An Update on Clinical Drug Interactions with the Herbal Antidepressant St. Johns wort

Abstract

St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. Limited clinical trials suggest that hypericum and standard antidepressants have similar beneficial effects, but current evidence regarding the antidepression effects of SJW extracts is inconsistent. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs. This review highlights and updates the knowledge regarding drug interactions with SJW by a systematic review of all the available evidence, including worldwide published literature and spontaneous case reports. A number of clinically significant interactions of SJW have been identified with conventional drugs. These interactions often result in a decrease in the concentration or effect of the combined drug, most probably due to the induction of cytochrome P450s (CYPs) and the key drug transporter P-glycoprotein (P-gp) by the major active constituents in SJW. SJW is a potent inducer of human CYP3A4 and P-gp in vitro and in vivo. In addition, pharmacodynamic interactions of SJW with some drugs (e.g. selective serotonin re-uptake inhibitors) have been identified, which are associated with an increased risk of adverse reactions. Since potential interactions of SJW with conventional drugs is a major safety concern, it is important to minimize and avoid these interactions by taking appropriate approaches. These include systematic research to identify SJW-drug interaction; close therapeutic drug monitoring when SJW is combined with conventional drugs with a narrow therapeutic window; proper dose and regimen adjustment; patient education and communication between the patient and physician; design of new preparations of SJW without inducing ability of CYP3A4 and P-gp while retaining its bioactivity; and appropriate regulation in herbal safety and efficacy. Further clinical and mechanistic studies are warranted to explore the interaction of SJW with other important drugs and clinical significance.

Emerging Significance of Flavonoids as P-Glycoprotein Inhibitors in Cancer Chemotherapy

“…Since then there are frequent reports of pharmacokinetic interactions of herbs with drugs, causing either beneficial or harmful effects (44,53). Combined use of herbs with drugs may mimic, increase, or reduce the effects of either component, resulting in herb-drug interactions (60). The herb-drug interactions can be hazardous if they cause increased drug levels reaching above toxic threshold.…”

Influence of Dietary Macronutrients on Induction of Hepatic Drug Metabolizing Enzymes by Coleus forskohlii Extract in Mice

“…In contrast, the measurement of liver weight was simple and the increased ratio of liver weight to body weight corresponded well to the induction of CYP by CFE (22); the correlation coefficient was 0.85 (n535, p,0.001). When the relationship between hepatic CYP content and liver weight to body weight was reanalyzed using the data from the CFE dose-response study (17), a significant positive correlation was also detected (r50.78, n526, p,0.001). Thus, we used the increase in the ratio of liver weight to body weight as a simple and reliable indicator of CYP induction following CFE treatment.…”

“…Drugs are metabolized by the Phase I and Phase II enzymes; the former is catalyzed by cytochrome P450 (CYP) enzymes, and the latter is catalyzed conjugation enzymes such as glutathione S-transferase (GST) and UDP-glucuronosyltransferase (16). Interactions between some herbal ingredients, such as St John's wort (17) and ginkgo biloba (18), have been documented and shown to be mediated by CYPs, but those for other herbal ingredients remain unknown. We previously showed that feeding mice a diet containing CFE (standardized with 10% forskolin) dose-and time-dependently induced hepatic CYPs and GST enzymes (19).…”

Herbal pathies (Unani, Ayurveda) need to review their way of research

“…Although herbs may well have undesirable side effects, there are no set "doses," and herb-drug or herb-herb interactions are possible. Several researches in this aspect are available from number of clinicians which provides the proof of herb-herb and herb-drug interactions in both positive and negative directions (Chavez et al, 2006;Iqbal et al, 2015;Shu, 1998;Thomas et al, 2004;Zhou et al, 2008). A major hypothetical advantage of botanicals over conventional single-component drugs is the presence of multiple active compounds that together can provide a potentiating effect that may not be achievable by any single compound.…”