St Johns Wort Hypericum Perforatum

St. John's wort has been used extensively by Americans for self-diagnosed depression and dysphoria. In Germany, it is the most widely prescribed antidepressant medication. It is now suggested that the active ingredient in St. John's wort that is responsible for its antidepressant effect is hyperforin and not hypericin, as previously suggested (101). Other similar compounds may also exert some effect (102). Through these active ingredients, St. John's wort is thought to selectively inhibit monamine oxidase activity as well as synaptic neurotransmitter reuptake (103). This results in elevated levels of serotonin, dopamine, and norepinephrine in specific areas of the brain.

A number of comprehensive reviews of clinical trials regarding St. John's wort have been completed. The largest meta-analysis included data from 27 trials on 2291 patients with predominantly mild-moderate depression (104). Most trials were less than 6 weeks in duration. The authors concluded that Hypericum preparations were significantly superior to placebo for the short-term treatment of mild to moderate depression. Effectiveness was found to be similar to tricyclic antidepressant medications (104). Additional reviews concurred with these conclusions (105,106). Head-to-head data comparing St. John's wort to selected serotonin reuptake inhibitors are limited. In one recent three-arm study, neither Hypericum nor sertraline showed significantly greater reduction on the Hamilton Depression Scale (HAM-D) compared with placebo (107).

In general, side effects of St. John's wort are mild and infrequent when compared to those of commonly prescribed antidepressants (108). The most commonly reported reactions include gastrointestinal irritations, allergic reactions, fatigue, dizziness, dry mouth, and headache. Reports of photosen-sitization and induction of mania in susceptible patients have also been documented (109,110).

Recent concerns have been raised over herb-drug interactions with use of St. John's wort. Rare cases of serotonin syndrome have been reported with the combination of St. John's wort and selective serotonin reuptake inhibitors (66). Additionally, St. John's wort has been found to induce enzymatic

Table 1 Potential Herb-Drug Interactions Due to St. John's Wort

Reported clinical

Drug Effect complication

Table 1 Potential Herb-Drug Interactions Due to St. John's Wort

Reported clinical

Drug Effect complication

Cyclosporin

Decreased

Transplant graft rejection

drug levels

Digoxin

Decreased

None to date

drug levels

Indinavir

Decreased

Increase in HIV viral load

drug levels

Oral contraceptives

Decreased drug

Unplanned pregnancies

effectiveness

Theophylline

Decreased drug

None to date

levels

Selective serotonin

Serotonin excess

Serotonin syndrome-

reuptake inhibitors

confusion, agitation,

(SSRIs)

diaphoresis, tremor,

rhabdomyolysis

Warfarin

Decreased drug

Reduced INR value

effectiveness

Source: Adapted from Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. St. John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002; 54:349-356.

Source: Adapted from Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. St. John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002; 54:349-356.

breakdown of a number of drugs through its activation of the cytochrome P450 system (111). Clinically significant interactions have been documented (Table 1).

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