The short answer
Discuss St John’s wort with the prescriber before combining it with protriptyline. An exact-pair serotonin-syndrome event or reduced protriptyline absorption is not established.
What this answer covers
Oral Hypericum perforatum with protriptyline hydrochloride tablets.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- protriptyline
Keep the exact label in view
Protriptyline’s current label has cardiovascular and other interaction precautions, but does not specifically name St John’s wort or serotonin syndrome. NCCIH provides a broader antidepressant precaution for the herb.
Extract effects can differ
One St John’s wort extract reduced alprazolam exposure, while a low-hyperforin preparation had no relevant probe effect. Neither result establishes protriptyline absorption or a predictable dose change.
Bring the complete mood regimen
Discuss the herb, extract, amount and other medicines before starting or stopping it. A general interaction precaution is not a measured rate of harm for this exact combination.
Keep medicine changes supervised
Do not increase protriptyline to counter a supplement or change regular treatment on your own. Bring the complete ingredient list, amounts and recent changes to the prescriber.
Evidence and practical considerations
Side effects & toxicity
General herb guidance supports conditional review; exact serotonin-toxicity and reduced-effectiveness claims remain insufficiently established.
- Exact scope
- Oral Hypericum perforatum with protriptyline hydrochloride tablets. with Exact oral protriptyline hydrochloride film-coated tablets. RxNorm IN8886 / PIN203199 hydrochloride tablets. Label describes activating properties and lack of sedative/tranquilizing properties; do not assume other tricyclic sedation applies.
- Medication form and route
- oral
- Timing or duration
- Source-specific single-dose, repeated-dose and observational exposures distinguished.
What remains uncertain
- Protriptyline label does not specifically name St John’s wort or serotonin syndrome; other-drug probe results cannot define this pair.
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 protriptyline.
Label describes activating properties and lack of sedative/tranquilizing properties. Cardiovascular, anticholinergic and MAOI precautions; no explicit serotonin syndrome or St John’s wort warning.
How this applies: RxNorm IN8886 / PIN203199 hydrochloride tablets. Label describes activating properties and lack of sedative/tranquilizing properties; do not assume other tricyclic sedation applies.
No universal supplement interval, event rate or preparation equivalence established.
Source 2: official botanical guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of Hypericum perforatum.
Certain antidepressant combinations may cause serious serotonin-related side effects; herb can reduce the effects of some medicines.
How this applies: General herb precaution, distinguished from the exact medicine label.
General antidepressant interaction guidance, not measured protriptyline concentrations or a protriptyline serotonin-syndrome case.
Source 3: 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 4: 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: 19a02a4381cb2b25
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.