How long does it take for Wellbutrin (bupropion) 150mg XL to be eliminated from the system after discontinuation?

Bupropion 150mg XL Elimination Timeline

Wellbutrin (bupropion) 150mg XL takes approximately 4-5 days to be substantially eliminated from your system after discontinuation, though complete clearance of all active metabolites requires approximately 8-10 days. 1

Pharmacokinetic Elimination Profile

The elimination of bupropion XL follows a predictable timeline based on its half-life and active metabolites:

Parent Drug Clearance

• Bupropion itself has a half-life of approximately 21 hours 1
• After 5 half-lives (the standard for near-complete elimination), bupropion is essentially cleared in 4-5 days 1
• The XL formulation has a Tmax of approximately 5 hours, meaning peak absorption is delayed compared to other formulations 1

Active Metabolite Clearance (The Critical Factor)

The complete elimination timeline is actually determined by bupropion's active metabolites, which persist longer than the parent drug:

• Hydroxybupropion (primary active metabolite): half-life of approximately 20 hours, cleared in 4-5 days 1
• Threohydrobupropion: half-life of approximately 37 hours, requiring 7-8 days for complete clearance 1
• Erythrohydrobupropion: half-life of approximately 33 hours, requiring 7-8 days for complete clearance 1

At steady state, hydroxybupropion concentrations are 4-7 fold higher than the parent drug, with an AUC approximately 10-fold greater, making metabolite clearance the rate-limiting step 1

Clinical Implications for Discontinuation

Withdrawal Symptom Timeline

While the drug clears within 8-10 days, withdrawal symptoms may emerge earlier and persist:

• Symptoms typically emerge within 1-2 days after discontinuation of antidepressants with shorter half-lives 2
• Common withdrawal symptoms include irritability, mood changes, sleep disturbances, anxiety, and fatigue 3
• These symptoms are usually mild and last 1-2 weeks, though they can be rapidly extinguished with reinstitution of medication 2

Tapering Recommendations

Gradual tapering is recommended to minimize withdrawal symptoms, even though the evidence base is limited 3, 4:

• Most studied tapering regimens lasted 4 weeks or less, though these may be too rapid for some patients 4
• If withdrawal symptoms emerge during tapering, slow the taper rate 3
• The Mayo Clinic recommends gradual tapering to minimize risk of withdrawal symptoms and potential relapse 3

Important Clinical Caveats

Distinguishing Withdrawal from Relapse

A critical pitfall is confounding withdrawal symptoms with relapse of depression, as withdrawal symptoms like low mood and anxiety can mimic depressive relapse 4. This distinction becomes relevant in the first 2 weeks after discontinuation when withdrawal symptoms are most likely 2.

Drug Interaction Considerations

Even after discontinuation, bupropion's effects on drug metabolism persist until complete clearance:

• Bupropion inhibits CYP2D6, which may affect clearance of other medications metabolized by this enzyme for up to 8-10 days 1
• Consider this timeline when initiating medications that interact with CYP2D6 1

Special Population Considerations

Elimination may be prolonged in certain populations:

• Patients with moderate to severe hepatic impairment may have delayed clearance, as bupropion is extensively metabolized by the liver 5, 1
• Patients with moderate to severe renal impairment may experience accumulation of metabolites, which are cleared renally 5