Wellbutrin XL
Celexa (Citalopram)
Zoloft (Sertraline)
Effexor XR (Venlafaxine)

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 hcl is a sedating antidepressant, and in practice it is widely used off-label to treat insomnia. The drug is particularly effective for insomnia exacerbated by other antidepressants1. Trazodone reduces anxiety and insomnia during withdrawal from alcohol14.

Trazodone is often used as a hypnotic for sleep difficulties even in non-depressed insomniacs. 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 important for restorative rest. This medication also increases total sleep time and decreases number of awakenings 15.

Trazodone dosage for insomnia

When used as hypnotic, the usual starting dose is 25-50 mg of Trazodone at bedtime. If needed, the dose can be increased up to 100 mg. But it is rarely necessary to increase the maximum dose. The 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 sleep-promoting effect. You should go to bed within 60-90 minutes after taking the dose. 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.

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 sleeping pill
  • Non-controlled substance
  • 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. It is considerably cheaper than modern hypnotics like Ambien, Sonata, Lunesta, or Rozerem.
  • Can be safely used in combination with SSRIs8.


  • Not FDA approved specifically for insomnia and the scientific evidence is relatively mixed regarding efficacy of trazodone as a hypnotic. Trazodone has been available as a cheap generic for many years, and there is very little chance that any pharmaceutical company will pay money for studies to gain official FDA approval for an old "off-label" prescription.
  • Next-day sedation and drowsiness.
  • Potential for drug interactions with inducers and/or inhibitors of CYP3A47.
  • Risk of drug-induced priapism due to alpha-adrenergic antagonist properties10.

Unlabeled uses

  • Primary or secondary insomnia1, 3
    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
  • Aggressive behavior
  • 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. Bossini L, Coluccia A, Casolaro I, Benbow J, Amodeo G, De Giorgi R, Fagiolini A. Off-Label Trazodone Prescription: Evidence, Benefits and Risks. Curr Pharm Des. 2015;21(23):3343-51.
  • 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
  • 14. Arnedt JT, Conroy DA, Brower KJ. Treatment options for sleep disturbances during alcohol recovery. J Addict Dis. 2007;26(4):41-54. PubMed
  • 15. Kaynak H, Kaynak D, Gözükirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med. 2004 Jan;5(1):15-20. PubMed

Written for, October 2009
Last modified: August, 2015

Interesting facts


  • Trazodone hydrochloride, a triazolopyridine derivative, is the most sedating, and least anticholinergic, of all the currently available antidepressants.
  • It is chemically and pharmacologically distinct from SSRIs.
  • 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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