Introduction to Diphenhydramine
Diphenhydramine is a first-generation antihistamine commonly found in over-the-counter (OTC) medications like Benadryl [1.4.4]. It works by blocking histamine receptors to relieve allergy symptoms such as runny nose, sneezing, and itchy eyes [1.4.4]. Its sedative properties have also led to its widespread use as a sleep aid [1.3.4]. However, because it is a potent anticholinergic agent and crosses the blood-brain barrier, it's not safe for everyone [1.4.4, 1.3.4]. Its anticholinergic effects interfere with bodily signals, leading to side effects like dry mouth, blurred vision, constipation, and drowsiness [1.4.4]. Due to these risks, it's vital to identify which populations should avoid this medication.
Specific Populations Who Should Avoid Diphenhydramine
Certain groups are at a higher risk for adverse effects from diphenhydramine and should generally avoid its use.
Older Adults (65+) The American Geriatrics Society's Beers Criteria strongly recommends that older adults avoid diphenhydramine [1.5.3]. This population is more sensitive to its anticholinergic side effects, which increases the risk of confusion, memory impairment, dizziness, sedation, constipation, and urinary retention [1.2.1, 1.3.2]. These side effects, particularly dizziness and confusion, significantly elevate the risk of falls [1.3.1]. Long-term use in older adults has been associated with an increased risk of cognitive decline and dementia [1.2.4, 1.5.4]. Safer, second-generation antihistamines are preferred for this age group [1.5.3].
Infants and Young Children Diphenhydramine is contraindicated in premature infants and neonates [1.3.1, 1.3.2]. The FDA warns that nonprescription cough and cold products containing diphenhydramine can cause serious side effects or death in children under two years old and should not be used in this age group [1.2.1]. For children between 2 and 6, it should only be used under a doctor's direction [1.2.1, 1.6.1]. In some children, diphenhydramine can cause a paradoxical reaction, leading to excitement, agitation, or irritability instead of drowsiness [1.2.3, 1.3.1]. It should never be used to induce sleep in children [1.2.2].
Pregnant and Breastfeeding Individuals While occasional short-term use during pregnancy may be considered safe, it should be avoided during the last two weeks of pregnancy due to a risk of eye disease in newborns [1.7.1]. For those who are breastfeeding, diphenhydramine is generally contraindicated because it is excreted into breast milk and can cause sedation and irritability in the infant [1.7.2]. High doses or prolonged use may also reduce milk supply [1.7.2, 1.7.4]. Non-sedating antihistamines are the preferred alternatives during lactation [1.7.1, 1.7.2].
Medical Conditions and Diphenhydramine Use
Individuals with certain pre-existing medical conditions should use diphenhydramine with extreme caution or avoid it altogether.
- Glaucoma: People with narrow-angle glaucoma should not take diphenhydramine. The drug's anticholinergic properties can dilate the pupil, potentially leading to a sudden, painful increase in eye pressure (an acute glaucoma attack) [1.2.2, 1.12.1, 1.12.2].
- Benign Prostatic Hyperplasia (BPH): Men with an enlarged prostate should avoid diphenhydramine. It can worsen urinary symptoms by preventing the bladder muscle from contracting properly, leading to urinary retention—the inability to fully empty the bladder [1.2.4, 1.13.2, 1.13.3].
- Respiratory Conditions: Individuals with asthma, chronic bronchitis, or COPD should use caution, as diphenhydramine can thicken bronchial secretions, making them harder to clear from the lungs [1.2.2, 1.8.4].
- Cardiovascular Disease: The medication can cause increased heart rate, palpitations, and changes in blood pressure, so it should be used cautiously in those with heart disease or hypertension [1.2.4, 1.8.4].
- Liver or Kidney Disease: Since diphenhydramine is metabolized by the liver and excreted by the kidneys, people with impaired function in these organs may be at greater risk for adverse effects due to drug accumulation [1.8.2, 1.8.4].
Dangerous Drug Interactions
Combining diphenhydramine with other substances can amplify its effects, leading to dangerous consequences.
- Alcohol and CNS Depressants: Taking diphenhydramine with alcohol, benzodiazepines (e.g., Xanax), opioids, or other sedatives has an additive effect, causing profound drowsiness, dizziness, impaired coordination, and an increased risk of overdose [1.2.1, 1.4.4].
- MAOIs: Monoamine oxidase inhibitors (MAOIs), a class of antidepressants, can prolong and intensify the anticholinergic effects of diphenhydramine [1.3.2, 1.4.3].
- Other Anticholinergic Drugs: Combining it with other medications that have anticholinergic properties (e.g., certain drugs for overactive bladder or Parkinson's disease) increases the risk of side effects like dry mouth, confusion, and urinary retention [1.4.4].
- Other Antihistamines: Taking diphenhydramine with other antihistamines (like Zyrtec or Claritin) can increase the risk of side effects without providing additional benefit [1.2.4].
Diphenhydramine Alternatives
| Condition | First-Generation (Avoid if Contraindicated) | Safer Second-Generation Alternatives | Other Alternatives / Notes |
|---|---|---|---|
| Allergies | Diphenhydramine | Cetirizine (Zyrtec), Loratadine (Claritin), Fexofenadine (Allegra), Levocetirizine (Xyzal) [1.7.1, 1.13.2] | Steroid nasal sprays (e.g., Flonase) can also be effective [1.13.2]. Second-generation options are less sedating [1.5.3]. |
| Insomnia | Diphenhydramine (e.g., in Tylenol PM, Advil PM) | Not applicable | The American Academy of Sleep Medicine recommends against using diphenhydramine for insomnia [1.3.4]. Consider melatonin or valerian root after consulting a doctor [1.9.1]. |
| Motion Sickness | Dimenhydrinate (Dramamine) - similar to diphenhydramine | Not applicable | Medication-free options include acupressure bracelets or ginger candy [1.13.2]. |
Conclusion
While diphenhydramine is an effective and accessible medication for many, its powerful anticholinergic and sedative effects make it unsafe for several key groups. Older adults, young children, pregnant or breastfeeding individuals, and those with conditions like narrow-angle glaucoma and BPH should avoid it. Furthermore, the potential for dangerous interactions with alcohol, CNS depressants, and other medications necessitates caution for all users. Always consult a healthcare provider to ensure a medication is safe for you, especially if you have pre-existing health conditions or are taking other drugs. Safer alternatives, such as second-generation antihistamines, are often a better choice [1.5.3].
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before starting or stopping any medication.
