A 1999 case series described 5 older adults who developed serotonin syndrome after combining this herb with prescription antidepressants. The combination is the hazard.
This page explains why, and what to do instead of mixing them.
Quick Answer: Can You Take St. John's Wort With an SSRI?
No. St. John's Wort should not be combined with an SSRI such as sertraline, escitalopram or fluoxetine. Together they can cause serotonin syndrome, with agitation, fast heartbeat, sweating, tremor and fever. Switching from one to the other is a prescriber decision, and the herb's enzyme effect lasts about 7 days after the last dose.
Key Takeaways
- A 1999 series described 5 cases of serotonin syndrome with antidepressants.
- PubMed holds 22 records linking this herb to serotonin syndrome.
- Buspirone, a non-SSRI drug, features in 1 serotonin syndrome case report.
- Enzyme induction from the herb fades about 7 days after stopping.
- Switching between the 2 is a prescriber decision, never a solo one.
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Why the Two Should Not Be Combined
The risk comes from 2 things acting on serotonin at once.
- SSRIs: Raise serotonin signalling by blocking its reuptake.
- The herb: Adds serotonin-related effects of its own.
- Together: A risk of serotonin syndrome.
- Separately: Each also has its own side effects.
The US government's complementary health centre warns that combining the herb with certain antidepressants or other serotonin-acting drugs may cause serious serotonin-related side effects.[1]St. John's Wort: Usefulness and Safety — National Center for Complementary and Integrative Health View source
What the herb is and why people take it is in the basics of this herb.
What the Case Reports Show
The evidence here is case reports rather than trials, which is normal for a hazard nobody would test on purpose.
| Report | Combination | Outcome |
|---|---|---|
| 1999 case series | Prescription antidepressants plus the herb | 5 cases of serotonin syndrome in older adults |
| 2002 case report | Buspirone plus the herb | Possible serotonin syndrome |
| 2000 case report | Sertraline plus the herb, with testosterone | A manic episode |
The 1999 series described 5 older adults with clinically diagnosed serotonin syndrome after combining prescription antidepressants with the herb.[2]St. John's wort and antidepressant drug interactions in the elderly — Journal of Geriatric Psychiatry and Neurology (1999) View source
The 2002 report involved buspirone, which is not an SSRI. That is why the warning covers serotonin-acting medicines in general.[3]Possible serotonin syndrome after combination of buspirone and St John's Wort — Journal of Psychopharmacology (2002) View source
The Enzyme Problem Adds to It
The herb also speeds up how the body clears many drugs, including some antidepressants.
- Named by NCCIH: Amitriptyline and bupropion can be weakened.
- Mechanism: CYP3A4 and the P-glycoprotein pump.
- Timing: Builds over days and fades about 7 days after stopping.
- Consequence: A switch can leave an awkward overlap.
After 14 days on the herb, CYP3A activity took about 7 days to return to its starting level.[4]The recovery time-course of CYP3A after induction by St John's wort administration — British Journal of Clinical Pharmacology (2008) View source The mechanism in full is how enzyme induction works.
Switching Is a Prescriber Decision
People ask whether they can move from an SSRI to the herb. That decision belongs to the prescriber, and it is never a solo one.
- Do not: Stop an antidepressant abruptly on your own.
- Do not: Overlap the 2, even for a few days.
- Do ask: About washout timing, which differs by drug.
- Do ask: What the evidence supports for your level of depression.
One case report describes a manic episode in a man who kept taking the herb alongside sertraline against medical advice.[5]Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline — Journal of Psychopharmacology (2000) View source Trials compared the 2 as alternatives, and the evidence against placebo and SSRIs is set out separately.
Recognising Serotonin Syndrome
It can begin within hours of a new combination or a dose change.
- Mind: Agitation, confusion and restlessness.
- Body: Fast heartbeat, heavy sweating and a high temperature.
- Muscles: Tremor, twitching or stiffness.
- Action: Same-day medical help; severe symptoms mean calling 911.
PubMed holds only 22 records on the herb and serotonin syndrome. Rare is not the same as safe when the outcome can be serious.
Other Products to Check
A few products carry the same risk under a different name.
- 5-HTP: Also adds serotonin effects, so never combine them.
- Mood blends: Some contain the herb, including our Depression Tamer.
- Other serotonin drugs: Ask a pharmacist before any combination.
- Your full list: Prescription, over-the-counter and supplements.
For someone on no antidepressant and no other serotonin-acting drug, our single-herb capsule is an option to discuss with a clinician first.
Speak to a Clinician Before Taking St. John's Wort If
- You take any prescription medicine, because this herb speeds up how the body clears many of them
- You take an antidepressant or any other medicine that acts on serotonin
- You rely on the pill or another hormonal method to prevent pregnancy
- You take warfarin, digoxin, cyclosporine, tacrolimus or any HIV medicine
- You are pregnant or breastfeeding, or have ever had a manic episode
- You have any thought of self-harm, which needs same-day help: call or text 988 in the US
Frequently Asked Questions
Can you take St. John's Wort while on Lexapro? +
No. Lexapro is escitalopram, an SSRI, and combining it with the herb risks serotonin syndrome. 1 series described 5 cases with antidepressants.
What supplements should not be taken with SSRI? +
St. John's Wort and 5-HTP head the list, because both add serotonin effects. Show your pharmacist every supplement, as 1 blend may contain the herb.
Does St. John's Wort increase serotonin or dopamine? +
Its mechanism is not fully settled, but NCCIH warns it adds to the serotonin effects of antidepressants. That is the 1 fact that matters for combining.
Does St. John's Wort affect antidepressants? +
Yes, in 2 ways: added serotonin effects with SSRIs, and weaker levels of some others, such as amitriptyline and bupropion.
What is serotonin syndrome? +
Excess serotonin activity causing agitation, sweating, fast heartbeat, tremor and fever. Severe cases are an emergency: call 911.
How long should I wait between an SSRI and St. John's Wort? +
That depends on the SSRI, and only your prescriber can set it. The herb's enzyme effect alone lasts about 7 days after stopping.
Can I switch from my antidepressant to St. John's Wort? +
Not on your own. The 2 must not overlap, stopping some SSRIs abruptly causes discontinuation symptoms, and the plan belongs to your prescriber.
Can St. John's Wort be taken with 5-HTP? +
No. Both add serotonin effects, and our 5-HTP pages list St. John's Wort among the 8 combinations to avoid.
Is St. John's Wort safer than an SSRI? +
It had fewer dropouts from side effects in pooled trials, an odds ratio of 0.53 in 1 review, but it carries far more drug interactions.
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