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How Long Does Trazodone Stay In Your System After Stopping?

Trazodone (brand name “Desyrel”) is a medication originally approved by the FDA in 1981 for the treatment of anxiety disorder and major depressive disorder.  It is also commonly utilized as a sleep-inducing agent in cases of insomnia, as well as an off-label option for conditions such as: alcohol withdrawal, bulimia nervosa, fibromyalgia, neuropathy, OCD, panic disorder, and schizophrenia.  It is classified as an SARI (serotonin antagonist and reuptake inhibitor), making it unique in its mechanism of action compared to other serotonergic antidepressants.

The drug functions principally as a 5-HT2A receptor antagonist, and to a lesser extent, a 5-HT1A partial agonist and serotonin transporter (SERT) inhibitor.  It is Trazodone’s 5-HT2A antagonism that is hypothesized to contribute most significantly to its anxiolytic and antidepressant properties.  Consequently, its 5-HT2A receptor antagonism may be the culprit for adverse effects experienced on Trazodone.

Common adverse effects experienced on Trazodone include: brain fog, dizziness, fatigue, headaches, sedation, and more.  As a result of experiencing these effects, many users opt to discontinue Trazodone with the hopes of finding a new medication or of functioning drug-free.  If you’ve ceased treatment, you may wonder how long Trazodone stays in your system after your last dose.

How long does Trazodone stay in your system after stopping?

If you’ve completely discontinued the drug, it is necessary to understand that you may experience Trazodone withdrawal symptoms.  These symptoms should be monitored by a medical professional and are generally a result of you stripping your neurophysiology of an exogenous chemical that it had adapted to receive.  In any regard, to calculate how long Trazodone is likely to remain in systemic circulation after you’ve ceased usage, you’ll need to consider its elimination half-life.

The elimination half-life of Trazodone is considered within the range of 5 to 9 hours; some sources estimate 7.3 hours.  This indicates that after you’ve discontinued, it’ll take around 7.3 hours to eliminate 50% of the drug from your body.  To completely clear Trazodone from your system, it’ll take an average of 1.67 days.

Most psychiatric drugs like Trazodone are ingested and broken down into various metabolites, some of which are thought to linger for a loner duration than the parent compound.  Trazodone forms a primary metabolite known as “m-chlorophenylpiperazine” (mCPP) which has a half-life of 2.4 to 6.8 hours.  However, other metabolites of Trazodone have been reported to carry an elimination half-life of up to 13 hours.

Although the parent drug (Trazodone) will have been excreted in under 2 days, elimination of various metabolites could take nearly 3 days (72 hours).  Even when considering variance in Trazodone’s half-life among different individuals – complete excretion of metabolites is unlikely to exceed 4 days.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/trazodone
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/1438031
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15467976
  • Source: Source: http://www.ncbi.nlm.nih.gov/pubmed/7018873

Variables that influence how long Trazodone stays in your system

It is necessary to understand that not everyone who stops taking Trazodone will excrete the drug from their system in under 1.67 days.  Some people may take longer than 2 days for full systemic clearance of Trazodone (and its metabolites).  Others may excrete the drug in less than a day-and-a-half.  Variance in excretion times are often a result of variables such as: the individual taking Trazodone, dosage taken, duration of administration, and co-ingestion of other drugs.

  1. Individual factors

Two people may simultaneously administer a single 50 mg dose of Trazodone, yet one person may excrete the drug at a faster rate than the other.  The reason one individual may excrete the drug from his/her system at a quicker rate than another is due to individual factors.  These factors can include things like: a person’s age, body mass, genetics, and hepatic function.

Age: Research shows that the half-life of Trazodone is extended among elderly patients (aged 65+).  A group of young adults (average age of 24) were noted to have excreted 50% of the drug within approximately 6.4 hours, whereas elderly individuals took 11.6 hours.  This suggests that elimination half-life of Trazodone among elderly could be 5.2 hours longer than average.

Going by the 11.6 hour half-life, it could be estimated to take nearly 2.66 days for complete systemic excretion among an elderly individual.  Clearance rates are notably decreased among elderly as well. Experts hypothesize that prolonged Trazodone retention among elderly may be a result of chronic illness and/or poorer physiologic function compared to younger adults.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/3321134/

Body mass/fat: Your body mass may have a minor impact on how quickly Trazodone is cleared from your system.  Specifically, the greater your body mass relative to the dosage you ingest, the faster you should expect to excrete it.  Contrarily, the lesser your body mass relative to the dosage you administer, the slower you should expect to excrete it.

Additionally, your body fat percentage may also dictate how long it takes to excrete Trazodone.  Some research suggests that among obese individuals with a high body fat percentage, the drug is distributed extensively throughout adipose tissue and more likely to accumulate in fat stores.  This accumulation often leads to slightly prolonged excretion periods and poorer clearance rates among obese individuals.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8403734

Genetics: It is important to realize that enzymes in the liver are responsible for metabolizing Trazodone.  Specifically, the CYP3A4 isoenzymes facilitate the breakdown of Trazodone into its prominent metabolite mCPP (m-chlorophenylpiperazine).  Since genes regulate the function of CYP3A4 isoenzymes, an individual could theoretically metabolize the drug quicker or slower than average.

Certain alleles of CYP3A4 may expedite metabolism or result in poor drug metabolism, which in turn can affect pharmacokinetics of Trazodone.  In other words, if you’re a poor metabolizer, you could exhibit slower clearance and an increased elimination half-life of the drug compared to an extensive metabolizer.  To a lesser extent, variation in CYP2D6 genes may also impact excretion speed of the mCPP metabolite.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9616194

Food intake/hydration: It is known that taking Trazodone along with food can affect its absorption and serum concentrations.  Food intake delays time to reach peak serum concentrations and also decreases maximum concentrations.  Eating a meal prior to taking the drug could be thought to have a subtle influence on its pharmacokinetics and elimination half-life.

Since food is thought to delay absorption and metabolism, elimination of the drug after ingestion may also be subject to postponement.  In addition, the degree to which a person is hydrated whilst taking the drug may affect its clearance and excretion.  Adequate hydration is known to increase urinary flow rate, which in turn expedites drug excretion; dehydration reduces urinary flow rate – which prolongs excretion.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/1438031

Liver function: Trazodone is subject to extensive hepatic metabolism, meaning if you have liver problems, you probably won’t excrete it as quickly.  Though the drug hasn’t been extensively studied among individuals with hepatic impairment (e.g. cirrhosis), the elimination half-life is speculated to be increased.  For this reason, one should expect that it could take several days for excretion of Trazodone among the hepatically impaired.

The degree to which you suffer from hepatic impairment will directly influence how long the drug remains in your system.  The more severe your impairment, the greater the extent to which its elimination half-life will increase.  Minor impairment may correlate with just a modest increase in elimination half-life.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23192413

Metabolic rate: A person’s metabolic rate is known to have a direct influence on drug metabolism and how long a drug remains in their system.  Individuals with a high BMR (basal metabolic rate) are burning more energy at rest.  Following ingestion of Trazodone, those with high BMRs are thought to metabolize and excrete the drug more efficiently than those with low BMRs.

Furthermore, there is often a correlation between a person’s BMR and body fat.  Another way BMR indirectly affects clearance of Trazodone is via body fat.  Low BMR individuals tend to have more body fat, resulting in greater accumulation of the drug in fat stores.  Greater accumulation of the drug in these fat stores is thought to prolong excretion.

Urinary pH: It is necessary to consider that urinary pH could have an influence on clearance rate and excretion speed of Trazodone.  Someone with a low pH urine is said to have “acidic” urine, whereas someone with high pH urine is said to have “alkaline” urine.  The lower the pH of your urine, the more efficiently you’ll likely excrete Trazodone.  The higher the pH of your urine, the more likely the drug is to get reabsorbed and recirculated through your body before excretion – resulting in a longer half-life.

  1. Dosage (Low vs. High)

Dosage can have an impact on how long the drug is likely to linger in your system.  As was mentioned earlier, the dosage administered relative to your body mass likely influences excretion time.  In general, the more of Trazodone you ingest, the longer you can expect to retain the drug (and its metabolites) in your system.

Assuming you were to take a single dose of 50 mg, you’d likely be able to metabolize and excrete this dose substantially quicker than a 300 mg dose.  At the lower dose, there’s less of the drug for your body to metabolize – this places less of a burden on your liver (namely the hepatic enzymes CYP3A4).  At the higher dose, a greater burden is placed on liver isoenzymes to metabolize such a large quantity of Trazodone.

As a result of the 300 mg dose, the metabolism process is less efficient.  Furthermore, once the larger dose is metabolized, there’s a greater amount of metabolites formed and an increased amount of the drug gets distributed throughout your body (relative to the smaller 50 mg dose).  This may result in greater accumulation of the drug within fat stores.

Additionally, there’s a greater total amount of the drug that needs to be excreted when administering the  larger dose.  This is why individuals taking exorbitant (supratherapeutic) doses of the drug often exhibit significant increases in elimination half-life.  Put simply: at lower doses, it’s easier for your body to metabolize and efficiently excrete the drug.

  1. Term/Frequency of Administration

Both the term over which you’ve taken Trazodone, along with the frequency of its administration can impact how long it’s likely to linger within your system after cessation.  A person who’s taken the drug on a daily basis for 10 years will likely take longer to excrete the drug and fully detoxify compared to someone who took the drug intermittently for 2 weeks.  Differences in excretion times between long-term/chronic users differ from those of short-term/intermittent users for number of reasons.

When administered consistently over a long-term, the drug is more likely to accumulate to peak levels within bodily tissues and in the bloodstream.  If administered infrequently over a short-term, the drug is less likely to accumulate to peak levels within tissues.  Furthermore, frequent usage over a long-term is often associated with administration of higher doses.

This is due to the fact that long-term users often build up tolerance to lower doses, requiring an upward titration in dosing – which is known to increase the drug’s half-life.  Short-term infrequent usage generally only requires a low dose because a user will not have built up tolerance to the drug’s effects; low doses are excreted quicker.  Understand that both frequency of ingestion and cumulative term of administration may have a subtle impact on systemic excretion.

  1. Co-ingestion of other drugs (CYP3A4)

If you’re taking other drugs along with Trazodone, it is important to understand their potential pharmacokinetic implications.  Certain substances are thought to interfere with the hepatic metabolism of Trazodone, thereby increasing its elimination half-life.  Other drugs may actually expedite its hepatic metabolism by increasing activation of CYP3A4 isoenzymes.

Should any other drugs you’re taking act as either CYP3A4 inhibitors or inducers, you can expect the half-life of Trazodone to possibly increase or decrease (respectively).  CYP3A4 inhibitors are known to decrease function of isoenzymes CYP3A4, prolonging the metabolism and ultimately excretion of Trazodone.  Examples of such CYP3A4 inhibitors include: Clarithromycin, Cobicistat, Indinavir, Ketoconazole, Nelfinavir, Ritonavir, and Saquinavir.

On the contrary, CYP3A4 inducers enhance functionality of CYP3A4 isoenzymes, facilitating a quicker metabolic breakdown of Trazodone.  As a result of this enzymatic induction in the liver, Trazodone’s half-life may be decreased.  Examples of prominent CYP3A4 inducers include: Carbamazepine, Modafinil, Oxcarbazepine, Phenytoin, Rifampicin, and St. John’s wort.

Trazodone: Absorption, Metabolism, Excretion (Details)

Following oral administration of Trazodone, it is efficiently absorbed by the gastrointestinal (GI) tract.  Consumption of food is known to enhance absorption, but can also delay it and prolong time to attain peak serum concentrations.  An estimated 89-95% of the drug binds to plasma proteins and is distributed extensively throughout the body, accumulating in bodily tissues.

After absorption, the drug undergoes extensive hepatic metabolism, getting broken down by CYP450 (cytochrome P450) isoenzymes. In detail, Trazodone’s pyridine ring is split via hydroxylation, N-dealkylation, and N-oxidation.  CYP3A4 specifically catalyzes formation of the drug’s chief (and pharmacologically active) metabolite “mCPP” (m-chlorophenylpiperazine).

Metabolites of Trazodone are then subject to conjugation with glucuronic acid or glutathione. CYP2D6 isoenzymes facilitate the 4′-hydroxylation of “mCPP” and some of its glutathione conjugates.  The inactive metabolite oxotriazolopyridinpropionic acid (OTPA) is also formed via Trazodone metabolism along with various OTPA metabolites.

Due to the fact that Trazodone is extensively metabolized in the liver, less than 1% of a dose is excreted as the drug “unchanged.”  Up to 75% of an oral dose is excreted by the kidneys in the form of various metabolites, with OTPA (oxotriazolopyridinpropionic acid) accounting for ~20%.  A smaller percentage of the drug undergoes biliary excretion where it appears in the feces.

The elimination half-life of Trazodone is considered biphasic in that it occurs in 2 phases.  The first phase has an elimination half-life of 3-6 hours, whereas the second phase takes 5-9 hours.  This suggests that full systemic excretion of Trazodone takes between 1.14 and 2.06 days.  The half-life of various metabolites formed via Trazodone metabolism has been reported to be 13 hours – taking just under 3 days for complete excretion.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/trazodone
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7018873
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/1438031
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9616194

Tips to clear Trazodone from your system

If you want to ensure that Trazodone has been fully excreted from your body after your last dose, there may be some extra steps you can take.  Keep in mind that you should always talk to a medical professional regarding safety and alleged efficacy of the suggestions listed below.  Realize that these tips may not be beneficial for everyone and that they may be detrimental to individuals using other medications.

  1. Cease ingestion: Getting Trazodone and its metabolites out of your system requires that you stop taking it. The simple fact is that the longer you’ve been off of the drug, the more likely it is to have been excreted from your body. If you haven’t stopped using Trazodone – you should expect it to remain in your system until you fully discontinue.
  2. Hydration: Staying hydrated is unlikely to significantly speed up excretion, but it may provide some benefit. Hydration is known to ramp up clearance speed of drugs that are excreted via urine. Obviously you’ll want to avoid going overboard with hydration (as this can be toxic), but staying properly hydrated after cessation of Trazodone can ensure that it gets eliminated quickly.
  3. Acidification: Your urinary pH may affect whether Trazodone is likely to get reabsorbed prior to excretion. Individuals with highly alkaline urine tend to reabsorb drugs like Trazodone before full excretion, leading to re-circulation throughout the body. For this reason, lowering your urinary pH to make it acidic could amplify excretion rate.
  4. Exercise: If you’re a long-term Trazodone user, you may want to consider getting some exercise after discontinuation. Getting exercise is known to burn body fat, some of which may be storing Trazodone metabolites. Doing any exercise that is known to burn body fat could help purge Trazodone from your system at a faster pace than remaining sedentary.
  5. Activated charcoal: Activated charcoal is a supplement that will ensure that unmetabolized Trazodone isn’t lingering in your liver. Though this should never be taken during a “taper” off of Trazodone, activated charcoal binds to toxins and remnants of drugs and detoxifies your body. For this reason I recommend it as among the best supplements for antidepressant withdrawal (assuming you’re done taking the drug).

How long has Trazodone stayed in your system after stopping?

If you’ve stopped taking Trazodone, mention how long you believe it lingered in your system along with its metabolites.  Do you think you were able to excrete the drug quicker than average in less than 2 days?  Or do you think that the elimination half-life of Trazodone was increased due to various individual factors?

To help others get a better understanding of your situation, share factors that you believe may have expedited/prolonged Trazodone excretion such as: age, dosage, CYP3A4 inducers/inhibitors, etc.  Realize that for most people, Trazodone will have been excreted within 48 hours of the final dosage.  Its metabolites should be fully excreted within approximately 72 hours of your last dose, meaning your system will be completely “drug-free” within 3 to 4 days.

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{ 2 comments… add one }
  • Frank Brandon November 9, 2015, 6:49 am

    My wife age 91, has Alzheimer’s and Parkinson’s. She was put on Trazodone (50mg/day), was substituted for Serequel for my wife (age 91, who has Alzheimer’s and Parkinson’s. It was prescribed to treat her dementia and sleep problem (sleeping too much). The result from the start, had the opposite effect. As soon as she started on Trazodone, she became extremely violent and could not sleep. After 2 months her condition had worsened to the point that her doctor discontinued the drug cold turkey, and put her back on Seroquel.

    Although the switch back to Seroquel had a noticeable positive effect to start with, she is continuing to have very bad mood swings and aggressive behavior. It appears that she is experiencing an extremely bad withdrawal. It should be noted that she is allergic to Remeron, a similar drug also used for depression and sleep disorders. Any suggestions? Thank you.

  • lbr August 21, 2016, 1:50 pm

    Dear Mr Brandon, Not a physician or nurse, I have no medical advice. This website puts no timestamp on the article or your comment, so it could be a decade old or more. You write a compelling story and my heart goes out to you. Your wife made a good choice marrying such an articulate, thoughtful, empathetic man. Best of best luck. Lee Roberts

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