Efficacy and safety of St. John's wort for the treatment of major depression

Nangia, Monica; Waqar, Syed; Doraiswamy, P. Murali

doi:10.1017/s1368980000000562

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…Here, hyperforin pharmacokinetics was linear for doses up to 600 mg whereas higher doses produced lower-than-expected plasma concentrations after linear extrapolation. In a study employing repeated doses, hyperforin accumulation was not be detected; steadystate plasma concentration after 900 mg/day of extract was~100 ng/ml (Biber et al, 1998) with a half-life of 9 h (Nangia et al, 2000) (Table 2).…”

Section: Pharmacodynamics and Pharmacokinetics Of Hypericum Perforatummentioning

confidence: 99%

“…After oral administration of single doses (range = 300–1800 mg ) of HP extract (0.3% of hypericin), hypericin was detectable in the blood after 1.3 h, and peak plasma concentrations were reached after ~4.6 h and steady‐state levels by 4 days (Brochmoller et al ., ; Staffeldt et al ., 1994; Upton, ). The plasma half‐life of hypericin is reported to be ~25 h (Nangia et al ., ), the prolonged duration of which is due to hypericin's affinity for albumin and lipoproteins (Bianchi et al ., ). Although the bioavailability of hypericin is ~14%, the therapeutic concentration of hypericin in brain remains unknown, and although it has been suggested that brain levels reach only 5% of plasma levels, hypericin's half‐life in the brain may be weeks (Upton, ).…”

Section: Pharmacodynamics and Pharmacokinetics Of Hypericum Perforatummentioning

confidence: 99%

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Hypericum perforatum : Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

et al. 2013

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Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP.

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Section: Pharmacodynamics and Pharmacokinetics Of Hypericum Perforatummentioning

confidence: 99%

Section: Pharmacodynamics and Pharmacokinetics Of Hypericum Perforatummentioning

confidence: 99%

Hypericum perforatum : Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

et al. 2013

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“…The antidepressant effects of SJW have been the focus of a number of controlled clinical studies that have been extensively reviewed [7,19,[24][25][26][27]. However, the mechanism(s) by which SJW exerts antidepressive effects in human subjects across certain types of depression remain to be elucidated.…”

Section: Effects Of St John's Wort On Depressionmentioning

confidence: 99%

Usefulness of studies on the molecular mechanism of action of herbals/botanicals: The case of St. John's wort

Choudhuri

Valerio

2005

J Biochem & Molecular Tox

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The use of herbals/botanicals has been gaining wide popularity in recent years in the United States as well as in other parts of the world. The mechanism of action of most of these herbals/botanicals has not been subjected to thorough scientific investigations. St. John's wort (Hypericum perforatum) represents a useful case study in this sense. Traditionally, it is used as a natural treatment for depression; however, in recent years its molecular mechanism of action has been elucidated by a number of laboratories across the world. Such studies have helped understand potential interactions of St. John's wort with drugs and other xenobiotics. St. John's wort activates a nuclear receptor called pregnane X receptor (PXR). PXR is a ligand-activated transcription factor that induces a number of xenobiotic-metabolizing enzymes and transporters including cytochrome P4503A4 (CYP3A4) in humans. Because CYP3A4 alone metabolizes about 60% of all clinically relevant drugs, induction of CYP3A4 may result in the rapid elimination of these drugs and a consequent reduction in drug efficacy. Ironically, such enzyme-inducing effects may not produce any immediate adverse symptomatology in the person taking St. John's wort. Therefore, the case of St. John's wort should serve as a good example of the usefulness and importance of studies on the mechanism of action of the herbals/botanicals, particularly those with widespread use. Scientists, physicians, and other health professionals can make use of the knowledge from such studies as an additional risk management tool.

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“…Hypericin remains intact through digestion, absorption into the blood stream, and passage through the liver, and is felt to be able to cross the blood-brain barrier, 13 with effects originally thought to be mediated through irreversible inhibition of monoamine oxidase (MAO). 14 However, these findings were not replicated and subsequent work has raised doubts as to the importance of hypericin as the primary active ingredient of hypericum.…”

Section: Chemical Constituentsmentioning

confidence: 99%

St. John's Wort:Clinical Status in Psychiatry

Meltzer‐Brody¹

2001

CNS spectr.

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Depression and anxiety are among the top 10 health problems for which complementary and alternative therapies (CATs) are most frequently used, and medicinal herbs are among the most popular of these treatments. St. John's wort (Hypericum perforatum) is a perennial herb that has become a widely used depression therapy. Extracts of hypericum have shown affinity for receptors within multiple neurochemical systems. The primary active substance responsible for the antidepressant effect is not well defined, but most work has concentrated specifically on the hypericin and hyperforin components. Although hypericum has demonstrated significant antidepressant and antianxiety effects in multiple studies, there are several recent studies that do not support the previous evidence. In all reported studies, hypericum extracts have been well tolerated. In addition, new psychiatric uses for hypericum in obsessive-compulsive disorder, generalized anxiety disorder, menopausal symptoms, and alcohol dependence have been reported. Because patients are choosing to pursue CAT as a first-line therapy, psychiatrists will need to have a better understanding of phytomedicines used for treating depression and anxiety, and thus be better prepared to serve as effective allies of their patients.

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Efficacy and safety of St. John's wort for the treatment of major depression

Abstract: Objective: Extracts of St. John's wort have been widely used in the treatment of depression. Our aim was to review information related to the efficacy and safety of St. John's wort as an antidepressant.

Cited by 14 publications

References 45 publications

Hypericum perforatum : Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

Hypericum perforatum : Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

Usefulness of studies on the molecular mechanism of action of herbals/botanicals: The case of St. John's wort

St. John's Wort:Clinical Status in Psychiatry

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