Which over‑the‑counter medications are safe to use with Lexapro (escitalopram)?

Over-the-Counter Medications Safe with Lexapro (Escitalopram)

Most common OTC medications are safe with Lexapro, but avoid combining it with NSAIDs without gastroprotection, dextromethorphan-containing cough medicines, and St. John's Wort, while using acetaminophen as the preferred pain reliever.

Pain Relievers

Acetaminophen (Tylenol)

• Acetaminophen is the safest OTC pain reliever to use with Lexapro as it does not interact with serotonin pathways and carries no increased bleeding risk 1, 2, 3.
• No dose adjustment needed; follow standard OTC dosing (maximum 3000-4000mg daily in divided doses) 1.

NSAIDs (Ibuprofen, Naproxen, Aspirin)

• NSAIDs significantly increase bleeding risk when combined with SSRIs like Lexapro, particularly gastrointestinal bleeding 4, 5.
• The American Academy of Child and Adolescent Psychiatry notes that SSRIs affect platelet serotonin, which when combined with NSAIDs creates additive bleeding risk 4.
• If NSAIDs are necessary, use the lowest effective dose for the shortest duration and consider adding a proton pump inhibitor for gastroprotection 5.
• Avoid chronic NSAID use (>10 days) without medical supervision when taking Lexapro 5.

Cold and Allergy Medications

Antihistamines (Diphenhydramine, Loratadine, Cetirizine)

• First and second-generation antihistamines are generally safe with Lexapro 1, 2.
• May cause additive sedation, particularly with diphenhydramine (Benadryl); use caution when driving or operating machinery 3.

Decongestants (Pseudoephedrine, Phenylephrine)

• Use with caution as these sympathomimetic agents may cause additive effects on blood pressure and heart rate 1.
• Monitor for increased anxiety, restlessness, or elevated blood pressure 2.

Cough Suppressants

• Avoid dextromethorphan-containing products as this can increase serotonin syndrome risk when combined with Lexapro 6, 4.
• Guaifenesin (expectorant) is safe to use 1.

Gastrointestinal Medications

Antacids and Acid Reducers

• Calcium carbonate, magnesium hydroxide, and aluminum hydroxide antacids are safe 3.
• H2 blockers (famotidine, ranitidine) are safe 3.
• Proton pump inhibitors like omeprazole may increase escitalopram levels by 51%, but this is not considered clinically significant and no dose adjustment is needed 3.

Anti-diarrheal Medications

• Loperamide (Imodium) is safe with Lexapro 1, 2.
• Bismuth subsalicylate (Pepto-Bismol) should be used cautiously due to salicylate content, which may increase bleeding risk similar to aspirin 5.

Sleep Aids

Melatonin

• Generally safe with Lexapro, though may cause additive sedation 1.
• Start with low doses (1-3mg) 2.

Diphenhydramine (Benadryl PM, Unisom)

• Safe but expect additive sedation and anticholinergic effects 3.
• Use lowest effective dose 1.

Supplements and Herbals to Avoid

St. John's Wort

• Absolutely contraindicated with Lexapro due to severe serotonin syndrome risk 6, 4.
• Can also reduce escitalopram effectiveness through enzyme induction 3.

Tryptophan and 5-HTP

• Avoid these serotonin precursors as they significantly increase serotonin syndrome risk 6, 4.

Critical Warning Signs Requiring Immediate Medical Attention

The American Academy of Child and Adolescent Psychiatry identifies these serotonin syndrome symptoms to monitor when combining any medications with Lexapro 6:

• Mental status changes: confusion, agitation, anxiety 6
• Neuromuscular symptoms: tremors, muscle rigidity, hyperreflexia, clonus 6
• Autonomic instability: fever, rapid heart rate, high blood pressure, sweating 6
• Severe symptoms: seizures, high fever, arrhythmias 6

Special Populations at Higher Risk

• Elderly patients have increased risk of adverse effects and bleeding complications when combining Lexapro with NSAIDs or multiple medications 6.
• Patients on anticoagulants or antiplatelet agents should avoid NSAIDs entirely due to compounded bleeding risk 4, 5.

Common Pitfalls to Avoid

• Reading labels carefully for hidden dextromethorphan in multi-symptom cold products 6.
• Assuming "natural" supplements are safe—many interact dangerously with SSRIs 6, 4.
• Taking multiple products containing the same active ingredient (e.g., acetaminophen in both pain reliever and cold medicine) 5.
• Ignoring the 24-48 hour high-risk window after starting any new medication with Lexapro 6.