St John's Wort and Sertraline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sertraline
No brand names on recordSt John's Wort
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Both of these raise serotonin, a brain chemical, and taking them together can push it too high. Sertraline is a prescription antidepressant, and St. John's Wort is an herbal supplement that acts in a similar way. When they stack up, some people can develop something called serotonin syndrome. Warning signs include a fast or pounding heart, high blood pressure, fever, sweating, shivering, muscle twitching, agitation, or confusion. There have also been reports of people feeling unusually high-energy or manic.
The good news is this is manageable. Please don't start, stop, or change either one on your own. Talk with your pharmacist or doctor first so they can guide you safely.
Mechanism: additive serotonergic effect. St. John's Wort inhibits serotonin reuptake and has mild MAO-inhibitory activity; combined with the SSRI sertraline this can precipitate serotonin syndrome. Neither agent requires activation, so effects are additive in the expected direction.
- Effect: increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, altered mental status); case reports also note mania/hypomania.
- Onset: rapid. Evidence: probable. Severity: major.
- Monitor: mental status, neuromuscular findings (clonus, hyperreflexia), autonomic signs, temperature.
- Management: avoid concurrent use. When switching, allow washout: 2 weeks after stopping St. John's Wort before restarting an SSRI; when replacing an SSRI, wait at least 5 half-lives of that SSRI.
What happens
An increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Published case reports document that symptoms consistent with serotonin syndrome, along with mania and hypomania, developed when St. John's Wort was combined with sertraline, FLUoxetine, and PARoxetine1542. In one instance, a patient developed a presentation similar to sedative/hypnotic intoxication after St. John's Wort was introduced alongside PARoxetine therapy 6. St. John's Wort is believed to block serotonin reuptake and may possess weak monoamine oxidase inhibitory activity 78; combining it with selective serotonin reuptake inhibitors may therefore produce serotonin syndrome.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
The main goal is to avoid taking these two together, and your care team can help you transition safely.
- Keep taking your sertraline as prescribed. Do not stop it or add St. John's Wort on your own.
- If a switch is planned, timing matters. Your team may advise waiting about two weeks after stopping St. John's Wort before restarting an SSRI, and, if replacing sertraline with the herb, waiting at least 5 half-lives for the sertraline to clear.
- Tell your pharmacist or doctor that you take (or are considering) St. John's Wort so they can guide the timing.
- Seek urgent care for fever, fast heartbeat, muscle twitching, agitation, or confusion.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) There have been five reported cases of serotonin syndrome in elderly patients who combined prescription antidepressants with St. John's Wort. In the first case, a woman experienced dizziness, nausea, vomiting, and a headache 4 days after beginning St. John's Wort 300 milligrams (mg) three times daily along with sertraline 50 mg daily. Her symptoms cleared 2 to 3 days after all medications were stopped. In the second case, a man experienced nausea, epigastric pain, and anxiety 3 days after beginning St. John's Wort 300 mg twice daily along with sertraline 75 mg daily. His symptoms resolved within one week after both medications were discontinued, and he restarted sertraline without difficulty. The third case involved a man who developed nausea, vomiting, anxiety, and confusion 2 days after beginning St. John's Wort 300 mg twice daily along with sertraline 50 mg daily. His symptoms improved within 4 to 5 days after both medications were stopped and he received cyproheptadine 4 mg three times daily. In the fourth case, a man developed nausea, anxiety, restlessness, and irritability 2 days after beginning St. John's Wort 300 mg three times daily along with sertraline 50 mg daily. He was given cyproheptadine 4 mg twice daily for seven days, and his symptoms improved within 1 week after the medication was stopped. Cases 1 through 4 restarted their prescribed sertraline once symptoms had subsided and had no additional problems. The fifth case involved a woman who developed nausea, vomiting, and restlessness 3 days after beginning St. John's Wort 300 mg three times daily along with nefazodone 100 mg twice daily. She kept taking St. John's Wort but stopped the nefazodone, and her symptoms improved over 1 week. She declined to restart nefazodone but continued St. John's Wort, and mild to moderate depression and anxiety symptoms returned 2.
b) A 50-year-old woman taking St. John's Wort 600 mg daily developed symptoms of sedative intoxication after she took a single dose of PARoxetine 20 mg. She was incoherent, groggy, moved slowly, and reported nausea and weakness. Before starting St. John's Wort, she had taken PARoxetine 40 mg daily for eight months without adverse effects. After sleeping through the night, she returned to her baseline mental status 3.
c) A 61-year-old woman developed restlessness and involuntary movements of her limbs after starting PARoxetine 20 milligrams (mg) two days after stopping St. John's Wort 600 mg daily. The patient reported agitation and akathisia 8 hours after taking the first dose of PARoxetine. She presented with diaphoresis and involuntary movement of all limbs along with hyperreflexia and rigidity. Blood pressure, heart rate, and temperature were normal. After she was admitted, blood pressure rose to 200/116 mmHg and heart rate rose to 145 beats per minute. Creatine kinase increased from an initial 212 units/liter (U/L) to 1024 U/L. The patient was treated with supportive care and LORazepam and was discharged after two days 4.
d) A 28-year-old man developed a manic syndrome after taking St. John's Wort together with sertraline. The patient was also receiving testosterone replacement therapy following bilateral orchidectomy 2 years earlier, but his testosterone levels were subtherapeutic. He was prescribed sertraline 50 milligrams daily for depression after a 2 week trial of St. John's Wort at the patient's preference (dose not specified). Before sertraline was initiated, the patient was told to stop St. John's Wort, but he continued it despite this instruction. The patient noticed improved mood and therefore did not return to his physician, believing he needed no further treatment. Over 2 months, the patient had an elated mood, was irritable, and overspent, buying a car he could not afford, and was eventually arrested for stealing fuel for the car. Upon arrest, he was referred to psychiatric services because of irritability and disinhibition. He was found to be over-aroused, distractible, with flight of ideas and grandiose delusions, resulting in a diagnosis of a manic episode. The authors note the possibility that the manic state was caused by sertraline therapy alone, and that St. John's Wort may have raised the risk through monoamine oxidase inhibition. Because the patient's testosterone level was subnormal, its contribution to the manic state was considered unlikely. However, the patient had elevated gonadotropin levels (luteinizing hormone and follicle-stimulating hormone), which may have predisposed him to mania 5.
e) A 42-year-old woman developed symptoms consistent with a mixed hypomanic episode after concurrent use of FLUoxetine, busPIRone, Ginkgo biloba, and St. John's Wort. The symptoms resolved after Ginkgo and St. John's Wort were discontinued. The patient was being treated for depression following a mild traumatic brain injury with FLUoxetine 20 milligrams (mg) twice daily and busPIRone 15 mg twice daily. Several weeks before presentation, busPIRone was increased to 20 mg twice daily for persistent anxiety, and the patient began taking Ginkgo biloba, melatonin, and St. John's Wort in unspecified doses. Melatonin was thought unlikely to have contributed to her symptoms. Ginkgo and St. John's Wort were regarded as possible contributors because they may potentiate antidepressants, and given the temporal relationship between the use of the herbs and the onset of symptoms and between discontinuation of the herbs and resolution of symptoms. However, the brain injury was also considered a possible contributor 1.
Common questions
Can I take St John's Wort and Sertraline together?
Combining sertraline with St. John's Wort can dangerously raise serotonin and trigger serotonin syndrome, so these are generally not used together. Talk to your pharmacist or doctor before starting, stopping, or switching either one, and get urgent help for fever, twitching, or confusion. Always confirm with your pharmacist or prescriber before making any change.
How serious is the St John's Wort and Sertraline interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the St John's Wort and Sertraline interaction managed?
The main goal is to avoid taking these two together, and your care team can help you transition safely. Keep taking your sertraline as prescribed. Do not stop it or add St. John's Wort on your own. If a switch is planned, timing matters. Your team may advise waiting about two weeks after stopping St. John's Wort before restarting an SSRI, and, if replacing sertraline with the herb, waiting at leas… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of St John's Wort or Sertraline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Spinella M & Eaton LA: Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury. Brain Injury 2002; 16(4):359-367. PubMed
- Lantz MS, Buchalter E, & Giambanco V: St. John's Wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol 1999; 12:7-10. PubMed
- Gordon JB: SSRIs and St. John's wort: possible toxicity?. Am Fam Physician 1998; 57:950-951.
- Waksman JC, Heard K, Jolliff H, et al: Serotonin syndrome associated with the use of St. John's Wort (Hypericum perforatum) and paroxetine (abstract). Clin Toxicol 2000; 38(5):521.
- Barbanel DM, Yusufi B, O'Shea D, et al: Mania in a patient receiving testosterone replacement post-orchidectomy taking St. John's Wort and sertraline. J Psychopharmacol 2000; 14:84-86. DOI
- Gordon JB: SSRIs and St. John's Wort: possible toxicity (letter)?. Am Fam Physician 1998; 57:950-951.
- Singer A, Wonnemann M, & Muller WE: Hyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+. J Pharmacol Exp Ther 1999; 290(3):1361-1368.
- Thiede HM & Walper A: Inhibition of MAO and COMT by hypericum extracts and hypericin. J Geriatr Psychiatry Neurol 1994; 7 (Suppl 1):S54-S56. DOI
Keep reading about Sertraline
Keep reading about St John's Wort
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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