Supplements and Antidepressants: SSRIs, SNRIs and MAOIs
Serotonin syndrome signs first, then what NIH, MedlinePlus and the NHS say about St. John's wort, SAMe and other supplements with SSRI, SNRI and MAOI antidepressants.
Content last updated . This page has not been medically reviewed.
Serotonin syndrome comes first. MedlinePlus calls serotonin syndrome a potentially life-threatening reaction to certain medicines, in which the body has too much serotonin. Symptoms occur within minutes to hours and may include agitation or restlessness, abnormal eye movements, diarrhea, fast heartbeat and high blood pressure, hallucinations, increased body temperature, loss of coordination, nausea and vomiting, and overactive reflexes. [1] It says to contact a provider right away if you have symptoms, and that untreated it can be deadly. [1] If someone is confused, has a seizure, collapses or has trouble breathing, call 911 (US). If you are in a mental health crisis in the US, call or text 988. MedlinePlus also says not to stop your medicine on your own; talk to your health care provider first. [1] See Serotonin syndrome and other medicine reaction signs.
The question
If you take an antidepressant, can a supplement change how it works or add to its effects? For St. John's wort, sources say clearly yes. For others the evidence is a possibility or is missing. This page does not suggest treating depression with a supplement; depression is a real illness and needs a clinician.Terms
- SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are common antidepressant groups; MedlinePlus names examples such as sertraline, fluoxetine and venlafaxine. [1]
- MAOIs (monoamine oxidase inhibitors) are older antidepressants. MedlinePlus says they can also cause serotonin syndrome when combined with SSRIs, SNRIs and certain other medicines, including meperidine, fentanyl and dextromethorphan (a cough medicine). [1]
- A review notes serotonin syndrome can occur through a single serotonin-active drug or through an interaction between two or more. [2] Another review lists some herbal supplements, such as St. John's wort, among the contributors and says it is more likely when a new medicine is added or a dose changes. [3]
What sources say, by supplement
| Supplement | What the source says | Our label |
|---|---|---|
| St. John's wort (Hypericum perforatum) | NCCIH: with certain antidepressants or other drugs that affect serotonin it may increase serotonin-related side effects, which can be serious; it may also weaken some antidepressants. [4] The NHS says not to use it with sertraline, fluoxetine or venlafaxine. [5][6][7] | Documented |
| SAMe (S-adenosyl-L-methionine) | NCCIH: it is possible SAMe might interact with antidepressants, L-tryptophan and St. John's wort, which raise serotonin. [8] | Theoretical |
| L-tryptophan | Named by NCCIH among substances that increase serotonin, in the SAMe page above. [8] See Tryptophan. | Named in a caution; no study detail |
| 5-HTP (5-hydroxytryptophan) | Proper evidence not found. A 2006 review names serotonin syndrome as a safety issue it examined, but its abstract gives no findings. [9] A 2004 review by authors at a supplement laboratory says no definitive cases of toxicity emerged after about 20 years of use, apart from one unresolved case. [10] | Not established in sources we read |
We searched PubMed, and the NCCIH, MedlinePlus and NHS pages we could open, for 5-HTP with antidepressants. The pages we could read did not state an interaction either way, so we make no claim. A lack of reports is not proof of safety.
MAOIs and supplements
Proper evidence not found. We read no source that lists which supplements interact with MAOIs. The sources we read name other medicines for MAOIs, not supplements. [1] Ask the prescriber or pharmacist about any supplement, and any food or over-the-counter medicine, before using it with an MAOI.Other points from the NHS
The NHS says taking some antidepressants with alcohol, some foods, or some other medicines can cause side effects and is not recommended, and it lists St. John's wort, cannabis and ketamine among the things to be careful with. [11] It also says to talk to your doctor if you want to stop an antidepressant, because they will agree a plan for gradually reducing the dose. [11]What a reader can do
- Tell your prescriber and pharmacist about every supplement, including any you use "for mood" or sleep. [12]
- Do not start, stop or switch an antidepressant on your own; ask the prescriber or pharmacist.
- Read about the herb separately: St. John's wort interactions and Herbs and antidepressants.
- For bipolar disorder and other conditions, see Mental health conditions and supplements.
Frequently asked questions
Can I take St. John's wort with an SSRI?
NCCIH says it may increase serotonin-related side effects, which can be serious, and the NHS says not to use it with sertraline, fluoxetine or venlafaxine. [4][5] Ask the prescriber or pharmacist first.
What are the signs of serotonin syndrome?
MedlinePlus lists agitation, fast heartbeat, high blood pressure, increased body temperature, overactive reflexes, diarrhea and loss of coordination among them, within minutes to hours. [1] Get urgent care; call 911 in the US for severe symptoms.
Is SAMe safe with antidepressants?
NCCIH says it is possible that SAMe might interact with drugs and supplements that raise serotonin, including antidepressants. [8] That is a possibility stated by the source, not a proven interaction. Ask your prescriber.
Is 5-HTP safe with antidepressants?
Proper evidence not found in the sources we read, so we cannot say it is safe. [9] Ask the prescriber or pharmacist.
Should I stop my antidepressant to use a supplement?
No. Ask the prescriber. The NHS says doses are lowered gradually under a plan agreed with a doctor. [11] If you are in crisis, call or text 988 (US).
References
- MedlinePlus (National Library of Medicine, US). Serotonin syndrome. Read 2026-10-23.
- Mikkelsen N, Damkier P, Pedersen SA. Serotonin syndrome: a focused review. Basic Clin Pharmacol Toxicol. 2023. PubMed 37309284. Abstract read 2026-10-23.
- Badar A. Serotonin syndrome: an often-neglected medical emergency. J Family Community Med. 2024. PubMed 38406216. Abstract read 2026-10-23.
- National Center for Complementary and Integrative Health (NIH, US). St. John's Wort: Usefulness and Safety. Last updated May 2025. Read 2026-10-23.
- NHS (England). Sertraline. Next review due 8 September 2028. Read 2026-10-23.
- NHS (England). Fluoxetine. Page last reviewed 1 June 2026. Read 2026-10-23.
- NHS (England). Venlafaxine. Read 2026-10-23.
- National Center for Complementary and Integrative Health (NIH, US). S-Adenosyl-L-Methionine (SAMe): In Depth. Read 2026-10-23.
- Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006. PubMed 16023217. Abstract read 2026-10-23; the abstract names serotonin syndrome as a safety issue reviewed but gives no figures.
- Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004. PubMed 15068828. Abstract read 2026-10-23; the authors are affiliated with a supplement laboratory.
- NHS (England). Antidepressants: overview. Page last reviewed 12 June 2025. Read 2026-10-23.
- National Center for Complementary and Integrative Health (NIH, US). Know the Science: Talk With Your Health Care Providers. Read 2026-10-23.