Brintellix (Vortioxetine) is an atypical antidepressant manufactured by Lundbeck and Takeda. It was approved by the FDA in 2013 for the treatment of major depressive disorder, but failed to meet clinical trial endpoints for the treatment of anxiety disorder. The drug is sometimes classified as a serotonin modulator and stimulator (SMS) in that it predominantly modulates the neurotransmission of serotonin.
Serotonergic modulation is facilitated by reuptake inhibition of the serotonin transporter (SERT), partial agonism of 5-HT1A/5-HT1B receptors, and antagonism of 5-HT3A/5-HT7/5-HT1D receptors. It also elicits some noradrenergic effects via inhibiting reuptake of the norepinephrine transporter (NET). As a result of its atypical mechanism of action, many individuals who’ve failed to derive benefit from other antidepressants may end up testing their luck with Brintellix.
Some users may find that this drug provides significant therapeutic benefit, while others may be unable to put up with Brintellix side effects such as: diarrhea, dizziness, nausea, and vomiting. In the event that a user experiences adverse effects or simply finds the drug ineffective for the treatment for depression, a medical professional may suggest discontinuation of treatment. When users stop taking Brintellix, they may wonder how long the drug stays in their system.
How long does Brintellix stay in your system?
If you’ve recently discontinued this medication, you’re likely to experience some wicked Brintellix withdrawal symptoms. These symptoms often leave users questioning whether the drug or its metabolites may be lingering in their system after they’ve ceased treatment. To determine how long Brintellix is likely to stay in your system after stopping, it is necessary to understand its elimination half-life.
The elimination half-life of Brintellix falls within the range of 57 to 66 hours, meaning it takes between 2.38 to 2.75 days (on average) to eliminate 50% of the drug from your system. Healthy young adults tend to fall on the faster end of the elimination half-life spectrum (e.g. 57 hours), while elderly may be on the slower end of the spectrum (e.g. 66 hours). Based on the range of 57 to 66 hours for 50% elimination, we can estimate that 100% systemic elimination will likely take between 13.06 and 15.13 days after your last dose.
Unlike many other psychotropic agents, Brintellix doesn’t have any pharmacologically active metabolites. It is extensively metabolized to form carboxylic acid and excreted thereafter. Therefore you won’t need to worry about pharmacologically active metabolites with potentially longer half-lives than the parent compound (Vortioxetine) lingering in your system.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25628505
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22448783/
- Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf
Variables that influence how long Brintellix stays in your system
Though it takes an average of 13 to 15 days to eliminate Brintellix from systemic circulation, elimination speed is often subject to some individual variation. Some individuals may eliminate the drug from their plasma in less than 13 days, while others may take longer than 15 days. Differences in systemic elimination are often a result of variables such as: the individual, dosage, term of administration, and co-administered drugs.
If two people took a single 10 mg dose of Brintellix simultaneously, it is unlikely that they’d both eliminate the drug from their systems at the exact same time. Though elimination times may be similar or fall within an average range, there are still differences due to individual factors. Individual factors that impact how long a drug remains in the plasma include: a person’s age, body mass, and genetics.
Age: Although not well researched, it is speculated that elderly adults may eliminate Brintellix slower from their systems compared to younger adults. Elderly patients (over 65 years of age) often exhibit diminishing hepatic blood flow and function compared to younger individuals. Since Brintellix is subject to extensive hepatic metabolism, the reduced blood flow and function is likely to delay elimination (at least slightly) among elderly.
Furthermore, many elderly individuals tend to have other health problems and may be taking other medications that interfere with the metabolism of Brintellix. Elderly individuals are also thought to have lower levels of plasma proteins (e.g. albumin) and diminished renal function – resulting in slower excretion. If you are a young adult, you should expect to excrete the drug quicker than an elderly person.
Body mass: It could be hypothesized that a person’s body mass may also have an impact on how quickly Brintellix is eliminated from systemic circulation. Usually, it is thought that the greater a person’s body mass relative to the dosage of Brintellix ingested – the quicker it is excreted. This is due to the fact that more massive systems are thought to process standard doses of drugs with greater efficiency than less massive ones.
Since Brintellix is lipophilic, it is possible that body fat percentage may directly influence its excretion. Though vortioxetine has a high affinity for peripheral tissue, it is possible that individuals with a greater body fat percentage may store the drug for a slightly longer duration (in adipose tissue) than those with lower body fat. The impact of body mass on elimination of Brintellix is usually considered “low” and not clinically relevant.
Genetics: Your genes are responsible for regulating the expression of various hepatic enzymes that facilitate metabolism of Brintellix. Specifically, the CYP2D6 gene regulates the expression of the CYP2D6 isoenzyme responsible for metabolizing vortioxetine. Research shows that individuals with certain CYP2D6 alleles are unable to efficiently metabolize vortioxetine and are thus considered CYP2D6 “poor metabolizers.”
If you are a CYP2D6 poor metabolizer, your vortioxetine plasma concentration will be approximately double that of a normative metabolizer. As a result, you can expect the drug to remain in systemic circulation for a longer duration, and the elimination half-life of Brintellix to be increased. On the other hand, individuals with optimal expression of CYP2D6 are considered ultra-rapid metabolizers and may excrete the drug faster than usual.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24766668
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23975654/
Hydration: In regards to renal excretion of Brintellix, it is thought that hydration may affect speed of excretion. The more hydrated a user of renally excreted drugs, the greater the amount they can expect to eliminate in a shorter-duration. This is due to the fact that hydration increases urinary flow rate, which in turn boosts the amount of an exogenous substance that gets excreted via the kidneys.
An individual with a low urinary flow rate is unlikely to excrete exogenous substances as quickly as those with faster flow rates. The more dehydrated you are, the less vortioxetine metabolites you can expect to eliminate via urine. Though these metabolites aren’t pharmacologically active, if you are concerned with complete detoxification speed (rather than just plasma clearance), hydration is a factor to keep in mind.
Hepatic/Renal function: Though not well researched, individuals with compromised hepatic function may eliminate Brintellix at a slower rate than average. This is due to the fact that Brintellix is subject to significant hepatic metabolism, primarily via the CYP2D6 isoenzyme. Various other enzymes that play a minor role in the hepatic breakdown of vortioxetine include: CYP3A4/5, CYP2C9, CYP2C19, CYP2C8, CYP2A6, and CYP2B6.
Individuals with hepatic impairment as evidenced by conditions like cirrhosis tend to exhibit reduced function of CYP450 enzymes. As a result, it takes substantially longer to metabolize vortioxetine and the drug may linger in the plasma for an extended period of time. In addition, renal function may have a slight effect on how long the drug stays in your system. Renal impairment may downregulate CYP2D6 activity and prolong excretion of metabolites.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22496396/
Metabolic rate: To a small extent, a person’s metabolic rate could impact how quickly Brintellix is metabolized and eliminated from their system. It is known that basal metabolic rate (BMR) can affect how long certain drugs stay in your system. Individuals with higher BMRs tend to eliminate drugs at a faster rate than those with lower BMRs.
A high BMR indicates that the body is burning more energy in a resting state, and therefore is likely to eliminate substances quicker. A low BMR indicates that the body is burning less energy at rest, and may retain various substances for a longer duration. Though the impact of BMR on elimination of drugs isn’t usually regarded as clinically significant, it may still have a slight effect.
Dosage (5 mg to 20 mg)
The dosage of Brintellix that you were taking may affect how long it stays in your system. Particularly, the higher the dosage of Brintellix you were taking, the longer you can expect it to stay in your system. Higher doses of Brintellix (e.g. 20 mg) stay in the plasma for a longer duration because there is a greater quantity of vortioxetine to metabolize and excrete.
A greater quantity of vortioxetine means a greater burden will be placed on hepatic enzymes such as CYP2D6 to efficiently metabolize the drug. At high levels, the efficiency of metabolism by these enzymes is reduced because there’s an increased amount to metabolize; the liver is working harder than usual. Furthermore, higher doses are associated with a greater amount of the drug being distributed to peripheral tissue and elevated levels of metabolites.
Increased distribution means there’s more vortioxetine that will need to be eliminated from peripheral tissue, which could prolong the process. The total excretion time will also be prolonged due to the fact that there’s more metabolites to excrete – thereby decreasing renal efficiency. If you are taking lower doses of Brintellix (e.g. 5 mg), you can expect quicker systemic elimination of vortioxetine.
Term of Administration
How long you’ve been taking Brintellix may influence its elimination half-life. It is known that steady-state concentrations of Brintellix are reached after about 14 days (2 weeks) of consistent (daily) dosing. If you’ve been taking the drug for less than 2 weeks and end up discontinuing treatment, the drug is unlikely to remain in your system as long as someone who’s been taking it long enough to attain steady state concentrations.
If you’ve only taken one or two doses of Brintellix and stop treatment, its half-life is likely to be considerably shorter than an individual taking it for longer than 2 weeks. The longer you’ve been taking the drug, the greater the extent to which it will have reached peak concentrations in peripheral tissue. Additionally, it is necessary to consider that long-term users are most likely to have built up tolerance to lower doses of Brintellix, and therefore probably increased their dosage.
Dosage increases among long-term users is another reason for an increased elimination half-life following discontinuation. Short-term users of Brintellix may not have reached steady state concentrations of the drug, will be taking lower doses, and experience reduced accumulation in peripheral tissues. For this reason, it is necessary to consider term of administration when contemplating systemic elimination of vortioxetine.
Co-administered drugs (CYP2D6)
If you’re taking other drugs (or supplements) along with Brintellix, you can expect that they may affect its elimination half-life. Drugs that are most likely to affect the elimination half-life of Brintellix are those that affect CYP450 isoenzymes, particularly that of CYP2D6. CYP2D6 is the chief isoenzyme responsible for facilitating the metabolism of vortioxetine.
Agents that are classified as “CYP2D6 inhibitors” are known to interfere with CYP2D6 function. This interference results in slower metabolism of vortioxetine, resulting in a prolonged elimination half-life. Examples of CYP2D6 inhibitors include: Cinacalcet, Paxil, Prozac, Quinidine, Ritonavir, and Wellbutrin.
On the other hand, certain agents called “CYP2D6 inducers” are thought to expedite metabolism of vortioxetine by enhancing CYP2D6 function. Examples of CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin. If you are taking a CYP2D6 inducer along with Brintellix, the drug may be eliminated from your system at a faster pace than average.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25628505
Brintellix: Absorption, Metabolism, Excretion (Details)
Following oral administration of Brintellix, its active ingredient “vortioxetine” is efficiently absorbed by the gastrointestinal (GI) tract with a ~75% bioavailability. Plasma concentrations are attained between 7 to 11 hours post-ingestion. Approximately 98% of the vortioxetine binds to plasma proteins and has a significant volume of distribution (2,600 L) within the body.
After ingestion, the drug is subject to significant hepatic metabolism by CYP450 (cytochrome P450) enzymes, principally the CYP2D6 isoenzyme. CYP2D6 facilitates oxidation, thereby breaking down vortioxetine to form its primary inactive “carboxylic acid” metabolite. To a minor extent, CYP3A4/5 and CYP2C9 enzymes are thought to contribute to the oxidation process.
Other hepatic enzymes that may aid in the metabolism of vortioxetine include: CYP2C19, CYP2C8, CYP2A6, and CYP2B6. Thereafter, the metabolites are subject to glucuronic acid conjugation and are excreted by the kidneys. Around 66% of the drug is eliminated in the form of inactive vortioxetine metabolites within the urine and approximately 33% is excreted within the feces.
The elimination half-life of vortioxetine ranges between 57 and 66 hours, meaning that the drug remains in plasma circulation for an average of ~14.1 days after discontinuation. Understand that excretion may be slightly influenced by urinary pH and flow rate.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26316764
- Source: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002717/WC500159449.pdf
Tips to clear Brintellix from your system
If you’ve recently stopped taking Brintellix, you may be in a hurry to fully detoxify your body from the drug. For individuals that want to ensure complete detoxification in the quickest possible time, below are some tips. Prior to implementing any of these suggestions, discuss their safety and efficacy with a medical professional.
- Fully discontinue: The only way to really get Brintellix (Vortioxetine) out of your system is to stop taking it. The discontinuation process is certainly not easy and should only be done under medical supervision; usually a slow taper is best. That said, you cannot expect your body to ever rid itself of the drug if you don’t completely cease usage.
- Hydrate yourself: An effective way to increase your urinary flow rate is to stay well-hydrated. Increasing your urinary flow rate is known to expedite excretion of various drugs via the kidneys. Since around 66% of vortioxetine metabolites are eliminated via renal excretion, if your goal is to detoxify as fast as possible, staying hydrated is essential.
- CYP2D6 inducers: Deliberately taking a CYP2D6 inducer could be dangerous if it has contraindications with Brintellix. However, CYP2D6 inducers are known to speed up the metabolism of vortioxetine by enhancing enzymatic function in the liver. If you want to ensure that the final dose gets eliminated with efficiency, an inducer of CYP2D6 could provide benefit.
- Exercise: Due to its lipophilicity, vortioxetine may remain in the body for longer than average among those with a high percentage of body fat. Therefore it is possible that engaging in exercise to burn excess body fat could promote quicker elimination and excretion of the drug. Exercise also has numerous other physiologically restorative effects that may aid in detoxification.
- Activated charcoal: Taking activated charcoal once may provide benefit in eliminating any remnants of the drug that linger in your system after you’ve stopped Brintellix. Keep in mind that taking activated charcoal too soon after stopping may be problematic, so be sure to wait at least a day or two after your final dose to take this stuff. This is generally one of the best supplements for withdrawal in that adsorbs various endotoxins.
How long has Brintellix stayed in your system after stopping?
If you’ve stopped taking Brintellix, share a comment regarding how long you believe it stayed in your system after your final dose. Do you think that the drug remained in systemic circulation for shorter or longer than average? Keep in mind that the average time it takes to fully eliminate vortioxetine from plasma circulation after reaching a steady state is between 13 and 15 days; around 2 weeks after your last dose.
To help others get a better understanding of your situation, mention factors that may affect elimination speed such as: whether you took CYP2D6 inhibitors/inducers, your age, and genetic expression of CYP2D6. Realize that even if these factors serve to expedite or prolong systemic clearance, the degree to which they do so is unlikely to be clinically significant. Therefore, you should still expect the elimination of vortioxetine to occur in just under/over 2 weeks.