Prozac (Fluoxetine) is a drug that was synthesized by Eli Lilly in the 1970s and approved by the FDA for the treatment of depression in 1987. Many regard Prozac as being the single most popular antidepressant medication of all time. As a result of its popularity, when a layman of the general public discusses antidepressants, rather than using the term “antidepressant” or specifying the particular drug, they often prefer to use the term Prozac as encompassing all antidepressants.
Despite the fact that Eli Lilly’s patent expired for Prozac in 2001, the generic formulation comprised of the chemical “fluoxetine” still remains a highly effective, popular treatment for depression. In addition to its widespread usage as an antidepressant, Prozac is often prescribed for other psychiatric conditions including: bulimia nervosa, OCD, panic disorder, and PTSD. It is also just one of few antidepressant medications approved for usage among licensed pilots.
The drug functions chiefly as a selective-serotonin reuptake inhibitor (SSRI). Blocking the reuptake of serotonin is known to increase serotonin levels extracellularly, thereby providing a mood boost. Though many people find Prozac effective for their depression, others experience adverse reactions (e.g. anxiety, decreased libido, insomnia) or long-term effects such as weight gain from Prozac. For these reasons, many people discontinue treatment, but wonder how long the Prozac will remain in their system after stopping.
How long does Prozac stay in your system after stopping?
Assuming you fully quit taking the drug, you may start to notice Prozac withdrawal symptoms slowly emerge within 2 to 4 weeks after discontinuation. Though Prozac is considered among the easiest antidepressants to discontinue due to its long half-life, it also stays in your system for a long time after stopping. The elimination half-life of the active ingredient “fluoxetine” ranges from 2 to 7 days.
This means that it could take up to a full week after you’ve completely stopped taking Prozac for your body to rid itself of just 50% of the fluoxetine. Based on the 2 to 7 day half-life, it can be calculated that complete systemic clearance of fluoxetine is likely to take anywhere from 11 to 38.5 days after stopping. However, just because the fluoxetine will have likely been cleared from your body in under 39 days does not mean that its metabolites will have also been excreted.
The primary metabolite of fluoxetine known as “norfluoxetine” has nearly double the half-life of fluoxetine itself – ranging from 4 to 15 days. This indicates that for complete systemic clearance of both fluoxetine and its metabolite “norfluoxetine,” it’ll take (on average) between 22 and 82.5 days. In other words, it’s likely to take between 1 and 3 months to have fully excreted Prozac and its metabolites following your final dose.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15597466
Variables that influence how long Prozac stays in your system
There is significant variability in the duration of how long it takes a person to fully excrete Prozac from their system. Some individuals may excrete the drug and its metabolites in around 22 days, while others may take nearly 3 months for complete systemic excretion. Differences in clearance times are usually due to variables such as: the individual taking the drug, term of administration, dosage, as well as co-ingestion of other substances.
Hypothetically speaking, two individuals could start 20 mg Prozac at precisely the same moment, take it for the same duration, and cease usage synchronously. Despite the same treatment parameters, one individual may excrete the fluoxetine (and norfluoxetine metabolites) substantially quicker than the other person. In this case, the differences in excretion speed are likely due to individual factors such as: age, body mass, and genetics.
Age and Sex: The pharmacokinetics of Prozac are often altered in elderly patients compared to younger healthy adults. Research has documented that the half-life of Prozac among elderly individuals (over the age of 65) exhibit higher plasma concentrations of fluoxetine and norfluoxetine. In addition, the half-life of the drug is markedly increased among elderly individuals.
Furthermore, there are some sex-specific differences in clearance times of fluoxetine and norfluoxetine among the elderly. Elderly women tend to retain the drug for a significantly longer duration in their systems compared to elderly men. That said there doesn’t appear to be sex-specific differences in clearance among non-elderly adults.
Reduced clearance of fluoxetine in elderly individuals may be due to a variety of age-related factors. Some hypothesize that reduced hepatic blood flow, lower levels of plasma proteins such as albumin, age-related health conditions, as well as less efficient physiologic function. For this reason, adolescents and young adults are likely to clear the drug quicker than the elderly population.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16439824
Body mass / Fat (%): A person’s body mass can affect the degree to which the drug accumulates throughout their bodily tissue, as well as how quickly it is excreted. A general principle is that the smaller a person’s body size (height/weight) relative to the dosage of Prozac administered, the longer the drug will remain in their system. On the other hand, the greater a person’s body mass relative to the dosage ingested, the more efficiently it will get metabolized and excreted.
It is also important to consider a person’s body fat percentage as potentially influencing Prozac’s half-life. Since Prozac is highly lipophilic, it binds to fat stores and tissues throughout the body. Individuals with a greater percentage of body fat will therefore accumulate more of the drug (and its metabolites) and take longer to excrete it.
Genetics: Your genetics could predict how long Prozac is likely to stay in your system after discontinuation. Since the drug is metabolized in the liver by cytochrome P450 isoenzymes, genetic variants associated with expression of these enzymes can affect metabolism, metabolite concentrations, and elimination half-life. Specifically, individuals with variants of CYP2D6 and CYP2C9 expression may metabolize the drug faster or slower than usual.
Those with compromised CYP2D6 expression are considered “poor metabolizers,” whereas those with enhanced expression are considered “rapid metabolizers.” Understand that these genetic-induced differences in enzymatic expression may create more (or less) norfluoxetine metabolites, resulting in altered clearance times. To determine how quickly you’re likely to eliminate Prozac from your system based on the aforementioned genes, consider utilizing the services of a company like GeneSight.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16236141
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24663076
Food intake / Hydration: Whether you take fluoxetine with or without food will not affect its bioavailability, but it can affect its absorption speed. Drugs that are absorbed by the gastrointestinal tract sooner are subject to metabolism sooner, and thus quicker clearance. For this reason, someone who administered the drug on a full stomach may take slightly longer to excrete it due to a 1-2 hour delay in absorption.
In addition to food, maintaining optimal hydration may affect the speed at which Prozac is eliminated via urine. Individuals that maintain a high urinary flow rate are thought to excrete drugs quicker than those with lower urinary flow rates. Since flow rate of urine is often influenced by hydration – whether you’re well-hydrated or dehydrated could influence excretion speed.
Hepatic function: There’s evidence to suggest that hepatic function affects the speed by which Prozac is cleared from your system. Individuals with hepatic impairment or cirrhosis typically exhibit increased plasma concentrations of fluoxetine following administration compared to those with normative liver function. As a result of poorer metabolism and elevated fluoxetine concentrations post-ingestion, elimination half-life is increased.
The degree to which elimination half-life is increased may be due to the severity of hepatic impairment. One study found that the half-life of fluoxetine tripled (from 2.2 days to 6.6 days) among those with cirrhosis compared to healthy volunteers. Plasma clearance rate was also reduced to 4.2 ml/min/kg compared to healthy volunteers (9.6 ml/min/kg).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8277145
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3262026
Metabolic rate: A person’s basal metabolic rate (BMR) is known to influence drug metabolism and excretion speed. Individuals with high BMRs are thought to metabolize and excrete drugs quicker than those with low BMRs. The degree to which BMR affects systemic clearance of Prozac (and its metabolites) isn’t well understood, but it is thought to play a role.
A high BMR indicates that an individual is burning more energy at rest than a person with a low BMR. As a result of this increased energy being utilized, individuals with high BMRs are thought to metabolize exogenous substances quicker. Furthermore, since those with higher BMRs tend to have less body fat (Prozac accumulates in this fat), those with low BMRs may be subject to slower systemic excretion.
Urinary pH: The pH of a person’s urine can affect the elimination and clearance of various drugs. Those with a high urinary pH tend to exhibit slower clearance rates due to the fact that their urine is highly alkaline. Alkaline urine allows the fluoxetine (and its metabolites) to get reabsorbed by the kidneys prior to complete excretion.
On the contrary, acidic urine prevents fluoxetine from getting reabsorbed by the kidneys prior to excretion. This means there’s minimal reabsorption, a faster clearance rate, and greater amount being excreted among those with low pH urine. The foods you consume regularly (i.e. your diet) can be used to estimate your urinary pH.
Term of Administration (Acute vs. Chronic)
The term over which you’ve been taking Prozac can dictate how quickly you’re likely to clear it from your system after stopping. Someone that’s been taking it for less than 4 weeks is unlikely to have attained “steady state” concentrations of the drug. Short-term users will not have accumulated fluoxetine (and norfluoxetine) throughout their bloodstream and bodily tissues to the same extent as a long-term user.
Someone that’s been taking Prozac for at least 5 weeks is likely to have attained “steady state” concentrations of fluoxetine. Long-term administration is associated with peak levels of both fluoxetine and its metabolites in the bloodstream as well as bodily tissues. If you’ve been taking the drug consistently (i.e. daily) for a long-term (e.g. several years) – it’ll take longer to excrete from your system due to accumulation.
If you’re a person that only took Prozac for 1 or 2 weeks, you’ll probably excrete the drug at a faster pace. Furthermore, short-term users typically use lower doses compared to long-term users who often require dosage increases over time due to fading efficacy (as a result of tolerance). The lower the dose of the drug administered, the less potential for accumulation, the faster it’ll be metabolized, and sooner it’ll be excreted.
Dosage (10 mg to 80 mg)
The dosage of Prozac you’ve been taking can affect how long it stays in your system. Someone that takes a single dose of 80 mg would be unlikely to clear the drug as quickly as if they took just 10 mg. This is due to the fact that as the dosage is increased, the efficiency by which enzymes in the liver are able to metabolize fluoxetine is decreased.
Anytime a high level of an exogenous chemical is ingested, the efficiency by which the body is able to process it is reduced. When a low level of an exogenous chemical like Prozac is ingested, enzymes in the liver metabolize the drug with greater efficiency. Furthermore, higher doses means more norfluoxetine metabolites are formed and circulate throughout the body prior to excretion.
The greater the level of fluoxetine and metabolites, the more likely they are to accumulate within tissue stores throughout the body. For this reason, lower dose users (especially relative to body mass) are thought to excrete the drug sooner than those using higher doses. Additionally, dosage often correlates with term of administration (which is known to affect elimination speed); high doses are associated with long-term usage, low doses are associated with short-term usage.
Co-Ingestion of Drugs
If you’re taking any other drugs (or substances) along with Prozac, or begin taking them after discontinuation, it could affect how long fluoxetine and norfluoxetine remain in your system. It is understood that Prozac is metabolized mostly by CYP2D6 isoenzymes in the liver, and as a result, drugs that affect CYP2D6 function will alter its half-life. Substances known as CYP2D6 “inhibitors” are known to decrease CYP2D6 function – increasing its half-life.
Potent inhibitors of CYP2D6 function include: Cinacalcet, Paxil, Quinidine, Ritonavir, and Wellbutrin. Should you be taking any of these drugs immediately after stopping Prozac, you can expect Prozac (and its metabolites) to remain in your system for a longer duration than usual. However, other drugs are classified as “inducers” of CYP2D6 in that they enhance its function.
Examples of potent CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin. If you’re taking any agent that induces activity of CYP2D6, you can expect that fluoxetine will be metabolized more efficiently and cleared from your system faster than usual. Also realize that substances may affect other CYP450 isoenzymes that play a smaller role in fluoxetine metabolism – resulting in quicker or slower clearance speed.
Prozac (Fluoxetine): Absorption, Metabolism, Excretion (Details)
Following oral ingestion of Prozac, its chemical ingredient “fluoxetine” is efficiently absorbed by the gastrointestinal (GI) tract. Should an individual administer the drug with food, the absorption could be delayed by up to 2 hours. After absorption, fluoxetine is subject to extensive first-pass metabolism in the liver where it undergoes demethylation to form norfluoxetine metabolites.
Specifically, biotransformation from S-fluoxetine to form S-norfluoxetine is facilitated by CYP2D6 isoenzymes. Demethylation of R-fluoxetine to form R-norfluoxetine is catalyzed by CYP2C9 isoenzymes. Other hepatic enzymes that contribute to the metabolism of Prozac include: CYP2C19, CYP3A4, and CYP3A5; these enzymes have a greater impact among chronic, high-dose users.
After metabolism, fluoxetine and norfluoxetine enantiomers (“S” and “R”) are circulated throughout the bloodstream and distributed (20-45 L/kg) throughout the body. Plasma concentrations of fluoxetine peak within 6 to 8 hours post-administration of a 40 mg oral dose. Approximately 95% of fluoxetine is bound to human serum proteins such as albumin and alpha-1-glycoprotein.
As a result of its highly lipophilic properties, fluoxetine accumulates in bodily tissues and fat stores of long-term users. Upon cessation of Prozac, it takes awhile for the body to clear the drug from systemic circulation. When considering the long half-life of fluoxetine (2 to 7 days) and the longer half-life of its metabolite norfluoxetine (4 to 15 days), it could take 2-3 months for complete excretion.
Hepatic enzymes facilitate Phase II glucuronidation of both fluoxetine and norfluoxetine prior to excretion. Fluoxetine and norfluoxetine are subject to oxidation (via O-dealklyation) to form p-trifluoromethylphenol, which is then converted to hippuric acid. A majority of these inactive metabolites are processed by the kidneys and excreted through the urine. Less than 10% is excreted as unchanged fluoxetine or fluoxetine glucuronide.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/fluoxetine
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/_S_-Norfluoxetine
- Source: https://www.pharmgkb.org/pathway/PA161749012
Tips to get Prozac out of your system
Most people that discontinue Prozac should enjoy the fact that it has a long half-life, thus making discontinuation symptoms less severe than SSRIs with short half-lives (e.g. Paxil). However, some people may dislike the idea that fluoxetine and norfluoxetine linger in their body between 1 and 3 months after stopping. Below are some tricks that may help clear the fluoxetine and its metabolites at a faster pace than usual. Prior to considering or implementing any of these tips, verify their safety with a medical professional.
- Discontinue usage: The only way to ensure that you get Prozac out of your system is to stop taking it. Even after you stop taking it, the drug will remain circulating throughout your bloodstream for awhile. It’ll take even longer for your body to clear fluoxetine and norfluoxetine metabolites from tissue stores. Realize that the sooner you stop taking Prozac, the sooner it’ll be excreted.
- Exercise to burn fat: Due to the highly lipophilic nature of fluoxetine, it will accumulate in fat stores to a significant extent – especially if you’ve been taking it for a long-term. When you cease usage, getting some daily exercise – particularly in the form of “cardio” may help you burn some of your body fat. Burning body fat via exercise may essentially release fluoxetine from fatty stores, resulting in quicker detoxification.
- Activated charcoal: There are certain supplements that a person could take that may expedite excretion of Prozac. I’ve made a list of the best supplements for antidepressant withdrawal, one of which happens to be activated charcoal. There’s some evidence to believe that activated charcoal may bind to toxins and possibly stores of unmetabolized fluoxetine throughout your body, leading to faster elimination. If you’re considering activated charcoal, verify its safety with your doctor. *Source: http://www.ncbi.nlm.nih.gov/pubmed/8936562
- CYP2D6 inducers: There’s some reason to believe that administration of a CYP2D6 inducer could expedite metabolism of fluoxetine, leading to quicker excretion. Enzymatic inducers have been shown to turn “extensive metabolizers” into “rapid metabolizers” and “poor metabolizers” into “intermediate metabolizers.” There are a variety of drugs and supplements that may ramp up the function of certain enzymes that help your body process Prozac faster.
- Urinary pH / Flow rate: A person’s urinary pH (acid vs. alkaline) can affect speed of drug clearance. Alkaline urine results in less efficient excretion and slower clearance of drugs compared to acidic urine. Therefore manipulating your diet as to ensure a low-pH (acidic) urine may speed up clearance of Prozac. Furthermore, increasing your urinary flow rate by staying hydrated may also prove beneficial.
How long has Prozac stayed in your system after stopping?
If you stopped taking Prozac, share a comment regarding how long you believe the fluoxetine and norfluoxetine stayed in your system after your final dose. Do you believe you excreted fluoxetine and its metabolites quicker than average or slower than average? To help others understand your situation, mention variables that may have either expedited or prolonged your excretion of Prozac.
Examples of such variables that you could share include your: age, dosage, duration of administration, genetics, and/or whether you had taken other drugs along with it. Realize that for most users, Prozac is likely to remain in the body for an average of 1-2 months after cessation. In relatively rare cases, it could take nearly 3 full months (90 days) for complete clearance of the norfluoxetine metabolite.