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How Long Does Wellbutrin Stay In Your System?

Wellbutrin (Bupropion) is an antidepressant that is hypothesized to function as a norepinephrine-dopamine reuptake inhibitor (NDRI).  It is believed to predominantly increase levels of norepinephrine and only affects dopamine to a minor extent.  As a result of its noradrenergic mechanism of action, it is considered “atypical” when compared to other serotonergic antidepressants.

Unlike serotonergic antidepressants, Wellbutrin has a favorable effect profile in that it may enhance cognition, increase energy, boost libido, and promote weight loss.  For this reason, it remains among the most popular atypical antidepressant agents on the market and is often prescribed as an adjunct agent to counteract unwanted side effects of SSRIs such as: brain fog, fatigue, sexual dysfunction, and weight gain.  Though many people respond well to the Wellbutrin, others have less pleasant experiences with adverse effects such as epileptic seizures.

Experiencing adverse effects or simply desiring to function “drug-free” may lead users to discontinue treatment.  With the help of a medical professional, many people are able to successfully stop taking Wellbutrin.  However, following discontinuation of treatment, many individuals aren’t sure how long the Wellbutrin lingers in their system.

How long does Wellbutrin stay in your system after stopping?

If you stopped taking this drug, you can expect to experience some irritating Wellbutrin withdrawal symptoms.  As these discontinuation symptoms increase in severity, many wonder whether the bupropion has been completely eliminated from systemic circulation.  To determine how long it takes for bupropion to leave your system after your last dose, it is necessary to consider its elimination half-life.

The elimination half-life of bupropion falls within the range of 8 to 39 hours, for an average of 21 hours.  Based on this information, it can be estimated that bupropion remains in your plasma for 1.83 days to 8.94 days after your last dose.  Considering the average elimination half-life of 21 hours, we can hypothesize that Wellbutrin will likely stay in your system for 4.81 days after you stop taking it.

That said, it is necessary to consider that bupropion forms various metabolites that may be eliminated at a slower rate.  Various metabolites formed upon metabolism of bupropion include: hydroxybupropion, threohydrobupropion, and erythrohydrobupropion.  Major metabolite hydroxybupropion has an elimination half-life of 20 hours, while minor metabolites threohydrobupropion and erythrohydrobupropion have respective half-lives of 37 and 33 hours.

This indicates that hydroxybupropion will get eliminated in 4.58 days (on average), which is usually quicker than the parent compound bupropion.  However, minor metabolites threohydrobupropion and erythrohydrobupropion could take 8.48 days and 7.56 days for complete respective elimination.  In other words, most people can expect bupropion and its metabolites to be cleared from plasma within 9 days of their last dose.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/bupropion
  • Source: http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-20-tab11A-Wellbutrin-Tabs-SLR028.pdf
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16368442

Variables that influence how long Wellbutrin stays in your system

On average, most users can expect to eliminate the bupropion in around 5 days, and various metabolites from their system in less than 9 days after their final dose.  However, not everyone fits the “average” elimination time estimations.  Some individuals will excrete the drug quicker than average, while others will excrete it at a slower pace.  Variables such as: hepatic function, individual factors, dosage, and term of administration can affect how long Wellbutrin stays in your system.

  1. Hepatic Function

It is well-documented that hepatic impairment can prolong the elimination of bupropion from the plasma, as well as its metabolites.  One study compared the elimination half-life of bupropion (and its metabolites) among those with alcoholic liver disease to those with normative liver function.  Among individuals with alcoholic liver disease, the elimination half-life of bupropion’s major metabolite “hydroxybupropion” was 32 hours, compared to just 21 hours for healthy individuals.

This suggests that hydroxybupropion can take around 7.33 days to excrete among those with alcoholic liver disease, compared to just 4.81 days among those with normative hepatic function.  On the extreme end of the spectrum, certain individuals with alcoholic liver disease took over 10 days to fully eliminate hydroxybupropion from plasma after just a single dose of Wellbutrin.  Other research suggests that bupropion’s half-life is around 10 hours greater among those with hepatic cirrhosis compared to healthy individuals.

Specifically, the study noted a 29 hour bupropion half-life among those with severe hepatic cirrhosis compared to a 19 hour half-life among healthy individuals.  Additionally, it was noted that the average half-lives of threohydrobupropion and erythrohydrobupropion increased by 5-fold and 2-fold (respectively).  A 5-fold increase in the 37 hour half-life of threohydrobupropion indicates that it could potentially remain in systemic circulation for 42.4 days after ingestion.

Realize that a person with normative hepatic function will excrete bupropion substantially quicker than those with alcoholic liver disease, cirrhosis, or any other form of liver impairment.  Generally the greater the degree of the hepatic impairment, the longer the drug will remain in systemic circulation.

  • Source: http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-20-tab11A-Wellbutrin-Tabs-SLR028.pdf
  1. Individual factors

Two healthy individuals may take a single 150 mg dose of Wellbutrin simultaneously, yet one person may eliminate the bupropion (and its metabolites) quicker than the other.  Though hepatic function plays a substantial role in metabolism and elimination, it is not the only factor to consider.  Other factors such as: a person’s age, body mass, and genetics  may influence how long bupropion stays in your system.

Age: Some research suggests that the average half-life of bupropion after a single dose is approximately 14 hours in young, healthy adults.  However, this figure increases by 20 hours in the elderly to 34 hours.  This means that among individuals 65 or older, it takes 7.8 days to eliminate bupropion from plasma; 2-fold as long as younger adults.

Elderly patients also appear to be at greater risk of accumulating bupropion and its metabolites when administered consistently over a long-term.  For this reason, the drug’s half-life among elderly may significantly exceed 34 hours when administered over a long-term (due to accumulation).  Multi-dosing of bupropion yields a half-life of 21 hours in healthy young adults, but this could be increased to 41 hours among elderly – taking nearly 10 days to fully eliminate.

If you are younger, you should be able to clear bupropion significantly faster than elderly individuals.  The longer half-life in elderly may be related to: diminishing hepatic (or renal) function, various health problems, lower levels of plasma proteins, co-administration of certain medications, and overall poorer physiologic function.

  • Source: http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-20-tab11A-Wellbutrin-Tabs-SLR028.pdf
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8786247

Body mass + Fat (%): Your body mass and body fat percentage may impact how long bupropion and its metabolites are likely to remain in your system after your last dose.  In most cases, the greater your body mass relative to the drug you’re taking, the quicker you can expect to eliminate it from plasma after ingestion.  If bupropion were administered to a large, massive individual at 150 mg and a small, less massive individual at the same dose – the larger person may excrete it sooner.

That said, since bupropion is considered lipophilic, its volume of distribution may increase.  This increase in distribution can result in an increased half-life and slower detoxification.  If you have very little body fat, the distribution of bupropion (and its metabolites) will likely be reduced, resulting in quicker overall detoxification.

Genetics: Wellbutrin is extensively metabolized by CYP450 (cytochrome P450) isoenzymes within the liver, specifically CYP2B6.  The function of CYP2B6 is directly influenced by the expression of the CYP2B6 gene.  Research shows that alleles such as *6B haplotypes significantly alter hydroxylation (metabolism) of bupropion, thereby affecting its elimination half-life.

Therefore it is necessary to consider your specific CYP2B6 alleles when contemplating how long it’ll take to metabolize and excrete bupropion (and its metabolites) from your system.  Research indicates that half-life of bupropion can vary by up to 5.5-fold and metabolite hydroxybupropion can vary by 7.5-fold in its half life.  Depending on your CYP2B6 expression, you may excrete bupropion and hydroxybupropion quickly in less than 3 days or it may take up to 9 days.

It should also be noted that expression of CYP2D6 genes may influence bupropion’s elimination half-life.  Some evidence suggests that CYP2D6 poor metabolizers tend to accumulate bupropion metabolites to a greater extent than normative (extensive) metabolizers.  Though the CYP2B6 gene has the greatest impact on bupropion metabolism, the CYP2D6 gene likely still makes a difference, albeit to a lesser extent.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/15083067
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8885123

Metabolic rate: A person’s basal metabolic rate (BMR) is thought to have a slight influence on the elimination half-life of medications.  Individuals with high BMRs are thought to metabolize and excrete exogenous substances like bupropion quicker than individuals with low BMRs.  If you consider yourself to have a high BMR, you may excrete bupropion (and its metabolites) faster than someone with a lower BMR.

BMR may also have an indirect influence on bupropion excretion via its effect on body fat.  Individuals with high BMRs tend to have less body fat, which is known to reduce distribution of bupropion throughout the body.  On the other hand, those with low BMRs may have more body fat, ultimately increasing distribution of bupropion throughout the body – resulting in a slower detoxification.

Renal function: A majority of bupropion is processed by the kidneys and excreted via urine.  Research indicates that renal function can influence the elimination of bupropion metabolites following hepatic metabolism.  Among individuals with renal impairment, bupropion metabolites accumulate to a significantly greater extent, indicating less efficient excretion.  The greater the extent of the renal impairment, the slower the excretion of bupropion metabolites.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15292684
  1. Term of Administration (Acute vs. Chronic)

The duration over which a person has taken Wellbutrin can affect how long it remains in their system after stopping.  An individual that took Wellbutrin for one day will likely excrete the drug significantly quicker than someone that’s taken the drug daily for several years.  This is due to the fact that the elimination half-life of a single dose is only 14 hours, compared to 21 hours for multiple doses.

Since most people don’t take random intermittent single doses of Wellbutrin, the single-dose half-life doesn’t apply.  However, if you happened to just take one dose of Wellbutrin, you’d likely eliminate the bupropion from your plasma within 3.21 days – compared to 4.81 days in a multi-dose user.  Research notes that steady-state plasma concentrations of Wellbutrin are attained after 8 days of consistent administration.

Individuals who’ve taken Wellbutrin for at least 8 days will take longer to eliminate the drug from their plasma than those who’ve used the medication for less than 8 days.  This is due to the fact that longer term users have attained peak concentrations of the drug within their system, whereas acute users haven’t.  Since acute users haven’t reached peak cumulative concentrations of the drug in their bloodstream and tissues – they’ll excrete it quicker.

Additionally, it is necessary to understand that long-term users are more likely to be taking higher doses of Wellbutrin than short-term users.  This is due to the fact that over the long-term, users build up tolerance to the effect of low doses and require increases (doubling, tripling, etc.) of their starting dose to maintain efficacy.  It is understood that when doses increase, accumulation of bupropion and its metabolites may also accumulate, and elimination efficiency is reduced.

  1. Dosage (Low vs. High)

The dosage of Wellbutrin that you were taking could affect how long it stays in your plasma following cessation.  Particularly, the greater the dosage that you ingested per day, the longer you can expect the drug to remain in your system after discontinuation.  If you were to ingest 300 mg of Wellbutrin, you’d take slightly longer to excrete the drug than if you were to take half of the dosage at 150 mg.

Going by the 21 hour half-life of bupropion, we can conclude that a person ingesting 300 mg of bupropion will have excreted 50% of their dose in 21 hours – meaning 150 mg is still in their system.  On the other hand, a person who took 150 mg will have excreted 50% of their dose in 21 hours, bringing them down to just 75 mg.  If you discontinue from a lower dose, the drug will be eliminated from your system at a slightly quicker rate than if you took a higher one.

Furthermore, lower doses place less of a burden on liver enzymes during hepatic metabolism.  Upon ingestion of a high dose, the efficiency of hepatic CYP2B6 enzymes may decrease, distribution of the drug may increase throughout the body, and renal clearance rate may also drop slightly.  Therefore, expect the elimination half-life of bupropion (and metabolites) to be slightly longer if you discontinued from a high dose.

  1. Co-ingestion of other drugs (CYP2B6)

Simultaneous ingestion of drugs (with bupropion) that affect CYP2B6 isoenzymes may alter metabolism and elimination of bupropion.  Agents that act as CYP2B6 inhibitors are thought to interfere with the metabolic breakdown of bupropion to form various metabolites.  Interference in this metabolism may result in a significant increase in bupropion’s elimination half-life, ultimately prolonging excretion.

Examples of some known CYP2B6 inhibitors include: Curcumin, Orphenadrine, ThioTEPA, and Ticlopidine.  Should you have taken any of these substances along with Wellbutrin, it’s likely that it’ll take longer-than-average to excrete.  On the other hand, agents known as CYP2B6 inducers tend to have the opposite effect of inhibitors.

CYP2B6 inducers serve to enhance functionality of CYP2B6 isoenzymes, thereby increasing the efficiency of bupropion metabolism.  Examples of such CYP2B6 inducers include: Carbamazepine, Phenobarbital, Phenytoin, and Rifampicin.  Ingestion of an enzymatic inducer may substantially expedite the elimination of bupropion from your system.

Note: CYP2B6 inhibitors/inducers differ in degree of inhibition/induction, with some being more potent than others.  Furthermore, the dosage of each aforementioned inhibitor/inducer is likely to affect the extent of inhibition/induction.

Wellbutrin (Bupropion): Absorption, Metabolism, Excretion

Following oral administration of Wellbutrin, the pharmacologically active chemical “bupropion” is absorbed by the gastrointestinal (GI) tract.  Peak plasma concentrations of bupropion appear approximately 5 hours post-ingestion of the “XL” (extended-release) version, 3 hours post-ingestion of the “SR” (sustained-release) version, and 1.5 hours post-ingestion of the “IR” (immediate-release) version.  An estimated 84% of bupropion binds to plasma proteins, with similar binding from the pharmacologically active metabolite hydroxybupropion.

Bupropion is subject to extensive first-pass hepatic metabolism, with only a small percentage of unchanged bupropion reaching systemic circulation.  Metabolism is predominantly facilitated by CYP2B6 isoenzymes, which convert bupropion to its principal (pharmacologically active) metabolite “hydroxybupropion” via hydroxylation of the tert-butyl group.  Minor metabolites are also formed from bupropion via carbonyl group reduction including: threohydrobupropion and erythrohydrobupropion – both of which are amino-alcohol isomers.

As a result of its lipophilic properties, bupropion is distributed throughout the body and is soluble in fat stores.  Peak concentrations of hydroxybupropion (as well as erythrohydrobupropion and threohydrobupropion) appear 7 hours after administration of Wellbutrin XL.  The elimination half-life of hydroxybupropion is approximately 20 hours, whereas respective half-lives of erythrohydrobupropion and threohydrobupropion are 33 and 37 hours.

Based on these half-lives, we can conclude that hydroxybupropion, erythrohydrobupropion, and threohydrobupropion are likely to remain in the system for averages of: 4.58 days (hydroxy), 7.56 days (erythro), and 8.48 days (threo).  Prior to renal excretion, oxidation of the bupropion side chain forms “metachlorobenzoic acid,” a glycine conjugate.  Research suggests that meta-chlorobenzoic acid is excreted as the major urinary metabolite.

An estimated 87% of an orally-administered bupropion dose will have been excreted via urine, whereas approximately 10% will be excreted via feces.  Of the excreted drug, only 0.5% will appear as unchanged bupropion.  A majority will appear as meta-chlorobenzoic acid, and to a lesser extent, other bupropion metabolites.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/bupropion
  • Source: http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-20-tab11A-Wellbutrin-Tabs-SLR028.pdf
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16368442

How to get Wellbutrin out of your system

Assuming you’ve recently stopped taking Wellbutrin, you may be doing everything in your power to detoxify your body.  If you’ve been taking the drug for awhile, you’re probably aware that it may have accumulated within bodily tissues (e.g. fat stores) and could take longer to fully excrete.  For this reason, you may want to consider taking extra steps to expedite the excretion of bupropion.  Prior to implementing any of the suggestions listed below, always confirm their safety and hypothesized efficacy with a medical professional.

  1. Stop taking it: The easiest way to ensure that the drug gets fully excreted from your body is to stop taking it. Discontinuation of Wellbutrin isn’t easy, and should only be attempted under professional medical guidance. However, the sooner you quit taking Wellbutrin, the faster your body can begin purging itself of bupropion and its various metabolites.
  2. Burn body fat: It is known that bupropion is a lipophilic chemical, meaning it is soluble in body fat. The greater your percentage of body fat, the more bupropion metabolites you may have accumulated within fat stores. If you want to really expedite the excretion of bupropion metabolites, you’ll want to burn off excess body fat.  Burning fat will force your body to eliminate metabolites rather than maintain them in storage.
  3. Hydration: Staying hydrated is good for your general health, but also can be beneficial for elimination of Wellbutrin via urine. Urinary excretion of Wellbutrin may be affected by urinary flow rate, which in turn is influenced by your level of hydration. The greater your level of hydration, the higher your urinary flow rate.  As urinary flow rate increases, excretion of drugs like Wellbutrin is optimized.
  4. Supplements: Any supplements that effectively optimize liver and kidney function may aid in the excretion of bupropion. Additionally, some individuals may want to consider taking activated charcoal if they suspect that Wellbutrin may be lingering in their system for longer than expected. Activated charcoal binds to exogenous substances and toxins within the body, significantly enhancing detoxification protocols.  A CYP2B6 inducer may also expedite metabolism and excretion of Wellbutrin as well.  Talk to your doctor about strategic supplement usage to detoxify after stopping Wellbutrin.

How long has Wellbutrin stayed in your system after stopping?

If you’ve discontinued Wellbutrin, share a comment regarding how long you believe the drug stayed in your system.  Do you believe that the bupropion and its metabolites were fully excreted in under 10 days?  Or do you think it took you substantially longer than usual to excrete the drug?

To help others get an accurate understanding of how long bupropion metabolites stayed in your system after your final dose, mention factors such as: your age, the dosage you had taken, how long you were taking it, hepatic function, genetics, and/or co-ingestion of other medications.  Realize that most people should expect Wellbutrin to have been out of their system (along with its metabolites) in less than 2 weeks after their final dose.

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{ 1 comment… add one }
  • Karen August 18, 2016, 4:00 pm

    I am on day 3 and having a terrible headache!

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