Alternative
St. John's Wort
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St. John's Wort
, St John's Wort, Hypericum perforatum, Hypericin
See Also
Herbal Medicine
Indications (evidence-based)
Dysthymia
Mild to moderate
Major Depression
Do not use for severe
Major Depression
Precautions
Potency and purity not regulated
Discontinue at least 5 days before surgery
Risk of
Serotonin Syndrome
when used with
Selective Serotonin Reuptake Inhibitor
s
Significant
Drug Interaction
s (see below)
Counters the activity of
Warfarin
, cardiac drugs, HIV agents, and
Oral Contraceptive
s
Ingredients
Derived from flowering plant Hypericum perforatum
Contents
Hypericin (Naphthodianthrone) is Active Ingredient
Amount of Hypericin in plant is quite variable
Mechanism
Hypericin
Inhibits
Serotonin
,
Norepinephrine
, and
Dopamine
uptake
Binds to
GABA Receptor
s in vitro
Hypericin is a
MAO Inhibitor
at high dose
Not present at standard doses described below
Pharmacokinetics
Hypericin
Half life: 24 to 48 hours
Peaks effect: 5 hours
Excretion mechanism unknown
Induces
Cytochrome P450
3A4
Efficacy
Effective in mild-moderate depression in recent trials
Better than
Placebo
in mild-moderate depression
Similar effect when compared to standard agents
Elavil
75 mg
Imipramine
100-150 mg
Fluoxetine
20 mg
Sertraline
75 mg
References
Kasper (2002) Psychopharmacology 164:301-8 [PubMed]
Lawvere (2005) Am Fam Physician 72:2249-54 [PubMed]
However trial results are inconsistent (despite above)
Several reviews have shown marginal efficacy
Do not use for severe
Major Depression
References
(2002) JAMA 287:1807-14 [PubMed]
Werenke (2004) J Clin Psychiatry 65:611-7 [PubMed]
Early clinical trials flawed
Placebo
response rate low
Trials of very short duration (most 4-8 weeks)
Depression diagnosis not well established
Hypericin dosages varied widely across studies
Compared with too low dose standard
Antidepressant
s
Linde (1996) BMJ 313: 253 [PubMed]
Adverse Effects
Transient Photosensitivity (most common side effect)
Elevated, pruritic, red lesions in response to sun
Neuropathic pain
Dry Mouth
Dizziness
Gastrointestinal side effects (e.g.
Constipation
)
Confusion
Allergic Reaction
Fatigue
Serotonin Syndrome
Drug Interactions
Effects
St. John's Wort has more cardiac
Drug Interaction
s than any other supplement
Induces
CYP3A4
and therefore decreases
CYP3A4
metabolized drug serum levels
More than half of all medications are 3A4 metabolized
Also affects
CYP2C9
,
CYP1A2
and the
P-Glycoprotein
transport
Protein
Drugs with increased effects
SSRI
and other serotinergic agents (
Serotonin Syndrome
Risk)
May interact with
Antidepressant
s (e.g.
SSRI
s),
Tramadol
or other causative agents
Consider 2 week "washout" when switching to
SSRI
Clopidogrel
(
Plavix
)
Increased bleeding risk
Drugs with decreased activity or serum levels when used with St. John's Wort (esp.
Cytochrome P450
)
Cyclosporine
Digoxin
Oral Contraceptive
s
Hall (2003) Clin Pharmacol Ther 74:525-35 [PubMed]
Nevirapine
and
Indinavir
used in
HIV Infection
management
de Maat (2001) AIDS 15:420-1 [PubMed]
Statin
s
Tegretol
Verapamil
Factor Xa Inhibitor
s (
Rivaroxaban
,
Apixaban
)
Warfarin
Reference
Markowitz (2003) JAMA 290:1500-4 [PubMed]
Zhou (2004) J Psychopharmacol 18:262-76 [PubMed]
Dosing
St. John's Wort 300 mg three times daily or
St. John's Wort 450 mg twice daily
Cost
$10 to $25 per month
References
(1997) Med Lett Drugs Ther 39(1014): 107-8 [PubMed]
Ang-Lee (2001) JAMA 286:208-16 [PubMed]
Cupp (1999) Am Fam Physician 59(5):1239-44 [PubMed]
Lawvere (2005) Am Fam Physician 72:2249-54 [PubMed]
Woelk (2000) BMJ 321: 536-9 [PubMed]
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