How Long Does Zoloft Stay In Your System After Stopping?

Zoloft (Sertraline) is a popular SSRI (selective-serotonin reuptake inhibitor) prescribed primarily for the treatment of major depressive disorder.  It is also utilized medically for the treatment of obsessive-compulsive disorder (OCD), panic disorder, PTSD, and social phobia.  The drug has been available as a prescription antidepressant since 1991 when it was introduced by Pfizer.

Though a variety of newer antidepressants have been introduced to the market since the inception of Zoloft, it is still considered an extremely common, effective medication for many.  In fact, in the year 2013, it was the single most prescribed antidepressant in the United States.  Though many individuals have attained therapeutic benefit from Zoloft, others may respond poorly or end up feeling worse.

Some users end up experiencing weight gain from Zoloft, along with an array of unwanted adverse effects such as: sexual dysfunction, diarrhea, and nausea.  Furthermore, many believe that administration of this drug over a long-term may yield deleterious iatrogenic effects (e.g. chronic fatigue).  As a result, many former Zoloft users have quit using the drug and hope to clear it from their systems as soon as possible.

How long does Zoloft stay in your system after stopping?

Assuming you’ve worked with a medical professional to gradually titrate your dosage downwards, eventually you’ll have to deal with some Zoloft withdrawal symptoms.  During withdrawal, everyone wonders how long until the drug will be fully cleared from their system.  To determine how long it takes to excrete Zoloft from your system, it is necessary to consider its elimination half-life, or time for 50% of the drug to be eliminated.

Most sources suggest that Zoloft’s average elimination half-life is 24 to 26 hours.  This means that after you’ve taken just one dose of the drug, it takes a full day thereafter for your body to clear half of that dose.  For complete systemic clearance of Zoloft (Sertraline), it will take (on average) between 5.5 and 6 days; slightly less than 1 full week.

However, just because the active ingredient Sertraline will have been eliminated doesn’t mean the chief (pharmacologically active) metabolite “Desmethylsertraline” will have been cleared.  Desmethylsertraline has an average elimination half-life of 66 hours, indicating that it stays in your system for a longer duration than Sertraline.  Complete systemic clearance of Desmethylsertraline takes an average of 15.13 days following your final dose.

• Source: https://pubchem.ncbi.nlm.nih.gov/compound/sertraline

Variables that influence how long Zoloft stays in your system

It is necessary to understand that the aforementioned clearance times are estimates based on “average” elimination half-lives of Sertraline and Desmethylsertraline.  As a result, certain individuals will fully excrete the drug at a much quicker pace than average, while others may take considerably longer than average.  When attempting to make an accurate estimation as to how long Zoloft is likely to stay in your system, it is necessary to consider additional variables.

1. Individual factors

Two individuals could begin taking 10 mg Zoloft at the same time, and discontinue the drug on the exact same date, yet one person may clear it quicker from his/her system than the other.  The difference in clearance speeds among these two Zoloft users is likely due to individual factors.  Examples of individual factors that may influence clearance speeds include: age, sex, genetics, and hepatic function.

Age / Sex: Research shows that a person’s age and sex can influence how quickly Zoloft (and its metabolite “desmethylsertraline”) are excreted from the body.  The elimination half-life of Zoloft in young adult females (ages 18 to 45), elderly females (age 65+), and elderly males (age 65+) is considered similar – ranging from 32.1 to 36.7 hours.  However, in young males (age 18 to 45) the elimination half-life is significantly less at 22.4 hours.

This suggests that elderly individuals eliminate Zoloft at the slowest rate, regardless of sex.  This could be due to numerous factors including: reduced hepatic blood flow, other health conditions, additional medications, poorer physiologic function, etc.  In younger adults (age 18 to 45), males appear to excrete Zoloft faster than females, as well as its metabolite desmethylsertraline.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/9068932
• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031932/

Body height/weight/fat: A person’s body mass (height and weight) may influence how long Zoloft stays in their system after ingestion.  Particularly, the greater a person’s overall size (body mass) relative to the dosage of Zoloft they take, the quicker they are likely to excrete it.  Therefore someone who is of smaller stature taking a large dosage of Zoloft may clear it from their system at a much slower rate than a person 2 feet taller.

That said, it is important to realize that taking Zoloft for an extended period of time results in accumulation of the drug (and its metabolites) in various tissues, including body fat.  The more body fat you have, the more likely it will be to retain remnants of the ingested Zoloft for a longer duration.  Someone with a lower percentage of body fat should clear the drug from their system at a faster pace.

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031932/

Genetics: There is often significant genetic variation that influences the speed by which Zoloft is metabolized and excreted.  Variations in metabolism are largely a result of genes responsible for producing CYP450 (cytochrome P450) enzymes in the liver.  Zoloft is metabolized primarily by CYP2B6 (via N-demethylation), but is also broken down by CYP2C19, CYP2C9, CYP3A4, and CYP2D6.

Unique genetic variants that influence CYP450 isoenzymes (most notably CYP2B6) will likely affect the clearance rate of Zoloft.  As a result, certain individuals may be classified as “rapid” metabolizers (from highly active CYP2B6 enzymes), whereas others may be considered “poor” metabolizers (from inefficient CYP2B6 functionality).  While many people will fall within the “norm,” others will excrete the drug quicker as a result of certain genes that regulate enzymes.

• Source: https://www.ncbi.nlm.nih.gov/pubmed/11452243

Food intake / Hydration: Zoloft can be taken with or without food, but whether it is taken on an empty stomach or after a big meal could affect its absorption.  Taking Zoloft tablets with a meal has been shown to significantly decrease the time it takes to reach peak concentrations in plasma.  As a result, it could be speculated that faster absorption contributes to expedited metabolism – thereby resulting in quicker clearance.

Since a significant percentage of Zoloft is eliminated from the body through the urine, your hydration could impact clearance speed.  Individuals that stay hydrated tend to have increased urinary flow, resulting in greater excretion (and less reabsorption prior to excretion).  Therefore someone who stays hydrated may clear the drug (and metabolites) faster than someone who’s dehydrated.

Liver function: It is well-documented that individuals with hepatic impairment (i.e. liver disease) aren’t able to efficiently metabolize nor excrete Zoloft.  As a result, the half-life of Zoloft (as well as its metabolites) are significantly increased among those with compromised liver functionality.  One study found that among individuals with cirrhosis, the half-life of sertraline was increased by 2.5-fold compared to those with healthy liver function.

Manufacturers of Zoloft have documented that those with mild forms of hepatic impairment retain approximately 3-fold the amount of Sertraline and 2-fold the amount of desmethylsertraline metabolites compared to healthy individuals.  Unless a person with hepatic impairment is already taking an extremely low dose (or using the drug less frequently), they will experience a prolonged clearance period.  Based on the 2.5-fold increase in half-life, estimations would suggest that it takes at least 12 days to fully excrete sertraline among those with cirrhosis (and over 30 days to excrete the metabolite desmethylsertraline).

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042671/

Metabolic rate: A person’s basal metabolic rate (BMR) can impact the speed by which drugs are metabolized and excreted.  Individuals with a faster basal metabolic rate are thought to process (metabolize) drugs like Zoloft faster than those with slower basal metabolic rates.  In part, basal metabolic rate may contribute to a person’s body fat percentage (which is known to affect Zoloft clearance).

Though metabolic rate is primarily influenced by genetics, it can be modified by exercise, diet, and even sleep.  For this reason, it is thought that engaging in some sort of exercise and eating healthy foods may speed up the clearance of Zoloft from your body.  On the other hand, eating unhealthy and remaining sedentary may slow your BMR – possibly prolonging clearance.

Urinary pH: A person’s urinary pH (acidic vs. alkaline) is known to influence how quickly drugs are excreted via the kidneys.  Someone with a highly alkaline urinary pH will reabsorb more of the “sertraline” and its metabolites (desmethylsertraline) prior to excretion, and thus clear the drug at a slower rate.  An individual with highly acidic urine (low pH) will excrete more of the drug at a faster pace because acidification inhibits reabsorption.

• Source: http://www.fda.gov/ohrms/dockets/ac/04/briefing/4006b1_06_zoloft-label.pdf

2. Dosage (25 mg to 200 mg)

The dosage of Zoloft administered on a daily basis can affect how quickly it is eliminated from a person’s system.  A general rule of thumb is that the greater the dosage of Zoloft ingested, the longer it will take to get eliminated from the body.  Though most users start out taking the minimal effective dose, eventually they titrate the dosage upwards when the initial dose loses efficacy (or stops working due to tolerance).

This increase in dosage has a greater degree of influence over an individual’s physiologic function.  Higher doses could theoretically: slow metabolism to a greater extent than lower doses, alter the microbiome more significantly, and affect hormone levels more substantially.  As a result of the widespread physiologic effects associated with higher Zoloft doses – clearance times of the drug itself could be prolonged.

Furthermore, higher doses of the drug means that there’s more of the active ingredient (Sertraline) that necessitates metabolism via the liver.  If a person is taking 200 mg, it will take much longer to metabolize and excrete than if that same individual was only taking 100 mg.  For this reason, it is important to consider that the dosage you were taking (and discontinued) could influence how long it takes to fully excrete the drug.

3. Taking Other Drugs (CYP2B6)

Those taking drugs that affect cytochrome P450 isoenzymes in the liver, especially CYP2B6, may expedite or prolong the clearance time of Zoloft from their system.  Since CYP2B6 facilitates a majority of Zoloft’s metabolism in the liver, any drug affecting its functionality will alter clearance.  There are two primary categories of drugs that alter CYP2B6 function including: “inducers” and “inhibitors.”

CYP2B6 inducers are considered drugs that enhance activity of CYP2B6 enzymes.  These drugs expedite the metabolism of Sertraline, and may significantly reduce its half-life.  In other words, those taking CYP2B6 inducers should excrete Zoloft at a quicker rate than others.  Examples of such “inducers” include: Rifampicin, Carbamazepine, Phenobarbital, and Phenytoin.

On the other hand, someone taking a CYP2B6 inhibitor will take much longer to clear Sertraline from their system.  CYP2B6 inhibitors interfere with the metabolism of Sertraline, thus significantly increasing its elimination half-life.  Examples of CYP2B6 inhibitors include: Orphenadrine, Curcumin, and Ticlopidine.

It is also necessary to understand that drugs affecting CYP2C19, CYP2C9, CYP3A4, and CYP2D6 – could also have a very subtle (nearly undetectable) effect on clearance rates.  Since these isoenzymes all contribute to metabolism of Sertraline, drugs that “inhibit” or “induce” their capacity will affect excretion time.  Keep in mind that certain enzymes matter more than others (in regards to clearance), and certain drugs are more potent than others (as inducers and inhibitors).

4. Frequency of administration

Most Zoloft users take the drug once per day, which is recommended by medical professionals.  However, some users may fail to follow medical instruction and end up taking it “as needed” or intermittently.  Though most would argue that intermittent administration of Zoloft is problematic in that therapeutic effects are unlikely and likelihood of adverse effects is increased, if administered on an intermittent basis, it would likely reduce overall systemic clearance time.

This is due to the fact that with frequent (daily) administration, Zoloft accumulates throughout various bodily tissues.  If administered intermittently, it would be unlikely to accumulate to the same extent as if administered on a daily basis.  This is because the “gap” between administrations would allow for some clearance time, thus potentially never reaching a “peak” or maximal tissue concentration.

If there’s less overall accumulation of Sertraline and metabolites (e.g. desmethylsertraline), clearance time should be reduced.  For this reason, if you happen to be an infrequent user of the drug (or are experimenting with a weird tapering strategy involving intermittent administration), you may clear your last dose sooner than someone who was taking it on a daily basis.

How Zoloft is Absorbed, Metabolized, and Excreted (Details)

Following ingestion of a (50 mg to 200 mg) Zoloft tablet, it is absorbed slowly by the gastrointestinal (GI) tract.  After absorption, the drug undergoes extensive first-pass metabolism within the liver, significantly reducing Sertraline’s concentration prior to systemic circulation.  Various cytochrome P450 enzymes such as: CYP2B6, CYP2C19, CYP2C9, CYP3A4, and CYP2D6 contribute to its metabolism.

CYP2B6 is responsible for a the greatest percentage of Sertraline’s metabolism, catalyzing a majority via N-demethylation to form the “desmethylsertraline” metabolite.  Deamination of Sertraline is facilitated by CYP3A4 and CYP2C19.  Monoamine oxidase B and monoamine oxidase A (at a slower rate) also catalyze deamination of Sertraline.

Both sertraline and desmethylsertraline also undergo reduction, hydroxylation, and glucuronidation (via UGT2B7) prior to excretion.  After the initial first-pass metabolism, Sertraline is dispersed throughout the bloodstream where it reaches maximum concentrations within 4.5 to 8.4 hours. An estimated 98% of Sertraline binds to proteins and is distributed throughout bodily tissues along with major metabolite desmethylsertraline.

It can accumulate within these tissues when administered repeatedly for at least 1 week.  Sertraline is slowly eliminated from the body starting 12 to 16 hours post-ingestion.  The elimination half-life of sertraline is ~25 hours, whereas its primary metabolite desmethylsertraline has a ~66 hour elimination half-life.  This means that it’ll take a person up to 6 days to fully excrete sertraline, and up to 16 days to fully excrete the desmethylsertraline metabolite.

Studies have estimated that 44% of the administered Zoloft dose is recovered in urine within 9 days post-ingestion, none of which was unchanged sertraline (solely metabolites).  Additionally, in the same period of 9 days post-ingestion, an estimated 44% was recovered within feces – including up to 14% unchanged sertraline.

• Source: https://pubchem.ncbi.nlm.nih.gov/compound/sertraline
• Source: http://www.fda.gov/ohrms/dockets/ac/04/briefing/4006b1_06_zoloft-label.pdf

Tricks to clear Zoloft from your system

If you’re struggling to clear Zoloft from your system, there are various tricks that could be used to expedite the process.  Understand that these tricks should never be implemented without consulting a medical professional.  Also realize that while certain suggestions may be effective for some people, they may be ineffective for others.

1. Complete discontinuation: If you want Zoloft fully out of your system, you’ll need to completely stop taking it. Stopping your medication should only be done with the help of a medical professional. For most people, it is generally best to employ a tapering strategy, gradually titrating the dosage downward in small increments over a long period prior to complete cessation.
2. Increase urinary flow rate: Though 50% of a Zoloft dose is excreted within , urinary excretion still accounts for a large percentage of clearance. Individuals that are dehydrated often lack urinary flow to maximize Zoloft metabolite excretion. To increase your urinary flow rate, one strategy is to increase water intake.  Obviously too much water can be dangerous, so stay hydrated without going overboard.
3. Aerobic exercise: Cardio exercise is known to improve blood flow/circulation, increase metabolism, and burn fat. Since some Zoloft (and metabolites) will be stored in body fat, exercise can help burn the fat, thus expediting their release into the bloodstream. Further, the enhanced blood flow/circulation can help ensure optimal liver/kidney function for metabolism/clearance.
4. CYP450 inducers: A team of CYP450 enzymes work together to metabolize an ingested dose of Zoloft. Though some play bigger roles than others, drugs that enhance these enzymes may also expedite clearance. Since CYP2B6 is thought to play the biggest role in metabolism of sertraline (via N-demethylation), inducers of this enzyme could speed up clearance.  Keep in mind that some inducers of one enzyme may have inhibitory effects on others.
5. Urinary acidification: There is evidence to suggest that low pH urine may aid in faster excretion of sertraline compared to high pH urine. If a person’s pH is low, it means it is acidic. Acidic urine prevents reabsorption of sertraline (and metabolites) and ramps up the clearance rate.  Acidification is possible by eating certain foods such as meats and cranberries.

How long has Zoloft (Sertraline) stayed in your system?

Many people quit taking Zoloft swear that it stays in their system for a long time.  Clearly we know that it takes an average of about 6 days to fully eliminate the Sertraline from your system.  However, we also know that it takes the average person over 15 days to completely eliminate the pharmacologically-active metabolite “desmethylsertraline.”

Even though most professionals point out that the drug will be completely “out of your system” within 1 week, the lesser active (but still active) metabolite desmethylsertraline is still in your system.  Should you end up on the slower end of the clearance spectrum, it could take over a week to fully clear the Sertraline and well over 2 weeks to clear the desmethylsertraline metabolites.  The variation in systemic clearance of Zoloft (and metabolites) may contribute to some variance in (and severity of) discontinuation effects.

Feel free to share a comment discussing how long you believe Zoloft stayed in your system after you stopped taking it.  Do you think that it took your body longer than 2 weeks to fully clear the drug?  In your answer, share various reasons as to why your clearance time may have been prolonged such as: age/sex, metabolism, body fat percentage, other medications, etc.

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