Effexor (Venlafaxine) is a SNRI (serotonin-norepinephrine reuptake inhibitor) medication prescribed primarily for the treatment of major depressive disorder. It was initially introduced to the market by Wyeth in 1993 when it became the first dual-reuptake inhibitor to attain FDA approval for depression. It differed from the SSRIs in that in addition to solely inhibiting reuptake of serotonin, it also inhibited the reuptake of norepinephrine.
Since research showed that certain individuals with depression often have low norepinephrine and serotonin, it made sense to target both with a pharmacological intervention. Though Effexor is known to target serotonin to nearly 30-fold the extent of norepinephrine, increasing levels of norepinephrine was believed to offset certain serotonergic side effects such as weight gain and sexual dysfunction. Furthermore, the slight norepinephrine increase was speculated to improve motivational deficits and cognitive impairment associated with depression.
Despite many people getting relief from Effexor as a standalone treatment, as well as via part of a combination such as “California Rocket Fuel,” others haven’t had as much luck. Unfortunately many people trying Effexor find that it increases suicidality and leads to adverse effects such as nausea, sleep abnormalities, excess sweating, and dizziness. As a result, many individuals responding poorly to Effexor discontinue hoping to clear it from their systems after stopping.
How long does Effexor stay in your system after stopping?
If you’ve completely ceased taking this drug, initially you may feel as if you’ve been hit by a semi-truck of Effexor withdrawal symptoms. As a result of the bizarre and often-debilitating neurophysiological discontinuation effects, many people wonder how long it’ll take for the drug to fully leave their system. To determine how long Effexor stays in your system, it is necessary to understand the metabolite of its active ingredient – Venlafaxine.
Venlafaxine has an elimination half-life of approximately 5 hours (+/- 2 hours) which is extremely short compared to other popular antidepressants. This means that the Venlafaxine should be fully cleared from your system in about 1.15 days (just over a day). However, when accounting for the +/- 2 hour variability of its half-life, some people may excrete the drug in just 16.5 hours, while others may take nearly 2 days (1.6 days) to completely excrete it.
However, just because the chemical Venlafaxine will have been eliminated doesn’t mean that its primary metabolite “O-desmethylvenlafaxine” will have been excreted. The elimination half-life of O-desmethylvenlafaxine is 11 hours (+/- 2 hours). For full systemic clearance of Venlafaxine as well as its O-desmethylvenlafaxine metabolite, it will take an average of 2.52 days. When accounting for the +/- 2 hours, certain individuals may excrete the metabolite in 2.06 days, while others could take nearly 3 days (2.98 days).
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/venlafaxine
Variables that influence how long Effexor stays in your system
Though the average clearance of Venlafaxine occurs in less than 2 days, and the average clearance of its primary metabolite (O-desmethylvenlafaxine) occurs in just under 3 days, certain individuals may take considerably longer-than-average to excrete them. Other individuals may excrete them in a much shorter duration. A variety of individual variables should be considered when contemplating how long Effexor (and its metabolic remnants) will remain in your system.
Two people may take Effexor at the same dose, starting at the exact same time, and quitting simultaneously – yet one person may clear the drug (and its metabolites) faster than the other individual. Differences in clearance rates are usually a result of individual factors. Examples of such factors include: a person’s age, body composition, genetics, and liver function.
Age: It is logical to assume that there are likely differences in systemic clearance times of Venlafaxine (and its primary metabolite) based on a person’s age. It is known that elimination half-life of Venlafaxine is substantially longer in neonates, ranging between 12 and 15 hours, and between 10 to 37 hours for the O-desmethylvenlafaxine metabolite. Furthermore, steady-state half-life of Venlafaxine is longer in elderly (age 65+) by an average of 24% and an average of 14% for O-desmethylvenlafaxine.
Numerous age-related factors such as restricted hepatic blood flow and decreased physiologic functionality may contribute to prolonged excretion in elderly. However, no significant differences in clearance times were observed in elderly compared to adults (age 18 to 44) after a single dose was administered. Only once steady-state concentrations are reached (after several days of treatment) does age influence clearance.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8888087
Body height/weight/fat: A person’s physical composition in regards to height, weight, and body fat percentage may affect how quickly Effexor is metabolized and excreted. Generally, the greater a person’s body mass (height/weight) relative to the dose of Effexor ingested, the quicker they’ll excrete the drug from their body; vice-versa also applies. A smaller individual taking a large dose of Effexor would likely excrete it at a slower rate because they ingested a greater quantity of the drug relative to the size of their system.
Due to the fact that Effexor is water-soluble (not fat soluble like other popular antidepressants), it is eliminated quickly from a person’s system. Individuals with greater body fat may eliminate the drug faster from their system than those with lower body fat. This is due to the fact that higher body fat is associated with less muscle, and muscles retain water. Therefore lower body fat individuals may retain Venlafaxine slightly longer than those with greater body fat.
Genetics: Genetic variation is thought to predict how efficiently an individual will metabolize Effexor, as well as how quickly they’ll excrete it. Genes responsible for regulating CYP2D6 isoenzymes in the liver often predict clearance times of Effexor. Someone carrying two inactive copies of CYP2D6 alleles is considered a “poor metabolizer,” whereas someone carrying over two active copies of CYP2D6 alleles will be considered an “ultra-rapid metabolizer.”
The differences in metabolism speed based on CYP2D6 alleles often also influence clearance times. It is also important to consider that poor metabolizers of the drug often require increased dosages (by up to 150%) to feel the effects of the drug compared to normal metabolizers. As a result of the poorer metabolism and greater dosing, clearance times may be prolonged.
- Source: http://www.ncbi.nlm.nih.gov/books/NBK305561/
Food intake / Hydration: Whether you take Effexor with food or on an empty stomach may influence how quickly your final dose is excreted from your system. Effexor is instructed to be taken with food to decrease its rate of absorption. Individuals taking the drug along with a meal (or after eating) may excrete their final dose at a slower rate as a result of the extended absorption period.
In addition to food, it is necessary to consider a person’s level of hydration. Since Venlafaxine is water-soluble, and urinary flow rate can affect excretion time, staying hydrated may facilitate a quicker clearance than dehydrated individuals. Though hydration level is unlikely to have a major impact on clearance, it may have a minor one.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9505987
Liver / kidney function: The functionality of your liver and kidneys play a major role in influencing the speed of Venlafaxine (and O-desmethylvenlafaxine) clearance. Individuals with poor liver function (e.g. cirrhosis) generally retain 50% more of the drug than those with healthy liver function. Furthermore, the elimination half-life of Venlafaxine (and its metabolite) are substantially prolonged due to hepatic abnormalities.
Additionally, individuals with poor kidney function (i.e. renal impairment) generally retain approximately 55% more of the dose than those with healthy kidneys. Renal impairment leads to a prolonged elimination half-life of Venlafaxine (and O-desmethylvenlafaxine). Individuals with simultaneous hepatic and renal dysfunction will likely retain the drug for a considerably longer duration than healthy individuals.
- Source: http://www.pfizer.ca/sites/g/files/g10023411/f/201505/Effexor%20XR_PM_182858_07May2015_E.pdf
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8033490
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22859791
Metabolic rate: The speed of your basal metabolic rate (BMR) is known to influence drug metabolism and excretion. If you have a fast BMR, it means your body is burning more energy in a resting state than someone with a slow BMR. Individuals with faster BMRs tend to metabolize and excrete drugs like Effexor quicker than those with slower BMRs.
Though it is unlikely that a person’s metabolic rate has a major impact on the clearance of Effexor, it likely has a marginal one. Keep in mind that BMR is significantly influenced by genetics, but can be modified (enhanced or reduced) as a result of dietary intake and exercise.
Urinary pH: Most medications are cleared substantially quicker when a person’s urinary pH is low or acidic. Maintaining a low urinary pH prevents reabsorption of Venlafaxine by the kidneys prior to reabsorption and ensures a fast excretion time. On the other hand, a person with a high urinary pH is likely to have a delayed excretion time. A high urinary pH or “alkaline” urine allows the drug to get reabsorbed prior to excretion, thus delaying complete clearance.
Dosage (75 mg to 375 mg)
Most people understand that the greater the amount of Effexor they ingest, the longer it’ll stay in their system before clearance. A person taking the lowest possible dose of Effexor at 75 mg per day will likely metabolize and excrete it substantially quicker than someone taking 375 mg per day. At 75 mg per day, there’s less of the Venlafaxine chemical circulating throughout a person’s system than at 375 mg (and less of the drug to clear).
Higher doses of Venlafaxine are associated with greater levels of the drug accumulating throughout the body. Though Venlafaxine doesn’t accumulate throughout tissues, high doses place greater burden on the liver (for metabolism) and kidneys (for excretion). The body can only metabolize a set amount of Venlafaxine at a time, and the kidneys can only excrete a set amount at a time.
Elevated levels of the drug (as a result of high doses) may cause the liver to work less efficiently, as well as the kidneys. Furthermore, higher doses yield greater levels of O-desmethylvenlafaxine – which has a longer half-life than Venlafaxine. For this reason, the greater the dose you’re on, the longer the drug will usually remain in your system following discontinuation.
Co-ingestion of drugs (CYP2D6)
Since Effexor is metabolized primarily by CYP2D6 enzymes in the liver, drugs (or other substances) affecting CYP2D6’s functionality can influence metabolism of Effexor. There are two classifications of drugs known to significantly affect CYP2D6 including: “inhibitors” and “inducers.” Inhibitors tend to interfere with CYP2D6, thus prolonging metabolism and excretion of Effexor.
Examples of some CYP2D6 inhibitors include: Bupropion, Cinacalcet, Quinidine, Ritonavir, SSRIs, and Terbinafine. Should you be taking any of these agents along with Effexor, you can expect that its clearance may be prolonged. On the other hand, you may be taking a drug known as a CYP2D6 “inducer.” CYP2D6 inducers enhance activation of CYP2D6 enzymes, allowing for quicker metabolism and excretion of Effexor.
Examples of some CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin. Should you be taking an inducer, you may clear Effexor from your system at a much quicker rate than average. That said, realize that the degree of enzymatic inhibition or induction is usually based on the specific drug, as well as its dosage.
Frequency of administration
How often you use Effexor will likely determine how long it stays in your system. The drug is medically recommended to be taken once daily in an extended-release (“XR”) format and twice daily in an instant-release format. Should an individual either exceed the daily recommended frequency of administration or scale back on administration, it could affect clearance.
Though not usually done under medical guidance, some people tinker with the frequency of Effexor administration on their own. This may result in one person ramping up the frequency of administration from twice to three times per day, or decreasing frequency of ingestion to “alternate-day” dosing. Individuals that increase the frequency of dosing are likely to experience longer clearance periods than those who decrease frequency of dosing.
With increased frequency of administration, a person will have accumulated a greater amount of Effexor throughout their system (as a result of an increased daily dosage). Those that infrequently administer Effexor (on an intermittent basis) are less likely to attain peak concentrations of the drug (and metabolites) throughout their system. As a result, frequent users generally take longer to fully detoxify than infrequent users.
How Effexor is Absorbed, Metabolized, and Excreted (Details)
Following ingestion, up to 92% of a Venlafaxine dose is efficiently absorbed by the gastrointestinal (GI) tract. Differences in absorption are often due to whether an individual took the drug on an empty stomach or with food. Eating food is known to prolong the rate of absorption, but does not affect the extent to which the drug is absorbed.
Furthermore, the specific format of Effexor taken (XR vs. IR) can influence absorption. Effexor XR is associated with a slower absorption rate than the immediate-release format. After the drug is absorbed by the GI tract, it undergoes first-pass metabolism in the liver, facilitated primarily by CYP2D6 isoenzymes. CYP2D6 is responsible for catalyzing Venlafaxine to form the metabolite O-desmethylvenlafaxine.
Other enzymes that aid in the metabolism of Venlafaxine to form O-desmethylvenlafaxine include CYP2C9 and CYP2C19. These enzymes contribute to a significantly lesser extent than CYP2D6. Another less prominent metabolite of Venlafaxine known as “N-desmethylvenlafaxine” is formed upon metabolism by CYP2C19, CYP2C9, and CYP3A4. Other minor metabolites such as N,O-didesmethylvenlafaxine are also formed during the enzymatic breakdown of Venlafaxine.
The drug is then processed via the kidneys, thereby getting excreted through the urine. An estimated 87% of an ingested Venlafaxine dosage is excreted within urine after 48 hours of ingestion. Urinary excretion consists of: 55% O-desmethylvenlafaxine (29% unconjugated and 26% conjugated), 5% unchanged Venlafaxine, and 27% minor inactive metabolites.
Though a substantial portion of an ingested dosage is eliminated via urine within 2 days post-ingestion, complete elimination of the drug will take slightly longer. Since the half-life of Venlafaxine is 5 hours, it’ll take 1.15 days to excrete 100% of the active ingredient. It will take around 2.52 days to completely excrete the O-desmethylvenlafaxine metabolite. As a result, most people will have fully cleared the drug from their body in under 3 days.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/venlafaxine
Tricks to clear Effexor from your system
There are several tricks that may expedite clearance of Effexor from a person’s system. Should you consider any of these tricks, always discuss them with a medical professional prior to implementation. Also keep in mind that certain suggestions may be effective for some people, and entirely useless for others.
- Complete discontinuation: Those hoping to clear Effexor from their system will need to completely cease using the drug if they want to fully detoxify. Stepping down to 0 mg from a clinically therapeutic dose should be conducted only under professional medical guidance. Only after you’ve ingested your final dose will your body be able to fully eliminate it.
- Hydration for urinary flow: Since some of Effexor is excreted through your urine, it is important to maintain a high urinary flow rate to expedite excretion. One way to maintain a high urinary flow rate is to drink plenty of water, thereby staying hydrated. Though overhydration can be dangerous (e.g. dilutional hyponatremia), sufficient hydration will ensure optimal urinary flow for excretion.
- CYP2D6 inducers: Substances that induce activity of CYP2D6 enzymes in the liver can expedite metabolism and may significantly reduce half-life of Effexor. If you are already taking a CYP2D6 inducer, you may be quicker-than-average to excrete the drug. CYP2D6 inducers should only be taken with medical approval to avoid adverse effects and contraindications.
- Urinary pH: Your urinary pH can affect how quickly a drug gets cleared from your system. Someone with acidic urine will usually excrete drugs like Effexor much more quickly than someone with alkaline urine. Alkalinity of urine results in prolonged excretion and reabsorption of the drug. Manipulating your urinary pH to become more acidic through your diet could enhance the excretion of Effexor.
- Daily exercise: After you’ve discontinued Effexor, you may want to consider getting some daily exercise. Daily exercise can ramp up your metabolism, decrease your body fat, and improve blood flow (throughout your body) – each of which could potentially expedite excretion. When coupled with a proper night’s sleep and certain dietary supplements, clearance speed could be sped up. Another possible benefit of exercise is that it could potentially ameliorate some withdrawal symptoms.
How long do you think Effexor stayed in your system?
If you’ve taken Effexor and discontinued, share a comment speculating how long you think it stayed in your system. Do you think that you were able to excrete Effexor (Venlafaxine) and its metabolite O-desmethylvenlafaxine quicker than average? Or do you think that the drug stayed in your body for a much longer duration?
To help others get a better understanding of your situation, mention any variables that you believe had a significant impact (either in expediting or prolonging) Effexor clearance. Examples of such variables could include: your age, other drugs you’re taking, and/or hepatic impairment. Keep in mind that though elimination is subject to slight individual variation, most people will have cleared both Venlafaxine and O-desmethylvenlafaxine in under 1 week.