Can I Take Unisom With Lexapro? A Comprehensive Guide

October 12, 2025 •

4 min read

While there is no a universally accepted guideline that strictly prohibits the combination, using Unisom with Lexapro can increase the risk of side effects such as enhanced drowsiness and impaired motor skills. This guide delves into the pharmacological reasons behind this interaction, potential risks, and safer alternatives for managing sleep disturbances while on antidepressants.

Quick Summary

Combining Unisom with the antidepressant Lexapro can lead to enhanced CNS depression, resulting in increased drowsiness, dizziness, and confusion. The interaction requires careful consideration, especially for individuals operating machinery or driving. Consulting a healthcare provider is essential before mixing these medications.

Key Points

Enhanced Sedation Risk: Combining Unisom and Lexapro can cause significantly increased drowsiness, dizziness, and confusion due to enhanced central nervous system (CNS) depression.
Impaired Judgment and Motor Skills: The combined sedative effects can impair your ability to think clearly and affect motor coordination, posing a risk when driving or operating machinery.
Active Ingredients Matter: Unisom's active ingredients (doxylamine succinate or diphenhydramine) are sedating antihistamines, which enhance the effects of Lexapro, an SSRI.
Theoretical Serotonin Syndrome Risk: While low, the theoretical risk of serotonin syndrome exists, especially if Lexapro is combined with other serotonergic drugs. Report any severe symptoms immediately.
Consult a Doctor First: It is critical to speak with a healthcare provider before combining these medications to assess your personal risk factors and explore safer alternatives.
Safer Alternatives Exist: Options like melatonin, improved sleep hygiene practices, and other prescription medications under medical supervision are safer alternatives for managing insomnia while on Lexapro.

Insomnia is a common side effect of depression and anxiety, and it can also be a side effect of some antidepressants, including Lexapro (escitalopram). This often leads individuals to seek over-the-counter (OTC) solutions, such as Unisom, to get a better night's sleep. However, combining prescription medications with OTC drugs should always be approached with caution due to the risk of drug interactions. Understanding the components and mechanisms of both Unisom and Lexapro is the first step toward making an informed decision with a healthcare provider.

The Pharmacology of Unisom and Lexapro

To understand the interaction, it's crucial to look at how each medication affects the body. Lexapro is a selective serotonin reuptake inhibitor (SSRI), and Unisom contains an antihistamine.

How Lexapro Works

Lexapro, with the active ingredient escitalopram, increases the level of serotonin in the brain. Serotonin is a neurotransmitter that helps regulate mood, emotions, and sleep. By blocking the reuptake of serotonin, Lexapro allows more of it to remain in the synaptic space, enhancing its effects. While this is beneficial for mood regulation, the change in serotonin levels can also interfere with the body's natural sleep-wake cycle.

How Unisom Works

Unisom comes in different formulations, but the most common sleep-aid versions contain either doxylamine succinate (e.g., Unisom SleepTabs) or diphenhydramine (e.g., Unisom SleepMelts). Both are first-generation antihistamines that cause drowsiness as a primary side effect. They work by blocking histamine H1 receptors in the central nervous system, which promotes sleep.

The Central Nervous System Depressant Interaction

The primary concern with taking Unisom and Lexapro together is the additive effect of central nervous system (CNS) depression. Both drugs can cause drowsiness independently. When combined, their sedative effects are magnified, leading to a higher risk of several side effects.

What are the risks?

Excessive Drowsiness and Sedation: This is the most common and immediate risk. You may feel excessively tired or sluggish during the day, even after a full night's sleep. This can impair daily functioning, including work and school performance.
Impaired Motor and Cognitive Skills: The enhanced CNS depression can affect your motor coordination, thinking, and judgment. This is particularly dangerous for activities that require mental alertness, such as driving or operating machinery.
Increased Risk in Elderly Patients: The elderly are especially vulnerable to the effects of combined CNS depressants. They may experience more pronounced confusion, motor coordination impairment, and difficulty with judgment.

The Anticholinergic Effects

First-generation antihistamines like doxylamine and diphenhydramine also have anticholinergic properties, which can cause side effects like dry mouth, constipation, and blurred vision. Combining these with an SSRI does not appear to cause a significant increase in these specific side effects, but it is an additional factor to consider, especially if a patient is sensitive to anticholinergic drugs.

Serotonin Syndrome: A Low but Serious Risk

While antihistamines like doxylamine and diphenhydramine do not significantly impact serotonin levels, the theoretical risk of serotonin syndrome exists when combining any serotonergic agent with a drug that has the potential to affect CNS activity. Serotonin syndrome is a potentially life-threatening condition caused by too much serotonin in the brain.

Symptoms: Range from mild (shivering, diarrhea) to severe (muscle rigidity, fever, seizures).
Increased Risk with Other Drugs: The risk of serotonin syndrome is much higher when Lexapro is combined with other highly serotonergic drugs, such as MAOIs, triptans, or St. John's Wort. However, any unusual symptoms should be reported to a doctor immediately.

Comparison of Sleep Aids with Lexapro


Feature	Unisom (Doxylamine)	Melatonin	Prescription Sleep Aids	Lifestyle Adjustments
Mechanism	Antihistamine; blocks histamine H1 receptors causing sedation.	Hormone; regulates sleep-wake cycle.	Various; e.g., Z-drugs like Ambien (zolpidem).	Improves sleep hygiene, promotes relaxation.
Risk with Lexapro	High risk of increased CNS depression (drowsiness, impaired coordination).	Generally considered safer; low risk of interaction.	Requires medical supervision; interactions possible.	Safest option; no drug interactions.
Side Effects	Dry mouth, constipation, confusion.	Headaches, nausea, dizziness.	Risk of dependence, next-day drowsiness, unusual behaviors.	None, but requires consistent effort.
Best for	Occasional, short-term use with caution and medical supervision.	People with disrupted circadian rhythms or mild insomnia.	Chronic insomnia or severe sleep issues under strict medical care.	Long-term, sustainable sleep improvement.

What to Do If You're Considering Combining

Talk to Your Doctor: This is the most crucial step. Your healthcare provider can assess your individual risk factors, including age, other medical conditions (like glaucoma or prostate enlargement), and other medications you are taking.
Explore Alternatives: As shown in the table above, safer alternatives are available. Melatonin is often a good option, especially for mild sleep issues, and has a lower interaction risk. In more severe cases, your doctor may suggest a different prescription sleep aid or an adjustment to your Lexapro dosing schedule.
Practice Good Sleep Hygiene: Before resorting to medication, focus on lifestyle changes. Maintaining a consistent sleep schedule, avoiding caffeine and screens before bed, and creating a relaxing bedtime routine can significantly improve sleep quality.

Conclusion

While it is possible to take Unisom with Lexapro, it is not recommended without explicit medical guidance due to the high risk of additive central nervous system depression. The severe drowsiness, dizziness, and impaired judgment can lead to dangerous situations. Given the potential for harm, the safest and most responsible course of action is to discuss any sleep disturbances with your doctor. They can help you weigh the risks and benefits, explore safer alternatives like melatonin or lifestyle adjustments, or recommend an alternative medication plan tailored to your specific needs. Combining medications without professional consultation puts your safety at risk and should be avoided.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before combining or changing medications.

Authoritative Outbound Link

For more detailed, professional-grade information on drug interactions, including those with doxylamine and escitalopram, consult the database on Drugs.com.

Frequently Asked Questions

The primary danger is the additive sedative effect on the central nervous system (CNS). Both Unisom (a sedating antihistamine) and Lexapro (an SSRI) can cause drowsiness, and when taken together, this effect is magnified, leading to excessive sleepiness, dizziness, and impaired coordination.

Different versions of Unisom contain different active ingredients (e.g., doxylamine succinate or diphenhydramine). Both are sedating antihistamines that interact negatively with Lexapro by increasing CNS depression. You should avoid combining any Unisom product with Lexapro without a doctor's explicit approval.

Safer alternatives for sleep include practicing good sleep hygiene (consistent sleep schedule, no screens before bed) or trying melatonin supplements under a doctor's guidance. Prescription sleep aids are also an option but must be managed by your doctor to avoid interactions.

Serotonin syndrome is a potentially life-threatening condition caused by excess serotonin. The risk is low with the Unisom/Lexapro combination, as antihistamines do not significantly raise serotonin. However, the risk increases when Lexapro is combined with other drugs that affect serotonin, like MAOIs, and any unusual symptoms should be reported immediately.

Yes, elderly patients should be particularly cautious. They are more susceptible to the CNS depressant effects, which can cause greater confusion, impaired judgment, and motor coordination problems.

It is not a matter of timing them apart. The central nervous system depressant effects of doxylamine (Unisom) can overlap with Lexapro's effects, and there is no specified waiting period that eliminates the interaction. Your doctor needs to evaluate the combination regardless of timing.

If you have already taken the combination, observe yourself for signs of excessive drowsiness, dizziness, or confusion. Avoid driving or operating machinery. If you experience severe symptoms like extreme dizziness, rapid heartbeat, or confusion, seek immediate medical attention. Always inform your doctor about all medications you are taking.