Description

Simple

A medication used to treat depression.

Clinical

A serotonin uptake inhibitor used to treat major depressive disorder.

Overview

Trazodone is triazolopyridine derivative from the serotonin receptor antagonists and reuptake inhibitors (SARIs) class of antidepressants.[11] It is used in adults and has been shown to be comparable in efficacy to other drugs such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine receptor inhibitor (SNRIs) in the treatment of depression.[20] A unique feature of this drug is that it does not promote the anxiety symptoms, sexual symptoms, or insomnia, which are commonly associated with SSRI and SNRI therapy.[20] Trazodone acts on various receptors, including certain histamine, serotonin, and adrenergic receptors, distinguishing it from other antidepressants that cover a narrow range of neurotransmitters.[Read more

Pharmacology

Indication

Trazodone is indicated for the treatment of major depressive disorder (MDD).[21] It has been used off-label for adjunct therapy in alcohol dependence, and off-label to treat anxiety and insomnia.[ Read more

Pharmacodynamic

Trazodone treats depressed mood and other depression-related symptoms and shows benefit in the treatment of insomnia due to its sedating effects.[20] It is kno... Read more

Mechanism of action

The mechanism of action of trazodone is not fully understood, however, it is known to inhibit the reuptake of serotonin and block both histamine and alpha-1-adrenergic receptors.[ Read more

Absorption

Trazodone is rapidly absorbed in the gastrointestinal tract after oral administration, with a bioavailability ranging from 63-91% [ Read more

Protein binding

The plasma protein binding of trazodone is 89-95% according to in vitro studies.[22]

Volume of distribution

A single-dose pharmacokinetic study of 8 volunteers taking trazodone determined a volume of distribution of 0.84 +/- 0.16 L/kg.[ Read more

Clearance

A decrease in total apparent clearance (5.1 versus 10.8 L/h) was seen elderly volunteers in the fasted state when compared with younger volunteers.[ Read more

Half life

The plasma elimination half-life was markedly prolonged (13.6 versus 6 hours) elderly volunteers in the fasted state when compared with younger volunteers.[ Read more

Route of elimination

Less than 1% of an oral dose is excreted unchanged in the urine.[22] In a pharmacokinetic study, about 60-70% of radiolabeled was excreted urine within 48 hours. Approximately 9-29% was found to be excreted in feces ov... Read more

Toxicity

The oral LD50 of trazodone is 690 mg/kg in rats.[22]

An overdose of trazodone may result in central nervous system, cardiac, respiratory effects. Signs and symptoms may include dyspnea, bradycardia, hypotension, men... Read more

Adverse Effects

Contraindications

  • Recommended Actions:
    • Do not coadminister within 14 days of discontinuing MAO inhibitors.
  • Regions: US
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996

Food Interactions

  • Avoid alcohol.
  • Food decreases the rate and extent of absorption.

Interactions

Type in a drug name to check for interaction with Trazodone
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
Trazodone may decrease the anticoagulant activities of (R)-warfarin.
(S)-Warfarin
Trazodone may decrease the anticoagulant activities of (S)-Warfarin.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Trazodone can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid
The risk or severity of hypertension can be increased when Trazodone is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazole
The risk or severity of hypertension can be increased when Trazodone is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Trazodone.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamine
The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Trazodone.
4-hydroxycoumarin
The risk or severity of bleeding can be increased when Trazodone is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Trazodone is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Trazodone is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Trazodone.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Trazodone.
Abatacept
The metabolism of Trazodone can be increased when combined with Abatacept.
Abciximab
The risk or severity of bleeding can be increased when Trazodone is combined with Abciximab.
Abediterol
The therapeutic efficacy of Abediterol can be decreased when used in combination with Trazodone.
Abexinostat
The risk or severity of QTc prolongation can be increased when Trazodone is combined with Abexinostat.
25 References
  1. 1 . Marek GJ, McDougle CJ, Price LH, Seiden LS: A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action. Psychopharmacology (Berl). 1992;109(1-2):2-11.PubMed: 1365657
  2. 2 . Jauch R, Kopitar Z, Prox A, Zimmer A: [Pharmacokinetics and metabolism of trazodone in man (author's transl)]. Arzneimittelforschung. 1976;26(11):2084-9.PubMed: 1037253
  3. 3 . Rotzinger S, Fang J, Baker GB: Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos. 1998 Jun;26(6):572-5.PubMed: 9616194
  4. 4 . Kalgutkar AS, Henne KR, Lame ME, Vaz AD, Collin C, Soglia JR, Zhao SX, Hop CE: Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4. Chem Biol Interact. 2005 Jun 30;155(1-2):10-20. Epub 2005 Apr 18.PubMed: 15978881
  5. 5 . Otani K, Yasui N, Kaneko S, Ishida M, Ohkubo T, Osanai T, Sugawara K, Fukushima Y: Trazodone treatment increases plasma prolactin concentrations in depressed patients. Int Clin Psychopharmacol. 1995 Jun;10(2):115-7.PubMed: 7673654
  6. 6 . Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P, Gruber G, Mandl M, Strobl R, Gollner D, Prause W, Saletu B: Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):249-60.PubMed: 11817501
  7. 7 . Fink HA, MacDonald R, Rutks IR, Wilt TJ: Trazodone for erectile dysfunction: a systematic review and meta-analysis. BJU Int. 2003 Sep;92(4):441-6.PubMed: 12930437
  8. 8 . Davis JL, Schirmer J, Medlin E: Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite m-chlorophenylpiperazine in the horse. J Vet Pharmacol Ther. 2018 Jun;41(3):393-401. doi: 10.1111/jvp.12477. Epub 2018 Jan 14.PubMed: 29333613
  9. 9 . Haria M, Fitton A, McTavish D: Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging. 1994 Apr;4(4):331-55. doi: 10.2165/00002512-199404040-00006.PubMed: 8019056
  10. 10 . Fagiolini A, Comandini A, Catena Dell'Osso M, Kasper S: Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. doi: 10.1007/s40263-012-0010-5.PubMed: 23192413
  11. 11 . Mandrioli R, Protti M, Mercolini L: New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs. Curr Med Chem. 2018;25(7):772-792. doi: 10.2174/0929867324666170712165042.PubMed: 28707591
  12. 12 . Jaffer KY, Chang T, Vanle B, Dang J, Steiner AJ, Loera N, Abdelmesseh M, Danovitch I, Ishak WW: Trazodone for Insomnia: A Systematic Review. Innov Clin Neurosci. 2017 Aug 1;14(7-8):24-34. eCollection 2017 Jul-Aug.PubMed: 29552421
  13. 13 . Blier P: Neurotransmitter targeting in the treatment of depression. J Clin Psychiatry. 2013;74 Suppl 2:19-24. doi: 10.4088/JCP.12084su1c.04.PubMed: 24191974
  14. 14 . Nutt DJ: Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69 Suppl E1:4-7.PubMed: 18494537
  15. 15 . Hoffmann P, Neu ET, Neu D: Penile amputation after trazodone-induced priapism: a case report. Prim Care Companion J Clin Psychiatry. 2010;12(2). doi: 10.4088/PCC.09l00816gry.PubMed: 20694124
  16. 16 . Nilsen OG, Dale O: Single dose pharmacokinetics of trazodone in healthy subjects. Pharmacol Toxicol. 1992 Aug;71(2):150-3.PubMed: 1438031
  17. 17 . Kale P, Agrawal YK: Pharmacokinetics of single oral dose trazodone: a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition. Front Pharmacol. 2015 Oct 2;6:224. doi: 10.3389/fphar.2015.00224. eCollection 2015.PubMed: 26483693
  18. 18 . Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58.PubMed: 9537821
  19. 19 . Stahl SM: Mechanism of action of trazodone: a multifunctional drug. CNS Spectr. 2009 Oct;14(10):536-46.PubMed: 20095366
  20. 20 . Justin J. Shin; Abdolreza Saadabadi. (2019). Trazodone, StatPearls. Stat Pearls.
  21. 21 . Trazodone Link
  22. 22 . Monograph, Trazodone Link
  23. 23 . Trazodone overdose, NIH Medline Link
  24. 24 . Rapid structure determination of microgram-level drug metabolites using HPLC-MS, fraction collection and NMR spectroscopy Link
  25. 25 . FDA application review, Trazodone Link