The short answer
Avoid adding St. John's wort to phenelzine. Both can affect serotonin, and the combination raises concern for serious serotonin toxicity. Do not replace prescribed treatment or try to manage the interaction by spacing doses yourself.
What this answer covers
Oral Hypericum perforatum preparations used for mood symptoms with oral MAOI treatment. Other botanical species, topical preparations and specific extract strengths are not assumed to be equivalent.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- phenelzine
Why a mood supplement matters
St. John's wort has pharmacologic effects and can interact with antidepressants. The relevant concern here is an added serotonin effect, not the assumption that every medicine is affected through the same drug-metabolism pathway.
How direct is the evidence?
The phenelzine label warns against serotonergic agents as a group. Applying that to oral St. John's wort uses its recognized serotonergic effects; the search did not establish a product-specific event rate.
Do not substitute a few hours of spacing
Changing the time of a supplement does not remove its pharmacologic effects. If you want to change depression treatment, discuss the specific products and any required medication-free interval with the prescriber managing the MAOI.
Recognize a serious reaction
New agitation or confusion together with fever, heavy sweating, diarrhea, tremor, muscle stiffness or jerking can signal serotonin toxicity. Seek urgent medical assessment and provide the complete list of medicines and supplements.
Evidence and practical considerations
Side effects & toxicity
NARDIL prohibits concomitant serotonergic agents; NCCIH identifies serious serotonin-related effects when St. John's wort is combined with certain antidepressants. No exact-pair controlled risk estimate was identified.
- Exact scope
- Oral Hypericum perforatum preparations used for mood symptoms with oral MAOI treatment. Other botanical species, topical preparations and specific extract strengths are not assumed to be equivalent. with Oral phenelzine tablets; current sulfate-tablet labeling uses the named active ingredient.
- Medication form and route
- oral
What remains uncertain
- The warning is label- and pharmacology-supported. This targeted search did not verify an exact-pair clinical case establishing the frequency of serotonin syndrome.
Factors that may matter: Exact supplement preparation and complete concomitant-medication list require assessment..
Read the supporting source summaries
Source 1: Current U.S. prescribing information
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: Patients prescribed oral phenelzine sulfate tablets.
The label prohibits sympathomimetics, L-tryptophan, L-tyrosine, phenylalanine and serotonergic agents. It warns about excessive caffeine and high-tyramine exposures.
How this applies: Primary authority for phenelzine oral-tablet precautions; each article identifies whether the supplement is named or the application is a constituent/class inference.
Regulatory instructions do not quantify an exact-pair event rate or validate every botanical formulation.
Source 2: Federal botanical safety information
nccih.nih.gov · Source check Sep 10, 2026
Population: People using Hypericum perforatum products.
The source warns about serious serotonin-related effects when combined with certain antidepressants.
How this applies: Does not give a quantified exact phenelzine or tranylcypromine risk. Other drug-metabolism interactions are not automatically transferred to these MAOIs.
Does not give a quantified exact phenelzine or tranylcypromine risk. Other drug-metabolism interactions are not automatically transferred to these MAOIs.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Initial targeted research draft. Inspected source material, adjudicated the current checker statements, and recorded preparation limits. Clinical review has not occurred. | |
| Research summary published |
Article revision: 9c2ad5c0ce9b3a02
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.