doxylamine

General Information

Doxylamine is a first-generation antihistamine marketed OTC as a sleep aid (e.g., Unisom SleepTabs and many generics). It is also used in the prescription combination doxylamine/pyridoxine (Diclegis) for nausea and vomiting of pregnancy (label/product-dependent).

Sedation is expected and often the reason it is used for sleep, but doxylamine is also strongly Anticholinergic. That increases constipation, urinary retention, blurred vision, and delirium risk, especially in older adults and in polypharmacy (Beers/clinical).

Doxylamine has a relatively long half-life for an OTC sleep aid (~10 hours; longer in older adults), increasing the risk of next-day grogginess, falls, and impaired driving (StatPearls/clinical).

Evidence for chronic insomnia benefit is limited. The AASM guideline recommends against routine sedating antihistamine use for chronic insomnia (weak recommendation), so treat doxylamine as a time-limited adjunct while addressing underlying drivers and prioritizing CBT-I.

The doxylamine compare view, evidence feed, and print page support side-by-side review and patient-friendly handouts for safe, time-limited use.

Doxylamine is inexpensive and widely accessible OTC, which can encourage chronic nightly use without reassessment. In older adults, Beers Criteria guidance generally supports avoiding chronic first-generation antihistamines because anticholinergic harms often outweigh benefits.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

H1 antagonism produces sedation (central histamine blockade) and reduces allergic symptoms.

Antimuscarinic (anticholinergic) activity contributes to dry mouth, constipation, urinary retention, blurred vision, and delirium risk.

Sedation can help with sleep onset, but repeated nightly use does not treat the underlying insomnia system and can lead to diminished benefit or “polypharmacy creep” (clinical).

• H1 receptor antagonist (sedation).
• Antimuscarinic (anticholinergic) activity.

Metabolism and Pharmacokinetics

• Doxylamine undergoes extensive hepatic metabolism and is excreted primarily in urine (StatPearls).
• StatPearls reports a half-life of ~10 hours, increasing to ~12–15 hours in older adults (StatPearls).
• Diclegis labeling reports a terminal elimination half-life of doxylamine of 12.5 hours (label).
• Longer half-life increases next-day impairment risk, especially when combined with alcohol or other sedatives (clinical).

Dosing and Administration

• OTC sleep aid labeling is product-dependent; one common direction is 25 mg once nightly about 30 minutes before bed.
• Avoid “middle-of-the-night catch-up dosing” because next-day impairment risk rises with higher total nightly dose and long half-life (clinical).
• If insomnia persists beyond a short course, avoid open-ended nightly use; prioritize CBT-I and treat comorbid contributors rather than stacking sedatives (AASM/clinical).
• Diclegis is used on a scheduled basis (not PRN) with a product-specific titration strategy for nausea/vomiting of pregnancy; do not substitute OTC sleep aid products without clarifying dosing equivalence (label/clinical).

Monitoring & Labs

• Sedation and next-day impairment (falls risk, driving safety).
• Anticholinergic effects (constipation, urinary retention, blurred vision).
• Confusion or delirium risk in older adults and polypharmacy (Beers).
• Avoid duplicate sedatives and document a stop plan if nightly use develops.

Adverse Effects

Interactions

• Additive CNS/respiratory depression with alcohol, opioids, benzodiazepines, sedating antipsychotics, and other hypnotics; avoid stacking sedatives when possible (clinical).
• Additive anticholinergic burden with other anticholinergics (tricyclics, low-potency antipsychotics, bladder antimuscarinics) increases delirium and urinary retention risk (clinical).

Other Useful Information

• AASM guidelines prioritize CBT-I and recommend against routine sedating antihistamine use for chronic insomnia; treat doxylamine as a time-limited adjunct while addressing underlying contributors.
• In older adults and in patients with high fall risk or cognitive vulnerability, first-generation antihistamines are often avoided when possible (Beers).
• If insomnia persists, consider evidence-backed options (e.g., DORAs, ramelteon, low-dose doxepin) and reassess for sleep apnea, substance use, and untreated mood symptoms.

References

1. Doxylamine succinate (OTC sleep aid) tablets label — DailyMed (2025)
2. Diclegis (doxylamine/pyridoxine) Delayed Release Tablets Label — DailyMed (2024)
3. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline — Journal of Clinical Sleep Medicine (2017)
4. 2023 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults — Journal of the American Geriatrics Society (2023)
5. Doxylamine (StatPearls) — StatPearls Publishing (NCBI Bookshelf) (2025)