St John's Wort (Herb/Suppl)

Oral: Depression (mild-moderate), psychosomatic disorder, obsessive-compulsive disorder, anxiety, premenstrual syndrome, burning mouth syndrome, neuropathy

Topical: atopic dermatitis, wound healing

Efficacy

Although controversy exists, available evidence suggests that for depression more effective than placebo and may be as effective as standard antidepressants with less side effects (Cochrane Review 2008)

However a JAMA report (2009) shows no improvement over placebo for severe depression, but then, sertraline didn't perform any better either for 2 of the primary outcomes

Increased rate of healing in 2nd and 3rd degree burns

Frequency Not Defined

Agitation

Anxiety

Dizziness

Dry mouth

Fatigue

GI discomfort

Headache

Hypomania

Insomnia

Irritability

Menstrual irregularities

Paresthesias

Photosensitivity

Restlessness

Skin rash

Contraindications

Hypersensitivity to ingredients

Coadministration with antineoplastics, anticoagulants, and anti-infectives (including antivirals), as well as cobicistat, boceprevir, voriconazole, and telaprevir

Alzheimer disease, bipolar disorder, psychosis, schizophrenia, tyramine-containing foods

Cautions

Avoid strong sunlight

Inducer of CYP3A4

May reduce efficacy of oral contraceptives and concentrations of CYP3A4 substrate drugs

Quality varies widely among commercial products; some contain very low quantities of hypericin

Drug may cause serious interactions with other medications

Worsening of dementia in people with Alzheimer disease suggested

May precipitate psychotic episodes in patients with schizophrenia

May precipitate mania symptoms in bipolar patients and may speed up the cycles between mania and depression

May precipitate mania symptoms in patients with major depression

May alter serotonin levels in the brain, may interfere with anesthesia, and may lead to serious heart complications during surgery; stop therapy two weeks prior to surgery

Pregnancy

Not recommended; studies on effects in the developing fetus lacking

Lactation

Hypericin and hyperforin detected in breast milk; avoid during lactation until long-term studies show a lack of toxicity in breastfeeding infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

A chemical in St. John's wort called hypericin has been suggested to have an effect on improving mood; more recently, information suggests other chemicals like hyperforin may play a larger role; the chemicals may act on messengers in the nervous system that regulate mood

Reports have shown that hyperforin may have a high affinity for GABA, adenosine, and glutamate receptors, inhibit monoamine oxidase type A (MAO-A) and type B (MAO-B), and may inhibit norepinephrine, serotonin, and dopamine reuptake; downregulation of beta-adrenergic receptors also reported

Topical: antibacterial, increased epithelialization

Absorption

Bioavailability: 15-20% (hypericin, pseudohypericin, hyperforin

Peak serum time: 0.5-3 hr (pseudohypericin); 4.6-8.1 hr (hypericin); 2.8-3.6 hr (hyperforin)

Steady-state levels: 4 days

Distribution

Protein-bound: Highly bound

Elimination

Half-life: 25 hr (hypericin); 9 hr (hyperforin)