Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

Abstract

Abstract. St John's wort (SJW) extracts, prepared from the aerial parts of Hypericum perforatum, contain numerous pharmacologically active ingredients, including naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols derivatives (e.g., hyperforin, which inhibits the reuptake of a number of neurotransmitters, including serotonin), and flavonoids. Such extracts are widely used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, relevant and, in some case, life-threatening interactions have been reported, particularly with drugs which are substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW interactions include (1) reduced blood cyclosporin concentration, as suggested by multiple case reports as well as by clinical trials, (2) serotonin syndrome or lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted pregnancies in women while using oral contraceptives and SJW, and (4) reduced plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to contribute to the antidepressant action of St John's wort, is also strongly suspected to be responsible of most of the described interactions.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments

“…66 In addition, serotonin syndrome and hypomania have been reported when SJW is used concurrently with antidepressants. 67,68 SJW is recommended as first-line monotherapy in mild to moderate MDD (Level 1 Evidence) and is recommended as a second-line adjunctive treatment for moderate to severe MDD (Level 2 Evidence) ( Table 3). …”

Antidepressant drug interactions: evidence and clinical significance

“…SJW has been shown to cause some dramatic interactions mainly as a result of its ability to induce CYP3A4, 2E1, 2C9 and P glycoproteins. 19 Examples of significant drug-SJW interactions include reducing cyclosporine and tacrolimus levels, which in some cases has resulted in transplant rejections, reducing the effectiveness of oral contraceptives causing unintended pregnancies, and studies demonstrate reduced levels and effective ness of warfarin, digoxin, methadone and some benzo diazepines. 19 It would be advisable to monitor carefully most other drugs when faced with a patient using SJW and consider alternative antidepressant choices.…”

Spices as Alternative Agents for Gastric Ulcer Prevention and Treatment

“…Other drugs interfering with St. John's wort CYP 3A4 induction include , oral contraceptives.and indinavir (156). Literature review of 128 case reports or case series, and 80 clinical trials have revealed that St John's wort-induced cytochrome P450 and P-glycoprotein induction, decreases plasma levels of a large variety and frequently used medications.…”