St. John's Wort and Lexapro (Escitalopram) Interaction
Do not combine St. John's Wort with Lexapro (escitalopram) due to the serious risk of serotonin syndrome, a potentially life-threatening condition. This combination is explicitly contraindicated in the FDA drug label for escitalopram 1.
Mechanism of the Dangerous Interaction
Serotonin Syndrome Risk
The concomitant use of escitalopram with St. John's Wort can cause serotonin syndrome, characterized by mental status changes (agitation, hallucinations, delirium, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia, diaphoresis), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia), seizures, and gastrointestinal symptoms (nausea, vomiting, diarrhea) 1.
The FDA explicitly warns that escitalopram should not be used with other serotonergic drugs including St. John's Wort, and patients must be made aware of the potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases 1.
Clinical case series have documented central serotonergic syndrome in elderly patients who combined prescription SSRIs with St. John's Wort 2.
Dual Pharmacokinetic and Pharmacodynamic Mechanisms
St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein, which can significantly decrease plasma concentrations of escitalopram, potentially leading to treatment failure 3, 4, 5.
This creates a paradoxical situation where serotonin syndrome can occur despite reduced drug levels, because St. John's Wort itself has serotonergic activity through hypericin and hyperforin 6, 7.
Clinical Management Algorithm
If Patient Is Currently Taking Both
Discontinue both medications immediately and seek emergency medical evaluation if any symptoms of serotonin syndrome are present (high fever, uncontrolled muscle spasms, stiff muscles, rapid changes in heart rate or blood pressure, confusion, loss of consciousness) 1.
If no acute symptoms are present, discontinue St. John's Wort immediately and continue escitalopram under close medical supervision 3.
Monitor for at least 24-48 hours after discontinuing St. John's Wort, as symptoms can emerge during this period 8.
If Patient Wants to Start One While Taking the Other
St. John's Wort must be discontinued at least 2 weeks before starting escitalopram to allow adequate washout and minimize interaction risk 1.
Escitalopram must be discontinued before starting St. John's Wort, though this is not recommended given the lack of FDA regulation and standardization of St. John's Wort preparations 3.
Important Prescribing Considerations
The American College of Physicians notes insufficient evidence about the applicability, purity, and potency of St. John's Wort preparations available in the United States 8.
St. John's Wort is not FDA-regulated, and there is no standardization of content or potency, making dosing and safety unpredictable 3.
Additional Drug Interactions to Consider
Other Medications Affected by St. John's Wort
Oral contraceptives: St. John's Wort can cause breakthrough bleeding and unplanned pregnancies by reducing contraceptive effectiveness 4, 5, 6.
Anticoagulants: Warfarin levels may be reduced, requiring more frequent INR monitoring 8, 3.
Immunosuppressants: Cyclosporine and tacrolimus levels can drop significantly, potentially leading to organ rejection 4, 5, 6.
Cardiovascular medications: Digoxin, statins (atorvastatin, simvastatin, lovastatin), and other CYP3A4 substrates may have reduced efficacy 8, 3, 4.
Common Clinical Pitfalls
Patients often fail to disclose herbal supplement use because they do not consider them "real medications." Always specifically ask about St. John's Wort and other herbal products when prescribing escitalopram 3, 1.
The interaction risk persists even with low doses of either agent, as both pharmacokinetic (enzyme induction) and pharmacodynamic (serotonergic effects) mechanisms are involved 4, 5.
Symptoms of serotonin syndrome can be mistaken for anxiety or agitation, which are also potential side effects of SSRI initiation, delaying recognition of this medical emergency 1.
Photosensitivity is increased when combining these agents, as both escitalopram and St. John's Wort can cause photosensitive reactions 8.