Trazodone


Description

Trazodone is triazolopyridine derivative from the serotonin receptor antagonists and reuptake inhibitors (SARIs) class of antidepressants.[

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Pharmacology

Indication

Trazodone is indicated for the treatment of major depressive disorder (MDD).[ Read more

Pharmacodynamic

Trazodone treats depressed mood and other depression-related symptoms and shows benefit in the treat... Read more

Mechanism of action

The mechanism of action of trazodone is not fully understood, however, it is known to inhibit the re... Read more

Absorption

Trazodone is rapidly absorbed in the gastrointestinal tract after oral administration, with a bioava... Read more

Protein binding

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

Volume of distribution

A single-dose pharmacokinetic study of 8 volunteers taking trazodone determined a volume of distribu... Read more

Clearance

A decrease in total apparent clearance (5.1 versus 10.8 L/h) was seen elderly volunteers in the fast... Read more

Half life

The plasma elimination half-life was markedly prolonged (13.6 versus 6 hours) elderly volunteers in... Read more

Route of elimination

Less than 1% of an oral dose is excreted unchanged in the urine.[ Read more

Toxicity

The oral LD50 of trazodone is 690 mg/kg in rats.[ Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Drowsiness US
  • Kind: experimental
    • Percent: 41%
  • Kind: placebo
    • Percent: 20%
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 34%
  • Kind: placebo
    • Percent: 20%
  • Clinical Trial
    Dizziness/lightheadedness US
  • Kind: experimental
    • Percent: 28%
  • Kind: placebo
    • Percent: 15%
  • Clinical Trial
    Drowsiness US
  • Kind: experimental
    • Percent: 24%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Hypertension US
  • Kind: experimental
    • Percent: 20%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Dizziness/lightheadedness US
  • Kind: experimental
    • Percent: 20%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 20%
  • Kind: placebo
    • Percent: 16%
  • Clinical Trial
    Blurred vision US
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 8%
  • Clinical Trial
    Nervousness US
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 11%
  • Clinical Trial
    Nausea and vomiting US
  • Kind: experimental
    • Percent: 13%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Nausea and vomiting US
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Hypotension US
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Blurred vision US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Aches/pains US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Abdominal/gastric disorder US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Weight Loss US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Nasal/sinus congestion US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Malaise US
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Syncope US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Confusion US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Aches/pains US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Tremors US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Incoordination US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Weight Gain US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Syncope US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Decreased concentration US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Malaise US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Head full-heavy US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Eye irritation (redness, tired, itchy) US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Tremors US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Nasal/sinus congestion US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Malaise US
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Paresthesia US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Retrograde ejaculation US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Tachycardia US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Shortness of Breath US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Palpitations US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Sinus Bradycardia US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Disorientation US
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Hallucinations US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Delusions US
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial

    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

    Trazodone may decrease the anticoagulant activities of (R)-warfarin.
    Trazodone may decrease the anticoagulant activities of (S)-Warfarin.
    The metabolism of Trazodone can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
    The risk or severity of hypertension can be increased when Trazodone is combined with 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-benzylimidazole.
    The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
    The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
    The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Trazodone.
    The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Trazodone.
    The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 4-Bromo-2,5-dimethoxyamphetamine.
    The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Trazodone.
    The risk or severity of bleeding can be increased when Trazodone is combined with 4-hydroxycoumarin.
    The risk or severity of adverse effects can be increased when Trazodone is combined with 4-Methoxyamphetamine.
    The metabolism of 5-androstenedione can be decreased when combined with Trazodone.
    The risk or severity of serotonin syndrome can be increased when Trazodone is combined with 5-methoxy-N,N-dimethyltryptamine.
    The metabolism of Trazodone can be decreased when combined with 6-Deoxyerythronolide B.
    The metabolism of 6-O-benzylguanine can be decreased when combined with Trazodone.
    The metabolism of Trazodone can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
    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 may increase the serotonergic activities of Trazodone.

    References

    • 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . Nutt DJ: Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69 Suppl E1:4-7. [PubMed: 18494537]
    • 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 . Nilsen OG, Dale O: Single dose pharmacokinetics of trazodone in healthy subjects. Pharmacol Toxicol. 1992 Aug;71(2):150-3. [PubMed: 1438031]
    • 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 . 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 . Stahl SM: Mechanism of action of trazodone: a multifunctional drug. CNS Spectr. 2009 Oct;14(10):536-46. [PubMed: 20095366]
    • 20 . Justin J. Shin; Abdolreza Saadabadi. (2019). Trazodone, StatPearls. Stat Pearls.
    • 21 . Trazodone [Link]
    • 22 . Monograph, Trazodone [Link]
    • 23 . Trazodone overdose, NIH Medline [Link]
    • 24 . Rapid structure determination of microgram-level drug metabolites using HPLC-MS, fraction collection and NMR spectroscopy [Link]
    • 25 . FDA application review, Trazodone [Link]

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