Safety of Lemon Balm and St. John's Wort with SSRIs
St. John's wort is absolutely contraindicated with SSRIs due to the risk of serotonin syndrome, while lemon balm should be avoided due to potential additive CNS depression effects. 1, 2, 3, 4
St. John's Wort: Absolute Contraindication
St. John's wort must never be taken concurrently with SSRIs. This combination creates a serious risk of serotonin syndrome, a potentially life-threatening condition. 1, 2, 3, 4
Mechanism of Interaction
- St. John's wort acts as a serotonergic agent that can dangerously potentiate the effects of SSRIs 3, 4, 5
- The FDA drug labels for both fluoxetine and sertraline explicitly warn against concomitant use with St. John's wort due to serotonin syndrome risk 3, 4
- Documented case reports confirm serotonin syndrome when SSRIs (including sertraline and paroxetine) are combined with St. John's wort 5, 6
Clinical Manifestations of Serotonin Syndrome
Patients must be monitored for: 4
- Mental status changes (agitation, hallucinations, delirium, coma)
- Autonomic instability (tachycardia, labile blood pressure, hyperthermia, diaphoresis)
- Neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea)
Switching Between Medications
- If transitioning from St. John's wort to an SSRI, monitor for at least 24-48 hours after discontinuing St. John's wort, as serotonin syndrome symptoms can emerge during this period 1
- When discontinuing SSRIs to start St. John's wort, appropriate washout periods must be observed based on the specific SSRI's half-life 3
Additional Drug Interaction Concerns
Beyond serotonin syndrome, St. John's wort is a potent inducer of CYP3A4 and P-glycoprotein, which significantly decreases plasma concentrations of numerous medications including: 7, 1, 5
- Oral contraceptives (risk of unintended pregnancy)
- Immunosuppressants (risk of transplant rejection)
- Anticoagulants (increased thrombotic risk)
- HIV medications
- Cancer chemotherapy agents
Lemon Balm: Not Recommended
Lemon balm should be avoided when taking SSRIs or other CNS-active medications. 7
Rationale for Avoidance
- The Society for Perioperative Assessment and Quality Improvement (SPAQI) recommends holding lemon balm for 2 weeks before surgery due to evidence suggesting additive CNS depression when combined with sedatives 7
- While the perioperative guideline specifically addresses sedatives and alcohol, the mechanism of additive CNS depression raises concern for interactions with SSRIs, which can also cause sedation 7
Clinical Considerations
- The evidence for lemon balm interactions is less robust than for St. John's wort, but the potential for additive effects warrants caution 7
- No specific studies have evaluated lemon balm safety with SSRIs, but the precautionary principle applies given the known CNS depressant effects 7
Common Pitfalls to Avoid
- Patients often fail to disclose herbal supplement use: Explicitly ask about all supplements, including "natural" or over-the-counter products 1, 8
- Assuming herbal products are safe because they're "natural": St. John's wort has serious, well-documented drug interactions that can be life-threatening 1, 5, 8
- Lack of FDA regulation: St. John's wort preparations in the United States have no standardization of content or potency, making dosing unpredictable 1, 2
- Underestimating interaction severity: Population studies have identified concerning rates of concurrent SSRI and St. John's wort use (11 cases identified in one Australian cohort), indicating this dangerous combination occurs in real-world practice 6