St. John's wort

ATC code

N06AX25

Therapeutic class

Herbal antidepressant · Phytoceutical

Forms

oral capsule, oral tablet

Brand names

Hipérico (ES) · Perika (US) · Kira (DE)

Overall confidence

medium

Regulatory sources consulted

Approved indications

Treatment of mild to moderate depressive episodes. Evidence supports its use as monotherapy in mild-to-moderate major depression.

Contraindications

Absolute

Concomitant use with drugs that are substrates of CYP3A4, CYP2C9, CYP2C19 and/or P-gp, where reduced plasma concentration could lead to loss of efficacy (e.g., cyclosporine, tacrolimus, HIV protease inhibitors, warfarin, oral contraceptives).
Pregnancy and lactation.

Clinical warnings

Major warning · Potent inducer of CYP450 enzymes and P-gp transporter, resulting in numerous clinically significant drug interactions that can reduce the efficacy of vital medications. — Clinical Knowledge
Risk of photosensitivity, especially in fair-skinned individuals and at high doses. Patients should be advised to avoid excessive sun exposure. — Clinical Knowledge
Major warning · Risk of serotonin syndrome when combined with other serotonergic agents (e.g., SSRIs, triptans). — Clinical Knowledge

Drug interactions

HighCyclosporineL04AD01
Mechanism: Potent induction of CYP3A4 and P-gp, drastically reducing cyclosporine concentrations and increasing the risk of transplant rejection.
Recommendation: Concomitant use is contraindicated.
PMID: 36144755
HighOral contraceptivesG03A
Mechanism: Induction of CYP3A4, which accelerates the metabolism of ethinylestradiol and progestins, reducing contraceptive efficacy.
Recommendation: Avoid concomitant use. Advise use of an additional or alternative barrier method of contraception.
Clinical Pharmacology Knowledge
HighWarfarinB01AA03
Mechanism: Induction of CYP2C9, which increases warfarin clearance, leading to a subtherapeutic INR and increased risk of thrombosis.
Recommendation: Avoid concomitant use. If unavoidable, very frequent INR monitoring is required when starting and stopping St. John's wort.
Clinical Pharmacology Knowledge
HighSertralineN06AB06
Mechanism: Pharmacodynamic interaction. Additive serotonergic effects increasing the risk of serotonin syndrome.
Recommendation: Use with caution and monitor closely for symptoms of serotonin syndrome (e.g., mental status changes, autonomic instability, neuromuscular abnormalities).
PMID: 36226689

Adverse events

Common (≥1%)

gastrointestinal discomfort · photosensitivity · dizziness · dry mouth · fatigue

Rare but serious

serotonin syndrome · severe drug interactions (e.g., transplant rejection, unintended pregnancy) · manic episodes in bipolar patients

Pregnancy and lactation

FDA category: N/A

Contraindicated during pregnancy and lactation due to lack of safety data and potential for drug interactions.

Recent literature (PubMed)

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.
Sarris J, et al. · World J Biol Psychiatry · 2022 · Relevance 5/5
Guía clínica internacional que evalúa la evidencia para nutracéuticos y fitofármacos en psiquiatría. La hierba de San Juan recibe una recomendación 'Recomendado' (+++) como monoterapia para la depresión mayor leve a moderada, basada en evidencia de Grado A (metaanálisis y múltiples ECA).
The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials.
Zhao X, et al. · Adv Clin Exp Med · 2023 · Relevance 4/5
Metaanálisis de 14 ensayos clínicos (2270 pacientes) que compara la hierba de San Juan (SJW) con ISRS y placebo. Concluye que SJW es comparable en eficacia a los ISRS para la depresión, con un perfil de efectos adversos potencialmente más bajo. El OR agrupado favoreció a SJW sobre los ISRS (OR 2.44).
Depression and Its Phytopharmacotherapy-A Narrative Review.
Dobrek L, et al. · Int J Mol Sci · 2023 · Relevance 3/5
Revisión narrativa que discute la fitoterapia para la depresión. Destaca que la hierba de San Juan ejerce efectos antidepresivos a través de mecanismos similares a los antidepresivos sintéticos, como la inhibición de la recaptación de monoaminas y la actividad de la MAO.
Medicinal Plants Used for Anxiety, Depression, or Stress Treatment: An Update.
Kenda M, et al. · Molecules · 2022 · Relevance 3/5
Revisión sobre plantas medicinales para trastornos del estado de ánimo. Confirma que la hierba de San Juan es efectiva para la depresión leve a moderada, pero enfatiza la necesidad de un uso cuidadoso debido a las significativas interacciones farmacológicas.
Anti-anxiety Properties of Selected Medicinal Plants.
Khan A, et al. · Curr Pharm Biotechnol · 2022 · Relevance 2/5
Revisión sobre las propiedades ansiolíticas de plantas medicinales. Menciona que la hierba de San Juan, junto con otras plantas, ha mostrado resultados positivos en estudios clínicos para la ansiedad, aunque el enfoque principal del artículo no es la depresión.