Diphenhydramine vs. Doxylamine

What's the Difference?

Diphenhydramine and Doxylamine are both antihistamines commonly used as sleep aids. They work by blocking the effects of histamine, a chemical in the body that promotes wakefulness. While they have similar mechanisms of action, there are some differences between the two. Diphenhydramine is known for its sedating effects and is often used to treat occasional sleeplessness. On the other hand, Doxylamine is generally considered to be more potent and longer-lasting, making it a preferred choice for individuals with chronic insomnia. Additionally, Diphenhydramine is more likely to cause drowsiness the next day, while Doxylamine has a lower risk of residual sedation. It is important to note that both medications should be used with caution and under the guidance of a healthcare professional, as they can have side effects and may interact with other medications.


Chemical FormulaC17H21NOC17H22ClNO
Brand NamesBenadryl, Nytol, SominexUnisom, Nighttime Sleep Aid
UsesAllergy relief, sleep aidSleep aid
Side EffectsDrowsiness, dry mouth, blurred visionDrowsiness, dry mouth, blurred vision

Further Detail


Diphenhydramine and doxylamine are both antihistamine medications commonly used to treat various conditions, including allergies, insomnia, and the common cold. While they belong to the same class of drugs and share some similarities, they also have distinct characteristics that set them apart. In this article, we will explore the attributes of diphenhydramine and doxylamine, comparing their efficacy, side effects, potential interactions, and other relevant factors.


When it comes to effectiveness, both diphenhydramine and doxylamine have proven to be reliable in treating allergies and providing temporary relief from symptoms such as sneezing, itching, and runny nose. However, diphenhydramine is often considered more potent in terms of its sedative effects, making it a popular choice for individuals seeking relief from insomnia. On the other hand, doxylamine is known for its longer duration of action, providing a more sustained effect throughout the night.

Side Effects

While diphenhydramine and doxylamine are generally safe when used as directed, they can both cause side effects. Common side effects of diphenhydramine include drowsiness, dizziness, dry mouth, blurred vision, and constipation. Doxylamine, on the other hand, may cause similar side effects, but it is also associated with a higher risk of causing drowsiness and sedation. It is important to note that both medications can impair cognitive and motor functions, so it is advised to avoid activities that require alertness, such as driving or operating heavy machinery, while under their influence.

Potential Interactions

When considering potential drug interactions, it is crucial to consult with a healthcare professional or pharmacist. Both diphenhydramine and doxylamine can interact with other medications, including prescription drugs, over-the-counter medications, and herbal supplements. They may enhance the sedative effects of other central nervous system depressants, such as alcohol, benzodiazepines, and opioids. Additionally, they can interact with medications that have anticholinergic properties, potentially leading to an increased risk of side effects. It is essential to disclose all medications and supplements you are taking to your healthcare provider to ensure safe and effective use of these antihistamines.

Formulations and Availability

Diphenhydramine and doxylamine are available in various formulations, including tablets, capsules, liquids, and even as ingredients in combination products. Diphenhydramine is commonly found in over-the-counter sleep aids, allergy medications, and cough and cold preparations. Doxylamine is also available in similar formulations, often marketed as a sleep aid. Both medications are widely accessible without a prescription, making them convenient options for individuals seeking temporary relief from their symptoms.

Special Considerations

While diphenhydramine and doxylamine are generally safe for most individuals, certain populations should exercise caution or avoid their use altogether. Pregnant and breastfeeding women should consult their healthcare provider before using these medications, as they can potentially cross the placenta or be excreted in breast milk. Additionally, individuals with certain medical conditions, such as glaucoma, urinary retention, asthma, or prostate enlargement, should use these medications with caution, as they can worsen symptoms or lead to complications. It is always best to seek professional medical advice before starting any new medication.


In conclusion, diphenhydramine and doxylamine are both effective antihistamines with similar uses and mechanisms of action. While diphenhydramine is often preferred for its potent sedative effects, doxylamine offers a longer duration of action. Both medications can cause side effects, interact with other drugs, and require special considerations for certain populations. Ultimately, the choice between diphenhydramine and doxylamine depends on individual needs, preferences, and guidance from healthcare professionals. It is important to use these medications responsibly and as directed to ensure safe and effective relief from symptoms.

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