Paxil (Paroxetine) is an antidepressant manufactured by GlaxoSmithKline that hit the market in 1992. It was originally approved by the FDA for the treatment of major depression in adults. The drug has since received FDA approval to treat a variety of other psychiatric and medical conditions including: generalized anxiety disorder, hot flashes, panic disorder, PTSD, and social phobia.
The drug functions principally as a potent selective-serotonin reuptake inhibitor (SSRI), thereby increasing serotonin levels (5-HT) extracellularly. In addition to its highly serotonergic properties, it elicits modest norepinephrine reuptake inhibition, but not substantially enough to be classified as an SNRI. Although many users derive therapeutic benefit from Paxil, others have a difficult time tolerating drug-related adverse effects.
Examples of some adverse effects associated with Paxil include: birth defects, blunted affect, nausea, increased suicidality, sexual dysfunction, and weight gain. Even among those who don’t experience adverse effects, many individuals report waning efficacy of Paxil over time (e.g. Paxil stops working) due to tolerance. As a result of adverse effects or waning efficacy, many users discontinue treatment, but wonder how long the Paxil stays in their system.
How long does Paxil stay in your system after stopping?
If you’ve completely discontinued treatment, you’re likely going to experience some brutal Paxil withdrawal symptoms. During this time, you may be confused regarding whether the Paxil is still in your system and causing side effects, or whether the drug is fully out of your system and your body is struggling to readjust to functioning without the drug. To determine how long Paxil stays in your system after stopping, it is necessary to consider its elimination half-life.
The elimination half-life of Paxil is documented as being 21 hours, suggesting that approximately 50% of the drug will be eliminated from systemic circulation in approximately 21 hours post-discontinuation. Based on this information, we can estimate that Paxil will stay in your system for around 4.81 days after your last dose. Other sources suggest that its half life is more likely to fall within a range of 21 to 24 hours, meaning that it could take up to 5.5 days for complete systemic elimination.
In any regard, you won’t need to worry about Paxil remaining in your body for a prolonged period after discontinuation; it is considered to be among antidepressants with the shortest half-lives. Unlike other psychiatric drugs that are broken down into metabolites with longer half-lives than their parent chemicals, the chief metabolite of Paxil known as “paroxetine catechol” isn’t thought to have a longer half-life than paroxetine itself. Therefore you won’t need to worry about metabolites potentially lingering in your body for a longer period than 5.5 days.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/paroxetine
Variables that influence how long Paxil stays in your system
Though Paxil is likely to stay in your system for an average of 4.81 to 5.5 days after your last dose, not everyone eliminates the drug in an average amount of time. Some people may eliminate the drug quickly in around 4 days time, while others may eliminate it slower in around 6 days time. Differences in systemic elimination of Paxil are generally due to variables such as: the individual, dosage, term of administration, and co-administered drugs.
Two people could simultaneously administer a 10 mg single dose of Paxil, yet one person may excrete the drug quicker than the other. Though both individuals may retain the paroxetine in their systems for a similar amount of time after stopping, the exact elimination times are often a result of individual factors. Individual factors that should be considered when contemplating how long Paxil stays in your plasma include: age, body mass, genetics, and hepatic function.
Age: Research has shown that the elimination half-life of paroxetine is extended among elderly individuals compared to younger adults. Those who are over the age of 65 and taking Paxil may eliminate the drug from their plasma at a slightly slower rate than younger adults for a variety of reasons. Prolonged elimination half-life of paroxetine among elderly patients may be a result of numerous age-related variables including: diminished hepatic blood flow, decreased plasma protein levels, and poorer overall physiologic function.
In addition, elderly adults are more likely to be taking additional medications to treat other medical conditions – these medications may increase Paxil’s half-life. Furthermore, the medical conditions themselves may interfere with the metabolism and excretion of paroxetine. Generally younger individuals are in better health, with superior physiologic function than elderly adults, resulting in faster systemic elimination of Paxil.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/2530794
Body mass: Many people suspect that the more massive an individual relative to the dosage of a drug they ingest, the quicker it is eliminated from their system. Assuming a short/light individual were to take 20 mg Paxil, and a tall/massive individual were to take this same dose, peak plasma concentrations would likely be less in the tall/massive person. This is due to the fact that more massive bodies are able to process standard doses with greater efficiency than less massive ones.
For this reason, it could be hypothesized that more massive individuals will eliminate a standard dose of Paxil with greater efficiency from their plasma than less massive people. However, it may be necessary to also consider body fat percentage. Since paroxetine is a highly lipophilic compound, it is extensively distributed throughout peripheral tissues following administration.
This extensive distribution may result in greater accumulation of the drug’s metabolites within bodily tissues of those with a high body fat percentage. A greater degree of accumulation is likely to facilitate prolonged retention, which in turn slows systemic elimination. Though the effect of body mass and fat on Paxil’s half-life may not be clinically significant, they likely have a minor impact.
Genetics: Your genetic expression of CYP2D6 is known to affect how you’ll respond to Paxil, as well as its pharmacokinetics. Individuals who are considered CYP2D6 ultrarapid metabolizers as a result of carrying 2+ CYP2D6 alleles will exhibit increased clearance and decreased elimination half-life of paroxetine. On the opposite end of the spectrum, those who are considered CYP2D6 poor metabolizers may have zero functional CYP2D6 alleles.
A CYP2D6 poor metabolizer will exhibit decreased clearance and an increased elimination half-life of paroxetine. Most people possess 1-2 active CYP2D6 alleles and therefore fall somewhere between the “poor” and “ultrarapid” metabolism extremes. When the extremes of alleles (e.g. poor vs. ultrarapid) are compared, substantial differences in paroxetine’s elimination half-life may be apparent.
The implications of CYP2D6 alleles are especially important to consider among pregnant women taking paroxetine. If you are unaware of your CYP2D6 expression, you may want to consider utilizing the services of a genetic analysis company such as GeneSight.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19743889
Hydration: Over half of a paroxetine dosage is excreted via the urine. Since urinary flow rate is influenced by hydration, and urinary flow rate affects excretion speed of drugs, hydration may also affect excretion speed of paroxetine. Hydration specifically increases urinary flow rate, which in turn expedites drug excretion.
Therefore those who are well hydrated may excrete paroxetine quicker than less hydrated individuals. Though hydration may not be clinically significant in its ability to influence systemic elimination / excretion, its impact shouldn’t be discounted when attempting to estimate precise excretion time.
Hepatic / Renal function: After administration, Paxil is subject to extensive hepatic metabolism – principally by CYP2D6 isoenzymes. It is the CYP2D6 isoenzyme function that may be compromised among those with hepatic impairment. Research shows that the elimination half-life of paroxetine significantly increases to around 83 hours among those with cirrhosis.
This would indicate that it could take up to ~19 days to completely eliminate paroxetine from plasma circulation after discontinuation. To a lesser extent, it is thought that renal impairment may prolong excretion of paroxetine metabolites and could indirectly compromise CYP2D6 expression, resulting in an increased elimination half-life. It should be assumed that among hepatically impaired patients, Paxil will remain in circulation for a longer duration.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1839532
Metabolic rate: A person’s metabolic rate may have a slight impact on how long Paxil remains in the system after ingestion. Research shows that certain drugs are excreted quicker among individuals with high BMRs (basal metabolic rates) compared to those with low BMRs. It is possible that paroxetine is cleared from systemic circulation at a quicker pace among individuals with high BMRs for various reasons.
One such reason may be that those with high BMRs tend to have lower body fat (as a result of the high BMR), thus potentially reducing the amount of paroxetine that accumulates in tissue. It is also possible that individuals with higher BMRs may exhibit more efficient physiologic processes that facilitate that metabolism and excretion of paroxetine (and other drugs).
The dosage of Paxil that you’ve been taking is likely going to affect how long it stays in your system. If you were to take a single 60 mg dose, it would take your body longer to eliminate it from the plasma than a 5 mg dose. Based on Paxil’s half-life, a person who took a 60 mg dose would have eliminated around 30 mg from circulation, leaving them with 30 mg still in their system after 21 hours.
On the other hand, a person who took just 5 mg would be down to just 2.5 mg after 21 hours. If you were taking a smaller dose of the drug, you can expect to have less significant quantities of the drug within your plasma in a quicker amount of time. Higher doses are also thought to place a greater burden on CYP2D6 enzymes within the liver, resulting in less efficient metabolism.
The greater the dose you’re taking, the tougher it is for hepatic enzymes to efficiently metabolize the exogenous paroxetine. For this reason, individuals with cirrhosis are often administered very low doses of the drug compared to those with healthy liver function. Additionally, high doses lead to an increased number of paroxetine metabolites, thereby increasing the potential of metabolite accumulation within fat stores.
Increased accumulation leads to a slower elimination and could also reduce efficiency of renal clearance. Low dose users are able to metabolize the drug with efficiency, less metabolites are formed, and excretion is generally quicker. One report indicated that an individual took 2 grams of Paxil in an “overdose,” bringing its elimination half-life to 195 hours; this would take over 44 days to clear from plasma.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12142644
Term of Administration
The longer the duration over which you’ve been taking Paxil, the longer it is likely to linger in your system after stopping. This is due to the fact that with a long-term of administration, you’re more likely to have reached steady state concentrations of the drug. Steady state concentrations of Paxil are reached in around 14 days.
This means that if you’ve been taking the drug for about one week, you’re unlikely to have reached steady state levels. If you discontinued the drug after a premature term of administration (e.g. several days), the elimination half-life would likely be less than 21 hours because the drug hasn’t fully accumulated within your body. On the other hand, if you’ve been taking Paxil consistently for over 2 weeks, it will have accumulated to peak concentrations and its half-life will be around 21 hours.
For this reason, someone who takes just a single dose of Paxil and stops will eliminate the drug faster than a person taking the drug daily for months or years. In addition, it is necessary to consider that the longer you’ve been taking the drug, the more likely you are to be on a higher dose. This is because over time Paxil may stop working as a result of tolerance, resulting in dosage increases to maintain efficacy.
With each consecutive dosage increase, you can expect the elimination half-life to slightly increase. What’s perhaps more interesting is that treatment with Paxil over a long-term is associated with altering CYP2D6 activity. Those that have taken Paxil for a longer period may also exhibit downregulated CYP2D6 enzyme function – resulting in slower elimination.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1531950
Co-administered drugs (CYP2D6)
If you’re taking other drugs along with Paxil, it is necessary to assess how they affect its pharmacokinetics. Because Paxil is metabolized primarily by CYP2D6 enzymes, drugs that affect CYP2D6 function via inhibition or induction will impact its elimination half-life. Drugs classified as CYP2D6 inhibitors interfere with CYP2D6 function, resulting in poorer metabolism of paroxetine and slower systemic elimination.
Examples of CYP2D6 inhibitors include: Cinacalcet, Prozac, Quinidine, Ritonavir, and Wellbutrin. Some users may be using Wellbutrin as an antidepressant augmentation strategy along with Paxil to potentiate its effects. Since it inhibits function of CYP2D6 enzymes to an extent, you could expect slowed elimination of Paxil from your body.
On the other hand, drugs classified as CYP2D6 inducers are known to enhance enzymatic function of CYP2D6. Therefore taking any agent classified as a CYP2D6 inducer is thought to speed up elimination of paroxetine. Examples of CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin.
Paxil (Paroxetine): Absorption, Metabolism, Excretion (Details)
Following oral administration of Paxil, the chemical “paroxetine” is absorbed slowly, yet completely through the gastrointestinal (GI) tract. Up to 95% of paroxetine binds to plasma proteins and as a result of its lipophilicity, it is extensively distributed throughout the body and central nervous system at 3.1 to 28 L/kg. Due to the fact that paroxetine is subject to extensive first-pass hepatic metabolism, it has a very low bioavailability.
After distribution, only around 1% of a paroxetine dose will remain in the plasma. Peak concentrations of paroxetine are believed to be attained between 3 to 8 hours post-ingestion, with most users exhibiting peak levels at around 6 hours post-ingestion. Steady state concentrations of paroxetine within the plasma occur in approximately 14 days of dosing.
Hepatic first-pass metabolism of paroxetine is facilitated by various CYP450 enzymes, but CYP2D6 plays the biggest role. CYP2D6 converts paroxetine (via demethylation) to form a catechol intermediate, appropriately referred to as “paroxetine catechol.” Other enzymes that may aid in the formation of paroxetine catechol (to a minor extent) include: CYP3A4, CYP1A2, CYP2C19, and CYP3A5 (in that order).
The paroxetine catechol then undergoes O-methylation via catechol-O-methyltransferase (COMT) at the C3 and C4 positions to synthesize various secondary metabolites including:
- “M1” or (3S,4R)-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine
- “M2” or (3S,4R)-4-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl)piperidine
- “M3” or (3S,4R)4(4-fluorophenyl)3(hydroxymethyl)piperidine)
The secondary metabolites M1, M2, and M3 are then subject to glucuronidation (conjugation with glucuronic acid) and sulfation (conjugation with sulfate) by various enzymes. None of the enzymes involved in glucuronidation and sulfation have been pinpointed by researchers. As a result of the drug’s half-life of 21 to 24 hours, it takes between 4 and 6 days to clear from the system after discontinuation.
An estimated 64% of a paroxetine dose is excreted from the body within urine, mostly in the form of metabolites (62%) with a small amount of unchanged paroxetine (2%). Approximately 36% of a paroxetine dose is excreted within feces, mostly as metabolites with less than 1% unchanged paroxetine.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12818234
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/paroxetine
- Source: https://www.pharmgkb.org/pathway/PA166121347
- Source: https://books.google.com/books?id=Xx7iNGdV25IC
Tips to clear Paxil from your system
If you recently stopped taking Paxil, you may wonder whether there’s anything you can do to clear the drug quicker from your system. Below is a list of suggestions that may provide some benefit if your goal is to completely detoxify your body from Paxil and its metabolites. Prior to implementing any of these suggestions, always consult a medical professional to verify safety and efficacy.
- Stop taking it: To ensure that Paxil has been cleared from your body, you’ll need to completely stop taking it. Taking short breaks from Paxil for one or two days will not result in elimination of the drug from your system, especially if you’ve been taking it for awhile (and have reached steady state concentrations). After you’ve completely stopped taking, your body will detoxify itself and clear paroxetine (and metabolites) as efficiently as possible.
- Burn fat: Since Paxil is considered a lipophilic drug, it is possible that some of its metabolites remain lingering within adipose tissue or fat stores throughout the body for longer than you’d like. For this reason, engaging in exercise to burn body fat may be of significant benefit if your goal is to detoxify as quickly as possible. Consider going for a jog each day for 10 to 30 minutes to get your body in fat burning mode.
- Stay hydrated: As was mentioned above, hydration may affect the efficiency of drug excretion via the kidneys. The majority of a Paxil dose (64%) is eliminated via the kidneys, and this elimination is thought to be affected by urinary flow rate. The greater a person’s urinary flow rate, the more of the drug they’ll eliminate. Staying hydrated increases urinary flow rate, and thus may provide a slight boost in metabolite excretion.
- Supplements: There are a multitude of supplements that may enhance detoxification and recovery after Paxil discontinuation. Certain supplements like activated charcoal are capable of binding to remnants of poorly absorbed drugs and/or various endotoxins in the gastrointestinal tract. I’ve written about the best supplements for antidepressant withdrawal, and consider activated charcoal to be an effective detoxification and repairative agent.
How long has Paxil stayed in your system after stopping?
If you’ve stopped taking Paxil, share a comment regarding how long you believe the drug stayed in your system after stopping. Discuss whether you think you were able to eliminate the drug quicker/slower than average from your plasma based on some of the aforementioned variables that affect elimination speed. Also realize that while many people are concerned with eliminating Paxil as quickly as possible from their systems after stopping, it is important to evaluate whether faster elimination is necessarily better.
Paxil is generally eliminated from plasma circulation within 4 to 6 days after your final dose – even if you were taking it for a long-term. When drugs are eliminated quickly (as a result of short half-lives) you are more likely to feel the wrath of unpleasant discontinuation symptoms; it is like ripping a bandage off of an open wound. Drugs with longer half-lives like Prozac take longer to eliminate from your body after stopping, but provide a more gradual readjustment phase and tolerable withdrawal as a result.
For this reason, many experts advocate using Prozac as a means to taper off of Paxil – even though it actually stays in the body for considerably longer after stopping. If you’ve been off Paxil for more than a week, it is highly unlikely that the drug is still circulating in your system. Many people mistakenly assume that since they are experiencing post acute withdrawals long after stopping Paxil, that the drug is still in their system. These symptoms are more due to neurophysiological readjustment (to homeostasis) rather than the drug remaining in the system.