How long does Wellbutrin stay in your bloodstream? An overview of its elimination

October 10, 2025 •

3 min read

According to the FDA, the mean elimination half-life of bupropion, the active ingredient in Wellbutrin, is approximately 21 hours after chronic dosing. The answer to how long does Wellbutrin stay in your bloodstream is complex, as several factors, including active metabolites and individual differences, affect its complete removal.

Quick Summary

Wellbutrin and its active metabolites typically clear the body within 4 to 7 days, with the half-life of the parent drug being around 21 hours. Its elimination is affected by metabolism, liver health, kidney function, and the medication's formulation.

Key Points

Bupropion Half-Life: The average half-life of the parent bupropion drug is approximately 21 hours.
Metabolites Extend Clearance: Wellbutrin is metabolized into active compounds with longer half-lives (up to 37 hours), meaning total clearance takes longer than the parent drug's half-life suggests.
Total Elimination Period: It takes roughly 4 to 7 days for Wellbutrin and its active metabolites to be completely cleared from the bloodstream after the last dose.
False-Positive Risk: Bupropion can trigger false-positive results for amphetamines on certain urine drug tests; confirmatory testing can distinguish between the substances.
Factors Impacting Rate: An individual's metabolism, liver function, and kidney health are among the most important factors influencing how quickly the drug is cleared.
Tapering is Essential: Abruptly stopping Wellbutrin can cause withdrawal symptoms; a gradual tapering schedule guided by a doctor is recommended for discontinuation.

Understanding Wellbutrin's Pharmacokinetics

Wellbutrin, known generically as bupropion, is an atypical antidepressant classified as a norepinephrine-dopamine reuptake inhibitor (NDRI). To understand its duration in the body, it's important to know the concept of half-life, which indicates the time required for half of a drug's concentration to be eliminated. Bupropion's half-life is about 21 hours. However, bupropion undergoes extensive metabolism in the liver by the enzyme CYP2B6, producing active metabolites with longer half-lives that also contribute to its presence and effects in the system.

The Role of Active Metabolites

Bupropion is metabolized into three primary active metabolites: hydroxybupropion, erythrohydrobupropion, and threohydrobupropion. These metabolites have significantly longer elimination half-lives than the parent drug.

Hydroxybupropion: Approximately 20 hours.
Erythrohydrobupropion: Approximately 33 hours.
Threohydrobupropion: Approximately 37 hours.

The extended half-lives of these metabolites mean that complete clearance of the drug and its byproducts takes longer than the parent drug's half-life alone. Steady-state levels of bupropion and its metabolites are typically reached within about eight days of regular dosing.

Timeline for Complete Elimination

Although the parent drug has a half-life of roughly 21 hours, full elimination from the body generally takes about five half-lives for most substances. Considering the longer half-lives of its active metabolites, Wellbutrin and its byproducts typically clear the bloodstream completely within approximately 4 to 7 days after the last dose.

Factors Affecting Clearance

Several individual factors can influence how quickly Wellbutrin is eliminated from the body. These include:

Liver Function: Since bupropion is metabolized in the liver, impaired liver function can slow down its processing and extend the time it stays in the system.
Kidney Function: The kidneys are responsible for eliminating the active metabolites. Problems with kidney function can affect this process.
Age and Genetics: Older individuals and those with specific genetic variations in metabolic enzymes may metabolize and eliminate bupropion more slowly.
Dosage and Duration of Use: Higher doses and long-term use can lead to greater accumulation, potentially increasing the time needed for complete elimination.
Drug Interactions: Certain medications can interfere with the enzyme that metabolizes bupropion, potentially increasing its concentration in the body.
Alcohol Consumption: Alcohol can interact with Wellbutrin, potentially increasing drug levels and the risk of side effects.

Wellbutrin Formulations: IR vs. SR vs. XL

Wellbutrin is available in different formulations that affect how quickly the drug is absorbed, but not the overall elimination half-life.


Feature	Immediate-Release (IR)	Sustained-Release (SR)	Extended-Release (XL)
Peak Absorption	Around 1.5 hours.	Around 3 hours.	Around 5 hours.
Dosing Frequency	Typically three times daily.	Typically twice daily.	Typically once daily.
Drug Release	Rapid release.	Releases over ~12 hours.	Releases over ~24 hours.
Elimination Half-Life	Bupropion half-life ~21 hours.	Bupropion half-life ~21 hours.	Bupropion half-life ~21 hours.

Drug Testing and False Positives

Most standard drug tests, including common pre-employment screens, do not specifically look for bupropion. However, because bupropion's chemical structure is similar to amphetamines, its metabolites can sometimes lead to a false-positive result for amphetamines or methamphetamines on certain urine screening tests. If this occurs, a more precise confirmatory test, such as gas chromatography/mass spectrometry (GC-MS), can distinguish between bupropion and actual amphetamine use. It is advisable to inform the testing facility if you are taking Wellbutrin.

Considerations for Discontinuation

Due to the elimination time of Wellbutrin and its metabolites, stopping the medication abruptly is not recommended. While Wellbutrin withdrawal symptoms are often less severe than those associated with some other antidepressants, a gradual tapering schedule under the guidance of a healthcare professional is the safest method. This allows the body to adjust slowly and minimizes the potential for withdrawal effects like mood changes, irritability, or fatigue. Always consult your doctor before making any changes to your prescription.

Conclusion

While the half-life of the parent drug bupropion is approximately 21 hours, its active metabolites have longer half-lives, extending the overall elimination period. Consequently, how long does Wellbutrin stay in your bloodstream? It typically takes about 4 to 7 days for the drug and its metabolites to be fully cleared. This timeframe can vary based on individual factors such as liver and kidney function. The different formulations (IR, SR, XL) impact absorption rate but not the elimination half-life. Be aware of the potential for false-positive amphetamine tests and always follow medical advice for safe discontinuation to avoid withdrawal symptoms. For comprehensive clinical details, refer to the FDA's information on bupropion.

Frequently Asked Questions

Yes, bupropion has a half-life of about 21 hours, whereas its active metabolites—hydroxybupropion, threohydrobupropion, and erythrohydrobupropion—have longer half-lives ranging from 20 to 37 hours. The metabolites take longer to clear the body.

Yes. Due to its chemical structure, bupropion can cause false-positive results for amphetamines on certain urine immunoassay screening tests. A follow-up confirmatory test, like gas chromatography/mass spectrometry (GC-MS), can differentiate it from actual amphetamine use.

While the absorption and release of Wellbutrin SR (sustained-release) and XL (extended-release) differ, they share a similar elimination half-life of about 21 hours. The different formulations primarily affect dosing frequency and how consistently levels are maintained in the body.

Missing a single dose might not cause a noticeable difference for many people. However, missing several doses could lead to a return of your original symptoms, such as low mood, fatigue, or nicotine cravings. You should not abruptly stop the medication without consulting a doctor.

You should always consult your doctor for a safe tapering schedule and to determine the appropriate washout period before starting a new medication. The relatively long half-life of bupropion's metabolites requires careful management to avoid drug interactions.

While there is limited specific research, drugs can typically be detected in hair for up to 90 days or longer. Like with urine tests, this is not a standard screening, and other factors affect detection.

Unlike some other antidepressants, withdrawal symptoms from Wellbutrin are often mild or non-existent, as it does not target serotonin. However, some people may experience irritability, headaches, or mood changes, which is why a doctor-supervised tapering is recommended.