Washout Period for St. John's Wort Before Starting Antidepressants
Patients should discontinue St. John's wort at least 2 weeks before initiating any antidepressant medication to avoid potentially life-threatening serotonin syndrome and allow adequate clearance of its enzyme-inducing effects. 1
Rationale for the 2-Week Washout Period
The 2-week discontinuation period is necessary for several critical safety reasons:
Serotonin syndrome risk: St. John's wort combined with SSRIs or MAOIs is contraindicated due to the risk of serotonin syndrome, a potentially fatal condition characterized by agitation, tremor, hyperthermia, and altered mental status. 1
Enzyme induction effects: St. John's wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, which significantly alters the metabolism of numerous medications including SSRIs and other antidepressants. 1 The 2-week period allows these enzyme systems to return toward baseline activity.
Surgical guideline precedent: The American College of Clinical Pharmacology recommends discontinuing St. John's wort at least 2 weeks before surgical procedures due to multiple drug interactions and serotonergic effects, establishing this timeframe as the standard for managing its pharmacologic effects. 1
Clinical Decision Algorithm
Step 1: Assess current St. John's wort use
- Confirm the patient is taking St. John's wort and document the dose and duration of use. 1
- Note that St. John's wort is not FDA-regulated, meaning content and potency vary unpredictably between products. 1
Step 2: Discontinue St. John's wort immediately
- Instruct the patient to stop all St. John's wort products. 1
- Document the discontinuation date to calculate the washout period accurately.
Step 3: Wait minimum 2 weeks
- Do not initiate any antidepressant therapy (SSRI, SNRI, TCA, MAOI, or other) until at least 14 days have elapsed. 1
- This applies to all classes of antidepressants due to the broad enzyme-inducing effects and serotonergic properties of St. John's wort. 1
Step 4: Initiate antidepressant therapy
- After the 2-week washout, begin the selected antidepressant according to standard dosing guidelines. 2
- Monitor closely for therapeutic response and adverse effects beginning within 1-2 weeks of initiation. 2
Important Clinical Caveats
Monitoring during washout: Patients with moderate depression may experience symptom worsening during the 2-week washout period. Close clinical monitoring is essential, with consideration for more frequent contact or interim supportive interventions if clinically indicated. 2
Drug interaction persistence: While 2 weeks is the minimum recommended washout, some enzyme induction effects may persist slightly longer in individual patients, particularly those who used St. John's wort chronically at high doses. 1
Patient education requirements: Patients must understand that St. John's wort is not simply a "natural" alternative but a pharmacologically active substance with serious drug interactions. 1 They should disclose its use to all healthcare providers. 1
Contraceptive considerations: If the patient is female and of childbearing potential, note that St. John's wort reduces oral contraceptive effectiveness. 1 Counsel on backup contraception during the washout period and after starting antidepressants, as some antidepressants also carry pregnancy risks.
No gradual taper needed: Unlike prescription antidepressants, St. John's wort does not require gradual dose reduction and can be stopped abruptly without withdrawal syndrome. 1