The short answer
Do not start St. John’s wort while taking isocarboxazid without the prescriber or pharmacist managing the combination. Marplan warns about serious reactions with serotonergic drugs, and St. John’s wort has serotonergic interaction reports with other antidepressants. This is class-based evidence rather than a study of this exact pair. Simple dose spacing is not an established solution.
What this answer covers
Oral Hypericum perforatum preparations, including St. John’s wort extracts. Product composition varies. This does not cover topical preparations.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- isocarboxazid
Why the combination raises concern
Marplan warns that serious reactions may occur when MAO inhibitors are given with serotonergic drugs. St. John’s wort can affect serotonin signaling and has produced serotonin toxicity with some other antidepressants.
Exact-pair evidence and class evidence differ
The Marplan label does not specifically name St. John’s wort, and the inspected clinical review does not contain an isocarboxazid pair study or case report. The concern is based on the drug’s serotonergic class warning plus evidence from St. John’s wort with other serotonergic agents. The exact risk and frequency remain uncertain.
Product strength can change the exposure
Hypericum extracts differ in constituents such as hyperforin. That variability can alter interaction potential, but it does not make any product predictably safe with Marplan.
Spacing is not a substitute for review
Taking the two products a few hours apart has not been shown to prevent an interaction. Do not start or stop St. John’s wort on your own because it can also change the effects of other medicines. A prescriber or pharmacist should decide whether avoidance and any washout are needed.
Evidence and practical considerations
Side effects & toxicity
The exact-pair evidence is absent: the current Marplan label does not name Hypericum, and no isocarboxazid plus Hypericum report was identified. The class-based concern comes from Marplan’s warning about serotonergic drugs and St. John’s wort toxicity reports with other serotonergic agents.
- Exact scope
- Oral Hypericum perforatum preparations. with Oral isocarboxazid tablets.
- Medication form and route
- oral
What remains uncertain
- The clinical reports summarized in the review concern other serotonergic drugs. Mechanistic and class-based plausibility do not establish exact-pair incidence.
Factors that may matter: Hyperforin and hypericin content varies by preparation.; Other serotonergic medicines can change the overall risk..
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 Marplan tablets for depression.
The label says excessive caffeine should be avoided. It separately states that tyrosine and tryptophan with Marplan may precipitate hypertension, headache, and related symptoms, and describes a neurologic and behavioral syndrome reported with MAO inhibitors plus tryptophan. It also warns that serious reactions may occur when MAO inhibitors are given with serotonergic drugs, with examples that do not include Hypericum perforatum.
How this applies: Primary authority for oral isocarboxazid. It does not name Hypericum perforatum, so it supplies medication context rather than direct pair evidence.
The label gives no safe caffeine threshold and no exact-pair event rates. It does not name Hypericum perforatum. Its tryptophan syndrome summary includes MAO-inhibitor class reports rather than an identified isocarboxazid case series.
Source 2: Clinical literature review
pmc.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Users of oral St John’s wort extracts and concomitant prescription drugs across clinical reports and studies.
The review reports serotonin syndrome with serotonin reuptake inhibitors or 5-HT receptor agonists and describes substantial preparation-dependent interaction potential. It does not report an isocarboxazid pair study.
How this applies: Supports serotonergic plausibility and product variability, but only indirectly for isocarboxazid.
Review evidence is not an exact isocarboxazid interaction study. Reported serotonergic cases involved other drugs and cannot determine an exact event rate or washout for this pair.
Source 3: Federal botanical safety information
nccih.nih.gov · Source check Sep 10, 2026
Population: Consumers using St. John’s wort, including people taking prescription medicines.
NCCIH warns that St. John’s wort can interact in dangerous, sometimes life-threatening ways with medicines and that products can affect serotonin and drug disposition.
How this applies: Authoritative context supporting professional review before oral use with a prescription antidepressant.
Not an exact isocarboxazid clinical study and does not establish a pair-specific washout interval.
Research assessment: · Open full citations ↗
Timing & monitoring
Professional review and avoidance of unsupervised co-use are prudent; no evidence supports a few-hours spacing strategy for this pair.
- Exact scope
- Oral Hypericum perforatum preparations. with Oral isocarboxazid tablets.
- Medication form and route
- oral
What remains uncertain
- No exact washout duration for St. John’s wort and isocarboxazid was established by the inspected sources.
Factors that may matter: Starting or stopping St. John’s wort can change other drug interactions..
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 Marplan tablets for depression.
The label says excessive caffeine should be avoided. It separately states that tyrosine and tryptophan with Marplan may precipitate hypertension, headache, and related symptoms, and describes a neurologic and behavioral syndrome reported with MAO inhibitors plus tryptophan. It also warns that serious reactions may occur when MAO inhibitors are given with serotonergic drugs, with examples that do not include Hypericum perforatum.
How this applies: Primary authority for oral isocarboxazid. It does not name Hypericum perforatum, so it supplies medication context rather than direct pair evidence.
The label gives no safe caffeine threshold and no exact-pair event rates. It does not name Hypericum perforatum. Its tryptophan syndrome summary includes MAO-inhibitor class reports rather than an identified isocarboxazid case series.
Source 2: Clinical literature review
pmc.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Users of oral St John’s wort extracts and concomitant prescription drugs across clinical reports and studies.
The review reports serotonin syndrome with serotonin reuptake inhibitors or 5-HT receptor agonists and describes substantial preparation-dependent interaction potential. It does not report an isocarboxazid pair study.
How this applies: Supports serotonergic plausibility and product variability, but only indirectly for isocarboxazid.
Review evidence is not an exact isocarboxazid interaction study. Reported serotonergic cases involved other drugs and cannot determine an exact event rate or washout for this pair.
Source 3: Federal botanical safety information
nccih.nih.gov · Source check Sep 10, 2026
Population: Consumers using St. John’s wort, including people taking prescription medicines.
NCCIH warns that St. John’s wort can interact in dangerous, sometimes life-threatening ways with medicines and that products can affect serotonin and drug disposition.
How this applies: Authoritative context supporting professional review before oral use with a prescription antidepressant.
Not an exact isocarboxazid clinical study and does not establish a pair-specific washout interval.
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 source-checked draft. Current claims were adjudicated against the current Marplan label and inspected clinical literature. Clinical review has not occurred. | |
| Research summary published |
Article revision: a94bcf3863110826
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.