Wellbutrin XL
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Trazodone HCl (Desyrel)

  • Generic name: Trazodone hydrochloride
  • Trade names: Desyrel, Trazon, Trialodine
  • Dosages: Tablets 50 mg, 100 mg, 150 mg
  • Pharmacologic category: antidepressant, triazolopyridine derivative, 5-HT(2) antagonist and 5-HT reuptake inhibitor
  • FDA approved: December 24, 1981
  • Pregnancy risk factor: C
Trazodone for sleep

Trazodone is a sedating antidepressant, widely used to treat insomnia. It is especially effective for insomnia caused by other antidepressants1. However, Trazodone is used for the treatment of sleep difficulties even in people without depressive symptoms. Polysomnographic studies of people with various kinds of insomnia have found that trazodone's main effect on sleep architecture is an increase in deep slow-wave (stages 3 and 4) sleep11,12, which is is important to restorative rest.

When used as sleep aid, the usual starting dose is 25-50 mg of Trazodone at bedtime. The dose can be increased if necessary up to 100 mg. There is little need to increase the maximum dose for this indication. Its sleep promoting effect starts within 1-2 hours and usually lasts about 8 hours.

Important notes:

  • Take trazodone with food. The absorption of the drug may be up to 20% higher when it is taken with food rather than on an empty stomach.
  • Trazodone has a narrow "window" of hypnotic effect. You should go to bed within 60-90 minutes after taking it. If you miss that window, you may feel very sleepy but unable fall asleep.

Trazodone may cause feelings of tiredness and grogginess ("hangover") on the next morning. However its advantage is that unlike most sleeping pills, it is not addictive and not habit forming.

Trazodone and Sleep Apnea
Trazodone may reduce apnea severity in some people with obstructive sleep apnoea (with a mildly compromised upper airway)3. It has been shown to increases the arousal threshold and to be a stimulant of upper airway muscle activity.

Pharmacological characteristics
  • Elimination half-life: 3-6 hours
  • Metabolism: Hepatic via CYP3A4 to an active metabolite (mCPP)
  • Excretion: Primarily urine (80%); secondarily feces (20%)
  • Effective antidepressant in treating major depressive disorder.
  • No risk of addiction and dependence.
  • Has a long safety record, and is relatively safe in overdose.
  • Low risk of anticholinergic effects, such as dry mouth, blurred vision, bowel movement disturbance, and delayed urine flow9.
  • Low cost - trazodone is one of the most inexpensive antidepressants for people without insurance.
  • Equal antidepressant efficacy with amitriptyline, imipramine, and fluoxetine
  • Can be safely used in combination with SSRIs8.
  • Potential for drug interactions with inducers and/or inhibitors of CYP3A47.
  • Risk of drug-induced priapism due to alpha-adrenergic antagonist properties10.
Unlabeled uses
  • Insomnia1
    Whereas trazodone is not FDA-approved to treat insomnia, several clinical studies and practical experience support its efficacy and safety. This medicine may be of advantage in depressed people with sleep difficulties and for treating insomnia caused by other drugs.
  • Panic, anxiety2
  • Bipolar depression
  • Chronic fatigue
  • Eating disorders
  • Alcohol withdrawal
  • Erectile dysfunction 13, including antidepressant-induced sexual dysfunction
Mechanism of action

Trazodone is a serotonin reuptake inhibitor and is also a 5-HT2 receptor antagonist. However, in contrast to the SSRIs, trazodone's antidepressant effects may be due to its antagonistic action at the 5-HT2 receptor site. It causes adrenoreceptor subsensitivity, and induces significant changes in 5-HT presynaptic receptor adrenoreceptors. This agent also blocks histamine (H1) and alpha1-adrenergic receptors.

User Reviews & Discussions
  • 1. Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994 Jul;151(7):1069-72. PubMed
  • 2. Mavissakalian M, Perel J, Bowler K, Dealy R. Trazodone in the treatment of panic disorder and agoraphobia with panic attacks. Am J Psychiatry. 1987 Jun;144(6):785-7. PubMed
  • 3. Heinzer RC, White DP, Jordan AS, Lo YL, Dover L, Stevenson K, Malhotra A. Trazodone increases arousal threshold in obstructive sleep apnoea. Eur Respir J. 2008 Jun;31(6):1308-12 PubMed
  • 4. Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. 1994 Apr;4(4):331-55. PubMed
  • 5. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry. 2005 Apr;66(4):469-76. PubMed
  • 6. Dossier Trazodone. 15/03/2007:
  • 7. Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metabolism Disposition 1998 Jun;26(6):572-5.
  • 8. Prapotnik M, Waschgler R, Konig P, Moll W, Conca A. Are there pharmacokinetic interactions involving trazodone and SSRIs? Int J Clin Pharmacol Ther. 2004 Feb;42(2):120-4.
  • 9. Gershon S, Newton R. Lack of anticholinergic side effects with trazodone. J Clin Psychiatry. 1980 Mar.
  • 10. Abber JC, Lue TF, Luo JA, Juenemann KP, Tanagho EA. Priapism induced by chlorpromazine and trazodone: mechanism of action. J Urol. 1987 May;137(5):1039-42.
  • 11. Parrino L, et al. Trazodone in chronic insomnia associated with dysthymia: polysomnographic variables and sleep quality. Psychopharmacology 1994;116:389-395.
  • 12. Montgomery I, et al. Trazodone enhances sleep in subjective quality but not in objective duration. Br J Clin Pharmacol 1983;16:139-144. PubMedCentral
  • 13. 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

Written for, October 2009
Last modified: February 10, 2015

Interesting facts


  • Trazodone hydrochloride, a triazolopyridine derivative, is the most sedating, and least anticholinergic, of all the currently available antidepressants.
  • Lately, trazodone is the second most commonly prescribed treatment for insomnia5 because of its effectiveness, sedative properties, perceived lack of hazards and serious problems, generic availability, and lack of restrictions for long-term use.

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