antihistamine-analgesic. ............... 72 Analysis 2.4. Comparison 2 Combination 2: Antihistamine-analgesic, Outcome 4 Side effects: all - Combination 2: Antihistamine-analgesic. 73 Analysis 3.1. Comparison 3 Combination 3: Analgesic-decongestants, Outcome 1 Global evaluation. 73 Analysis 3.2. Comparison 3 Combination 3: Analgesic-decongestants, Outcome 2 Side effects: drowsiness, hypersomnia, lethargy and excessive sleepiness - Combination 3: Analgesic-decongestant. 74 Analysis 3.3. Comparison 3 Combination 3: Analgesic-decongestants, Outcome 3 Side effects: dry mouth - Combination 3:Analgesic-decongestant. 75 Analysis 3.4. Comparison 3 Combination 3: Analgesic-decongestants, Outcome 4 Side effects: gastrointestinal side effects Combination 3: Analgesic-decongestant. ...... 76 Analysis 3.5. Comparison 3 Combination 3: Analgesic-decongestants, Outcome 5 Side effects: dizziness, light headedness - Combination 3: Analgesic-decongestant. ...... 77 Analysis 3.6. Comparison 3 Combination 3: Analgesic-decongestants, Outcome 6 Side effects: all - Combination 3: Analgesic-decongestant. 78 Analysis 4.1. Comparison 4 Combination 4: Antihistamine-analgesic-decongestant, Outcome 1 Global evaluation: after 3 days of treatment - Combination 4: Antihistamine-analgesic-decongestant. 79 Analysis 4.2. Comparison 4 Combination 4: Antihistamine-analgesic-decongestant, Outcome 2 Global evaluation: after 5 daysoftreatment. ... ... ... ... ... ... ... ... ... ... .. 79 Analysis 4.3. Comparison 4 Combination 4: Antihistamine-analgesic-decongestant, Outcome 3 Global evaluation: on the morning after evening dosing. 80 ADDITIONALTABLES. 80 APPENDICES ..................................... 96 Oral antihistamine-decongestant-analgesic combinations for the common cold (Review) i Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. WHAT’SNEW..................................... 98 HISTORY....................................... 99 CONTRIBUTIONSOFAUTHORS . 99 DECLARATIONSOFINTEREST . 99 SOURCESOFSUPPORT . 99 INDEXTERMS .................................... 100 Oral antihistamine-decongestant-analgesic combinations for the common cold (Review) ii Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Oral antihistamine-decongestant-analgesic combinations for the common cold An IM De Sutter1,2, Mieke L van Driel1,3,4, Anna A Kumar4, Olivia Lesslar4, Alja Skrt5 1Department of General Practice and Primary Health Care, Ghent University, Ghent, Belgium. 2Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium. 3Discipline of General Practice, School of Medicine, The University of Queensland, Brisbane, Australia. 4Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia. 5Koper, Slovenia Contact address: An IM De Sutter, [email protected]. Editorial group: Cochrane Acute Respiratory Infections Group. Publication status and date: New, published in Issue 2, 2012. Review content assessed as up-to-date: 16 December 2011. Citation: De Sutter AIM, van Driel ML, Kumar AA, Lesslar O, Skrt A. Oral antihistamine-decongestant-analgesic com- binations for the common cold. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD004976. DOI: 10.1002/14651858.CD004976.pub3. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Although combination formulas containing antihistamines, decongestants and/or analgesics are sold over-the-counter (OTC) in large quantities for the common cold, the evidence of effectiveness is limited. Objectives To assess the effectiveness of antihistamine-decongestant-analgesic combinations in reducing the duration and alleviating the symptoms of the common cold in adults and children. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Group’s Specialised Register, OLDMEDLINE (1953 to 1965), MEDLINE (1966 to November Week 3, 2011) and EMBASE (1990 to December 2011). Selection criteria Randomised controlled trials (RCTs) investigating the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo, other active treatment (excluding antibiotics) or no treatment in children and adults with the common cold. Data collection and analysis Two review authors independently extracted and summarised data on general recovery, nasal obstruction, rhinorrhoea, sneezing, cough and side effects. We categorised the trials according to the active ingredients. Main results We included 27 trials (5117 participants) of common cold treatments. Fourteen trials studied antihistamine-decongestant combinations; two antihistamine-analgesic; six analgesic-decongestant; and five antihistamine-analgesic-decongestant combinations. In 21 trials the control intervention was placebo and in six trials an active substance. Reporting of methods in most trials was poor and there were Oral antihistamine-decongestant-analgesic combinations for the common cold (Review) 1 Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. large differences in design, participants, interventions and outcomes. Pooling was only possible for a limited number of studies and outcomes. Antihistamine-decongestant: 12 trials. Eight trials report on global effectiveness, six could be pooled; n = 309 on active treatment, n = 312 placebo) the odds ratio (OR) of treatment failure was 0.27 (95% confidence interval (CI) 0.15 to 0.50); the number needed to treat for an additional beneficial outcome (NNTB) was four (95% CI 3 to 5.6). On the final evaluation day 41% of participants in the placebo group had a favourable response compared to 66% on active treatment. Of the two trials that were not included in the pooling, one showed some global effect, the other showed no effect. Antihistamine-analgesic: three trials. Two reported on global effectiveness, data from one study was presented. (n = 290 on active treatment, n = 292 ascorbic acid). The OR of treatment failure was 0.33 (95% CI 0.23 to 0.46) and the NNTB was 6.67 (95% CI 4.76 to 12.5). After six days of treatment 43% were cured in the control group and 70% in the active treatment group. The second study also showed an effect in favour of active treatment. Analgesic-decongestant: six trials. One trial reported on global effectiveness: 73% benefited compared with 52% in the control group (paracetamol) (OR 0.28, 95% CI 0.15 to 0.52). Antihistamine-analgesic-decongestant: Five trials. Four trials reported on global effectiveness, two could be pooled: global effect reported (less than one severity point on a four or five-point scale) with active treatment (52%) and placebo (34%); the OR of treatment failure was 0.47 (95% CI 0.33 to 0.67) and the NNTB was 5.6 (95% CI 3.8 to 10.2). Two other trials found no beneficial effect. Two other studies did not show any effect. Two studies with antihistamine-decongestant