Clinical Question

Are over-the-counter formulas containing antihistamines, analgesics, and/or decongestants effective in treating symptoms of the common cold?

Evidence-Based Answer

Antihistamine/analgesic/decongestant combinations have some general benefit in adults and older children. However, these benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children.¹ (Strength of Recommendation: B, inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

The common cold is an umbrella term for a wide range of noninfluenza viral respiratory tract infections characterized by nasal congestion, rhinorrhea, cough, sore throat, and sneezing. Although symptoms typically self-resolve within one to two weeks, patients seeking treatment account for approximately 110 million physician visits and 23.2 million physician telephone calls in the United States each year.² Although there is no cure, treatment options for cold symptoms are available, including combinations of analgesics for sore throat, decongestants for rhinorrhea, and antihistamines for coughing and sneezing. The authors of this review evaluated the effectiveness of these interventions.

This Cochrane review included 30 randomized trials involving 6,304 participants in the United States, Australia, Europe, and South America.¹ The control intervention was placebo in 26 trials and an active substance (acetaminophen, chlorphenindione plus phenylpropanolamine plus belladonna, or diphenhydramine [Benadryl]) in five trials. There were notable differences in study design, participants, interventions, and outcomes. Children participated in only nine of the trials. Three trials included children six months to five years of age, and six trials included children two years to 16 years of age. All four medication combinations demonstrated a general benefit in adults and children older than six years.

Six trials investigating oral antihistamine/decongestant combinations (n = 565) could be pooled into a meta-analysis; outcomes were usually physician or researcher judgments about treatment effectiveness. The authors concluded that this treatment combination had an overall beneficial effect (number needed to treat [NNT] for one additional participant to judge the intervention as beneficial = 4; 95% CI, 3 to 5; moderate-certainty evidence). On the final evaluation day (three to 10 days of follow-up), more patients in the treatment group were judged to have had a favorable response (70% vs. 55% in the placebo group); however, the antihistamine/decongestant group also experienced more adverse effects than the placebo group (31% vs. 24%).

Four trials evaluated antihistamine/analgesic combinations, including two that reported on global effectiveness; data could not be pooled because one of the trials used an active control. In the remaining trial that provided data on global effectiveness, the proportion of participants who were completely cured at the end of the trial (six days) was 70% with treatment vs. 43% with control (ascorbic acid), with an NNT of 7 (95% CI, 5 to 13; n = 582; moderate-certainty evidence). The antihistamine/analgesic group did not experience notably more adverse effects compared with placebo.

Seven trials evaluated analgesic/decongestant combinations; one trial (n = 181) demonstrated that treatment was beneficial in subjective global effectiveness (i.e., a patient's response to the question, “On the whole, do you think the tablets have helped you?”; odds ratio [OR] = 0.28; 95% CI, 0.15 to 0.52; moderate-certainty evidence). Six trials reported one or more adverse effects, with more patients who took an analgesic/decongestant combination experiencing dizziness or lightheadedness (number needed to harm = 18; 95% CI, 9 to 59; n = 1,797) compared with the control group.

Of the six trials that evaluated a combination of antihistamine, analgesic, and decongestant, five trials reported on global effectiveness; two studies in adults could be pooled (n = 548). More participants reported the treatment as beneficial when measured the morning after taking an evening dose (OR = 0.47; 95% CI, 0.33 to 0.67; NNT = 6; 95% CI, 4 to 10; low-certainty evidence). However, when asked on days 3 and 5, participants reported that treatment provided no notable benefit.

This review included several studies from the 1980s and earlier; it was limited by a lack of trials investigating the effectiveness of individual monotherapies and instead focused on the potential benefit of combination products to treat the common cold. Additionally, it was unclear whether participants were recruited or sought care for common cold symptoms. Some trials did not report adverse effects, which raises concern that adverse effects were underestimated.

The U.S. Food and Drug Administration advises against the use of over-the-counter cough and cold medications in children younger than two years and recommends caution when using in children two years or older.³ However, the American Academy of Pediatrics advises against the use of these medications in children younger than four years.⁴ An American College of Chest Physicians consensus expert panel in 2017 recommended against the use of cough medications in adults and children until more convincing evidence is available.⁵

This review supports a modest benefit of combination medications for the common cold in older children and adults, but further high-quality studies are needed to provide additional support for their use. Physicians should counsel their patients on the self-limited nature of these illnesses and explain that, despite the over-the-counter availability of these medications, the modest potential for benefit must be balanced against the risk of adverse effects.

The practice recommendations in this activity are available at https://www.cochrane.org/CD004976.