HERBAL MONOGRAPHS ST. JOHN'S WORT/721
Central Nervous System Effects: Restlessness (0.3%) and
fatigue (0.4%) occurred in 3250 patients in one study of
depressed patients (Woelk, 1994). In another study, fatigue/
tiredness was reported in 5% of subjects, and restlessness in
6% (Vorbach, 1997). Symptoms are difficult to evaluate
since the herb is being used to treat depression, which may
have similar symptoms. Headache was noted in 7% of
studies reviewed (Wheatley, 1998).
Fertility Effects: High concentrations of St. John's Wort in
vitro, was mutagenic to sperm cells and adversely effected
oocytes. The data suggests St. John's Wort given at high
concentrations damages reproductive cells (Ondrizek, 1999).
Gastrointestinal Effects: Gastrointestinal effects were noted
in 0.6% of patients in one study. Anorexia occurred in 0.55%
(n=18), diarrhea occurred in 0.55% (n=18), nausea occurred
in 0.55% (n=18), and gastrointestinal pain or stomachache
occurred in 0.55% (n=18) of 3250 patients taking Hypericum
extract 300 milligrams 3 times daily (Woelk, 1994). Three
percent of patients in one study developed dry mouth and 5%
had gastrointestinal complaints Vorbach, 1997). Constipation
was reported in 5% of cases reviewed (Wheatley, 1998).
Dertnatologic Effects: Photosensitization has been observed
in animals following intakes of large quantities of the drug
(starting at 3 g per kg body weight, which would be 150 g
for a person weighing 50 kg). St. John's Wort photosensiti-
zation is dose-related, and has occurred with plasma
concentrations of 50 meg of hypericin per ml, according to
Schulz' Rational Phytotherapy—six orders of magnitude
above that of patients taking an extract of 300 mg of 0.6%
hypericin three times a day. Hypericism is defined as a
sensitivity to light seen in animals who have ingested certain
Hypericum species. The Hypericum pigments are carried to
the skin, and in the unpigmented, unhaired portions of the
skin of sheep, cattle, horses, goats and swine may produce
sunlight induced rash and blisters (Giese, 1980; Southwell &
Campbell, 1991). However, such a reaction is unlikely with
administration of therapeutic dosages in humans.
- Hypericum extract, especially at higher doses or with
long-term use, may cause photosensitivity with sunburn-like
lesions and inflammation of the mucous membranes, at least
in animals (Duran & Song, 1986). Photosensitization has
been demonstrated in a controlled clinical trial using metered
doses of hypericin and subsequent exposure to UVA/UVB
radiation (Roots, 1996).
- Significant phototoxicity did occur in HIV-infected
persons administered intravenous hypericim, 0.25-0.5 mg/kg
twice weekly, or 0.25 mg three times weekly, or oral
hypericin 0.25 mg/kg daily (Gulick, 1999).
- Pruritus and exanthema occurred in 17 of 3250 patients
(0.52%) taking Hypericum extract 300 milligrams three
times a day (Woelk, 1994). Pruritus was found in 2% of
patients taking Hypericum for depression (Wheatley, 1998).
- A case report involved one patient taking St. John's Wort
who developed subacute polyneuropathy after sun exposure
(Bove, 1998).
Drug Interactions:
MAOI—Although there is poor documentation, concomitant
administration of St. John's Wort and a MAOI , such as
tranylcypromine, phenelzine, may lead to increased effects
and possible toxicity (hypertensive crisis)-See~Contraindica-
tions (Hoelzl & Ostrowski, 1986; Mueller & Schaefer, 1996;
Suzuki, 1984). It is prudent to avoid concomitant use with
beta-sympathomimetic amines, e.g., ma huang or pseu-
doephedrine (Miller, 1998).
SSRFs—St. John's Wort taken concomitantly with an SSRI,
such as fluoxetine, paroxetine, sertraline, fluvoxamine or
citalopram, may lead to an increased effect and possible
toxicity "serotonin syndrome", e.g., sweating, tremor,
flushing, confusion and agitation. St. John's Wort has slight
serotonin reuptake properties. A case report suggests that co-
administration of St. John's Wort with paroxetine has
resulted in a clinical syndrome resembling a sedative/hypnot-
ic intoxication (Gordon, 1998).
Tannic acids present in St. John's Wort may inhibit the
absorption of iron (Miller, 1998).
Concomitant use with other photosensitizers, such as tetracy-
clines, sulfonamides, thiazides, quinolones, piroxicam and
others should be avoided (Miller, 1998).
Hypericum extract has been reported to significantly prolong
narcotic-induced sleeping times and to antagonize the effects
of reserpine (Okpanyi, 1987).
Cyclosporine — Decreased serum concentrations have
occurred with use of St. John's Wort (Bon, 1999). Acute
cellular transplant rejection in heart transplant patients due to
an interaction between St. John's Wort and Cyclosporine has
been reported. St. John's Wort has been proven to induce the
cytochrome P450 enzyme system, the major pathway for
cyclosporine metabolism. Heart transplant rejection has been
reported as soon as 3 weeks after St. John's Wort is added to
the drug regimen of heart transplant patients maintained on
cyclosporine therapy (Ruschitzka, et al., 2000).
Indinavir — An open label study was conducted involving
healthy volunteers that were administered 800 mg indinavir
every 8 hours along with 300 mg St. John's Wort standard-
ized to 0.3% hypericin 3 times daily. Results showed a 57%
reduction in the area under the curve for the protease
