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How Long Does Abilify Stay In Your System After Stopping?

Abilify (Aripiprazole) is a medication that was developed by Otsuka Pharmaceuticals and approved by the FDA in 2002 for the treatment of schizophrenia.  Approximately 2 years thereafter (in 2004) it was approved for the treatment of acute mania and mixed episodes associated with bipolar disorder.  By 2007, it had attained approval for the treatment of major depression as an adjunct (“add-on”) intervention when prescribed with a traditional antidepressant.

As a result of its approval to treat an array of psychiatric conditions, it emerged as among the top selling psychiatric drugs from 2013 to 2014.  The drug functions primarily as a D2 receptor partial agonist, thereby modulating dopamine concentrations in the brain to combat positive and negative symptoms of schizophrenia, as well as acute mania.  It also affects the serotonergic system to elevate mood via acting as a 5-HT1A receptor partial agonist, as well as a 5-HT7 receptor and 5-HT2C receptor agonist.

Though many people have had success with this drug, others have a difficult time tolerating Abilify side effects such as: agitation, constipation, headaches, insomnia, nausea, etc.  Others may be upset that they’re gaining weight while taking Abilify or could be concerned with long-term health implications of using atypical antipsychotics.  For these reasons, many individuals have ceased usage of Abilify and may be wondering how long it stays in their system after stopping.

How long does Abilify stay in your system after stopping?

If you’ve recently stopped taking this medication, you may be dealing with debilitating Abilify withdrawal symptoms.  As you attempt to cope with these discontinuation symptoms, you’re probably wondering how long the Abilify, or more specifically the active ingredient “Aripiprazole” will remain in your body.  To understand how long Abilify remains in your system after you stop taking it, it is necessary to examine its elimination half-life.

The elimination half-life of Aripiprazole is generally considered to fall within the range of 75 hours to 146 hours.  This means that it could take anywhere from 3.13 days to 6.08 days for just 50% of the Aripiprazole to get excreted from your system.  Some research suggests that among poor metabolizers of Aripiprazole, the half-life could be extended up to 165 hours – taking up to 1 week to clear just half of the drug.

Based on the suggested range of half-life range of 75 to 146 hours, it will likely take between 17.18 and 33.45 days to completely excrete Aripiprazole from your body.   Most people will excrete the drug in just over a couple weeks after their final dose, whereas others will take considerably longer.  Usually those who take longer to excrete the drug are considered “poor metabolizers” in that they lack specific enzymes that aid in metabolism of the drug.

Though you may have fully excreted Aripiprazole from your system in just over 1 month, you will likely not have excreted its chief metabolite known as “Dehydro-aripiprazole.”  Dehydroaripiprazole has an elimination half-life of 94 hours, which generally means that it will take longer to excrete than Aripiprazole itself.  On average, most people will have excreted dehydroaripiprazole in about 21.54 days.

Most people will have fully cleared the drug from their system within two months, though in rare circumstances, it could take slightly over a month.  Keep in mind that the aforementioned clearance times are estimated based on statistical averages from research.  Not everyone will necessarily excrete the drug in an “average” amount of time.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/Aripiprazole
  • Source: https://books.google.com/books?id=CCZ1CQAAQBAJ

Variables that influence how long Abilify stays in your system

When contemplating how long it’ll take you to excrete Abilify (and its metabolites) from your system, it is necessary to consider influential variables.  Certain variables may expedite the excretion time of Abilify, whereas others may prolong its clearance.  As a result of these variables, you may excrete the drug “faster” or “slower” than average.

  1. Genetic Variation (Extensive vs. Poor Metabolizers)

Perhaps the most influential variable to consider when estimating half-life and clearance time of Abilify is genetic variation.  Abilify is metabolized by CYP450 (cytochrome P450) enzymes within the liver, primarily facilitated by CYP2D6 isoenzymes.  Genetic variants responsible for the expression of CYP2D6 isoenzymes have a significant impact on excretion speed of Abilify.

Ultrarapid metabolizers (UM): Individuals who are considered “ultrarapid metabolizers” tend to metabolize and excrete aripiprazole much quicker than average.  These individuals are expressing multiple copies of the CYP2D6 gene and have superior CYP2D6 function.  If you are an ultrarapid metabolizer, you can expect to clear Abilify and its metabolizes from your system in around 2 weeks.

Extensive metabolizers (EM): Those classified as CYP2D6 “extensive metabolizers” have normative function of CYP2D6 isoenzymes.  Research has shown that among those considered to have normal CYP2D6 expression, the half-life of aripiprazole is closer to the 75 hour end of the spectrum.  This indicates that most extensive metabolizers should excrete aripiprazole within 3 weeks after their final dose.

Intermediate metabolizer (IM): Those considered intermediate metabolizers will metabolize and excrete drugs on a spectrum between extensive and poor metabolizers.  This would mean we could take an average between 75 hours and 146 hours and come up with ~110.5 hours for the half-life of an intermediate metabolizer.  Total excretion in an intermediate metabolizer will likely take 3 to 4 weeks.

Poor metabolizer (PM): Poor metabolizers of aripiprazole tend to have either little or no actual CYP2D6 function.  As a result, the drug fails to get efficiently metabolized and accumulates within the body for a longer-than-usual amount of time.  The elimination half-life of aripiprazole in a poor metabolizer is thought to range between 146 and 165 hours following ingestion.  This means that in a poor metabolizer, the aripiprazole may not fully clear for 67 to 76 days after complete discontinuation.

It is understood that you may be unaware of your particular genetic variants to help you estimate how quickly you’ll excrete aripiprazole.  However, genetic tests such as “GeneSight” can be taken to better understand how long it’ll take to clear Abilify from your system.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21739267
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20361061
  1. Individual attributes

Though genetic variation has a major impact on clearance speed of Abilify (and its metabolites) from your system, individual factors can also play a role.  Two extensive-metabolizers (EMs) could take the same dose of Abilify, for the same duration, and stop taking it at precisely the same moment – yet one may clear it from his/her system quicker than the other.  Various individual factors such as your age, body mass, body fat, and even your urinary pH are known to affect clearance speed.

Age: In general, elderly individuals (age 65+) tend to metabolize and excrete drugs slower than young adults and adolescents.  Slowed clearance in the elderly may be due to a variety of causes such as reduced hepatic blood flow, additional health problems, usage of other medications, and poorer physiologic efficiency that accompanies old age.  Additionally, research has specifically shown that elderly patients are more likely to have lower levels of albumin.

As a result of low albumin levels, free aripiprazole concentrations tend to increase and the drug accumulates within the body to a greater extent.  For this reason, some sources suggest dosage reductions for elderly patients.  Younger adults tend to have adequate serum albumin concentrations, adequate hepatic blood flow, and optimal physiologic function – allowing for faster excretion of aripiprazole.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20361061
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/759470

Body mass / Fat: A person’s body mass index (BMI) is thought to influence how long aripiprazole stays in their system.  Particularly, the greater your body mass relative to the dosage of Abilify you ingest, the quicker you are likely to clear it from your system.  On the other hand, the lower your body mass relative to the dosage you were taking, the slower it may take for complete systemic clearance.

Additionally, the greater the percentage of body fat you have, the more likely you’ll retain aripiprazole for a longer duration prior to excretion.  This is due to the fact that aripiprazole is lipophilic, means it is “fat soluble.”  Over time, it is dispersed throughout your body and accumulates within fat stores.  The greater your body fat percentage, the longer it’ll take to excrete.

  • Source: http://www.medsafe.govt.nz/profs/datasheet/a/abilifytab.pdf

Food intake / Hydration: Whether you took your final dose of Abilify with food could influence how long it’ll take to excrete.  When taken with a high-fat meal, its absorption is thought to be prolonged, and its serum concentration peaks 3 hours later than if taken without food or a non-high fat meal.   Furthermore, high fat meals can increase maximum concentrations of both aripiprazole and the metabolite dehydroaripiprazole (by ~11%).

The degree to which you maintain hydration may also affect the duration over which Abilify remains in your body.  Those who are optimally hydrated tend to have a greater urinary flow rate, which is known to expedite drug clearance.  Individuals who are suboptimally hydrated (or dehydrated) tend to have poorer urinary flow rates and retain Abilify for a longer period.

Liver / Kidney function: Hepatic and renal functionality aren’t thought to play a big role in the clearance of Abilify.  That said, it is known that individuals with cirrhosis and hepatic impairment may retain aripiprazole in their system for a longer duration than those with normative hepatic function.  This is largely due to the fact that aripiprazole is metabolized by CYP2D6 enzymes within the liver.

Anyone with an impaired liver may exhibit poorer expression of CYP2D6, resulting in a prolonged half-life.  Though renal impairment doesn’t significantly impact the clearance of aripiprazole, it could have a subtle influence.  Around 25% of a dose is excreted via urine, and with renal impairment, urinary excretion may be slightly compromised.

Metabolic rate: A person’s BMR (basal metabolic rate) indicates how much energy they are burning at rest.  Usually BMR is determined by an array of complex factors such as genetics, diet, exercise, and  sleep. Research has shown that among individuals with extremely low BMRs, drug clearance times are often prolonged.

On the other hand, those with high BMRs are thought to metabolize and excrete drugs quicker than average.  Therefore, we should expect someone with a high BMR to metabolize and excrete Abilify (and its metabolites) at a faster rate than those with low BMRs.  Things that influence BMR can include: genetics, diet, exercise, and sleep.

Urinary pH: The pH of your urine can also predict how quickly you’ll clear aripiprazole from your system.  Individuals with a high urinary pH (alkaline urine) tend to retain drugs for a longer period, reabsorbing them prior to elimination.  If you’re eating a lot of alkaline foods or are on an alkaline diet, just know that aripiprazole’s half-life may be extended by hours, resulting in an extended clearance.

Those with a low urinary pH (acidic urine) excrete a greater quantity of drugs at a quicker speed than usual.  Acidic urine prevents reabsorption of the drug prior to excretion and is thought to maximize clearance of both aripiprazole and dehydroaripiprazole.  If you’re eating foods like meat, grains, and peanuts – you’ll probably clear Abilify faster than someone eating an alkaline diet.

  1. Term of Administration

The term over which you took Abilify can have an impact on how long it’ll stay in your body upon cessation.  Someone that only took the drug for a few days and quit will likely excrete aripiprazole (and dehydroaripiprazole) substantially quicker than an individual who took it for a full calendar year.  In other words, it probably won’t take over a month to clear the drug from your system if you only took it for a few days.

On the other hand, if you ingested Abilify daily for at least 2 weeks, you will have accumulated more of the drug throughout your system and bodily tissues.  Individuals that take the drug for over 14 days will have reached steady state plasma concentrations of aripiprazole that are 4-fold higher the concentrations of a person who just took the drug for a single day.  It is thought that the longer the term over which you take the drug, the greater the extent to which aripiprazole accumulates within fat stores.

In part this may be due to the fact that long-term administration often requires titrations upward in dosing due to tolerance.  As a result of a greater time span over which the drug is accumulated, and the higher doses administered among long-term users, the elimination half-life may also be extended.  A short-term user is more likely to have taken a low dose of the drug, will not have accumulated peak levels of aripiprazole in bodily tissues, and should clear it from the body at a faster rate.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15257633
  1. Dosage (2 mg to 30 mg)

Abilify is manufactured in dosing increments of 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg.  Most people start by taking a low dose and titrate upwards until they reach the minimal effective dose necessary to manage psychiatric symptoms.  Research has shown that Abilify’s half-life is affected by the dosage someone takes.  Specifically, the higher the dosage of Abilify a person takes, the longer it takes to fully excrete.

This is likely due to the fact that the body can likely only efficiently metabolize and eliminate a certain amount of the drug at a time.  When high doses of Abilify are taken, certain physiologic processes are overwhelmed, resulting less efficient excretion.  Low doses, on the other hand, are less physiologically taxing, which allows the body to excrete them at a fast pace.

It is also necessary to consider that when a person takes lower doses, less total aripiprazole will accumulate throughout the body, and less dehydroaripiprazole metabolites will be formed.  With less overall aripiprazole (and dehydroaripiprazole) circulating and/or stored throughout the body, it can be excreted at a quicker pace.  A person taking 2 mg of Abilify will likely excrete the drug quicker than someone taking 30 mg.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/14747427
  1. Co-administration of drugs

There are a variety of other drugs (and supplements) and could impact the metabolism and excretion of Abilify.  Abilify is primarily metabolized by enzymes such as CYP2D6 and CYP3A4.  Therefore any drugs that either interfere with or enhance CYP2D6 or CYP3A4 function are likely to affect the speed by which it is excreted from the body.

Drugs that act as inhibitors of CYP2D6 or CYP3A4 interfere with Abilify’s metabolism, resulting in longer clearance times.  Examples of some potent CYP2D6 inhibitors include: Cinacalcet, SSRIs (Paxil and Prozac), Quinidine, Ritonavir, and Wellbutrin.  Examples of CYP3A4 inhibitors include: Clarithromycin, Indinavir, Nefazodone, and Ritonavir.

Oppositely, drugs that increase function of CYP2D6 and CYP3A4 isoenzymes are known as “inducers.” CYP2D6 and CYP3A4 inducers expedite metabolism and clearance of Abilify, leading to quicker overall excretion.  Examples of CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin.  Examples of some CYP3A4 inducers include: Butalbital, Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin, Rifampicin, and St. John’s wort.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20361061

Abilify (Aripiprazole): Absorption, Metabolism, Excretion (Details)

Following oral ingestion of Abilify, it is absorbed efficiently by the gastrointestinal (GI) tract.  Taking Abilify with or without food is not thought to affect absorption, however, a high-fat meal is known to delay the peak serum concentration time by approximately 3 hours for aripiprazole.  The delay of peak serum concentration times for dehydroaripiprazole are delayed by up to 12 hours as a result of high fat intake.

Peak plasma concentrations of aripiprazole are typically attained within 3 to 5 hours post-ingestion.  The drug is distributed throughout the body at 4.9 L/kg, with over 99% of an ingested dose binding to albumin serum proteins.  Unlike many other psychiatric drugs, Abilify is not subject to extensive first-pass metabolism; it is metabolized to a minimal extent prior to systemic circulation.

Steady state concentrations of aripiprazole are attained after 14 days of daily administration.  Due to the fact that it is highly lipophilic, the drug is thought to accumulate within bodily tissues and fat stores when administered over a long-term.  The circulating aripiprazole eventually is metabolized by CYP450 isoenzymes in the liver, where it undergoes biotransformation via dehydrogenation, hydroxylation, and N-dealkylation to form the metabolite “dehydroaripiprazole.”

CYP3A4 and CYP2D6 facilitate both dehydrogenation and hydroxylation, whereas N-dealklyation is solely catalyzed by CYP3A4.  The dehydroaripiprazole is pharmacologically active, and exerts effects primarily on D2 receptors.  It should be noted that concentrations of aripiprazole and dehydroaripiprazole following hepatic metabolism are largely subject to genetic variation based on CYP2D6 gene expression.

Those with low CYP2D6 function are considered “poor metabolizers” and tend to exhibit 80% more aripiprazole, but 30% less dehydroaripiprazole metabolites than those with normative CYP2D6 function.  Poor metabolizers are thought to account for approximately 8% of Caucasians.  The elimination half-life among poor metabolizers increases to approximately 150 hours, whereas the elimination half-life among normative metabolizers is near 75 hours for aripiprazole and 94 hours for dehydroaripiprazole.

An estimated 55% of an Abilify dose is excreted through the feces, whereas 25% is excreted through urine.  Approximately 18% of the fecal excrement is unchanged aripiprazole, whereas less than 1% of urinary excrement is unchanged aripiprazole.  The rate of total body clearance of aripiprazole is estimated to be 0.7 mL/min/kg.

On average, the drug will have been completely eliminated from the body within 35 days in extensive metabolizers, and could take as long as 34 days in poor metabolizers.  Elimination of the dehydroaripiprazole metabolite is thought to take around 22 days.  After complete discontinuation, most users will have excreted aripiprazole and dehydroaripiprazole within 2 months.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/Aripiprazole
  • Source: http://www.medsafe.govt.nz/profs/datasheet/a/abilifytab.pdf

Tips to clear Abilify from your system

Everyone wants to know how they can clear Abilify from their system as quickly as possible.  If your goal is to optimize the speed at which you excrete Abilify, you may want to consider some tips.  Keep in mind that the suggestions listed below should always be discussed with a medical professional to verify safety and efficacy prior to implementation.

  1. Complete discontinuation: The most obvious tip to clear Abilify from your system is to stop taking it and stay off of it. Only your doctor knows when it’s the right time to stop taking Abilify, so work with him/her as you taper down or cease usage. Realize that the sooner you stop taking it, and the longer you remain off of it, the closer you will be to a state of sobriety.
  2. Daily exercise: Since Abilify accumulates throughout your body in fat stores and tissues, its half-life may be prolonged among those with a high body fat percentage. To expedite the clearance speed of Abilify, daily cardiovascular exercise may be necessary. Cardiovascular exercise will help you burn fat and ramp up your metabolism, both of which can enhance excretion speed.
  3. CYP450 inducers: Though no drugs or supplements should be taken without medical approval during withdrawal, certain substances may aid in the metabolism and excretion of Abilify. Taking supplements or drugs that act as CYP2D6 and CYP3A4 inducers may substantially decrease the time it take for you to excrete aripiprazole (and dehydroaripiprazole). The effect to which these “inducers” affect clearance speed may be subject to variation based on the drug and dosage taken.
  4. Urinary acidification: There is evidence that acidification of urine can expedite drug excretion. If you have a highly alkaline urinary pH, acidification may reduce the half-life of Abilify by hours. Reducing the half-life of Abilify by hours indicates that it could be cleared from your body several days earlier than if you had alkaline urine.  Though only 25% of a dose is excreted through urine, acidification should have a slight impact on excretion speed by preventing reabsorption.
  5. Hydration: Staying properly hydrated after you’ve stopped taking Abilify may be helpful for clearance via urine. Approximately 1/4th of an ingested dose is excreted through urine, but the speed by which it is eliminated can be affected by urinary flow rate. Individuals who are more hydrated tend to have greater urinary flow rates, and as a result, clear Abilify quicker than those who are dehydrated.

How long has Abilify stayed in your system after stopping?

If you’ve stopped taking Abilify (Aripiprazole), discuss how long you believe it stayed in your system following your last dose.  Do you think you excreted (or will excrete) the aripiprazole quickly in around 17 days, or slowly in around 34 days?  To help others understand your situation, mention how long you had been taking Abilify, the dosage you were taking, as well as how long it’s been since you’ve ceased usage.

Also note any factors that you believe could affect excretion such as: whether you’re taking other medications (CYP450 inducers or inhibitors), are considered a CYP2D6 poor metabolizer, and/or are above age 65.  The truth is that aripiprazole and dehydroaripiprazole (metabolites) remain in the body (on average) for between 17 and 34 days following a final ingested dose.  If you know of anything that can be done to expedite systemic excretion of Abilify, share it in your comment.

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