What does the research show about cough medicines?

Cough medicines

A pooled analysis found one dose of dextromethorphan cut cough bouts in adults with colds, while a Cochrane review called cough medicine trials variable. In children, most trials found dextromethorphan no better than placebo. Codeine did not differ from placebo for cold cough. FDA limits codeine cough medicines to adults and advises against cough and cold medicines under age 2.

Add to Bio HackChecked 2026-11-14

Status: Dextromethorphan and guaifenesin are sold over the counter in the US, under FDA's OTC monograph or, for Delsym and Mucinex, under FDA-approved applications. Benzonatate is a prescription drug for symptomatic relief of cough. Codeine cough and cold medicines are prescription drugs limited by FDA since 2018 to adults 18 and older, though FDA notes some are sold over the counter in a few states. FDA advises against over-the-counter cough and cold medicines under age 2.
Also called: dextromethorphan, dextromethorphan hydrobromide, DM, DXM, Robitussin DM, Delsym, guaifenesin, Mucinex, Robitussin Chest Congestion, expectorant, cough suppressant, antitussive, codeine cough syrup, benzonatate, Tessalon Perles, cough syrup
Taken for: cough, cold cough, dry cough, chest congestion, loosening mucus, phlegm, night cough, sleep with a cough, children's cough

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help1

ModerateShown in 6 pooled trials to reduce cough bouts for 3 hours after one 30 mg dose in adults with colds. A Cochrane review called antitussive results variable.

Reported risks6

LimitedA Cochrane review found more side effects with preparations containing dextromethorphan or antihistamines. In children, dextromethorphan was linked to insomnia, diphenhydramine to drowsiness.Common
LimitedFDA states the risks of slowed breathing, misuse, addiction, overdose and death with opioid cough medicines outweigh their benefits under 18, and added these to the Boxed Warning.How often is not known
LimitedFDA advises against over-the-counter cough and cold medicines under age 2 because of serious, possibly life-threatening effects. A review judged 40 child deaths related.How often is not known
LimitedThe label warns that accidental ingestion has killed children under 10 within an hour, and that chewing or sucking the capsule has caused severe reactions.How often is not known
LimitedPoison center calls about intentional dextromethorphan abuse tripled from 2000 to 2006, with the highest rate in adolescents aged 14 to 17, then fell 56% by 2015.How often is not known
LimitedThe labels say not to use dextromethorphan with a prescription MAOI, or for 2 weeks after stopping one.How often is not known

What people take it for, and what was found

Shown to help1

Moderate

Acute cough in adults, dextromethorphan

Shown in 6 pooled trials to reduce cough bouts for 3 hours after one 30 mg dose in adults with colds. A Cochrane review called antitussive results variable.

Compared with placebo [1][2]

The numbers and sources

Effect: After a single 30 mg dose, cough bouts, cough components and cough effort fell more than on placebo, and the time to the next cough lengthened, measured by computerized cough recording over 3 hours [1]. A Cochrane review of 19 adult trials found six trials of antitussives against placebo with variable results, and judged the trials too different to pool [2].
Population: 710 adults with cough from an uncomplicated upper respiratory infection in 6 single-dose trials in South Africa and India [1]; 19 placebo-controlled trials in adults in community settings [2].
Sources: [1], [2]
Caveats: The pooled analysis covers one dose over 3 hours, not a full cold [1]. The Cochrane review found many trials poorly reported [2].

Mixed results3

ModerateStudied in children

Acute cough in children, dextromethorphan

Mixed results: most trials in children found dextromethorphan no better than placebo for cough or sleep, while one industry-sponsored trial found 21% fewer coughs over 24 hours.

Compared with placebo [2][3][4]; diphenhydramine [3]; honey [5]

The numbers and sources

Effect: In a Cochrane review, antitussives in three studies in children did not differ from placebo [2]. For night cough from a cold, neither dextromethorphan nor diphenhydramine gave more benefit than placebo for cough frequency, severity, or the child's or parent's sleep, and all groups improved on the second night [3]. In children aged 6 to 11, total coughs over 24 hours fell 21.0% and daytime cough frequency 25.5% more than on placebo, with no difference in night cough or sleep [4]. Honey and dextromethorphan did not differ for cough frequency (MD -0.07 on a 7-point scale, 95% CI -1.07 to 0.94, low certainty) [5].
Population: 10 trials with 1,036 children [2]; 100 children with upper respiratory infections [3]; 128 children aged 6 to 11 [4]; 2 trials with 149 children comparing honey with dextromethorphan [5].
Sources: [2], [3], [4], [5]
Caveats: The positive trial was a pilot by authors employed by makers of cough medicines, published under an industry trade group's copyright [4]. Most trials lasted one night [5].

Limited

Chest congestion and cough, guaifenesin

Mixed results: of three placebo-controlled trials in adults, one found a benefit. One trial found no effect on measured cough, while more people reported thinner mucus.

Compared with placebo or the syrup without guaifenesin [2][6][7]

The numbers and sources

Effect: A Cochrane review found three adult trials of guaifenesin against placebo, one showing a significant benefit and two not [2]. In young adults with colds, tape-recorded cough frequency over 36 hours did not differ from the syrup vehicle. Of those with a productive cough, 96% on guaifenesin reported thinner sputum against 54% on the vehicle, and 88% against 62.5% reported less sputum, a difference that was not significant [6]. In a pilot trial of extended-release guaifenesin 1,200 mg every 12 hours for 7 days, symptom diaries favored guaifenesin most clearly on day 4 [7].
Population: 3 adult trials [2]; 65 young adults with colds, 42 with recorded coughs [6]; 378 adults with upper respiratory infections [7].
Sources: [2], [6], [7]
Caveats: The pilot trial was designed to validate symptom questionnaires, and one author worked for the maker of extended-release guaifenesin [7]. No trials of expectorants in children met the Cochrane criteria [2].

Limited

Cough, benzonatate

Limited evidence: a systematic review found benzonatate's effect rests on very small early studies with a high risk of bias, and no large trials.

Compared with comparators the review abstract does not describe [10]

The numbers and sources

Effect: The review located 37 articles, 21 cohort studies, 5 experimental studies and 11 case reports and series, from 1956 to 2022. Early studies of benefit were very small and in limited settings, and quality assessment found high risk of bias. The authors stated its approval rests on evidence that would not meet current regulatory review [10].
Population: 37 published studies of benzonatate [10].
Sources: [10]
Caveats: No effect size is given [10].

Not shown to help1

Limited

Acute cough in adults, codeine

Two small trials found codeine no different from placebo for cough from colds, measured by recorded cough frequency, cough sound and symptom scores.

Compared with placebo or syrup vehicle [8][9]

The numbers and sources

Effect: Codeine syrup 30 mg, as a single dose or 120 mg a day for 4 days, did not differ from the syrup vehicle in cough frequency or severity at any time point in the lab or at home [8]. A single 50 mg dose did not differ from placebo in cough sound pressure, cough frequency or symptom scores at 90 minutes, while both groups improved [9].
Population: Adults with cough from upper respiratory infections [8]; 82 adults, 51 women and 31 men, mean age 23.5 [9].
Sources: [8], [9]
Caveats: Small trials. The 1992 abstract does not give the number of participants [8].

Doses studied

The pooled dextromethorphan trials used a single 30 mg dose [1]. Delsym holds the equivalent of 30 mg dextromethorphan hydrobromide in 5 mL, labeled 10 mL every 12 hours from age 12 [11]. A Robitussin DM dose of 20 mL holds dextromethorphan 20 mg and guaifenesin 400 mg, every 4 hours up to 6 doses a day from age 12 [12]. The guaifenesin pilot trial used 1,200 mg extended-release every 12 hours for 7 days [7], and the Mucinex label directs 1 or 2 tablets of 600 mg every 12 hours, no more than 4 a day, from age 12 [13]. The codeine trials used 30 mg four times a day for 4 days [8] or a single 50 mg dose [9]. The benzonatate label lists 100 or 200 mg three times a day, up to 600 mg a day, for people over 10 [14].

Risks

Reported risks6

LimitedCommon

Side effects in trials

A Cochrane review found more side effects with preparations containing dextromethorphan or antihistamines. In children, dextromethorphan was linked to insomnia, diphenhydramine to drowsiness.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Across 21 trials reporting adverse effects, rates varied widely and were higher with preparations containing antihistamines and dextromethorphan [2]. In children, insomnia was more frequent on dextromethorphan and drowsiness on diphenhydramine than on placebo [3]. Nervousness, insomnia or hyperactivity occurred in 2.7% of children on dextromethorphan against 9.3% on honey, and somnolence in 7.5% on diphenhydramine [5].
Population: 21 trials in children and adults [2]; 100 children [3]; 149 children in 2 trials, and 80 in 1 trial of diphenhydramine [5].
Sources: [2], [3], [5]
Caveats: Low-certainty evidence from short trials [5].

LimitedHow often is not known

Boxed warning: prescription codeine and hydrocodone cough medicines

FDA states the risks of slowed breathing, misuse, addiction, overdose and death with opioid cough medicines outweigh their benefits under 18, and added these to the Boxed Warning.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 2018, after an FDA review and an outside expert panel, FDA required prescription cough and cold medicines containing codeine or hydrocodone to be limited to adults 18 and older, and added misuse, abuse, addiction, overdose, death and slowed or difficult breathing to the Boxed Warning. FDA lists common side effects of opioids as drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath and headache. It warns that alcohol and other central nervous system depressants raise the risk of serious and life-threatening effects, and advises against breastfeeding during treatment [15].
Population: FDA review of reports and expert panel [15].
Sources: [15]
Caveats: FDA gives no rate. The action covers prescription products [15].

LimitedStudied in childrenHow often is not known

Cough and cold medicines in young children

FDA advises against over-the-counter cough and cold medicines under age 2 because of serious, possibly life-threatening effects. A review judged 40 child deaths related.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: FDA advises against over-the-counter cough and cold medicines under age 2, and manufacturers label them not for use under age 4 [16]. FDA reports convulsions, rapid heart rates and death with decongestant or antihistamine products in children under 2, and an estimated 1,519 children under 2 treated in US emergency departments in 2004 to 2005 for adverse events, including overdoses [17]. An expert panel judged 40 of 180 deaths in children under 12 from 2008 to 2016 related or possibly related to a cough and cold medicine. 60% were under age 2, 55% involved a caregiver giving it without therapeutic intent, and diphenhydramine was involved in 70% [18].
Population: FDA review [16][17]; 180 deaths in children under 12 captured by a national surveillance system [18].
Sources: [16], [17], [18]
Caveats: No rate among children given these medicines. Many deaths involved deliberate misuse by a caregiver [18].

LimitedHow often is not known

Benzonatate: accidental ingestion by children and chewing the capsule

The label warns that accidental ingestion has killed children under 10 within an hour, and that chewing or sucking the capsule has caused severe reactions.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states accidental ingestion resulting in death has been reported in children below age 10, with symptoms within 15 to 20 minutes and death within one hour. It reports bronchospasm, laryngospasm and cardiovascular collapse possibly related to local anesthesia from chewing or sucking the capsule, and isolated confusion and visual hallucinations with other drugs [14]. Of 4,689 pediatric benzonatate exposures reported to US poison centers from 2010 to 2018, 77% of single-substance cases were unintentional, mostly in children 0 to 5. Intentional ingestion rose among children 10 to 16 [19].
Population: Labeling statement [14]; pediatric poison center cases, 2010 to 2018 [19].
Sources: [14], [19]
Caveats: Poison center data give no rate among people prescribed it. The proportion of serious effects was low [19].

LimitedHow often is not known

Misuse of dextromethorphan

Poison center calls about intentional dextromethorphan abuse tripled from 2000 to 2006, with the highest rate in adolescents aged 14 to 17, then fell 56% by 2015.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The annual rate of single-substance dextromethorphan abuse calls tripled from 2000 to 2006 and then plateaued. Adolescents aged 14 to 17 had about 1,761 calls a year, 103.6 per million population, and their rate fell 56.3% from 2006 to 2015 [20].
Population: US National Poison Data System calls, 2000 to 2015 [20].
Sources: [20]
Caveats: Calls per population, not a rate among people who use it [20].

LimitedHow often is not known

Interaction with MAOI antidepressants, dextromethorphan

The labels say not to use dextromethorphan with a prescription MAOI, or for 2 weeks after stopping one.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Delsym and Robitussin DM labels say not to use the product while taking a prescription monoamine oxidase inhibitor, used for depression, psychiatric or emotional conditions or Parkinson's disease, or for 2 weeks after stopping it [11][12].
Population: Labeling statements [11][12].
Sources: [11], [12]
Caveats: No rate of harm is given.

Checked, no increase found1

LimitedStudied in pregnancy

Pregnancy, dextromethorphan

One controlled cohort found major malformations in 2.3% of babies exposed to dextromethorphan in the first trimester, against 2.8% in matched controls.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Among 128 women who used dextromethorphan in the first trimester, 3 babies had major malformations (2.3%). In matched controls with colds not treated with it, 5 had major malformations (2.8%). Mean birth weight was 3,381 g against 3,446 g [21]. The benzonatate label states it is not known whether benzonatate can cause fetal harm, and no animal reproduction studies were done [14].
Population: 184 pregnant women counseled by a teratology service and matched controls [21].
Sources: [21], [14]
Caveats: One small cohort [21]. The over-the-counter labels ask pregnant or breast-feeding women to consult a health professional first [11][13].

Claims tested and not found

That codeine quiets cough from a cold. Two placebo-controlled trials found no difference in cough frequency, sound or severity [8][9].
That cough medicine helps a child with a cold sleep. Neither dextromethorphan nor diphenhydramine improved night cough or the sleep of children or parents more than placebo [3].
That guaifenesin lowers how often a person coughs. Recorded cough frequency over 36 hours did not differ from the syrup vehicle in young adults with colds [6].

Sources

Pavesi L, Subburaj S, Porter-Shaw K. Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis. Chest. 2001. https://doi.org/10.1378/chest.120.4.1121
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. https://doi.org/10.1002/14651858.cd001831.pub5
Paul IM, Yoder KE, Crowell KR, et al. Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics. 2004. https://doi.org/10.1542/peds.114.1.e85
Meeves SG, Cruz-Rivera M, Leyva RA, et al. Objective and self-reported evidence of dextromethorphan antitussive efficacy in children, aged 6-11 years, with acute cough due to the common cold. Pediatric Pulmonology. 2023. https://doi.org/10.1002/ppul.26416
Oduwole O, Udoh EE, Oyo-Ita A, Meremikwu MM. Honey for acute cough in children. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.cd007094.pub5
Kuhn JJ, Hendley JO, Adams KF, Clark JW, Gwaltney JM. Antitussive effect of guaifenesin in young adults with natural colds. Objective and subjective assessment. Chest. 1982. https://doi.org/10.1378/chest.82.6.713
Albrecht H, Vernon M, Solomon G. Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms. Respiratory Research. 2012. https://doi.org/10.1186/1465-9921-13-118
Eccles R, Morris S, Jawad M. Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. Journal of Clinical Pharmacy and Therapeutics. 1992. https://doi.org/10.1111/j.1365-2710.1992.tb01289.x
Freestone C, Eccles R. Assessment of the antitussive efficacy of codeine in cough associated with common cold. Journal of Pharmacy and Pharmacology. 1997. https://doi.org/10.1111/j.2042-7158.1997.tb06039.x
Costantino RC, Leonard J, Gorman EF, et al. Benzonatate Safety and Effectiveness: A Systematic Review of the Literature. Annals of Pharmacotherapy. 2023. https://doi.org/10.1177/10600280221135750
U.S. Food and Drug Administration. DELSYM 12 Hour Cough Relief (dextromethorphan) extended-release suspension, drug facts label. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e3e1d126-76c2-4776-8ce0-449625b7e6ba
U.S. Food and Drug Administration. ROBITUSSIN MAXIMUM STRENGTH COUGH PLUS CHEST CONGESTION DM (dextromethorphan HBr, guaifenesin) solution, drug facts label. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d022dd-c2ca-497f-87d5-9ef3e20e8ea7
U.S. Food and Drug Administration. MUCINEX (guaifenesin) extended-release tablet, drug facts label. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd379cdd-90ab-42e0-ad89-f50d3220f611
U.S. Food and Drug Administration. BENZONATATE capsule, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=93f4935b-ba15-4a99-bfa9-96ca99a1ddc1
U.S. Food and Drug Administration. FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. Drug Safety Communication. 2018. https://www.fda.gov/files/drugs/published/Drug-Safety-Communication--Opioid-Cough-and-Cold-Meds.pdf
U.S. Food and Drug Administration. Should You Give Kids Medicine for Coughs and Colds? Consumer Update. Accessed 2026. https://www.fda.gov/consumers/consumer-updates/should-you-give-kids-medicine-coughs-and-colds
U.S. Food and Drug Administration. Frequently Asked Question on Children's Cough and Cold Medicines. Accessed 2026. https://www.fda.gov/drugs/information-drug-class/frequently-asked-question-childrens-cough-and-cold-medicines
Halmo LS, Wang GS, Reynolds KM, et al. Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications. Pediatrics. 2021. https://doi.org/10.1542/peds.2020-049536
Kim I, Goulding M, Tian F, et al. Benzonatate Exposure Trends and Adverse Events. Pediatrics. 2022. https://doi.org/10.1542/peds.2022-057779
Karami S, Major JM, Calderon S, McAninch JK. Trends in dextromethorphan cough and cold products: 2000-2015 National Poison Data System intentional abuse exposure calls. Clinical Toxicology. 2018. https://doi.org/10.1080/15563650.2017.1416124
Einarson A, Lyszkiewicz D, Koren G. The safety of dextromethorphan in pregnancy: results of a controlled study. Chest. 2001. https://doi.org/10.1378/chest.119.2.466

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