Trazodone Half-Life: Its Mechanism Of Actions And How Long Does It Stay In System?

Last Updated: November 1, 2021

Authored by Nena Messina, Ph.D.

Reviewed by Michael Espelin APRN

Sold under different brand names, Trazodone belongs to the drug class called serotonin modulators. These drugs are used for the treatment of depression and some doctors prescribe them for patients experiencing insomnia. In 2019, around 24 million prescriptions of Trazodone were issued in the United States. With these statistics, it is important for every patient using this medication to know how this drug works and how long it stays in the system.In this article, information about the Trazodone MOA and its effects, Trazodone half-life, its relation to drug tests, and how to safely remove it from one’s system will be provided.

Trazodone Mechanism Of Action

All medications, including Trazodone, have a mechanism of action: the way the medication acts on the body to produce the desired effects. However, the Trazodone mechanism of action is not perfectly understood. The medical community understands quite a bit about how this medication does work and what are its effects, but as is true for all serotonin reuptake inhibitors, there is still some mystery there.

When studied in animals, what Desyrel does is selectively inhibit serotonin uptake by brain synaptosomes and then amplifies the changes in behavior caused by 5-hydroxytryptophan. It does this by binding to the 5-HT2 receptor. Moreover, how it impacts serotonin depends on the dosage taken; at a low dose, it functions as a serotonin antagonist, while at a high dose it becomes a serotonin agonist. When there is a serotonin uptake (recycling), the tendency is that serotonin levels might become low and this may lead to depression. Because of this, Trazodone moa works by inhibiting the uptake of serotonin, thereby preventing depression.

A girl holds Trazodone pills in her hand.

How Long Does Trazodone Take to Work?

Many patients wonder how long does Trazodone take to work. The answer to this depends on what the medication is being used to treat. For example, when treating depression, this medication works in approximately one to two weeks before the benefits are noticeable. But, when treating insomnia, the effects take anywhere from 30 minutes to a couple of hours. While the Trazodone mechanism of action results in effective treatment for many, it is not successful in every case. Patients should always work closely with a doctor when using the drug.

How Long Does Trazodone Stay In Your System?

If one is wondering, how long does Trazodone stay in your system? The answer may vary depending on different factors such as the dosage of Desyrel consumed and the biological factors of the patient. Moreover, there are different tests where Desyrel can be screened.

Blood test

A blood test is usually done when there is a suspicion that the person is still actively under the influence of a drug. Every 5-13 hours, the medication loses 50% of its concentration in the blood. Therefore, Desyrel metabolites can be traced in the blood for up to three days.

Urine test

The parent drug, Trazodone, is eliminated from the body in a maximum of two days, but some of its metabolites can linger for longer. That is why urine tests can trace metabolites even 26 days after the last dose.

Saliva test

Saliva testing can show drug use in the first few hours after administration, a time window that could be missed by urine testing. As of today, there is no study yet about how long Desyrel can stay in the saliva. However, its primary metabolite, meta-chlorophenylpiperazine, often causes false positives on amphetamines and this can be tested in the saliva for up to 3 days.

Hair test

It is preferably safer to stop Desyrel, like any other medication, for about three months before going for any drug screening, as any substance one takes may remain in hair cells for up to 90 days. The standard hair drug testing offers up to a 90-day window for drug detection. However, when stopping a medication, a doctor’s medical intervention is required.

Drug test of Trazodone.

Trazodone And Standard Pre-Employment Drug Test

Drug testing is usually used in the workplace, criminal settings, and health care, and has become frequently used over the past ten years. In fact, in the United States, there are different drug-testing programs such as pre-employment testing for job applicants, cause-testing of employees during accidents, and post-employment testing where there is a random call for a drug test. These programs led to an increase in the productivity of every worker. Furthermore, drug testing is mostly done using urine screening because of the ease of sampling.

In terms of Desyrel, the medication is not among the prohibited substances, and there is no test required for prescribed antidepressants. Besides that, antidepressants are not among the drugs an employer is looking for during a pre-employment drug screening. Specific additional tests would be required to detect antidepressants. For example, tricyclic antidepressant (TCA) testing can be used to check a sample of blood and urine for TCA contents.

False Positive Test With Trazodone

The false-positive test result is possible with the Trazodone drug. This happens when a drug with a similar chemical structure is fragmented into a component that is similar to the targeted drug. Unfortunately, the screening test sometimes fails to differentiate an antidepressant, such as Desyrel, and crystal methamphetamine. Although Desyrel is not a prohibited substance, one thing to know is that one of its by-products, the meta-Chlorophenylpiperazine, is a powerful hallucinogen and an abused stimulant. In a standard drug test, this compound has the cross-reaction with amphetamines, and this leads to a false-positive result.

Hence, Desyrel is among antidepressant drugs that are highly prone to false-negative results. This result can be affected by several factors such as the quantity of the drug ingested, dilute urine, and the duration between ingestion of Desyrel and the time of testing. According to the study of medical doctors from the United States, 3 out of 6 patients who took Desyrel tested falsely positive for meth.

Moreover, take note that false-positive test results with Trazodone also depend on the dose consumed. According to medical doctors from Boston, USA, consuming 3 micrograms per mL of Trazodone could already yield a false-positive result, owing to the active metabolite mCPP as this has a similar structure with MDMA (ecstasy).

Removing Trazodone From The System Safely

Although the best thing to do is to wait for the drug to be customarily eliminated from the organism, there are some steps to take to make this process faster. Note that this should be done only after asking information from a medical professional about the efficacy and safety of the following suggestions since they might be detrimental for those using other medications besides Desyrel.

  • Hydration– Drinking liquids will not significantly speed up the drug’s excretion for the body, but it might offer some benefits such as avoiding overdose. Hydration increases the clearance speed of drugs which are eliminated through urine.
  • Acidification– The urine’s pH might also influence if the drug will get reabsorbed before excretion. People with highly alkaline urine are more prone to reabsorb drugs such as Desyrel before it is entirely excreted. This leads to re-circulation in the body. Get the urine close to a neutral pH by avoiding alcohol, coffee, orange and cranberry juices, as well as red meat.
  • Exercise– Exercise burns body fat, some of which can be responsible for storing Desyrel metabolites, especially in patients who have been long-term users, as Desyrel may cause weight gain in some patients. According to a study from medical doctors from the United States, exercising can also help with drug addiction. It can be an adjunct with another drug addiction treatment.
  • Activated charcoal– Activated charcoal is a supplement that binds to remnants of drugs and toxins, cleaning the body. This is also great for patients who undergo antidepressant withdrawal.

Knowing that a Desyrel false-positive test result is a possibility, the worst thing one can do is to stop the medication or even reduce the dosage without medical advice. Even a short-term interruption of Desyrel dosage for insomnia or depression can imply side effects and complications to the health, such as antidepressant discontinuation syndrome or ADS. This syndrome may require drug abuse treatment. Anyone concerned about Trazodone on a drug test should first talk to a health provider so that the drug screen is taken safely and without any stress. The drug rehabilitation clinics also offer detoxification methods to flush the medication from the body faster.

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Page Sources

  1. Algren, D. A., & Christian, M. R. (2015). Buyer beware: pitfalls in toxicology laboratory testing. Missouri medicine, 112(3), 206.
  2. Baron, J. M., Griggs, D. A., Nixon, A. L., Long, W. H., & Flood, J. G. (2011). The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results. Journal of analytical toxicology, 35(6), 364-368.
  3. Bryant, S. G., & Ereshefsky, L. (1982). Antidepressant properties of trazodone. Clinical pharmacy, 1(5), 406-417.
  4. Buysse, D. J., & Tyagi, S. (2017). Clinical pharmacology of other drugs used as hypnotics. In Principles and practice of sleep medicine (pp. 432-445). Elsevier.
  5. Camacho, L. D., Stearns, J., & Amini, R. (2019). Management of trazodone overdose with severe hypotension. Case reports in emergency medicine, 2019.
  6. Fabre, L. F. (1990). Trazodone dosing regimen: experience with single daily administration. The Journal of clinical psychiatry, 51, 23-26.
  7. Frecska, E. (2010). Trazodone--its multifunctional mechanism of action and clinical use. Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakologiai Egyesulet Lapja= Official Journal of the Hungarian Association of Psychopharmacology, 12(4), 477-482.
  8. Hadelman-Englert, C. (2021). Tricyclic Antidepressant Screen - Health Encyclopedia - University of Rochester Medical Center. University of Rochester Medical Center. https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=tricyclic_antidepressant
  9. Kale, P., & Agrawal, Y. K. (2015). Pharmacokinetics of single oral dose trazodone: a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition. Frontiers in pharmacology, 6, 224.
  10. Kane, S. P. P. (2019). Trazodone - Drug Usage Statistics, ClinCalc DrugStats Database. ClinCalc. https://clincalc.com/DrugStats/Drugs/Trazodone
  11. Lynch, W. J., Peterson, A. B., Sanchez, V., Abel, J., & Smith, M. A. (2013). Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis. Neuroscience & Biobehavioral Reviews, 37(8), 1622-1644.
  12. Marin, S. J., Doyle, K., Chang, A., Concheiro-Guisan, M., Huestis, M. A., & Johnson-Davis, K. L. (2016). One hundred false-positive amphetamine specimens characterized by liquid chromatography time-of-flight mass spectrometry. Journal of analytical toxicology, 40(1), 37-42.
  13. NHS website. (2021, January 14). Trazodone. Nhs.Uk. https://www.nhs.uk/medicines/trazodone/
  14. Normand, J., Lempert, R. O., O'Brien, C. P., & National Research Council. (1994). Impact of Drug-Testing Programs on Productivity. Under the Influence? Drugs and the American Work Force.
  15. Saitman, A., Park, H. D., & Fitzgerald, R. L. (2014). False-positive interferences of common urine drug screen immunoassays: a review. Journal of analytical toxicology, 38(7), 387-396.

Published on: April 1st, 2019

Updated on: November 1st, 2021

About Author

Nena Messina, Ph.D.

Nena Messina is a specialist in drug-related domestic violence. She devoted her life to the study of the connection between crime, mental health, and substance abuse. Apart from her work as management at addiction center, Nena regularly takes part in the educational program as a lecturer.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.