Latin name:Hypericum perforatum
Pharmacopoeial name: Hyperici herba
Other names:- hypericum, Klamathweed
About St John’s Wort
St John’s wort is a herbaceous perennial plant native to Europe and Asia. There are several explanations as to the origins of the names hypericum and St John’s wort. Commonly, the name hypericum is believed to be derived from the Greek words hyper (over) and eikon (image), and the name St John’s wort may have arisen as the ﬂowers bloom around St John’s Day (June 24).
Scientific research on St John’s wort began with investigations of its chemistry in the early twentieth century. The extract is a whole plant extract and contains the following marker constituents: Flavonoids (as rutoside); Naphthodianthrones (Hypericin derivatives calculated as hypericin) Acylphloroglucinol (Hyperforin derivatives calculated as hyperforin)
The exact biochemical mechanism of action of St John’s wort extract is not clearly understood. This is due, in large part, to the chemical complexity of the extract. Initially, research focused on hypericin as it was thought to be the active compound that is responsible for the effects on the central and peripheral nervous system. Hypericin has been shown to act as a monoamine oxidase inhibitor (MAOI) (1). However, more recent research has revealed that hyperforin and flavonoid constituents are important for pharmacological action (2,3). Reports have shown that St John’s wort extract exhibits serotonergic activity (4), whilst other reports suggest that the extract acts like a weak serotonin reuptake inhibitor (SSRI), but with fewer side-effects than conventional SSRI drugs (5). Further evidence suggests that the St John’s wort extract affects other neurotransmitter levels in the brain, including noradrenaline, dopamine and γ-aminobutyric acid (GABA) (6-8), leading to an increase in synaptic availability of these neurotransmitters.
Uses of St John’s Wort
Mild to moderate depression
A large body of clinical evidence exists suggesting that St John’s wort extract is effective in relieving symptoms of temporary mild to moderate depressive symptoms. A systematic review and meta-analysis of randomised controlled trials of preparations of St John’s wort extract included 23 trials involving a total of 1757 patients with depressive disorders (9). This has been updated to include new studies and published as a Cochrane review of 27 randomised controlled trials of St John’s wort extract in patients with ‘‘neurotic depression’’ and mild-to-moderately severe depressive disorders (10). The results of the meta-analysis showed that St John’s wort preparations were signiﬁcantly superior to placebo in the short-term treatment of mild-to-moderately severe depressive disorders, and as eﬀective as conventional anti- depressant agents.
Another meta-analysis used tighter inclusion criteria for trials in an attempt to increase the validity of the analysis (11). Six such trials involving 651 patients with mainly mild-to-moderately severe depressive disorders were included. This meta-analysis showed that the response rate for St John’s wort was signiﬁcantly greater than that for placebo (73.2% vs 37.9%) and similar to that observed with tricyclic antidepressants. Tricyclic antidepressants were associated with a higher proportion of reported side eﬀects than were St John’s wort preparations (47% vs 26.4%, respectively).
Several randomised, controlled trials of mono- preparations of St John’s wort involving patients with depressive disorders (12-18) have been published since the Cochrane review (10). Two trials compared St John’s wort against placebo only (12,13), others compared St John’s wort with ﬂuoxetine (16), sertraline (17), and imipramine (18), and one was a 3-arm study comparing St John’s wort with imipramine and placebo (15) In a study comparing St John’s wort with a selective serotonin reuptake inhibitor (16), at the end of the treatment period, 71.4% of St John’s wort recipients and 72.2% of ﬂuoxetine recipients were classiﬁed as responders according to recognised, pre-deﬁned criteria. Similar eﬃcacy for both St John’s wort and ﬂuoxetine was demonstrated when data from subgroups of patients with mild depression and moderate depression were analysed.
In another randomised controlled trial involving 240 patients with mild-to-moderate depression, St John’s wort extract was compared with ﬂuoxetine (14). At the end of the study, St John’s wort extract and ﬂuoxetine were reported to be equipotent. The frequency of adverse events in hypericum-and ﬂuoxetine-treated patients was 8 and 23%, respectively.
In addition, there have been a number of clinical studies carried out on the use of the extract in relieving symptoms experienced by patients suffering from sub-threshold depressive symptoms. The following demonstrate the benefit of St John’s wort for the treatment of low mood as a symptom of common minor ailments such as Premenstrual Syndrome (PMS), menopausal symptoms, Seasonal Affective Disorder (SAD) and fatigue.
Anxiety and depression
The authors sought to examine these issues in a cohort of members of the depression self-help organisation Depression Alliance UK (n=39). Hospital Anxiety and Depression (HADS) scales were used at baseline, prior to St John’s wort administration, and for subsequent assessments at weeks 4, 8 and 12. HADS scores compared well with patient improvement ratings, indicating the feasibility of use in this population. Controlled studies are needed in a larger cohort to examine these findings, before definitive conclusions can be made (19).
To investigate whether Hypericum perforatum could relieve symptoms of premenstrual syndrome in a small group of women, Stevinson et al conducted a prospective, open, uncontrolled, observational study in 19 with premenstrual syndrome who were in otherwise good physical and mental health and not taking other treatments for premenstrual syndrome. There were significant reductions in all outcome measures. The degree of improvement in overall premenstrual syndrome scores between baseline and the end of the trial was 51%, with over two-thirds of the sample demonstrating at least a 50% decrease in symptoms severity (20).
This drug-monitoring study investigated 12 weeks of treatment with St. John’s wort, one tablet three times daily (900 mg St John’s wort), in 111 women from a general medical practice. The patients, who were between 43 and 65 years old, had climacteric symptoms characteristic of the pre- and postmenopausal state. Substantial improvement in psychological and psychosomatic symptoms was observed. Climacteric complaints diminished or disappeared completely in the majority of women (76.4% by patient evaluation and 79.2% by physician evaluation). Of note, sexual well-being also improved after treatment with St. John’s wort extract (21).
Seasonal Affective Disorder (SAD)
Volunteers from the membership of the SAD Association took part in a postal survey, before and after eight weeks treatment with St John’s wort, using an 11-item rating scale. The maximum score is 44 and the mean score in 168 patients using St John’s wort alone was 21.3. This fell to 13 at endpoint (p < 0.001). The corresponding figures for 133 patients using St John’s wort + light therapy were 20.6 and 11.8, respectively (p < 0.001). In both groups, there was significant improvement in anxiety, loss of libido and insomnia. There were no significant between-group differences on any measure except that improvement in sleep was greater in the St John’s wort + light group (22).
This pilot study aimed to investigate the effect of Hypericum (St John’s wort) on fatigue in a small group of patients. Compared to baseline values, perceived fatigue was significantly lower after 2 weeks of treatment and reduced significantly further after 6 weeks. Symptoms of depression and anxiety were also reduced (23).
Antiviral activity has been reported for hypericin against HIV and hepatitis C . Several uncontrolled studies in HIV-positive patients who received St John’s wort extract have reported immunologic and clinical beneﬁts, including increases in CD4 cell counts in some patients (24,25).
St John’s wort has been well tolerated during controlled clinical trials with long term applications and with high dosages. Potential side effects/adverse drug reactions of St John’s wort are rare and include gastro-intestinal disorders (dyspepsia, anorexia, nausea, diarrhoea and constipation), allergic reactions (reddening of the skin, swelling, itching), tiredness and restlessness, which are symptoms of “serotonin syndrome” . The incidence of side effects of St John’s wort is 1-3%, which is one twentieth of the side effects of tricyclic antidepressants.
It is now recognised that St John’s wort interacts with many conventional medicines including anticoagulants such as warfarin, hormonal contraceptives, anti-depressants and some heart medications such as digoxin. St John’s wort has been shown to induce the cytochrome P450 isoenzymes CYP1A2, CYP2C9 and CYP3A4 in the liver, as well as the transport protein P-glycoprotein from the intestinal wall. Many conventional drugs are metabolised by these enzymes and potential interactions may occur with St John’s wort by either increasing or decreasing the circulating levels of drug.
In very rare cases photosensitivity to St John’s wort can occur, particularly in light-skinned individuals resulting in sunburn-like reactions on exposure to intense sunlight, sunbeds or solariums. Cases of photosensitivity have occurred mainly in HIV patients when taking larger dosages for an antiviral effect. Clinically significant interactions have been reported with for example: warfarin, ciclosporin, HIV protease inhibitors, theophylline, digoxin, oral contraceptives, and anticonvulsants. Users of oral contraceptives taking St John’s wort (Hypericum perforatum) may experience intracyclic menstrual bleeding and risk of contraception failure is increased. Clinically significant pharmacodynamic interactions have also been identified with the SSRI antidepressants, and the triptan group of medicines used to treat migraines. Due to the increased risk of undesirable effects associated with these interactions this product should not be used concomitantly with these types of medicines.
Safety of the product during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended.
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