The short answer
Trazodone explicitly warns about St John’s wort and serotonin syndrome. Review the combination before use; a spacing interval has not been shown to make it safe.
What this answer covers
Oral Hypericum perforatum with immediate-release trazodone; extracts vary in hyperforin content.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- trazodone
The warning names St John’s wort
The current trazodone label includes the herb among serotonergic products of concern. That is separate from any proposed effect on blood levels.
Metabolism findings depend on preparation
One St John’s wort extract lowered alprazolam exposure, while a low-hyperforin extract had no relevant effect on tested probes. Neither was a trazodone trial.
Do not adjust trazodone from another drug’s result
The label addresses strong CYP3A4 modifiers, but the actual herb and patient context require review. No fixed gap or automatic dose increase follows.
Recognize concerning symptoms
Seek urgent medical care for a combination of agitation or confusion, fever or heavy sweating, tremor, muscle rigidity or repeated twitching. These can be signs of serotonin syndrome; a single nonspecific symptom does not establish the diagnosis.
Evidence and practical considerations
Side effects & toxicity
Exact-label conditional serotonin precaution; reduced trazodone effectiveness or absorption remains an unquantified extrapolation.
- Exact scope
- Oral Hypericum perforatum with immediate-release trazodone; extracts vary in hyperforin content. with Exact oral trazodone hydrochloride immediate-release tablets. RxNorm IN 10737/PIN 82112 hydrochloride; current immediate-release tablet scope. Oral solutions and modified-release products are not automatically equivalent.
- Medication form and route
- oral
- Timing or duration
- Source-specific single-dose, repeated-dose and observational exposures distinguished.
What remains uncertain
- Other-drug CYP3A probe studies establish preparation differences, not exact trazodone exposure or a universal dose change.
Factors that may matter: preparation and plant part; clinical indication; dose; other medicines; baseline alertness.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed oral trazodone.
Exact label names tryptophan and St John’s wort in serotonin warnings; strong CYP3A4 modifiers may change exposure. Drowsiness, orthostatic effects and QT warnings are distinct.
How this applies: RxNorm IN 10737/PIN 82112 hydrochloride; current immediate-release tablet scope. Oral solutions and modified-release products are not automatically equivalent.
No universal supplement interval, event rate or preparation equivalence established. Original label distinguishes warnings from measured pair-specific results.
Source 2: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Twelve healthy volunteers in an open-label fixed-order crossover.
Alprazolam exposure fell about one-half and clearance increased; elimination half-life shortened.
How this applies: Preparation-specific original evidence; no untested antidepressant or route transfer.
Single extract and short exposure, healthy volunteers; no anxiety-treatment failure endpoint. Does not imply reduced gut absorption or transfer to predominantly conjugated benzodiazepines.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Healthy participants in randomized placebo-controlled studies.
Changes in probe exposures were small and judged clinically irrelevant; hyperforin levels were below quantification.
How this applies: Preparation-specific original evidence; no untested antidepressant or route transfer.
Preparation-specific result, not permission to assume all retail products are low-hyperforin or all doses safe.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Current exact available claims adjudicated using original captures and explicit identity and comparator limits. | |
| Research summary published |
Article revision: 372b16156f6e6233
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.
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Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.