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How Long Does Pristiq Stay In Your System After Stopping?

Pristiq (Desvenlafaxine) is an SNRI antidepressant developed by Wyeth as an improved successor to the older drug Effexor (Venlafaxine).  Pristiq is engineered to contain solely the pharmacologically active metabolite of Venlafaxine known as “O-desmethylvenlafaxine” in a synthetic format dubbed “desvenlafaxine.”  The drug was approved by the FDA in 2008 for the treatment of major depression in adults, and is under investigation as a non-hormonal intervention for menopause.

It functions primarily by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine, thereby increasing their respective extracellular concentrations.  Pristiq is known to target serotonin to approximately 10-fold that of norepinephrine; this differs from its predecessor Effexor that targets serotonin to ~30-fold the extent of norepinephrine.  As a result of Pristiq’s dual reuptake inhibition, it is capable of rapidly ameliorating depressive symptoms, especially among those who respond to noradrenergic increases.

Despite its efficacy for the treatment of depression, many Pristiq users experience unwanted adverse effects during treatment including: dizziness, fatigue, headaches, insomnia, nausea, etc.  In addition to these adverse effects, many users worry about the lack of data on possible deleterious long-term effects associated with treatment.  For these reasons, many users decide to discontinue treatment, hoping to clear Pristiq from their systems.

How long does Pristiq stay in your system after stopping?

If you’ve recently stopped taking this drug, you’ll likely experience a host of disturbing Pristiq withdrawal symptoms such as “brain zaps.”  While experiencing these symptoms, you’re probably wondering how long Pristiq stays in your system after cessation.  To determine how long Pristiq is likely to remain in your body following discontinuation, it is necessary to consider its half-life of 11.1 hours.

Based on the 11.1 hour half-life, it is possible to suggest that (on average) Pristiq will remain in your system for 2.54 days after your final dose.  This indicates that for a majority of users, the drug is unlikely to linger within your system for more than 72 hours post-final dose.  Despite the fact that the drug may be excreted relatively quickly, it doesn’t automatically mean that your body will have readapted to functioning without it.

Pristiq will have induced numerous neurophysiological changes, many of which will take time to reverse.  The drug will have been cleared from your body quickly, but the changes it made to your brain, nervous system, etc. while you were taking it can be lasting.  It is this reason that people may report “side effects” they experienced on the drug, even after the chemical is no longer present within the body.

  • Source: http://pubchem.ncbi.nlm.nih.gov/compound/Desvenlafaxine

Variables that influence how long Pristiq stays in your system

It is important to avoid assuming that everyone will eliminate Pristiq from their system in exactly 2.54 days – this is an average figure.  This means that some people may excrete the drug in less than 2.54 days, while others may take longer (possibly over 3 days).  Variables that may account for interindividual differences in excretion speed of Pristiq include: hepatic/renal function, individual factors, dosage, term of administration, and co-ingestion of other drugs.

  1. Hepatic / Renal Function

Evidence suggests that clearance time is delayed among those with hepatic impairment.  Some sources indicate that the elimination half-life of Pristiq (desvenlafaxine) increases from ~11 hours to 13-14 hours among individuals with hepatic impairment.  If you suffer from a condition such as cirrhosis and exhibit decreased liver function, you can expect to retain the drug for a longer duration than those with healthy liver function.

In cases of moderate hepatic impairment, the elimination half-life of Pristiq is around 13 hours.  This indicates that if you suffer from a moderately impaired liver, you’ll excrete the drug from your body in 2.98 days (just under 3 days).  Furthermore, if you suffer from a severely impaired liver, the half-life will increase to 14 hours – indicating that the drug will be eliminated in 3.21 days.

In addition, not only does your hepatic function affect the excretion of Pristiq, but so does your renal function.  Individuals with mild, moderate, severe, and end stage renal disease took Pristiq were compared with healthy controls.  Researchers noted that half-life of desvenlafaxine was significantly prolonged in direct proportion to the degree of renal impairment.  Should you suffer from hepatic impairment, renal impairment, or a combination of both – expect the drug to remain in your body for a longer period after stopping.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/Desvenlafaxine
  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695227/
  1. Individual factors

Realize that two healthy people may take a single 50 mg dose of Pristiq simultaneously, yet one person could excrete the drug slightly (or substantially) quicker than the other individual.  The differences in elimination of the drug are often a result of individual factors such as: a person’s age, body mass, and genetics.  Therefore, if you’re attempting to estimate how long Pristiq will stay in your system – these factors should be taken into consideration.

Age: It is thought that the half-life of most drugs, including Pristiq, will be increased among elderly individuals (over 65 years of age).  Elderly individuals often exhibit diminishing hepatic and renal function, both of which are thought to increase the drug’s elimination half-life by 2-3 hours (depending on severity).  Additionally, elderly individuals are often dealing with age-related medical conditions and taking medications.

Medical conditions and simultaneous ingestion of certain medications are also thought to prolong excretion of Pristiq.  Therefore if you consider yourself a healthy young adult, you should excrete Pristiq sooner than if you were elderly.  Younger individuals also exhibit overall enhanced physiologic efficiency compared to elderly counterparts.

Body mass: The greater your body mass relative to your last dosage of Pristiq, the sooner you can expect to clear it from your system.  A more massive individual is typically capable of not only handling greater doses of exogenous substances, but also excretes them more efficiently than a less massive individual.  Assuming two people were given a 50 mg dose of Pristiq, it would be logical to conclude that the more massive individual is likely to excrete the drug quicker than the less massive person.

Don’t think that body mass has a major impact on drug excretion, but it may have a minor one in most cases.  Therefore if you are a small, petite person – you may retain the drug for slightly longer duration after your final dose than someone with bigger size.

Genetics: It is understood that CYP3A4 isoenzymes facilitate N-demethylation of desvenlafaxine.  In other words, they convert desvenlafaxine into metabolites – to a minor extent.  A small percentage of individuals inherit certain alleles that decrease the function of CYP3A4, leading to poorer metabolism of drugs like Pristiq.  If you happen to be in the small percentage of poor metabolizers, you may retain the drug for a slightly (possibly negligible) duration longer than average.

Hydration: A significant percentage of Pristiq is excreted via urine within 72 hours of administration.  Hydration is known to influence the flow rate of urine, and the flow rate is known to affect excretion speed.  Therefore if you are well-hydrated, you’d be likely exhibit an optimal urinary flow rate – excreting slightly more of the drug at a faster pace than if you had been dehydrated.

Metabolic rate: The metabolism and excretion of drugs is influenced by a person’s metabolic rate.  If you have a high BMR (basal metabolic rate), you may metabolize and excrete Pristiq quicker than someone with a low BMR.  This is due to the fact that individuals with high BMRs are burning more energy at rest, resulting in faster physiologic processing of an exogenous substance such as desvenlafaxine.

Other drugs: The desvenlafaxine within Pristiq is metabolized by CYP3A4 enzymes to a minor extent.  Therefore if you’re taking drugs that affect CYP3A4 function, you can expect its metabolism (and pharmacokinetics) to be altered.  Drugs that inhibit CYP3A4 function include: Clarithromycin, Cobicistat, Indinavir, Ketoconazole, Nelfinavir, Ritonavir, and Saquinavir.

If you’re taking any of these inhibitors, expect that the desvenlafaxine will not be as efficiently metabolized and may take longer to clear from your body.  On the other hand, if you’re taking a drug that induces CYP3A4 function, you should expect to metabolize (and excrete) desvenlafaxine quicker than average.  Examples of CYP3A4 inducers include: Carbamazepine, Modafinil, Oxcarbazepine, Phenobarbital, Phenytoin, Pioglitazone, Rifampicin, and St. John’s wort.

  1. Dosage (50 mg to 400 mg)

The dosage of Pristiq you take may also impact how long it stays in your body after discontinuation.  Individuals taking 50 mg of the drug will likely excrete it slightly quicker than those taking 100 mg or 400 mg.  Though there’s no evidence to suggest that dosages exceeding 50 mg provide additional benefit for the treatment of depression, many medical professionals still prescribe 100 mg, 150 mg, and even higher doses when low doses lose their therapeutic efficacy.

When you take a higher dose of Pristiq (or any drug), your body needs to metabolize a greater amount of desvenlafaxine.  Not only will the metabolism take longer, but a greater amount of the drug (and its metabolites) will be distributed throughout the body.  With a greater quantity of the drug getting distributed, a greater amount of desvenlafaxine will also necessitate excretion.

The lower the dose of Pristiq you take, the easier the time your kidneys have with excretion.  Once a certain threshold is reached such as after doubling, tripling, or quadrupling of dosage – the kidneys are placed under greater stress.  As a result, excretion rates become slower among higher dose users, with full detoxification taking a longer duration than an individual taking a minimal (50 mg) dose.

  1. Term of Administration

Sometimes the term over which you’ve been taking Pristiq may impact the speed by which it is excreted from your body.  A person taking just a single dose of the drug, for example, may excrete it substantially quicker than an individual that has been taking it daily for a period of 4 weeks.  In part this is due to the fact that steady state concentrations of desvenlafaxine are attained in approximately 5 days.

If you’ve taken the drug for less than 5 days and cease usage, your body will have an easier time eliminating it because it will not have accumulated to a peak, steady concentration.  On the other hand, someone that’s been taking the drug for a longer term will certainly have attained peak, steady concentrations of desvenlafaxine.  In addition to the factor of “steady state” being influenced by term of administration, dosage is also usually affected based on how long you’ve taken Pristiq.

Someone that’s taken Pristiq for just a short-term will likely stay at the 50 mg dose.  However, a long-term user may find that the 50 mg dose “wears off” after a year or two, thus no longer providing therapeutic antidepressant effects.  As a result, long-term users often necessitate upward titrations (increases) in dosing for continued therapeutic benefit; dosage increases are known to prolong excretion.

Pristiq (Desvenlafaxine): Absorption, Distribution, Excretion

Following administration of Pristiq, the synthetic chemical “desvenlafaxine” is absorbed and distributed throughout the body at 3.4 L/kg.  Its absorption isn’t significantly affected by food intake and its bioavailability is estimated to be 80%.  Only 30% of desvenlafaxine binds to plasma proteins and peak plasma concentrations are attained in approximately 7.5 hours post-ingestion.

Desvenlafaxine undergoes metabolism primarily via UGT isoform conjugation.  To a modest extent, the drug is subject to oxidative metabolism via CYP3A4 hepatic isoenzymes.  CYP3A4 facilitates conversion (N-demethylation) of desvenlafaxine to the metabolite “N,O-didesmethylvenlafaxine.”  Since the CYP2D6 pathway isn’t involved in breakdown of desvenlafaxine, pharmacokinetics aren’t significantly altered in CYP2D6 poor metabolizers.

It takes approximately 11.1 hours for 50% of a desvenlafaxine dose to get cleared from the plasma.  For 100% clearance of desvenlafaxine from plasma, it takes around 2.54 days.  Desvenlafaxine is processed by the kidneys and excreted via urine within 72 hours as: 45% unchanged desvenlafaxine, 19% glucuronide metabolites, and 5% N,O-didesmethylvenlafaxine.

  • Source: http://pubchem.ncbi.nlm.nih.gov/compound/Desvenlafaxine
  • Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021992s020lbl.pdf

Tips to clear Pristiq from your system

There are several things that can be done to ensure complete systemic excretion of Pristiq after your final dose.  Realize that the drug is unlikely to linger in your body for a long duration after stopping.  Below are some tips that may aid in detoxification from Pristiq.  Keep in mind that none of the suggestions should be implemented without prior consent from a medical professional.

  1. Stop taking it: The easiest way to ensure that Pristiq has been fully cleared from your body is to stop taking it. It is advised to discontinue only under supervision of a medical professional, as it could be dangerous to do on your own. After you’ve stopped taking the drug, your body will excrete the majority within 72 hours of your final dose.
  2. Hydrate: Staying well-hydrated is associated with an increased urinary flow rate. As was discussed above, a heightened urinary flow rate is known to expedite clearance of exogenous substances via the kidneys. If you are dehydrated, your urinary flow rate may be slow, resulting in a prolonged excretion of the drug from your body – compared to a person who’s well-hydrated.
  3. Supplement: It may be beneficial to take supplements that enhance renal function; the kidneys are responsible for excreting most of the Pristiq from your system. If you’re worried about unmetabolized desvenlafaxine, you could consider a CYP3A4 inducer to speed up N-demethylation; but this would be very minor. You could also consider taking activated charcoal several days after your last dose to essentially mop up any remnants/toxins of desvenlafaxine.

How long has Pristiq stayed in your system after stopping?

If you’ve recently stopped taking Pristiq, share a comment regarding how long you believe it stayed in your system.  Do you think the desvenlafaxine (and its metabolites) stayed in your body for a longer duration than average?  Or do you think you excreted the drug much quicker than average based on certain individual factors?

To help others get an idea of your situation and speculate plasma clearance time, mention things like: your age, renal function, hepatic function, whether you take any other drugs (e.g. CYP3A4 inducers/inhibitors), etc.  Understand that for the majority of Pristiq users, the drug should be out of your plasma in less than 3 days.  Complete systemic excretion via urine and bile could take slightly longer, but don’t think that the drug is still somehow lingering in your body for weeks after you’ve stopped taking it.

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6 thoughts on “How Long Does Pristiq Stay In Your System After Stopping?”

  1. My doctor put me on Pristiq for mild depression but after about 4-5 weeks, I decided that it was really unnecessary. I started decreasing over a 2 week period and took my last half dose 3 days ago. I have started experiencing lightheadedness, heart pounding, bright flashes occasionally and quite a bit of mild brain zapping.

    My BP dropped from 166/81 to 123/73 over the last few weeks from being on a strict keto diet but now realize that these symptoms are not due to the diet and sudden bp change but from the discontinuation of this drug. I sure hope these zaps go away soon.

  2. Currently coming off 50mg this is day 4 of no meds. Yesterday & today side effects have kicked in big time. Nightmares, palpations, hot & cold flushes. Feeling light headed/dizzy (my eyes feel like they are rolling back in my head) really unpleasant.

  3. I have just stopped taking Pristiq. Initially I forgot to take it for a couple of days so after that I decided to not go back on it. I was on 50mg once a day. I looked up the side effects and I haven’t noticed any. Although I do have a pretty bad case of the flu right now. Today my head is a little “over-thinky” which could be lack of the drug in my body or the illness (I overly worry while I’m ill and feel unloved). I don’t feel as if there is any of the drug left in my system.

  4. I would be interested to know if taking any specific supplement or vitamins can assist the body to re-boot normal neurotransmitter levels after some one who has stopped taking Pristiq completely. My daughter has been on it for 3 years now.

    • I don’t recommend this. I took some supplements while going through Paxil withdrawal. The only thing they did for me was worsen the withdrawal symptoms. I became waaay more agitated, anxious, etc. I read the reason why this happened is because the brain is in chaos and can’t take any further stress.

    • Hi, For the just over 12 months that I was on Pristiq (I’ve just taken myself off it) I have always taken St John’s Wort along with it. My Dr said it was safe to do so. It can have contradictions to some medications. And I actually wonder if the SJW did me more good than the Pristiq. I was on 50mg a day.


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