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Trazodone (Desyrel)

Trazodone in Brief
  • Active ingredient: trazodone hydrochloride
  • Common brand names: Desyrel, Trazon, Trialodine
  • Drug class: Antidepressant, Serotonin Reuptake Inhibitor/Antagonist
  • FDA Approved: 12/24/1981
  • Chemical Formula: C19H22ClN5O
  • Pregnancy Category: C
  • Habit forming? No
  • Originally discovered: 1960s, Italy Italy

History

Trazodone was originally discovered and developed in Italy in the 1960s as a second-generation antidepressant by Angelini research laboratories. This agent was developed according to the mental pain hypothesis, which was postulated from studying patients and which proposes that depression is associated with a decreased pain threshold 27.

In Italy, this drug is fully reimbursed by the National Health System and is available in tablets, drops and injectable solution. Trazodone was patented and marketed in many countries all over the world and became the market leader in the United States during the 1980s.

FDA approved indications
  • Major Depressive Disorder

Off-label & Investigational uses
  • insomnia 2, 3, 9, 12
  • panic disorder 4
  • generalized anxiety disorder 5
  • diabetic neuropathy 6
  • migraine 7
  • bulimia nervosa 8
  • obsessive-compulsive disorder 14, 23
  • alcohol withdrawal 15, 17, 19
  • schizophrenia 16, 20
  • erectile dysfunction 21

Panic disorder
There was significant improvement on all symptom dimensions, which suggests that trazodone may have specific antipanic and antiphobic actions and underscores the importance of serotonergic mechanisms in these anxiety disorders.

Migraine
A double-blind, placebo-controlled cross-over trial showed that, trazodone is a valid prophylactic agent for juvenile migraine. The study has been shown that trazodone can reduce frequency and the duration of the migraine episodes 7.

Bulimia nervosa
Trazodone appears to be effective in the treatment of bulimia nervosa. It is particularly attractive treatment for bulimia nervosa because of its low anticholinergic side-effects profile.

Chronic schizophrenia and tardive dyskinesia
Results of double-blind, placebo-controlled study 16 indicated that trazodone, when used in conjunction with neuroleptics, is safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia. Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia.

Erectile dysfunction
While trazodone is not designed for treatment of erectile dysfunction, its combined central and peripheral activity does improve erectile function in men with mild ED. Trazodone may be especially helpful for problems dealing with male arousal.

Trazodone may be beneficial in the management of SSRI-induced sexual dysfunction11.

The study have been shown that combination of yohimbine and trazodone may be a safe and effective treatment for psychogenic impotence 22.

Alcohol withdrawal
Trazodone is helpful in the treatment of lasting alcohol withdrawal symptoms, such as sleep disturbances and cravings. This agent is also efficient for the treatment of the acute phase of alcohol withdrawal treatment.

Trazodone "pros" and "cons"

Advantages:

  • not addictive or habit forming
  • no restrictions on long-term use
  • in comparison with tricyclic antidepressants, trazodone is relatively safe in overdose and has fewer cardiovascular and anticholinergic side effects 10
  • effective as amitriptyline, imipramine, and fluoxetine in relieving depressive symptoms 10
  • low incidence of serious adverse effects
  • may be helpful in men with erectile dysfunction and psychogenic erectile dysfunction 13
  • beneficial for insomnia combined with depression or anxiety
  • has an advantage over traditional hypnotics in that it does not depress respiration, an attribute that could be relevant in patients with sleep apnea
  • can increase libido in women 18

Disadvantages:

  • sedation may limit use in the elderly
  • risk of serious, though uncommon, adverse effects such as orthostatic hypotension, cardiovascular effects and priapism 24, 25, 26
  • frequently causes headache, sometimes quite severe28

Mechanism of action

Although trazodone’s mechanism of action is not yet entirely clear, it is known that both trazodone and its metabolite m-chlorophenylpiperazine act on signal-sending neurons and on receptors located on the message-receiving neuron. The action of trazodone on the synapses of the message-sending neuron prevents neurotransmitter re-uptake, especially of serotonin. In this way, it facilitates the delivery of the message to the destination receptor. This partly explains why trazodone is effective in the treatment of depression.

The action on receptors located along the receiving neuron is another of the drug-induced effects, including side effects. In fact, when trazodone binds to special types of such receptors, this agent prevents the neurotransmitter - serotonin - from delivering the message to the receiving neuron. With trazodone, the resulting pharmacological activity is mostly sedative, and this side effect can be a benefit for patients, especially if they also suffer from sleeplessness.

Is trazodone addictive?

Trazodone is non-addictive and not habit forming antidepressant.

Time to clear out of the system

Trazodone has biphasic elimination with a redistribution half-life of about one hour and an elimination half-life of 10-12 hours.

Onset of action
  • Antidepressant effect: it takes about 1-3 weeks to notice effects.
  • Sleep aid effect: 1-3 hours.

Further reading


References
  • 1. U.S. FDA Trazodone Prescribing Information. Available at: www.fda.gov/medwatch/SAFETY/2004/Desyrel_PI.pdf
  • 2. Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994 Jul;151(7):1069-72.
  • 3. 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
  • 4. 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.
  • 5. Rickels K, Downing R, Schweizer E, Hassman H. Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry. 1993 Nov;50(11):884-95. PubMed
  • 6. Wilson RC. Trazodone in the treatment of painful diabetic neuropathy.J Am Podiatr Med Assoc. 1999 Sep;89(9):468-71.
  • 7. Battistella PA, Ruffilli R, Cernetti R, Pettenazzo A, Baldin L, Bertoli S, Zacchello F. A placebo-controlled crossover trial using trazodone in pediatric migraine. Headache. 1993 Jan;33(1):36-9. PubMed
  • 8. Pope HG Jr, Keck PE Jr, McElroy SL, Hudson JI. A placebo-controlled study of trazodone in bulimia nervosa. J Clin Psychopharmacol. 1989 Aug;9(4):254-9. PubMed
  • 9. Kaynak H, Kaynak D, Gozukirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med. 2004 Jan;5(1):15-20. PubMed
  • 10. 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. PubMed
  • 11. Stryjer R, Spivak B, Strous RD, Shiloh R, Harary E, Polak L, Birgen M, Kotler M, Weizman A. Trazodone for the treatment of sexual dysfunction induced by serotonin reuptake inhibitors: a preliminary open-label study. Clin Neuropharmacol. 2009 Mar-Apr;32(2):82-4.
  • 12. Scharf MB, Sachais BA. Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. J Clin Psychiatry. 1990 Sep;51 Suppl:13-7. PubMed
  • 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. Prasad A. Efficacy of trazodone as an anti obsessional agent. Pharmacol Biochem Behav. 1985 Feb;22(2):347-8. PubMed
  • 15. Roccatagliata G, Albano C, Maffini M, Farelli S. Alcohol withdrawal syndrome: treatment with trazodone. Int Pharmacopsychiatry. 1980;15(2):105-10. PubMed
  • 16. Hayashi T, Yokota N, Takahashi T, Tawara Y, Nishikawa T, Yano T, Furutani M, Fujikawa T, Horiguchi J, Yamawaki S. Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study. Int Clin Psychopharmacol. 1997 Jul;12(4):199-205. PubMed
  • 17. Le Bon O, Murphy JR, Staner L, Hoffmann G, Kormoss N, Kentos M, Dupont P, Lion K, Pelc I, Verbanck P. Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations. J Clin Psychopharmacol. 2003 Aug;23(4):377-83. PubMed
  • 18. Gartrell N. Increased libido in women receiving trazodone. Am J Psychiatry. 1986 Jun;143(6):781-2.
  • 19. Borras L, de Timary P, Constant EL, Huguelet P, Eytan A. Successful treatment of alcohol withdrawal with trazodone. Pharmacopsychiatry. 2006 Nov;39(6):232. PubMed
  • 20. Decina P, Mukherjee S, Bocola V, Saraceni F, Hadjichristos C, Scapicchio P. Adjunctive trazodone in the treatment of negative symptoms of schizophrenia. Hosp Community Psychiatry. 1994 Dec;45(12):1220-3
  • 21. Chiang PH, Tsai EM, Chiang CP. The role of trazodone in the treatment of erectile dysfunction. Gaoxiong Yi Xue Ke Xue Za Zhi. 1994 Jun;10(6):287-94. PubMed
  • 22. Montorsi F, Strambi LF, Guazzoni G, Galli L, Barbieri L, Rigatti P, Pizzini G, Miani A. Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology. 1994 Nov;44(5):732-6.PubMed
  • 23. Pigott TA, L'Heureux F, Rubenstein CS, Bernstein SE, Hill JL, Murphy DL. A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder. J Clin Psychopharmacol. 1992 Jun;12(3):156-62. PubMed
  • 24. Carson CC 3rd, Mino RD. Priapism associated with trazodone therapy. J Urol. 1988 Feb;139(2):369-70. PubMed
  • 25. van de Merwe TJ, Silverstone T, Ankier SI, Warrington SJ, Turner P. A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder. Psychopathology. 1984;17 Suppl 2:64-76. PubMed
  • 26. Krahn LE, Hanson CA, Pileggi TS, Rummans TA. Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia. J Clin Psychiatry. 2001 Feb;62(2):108-10. PubMed
  • 27. Silvestrini B. Trazodone: from the mental pain to the "dys-stress" hypothesis of depression. Clin Neuropharmacol. 1989;12 Suppl 1:S4-10. PubMed
  • 28. Chen HC, Tsai SJ. Trazodone-induced severe headache. Psychiatry Clin Neurosci. 2011 Dec;65(7):681-2.

Published: March 31, 2008
Last updated: April 01, 2014

Interesting facts

Trazodone facts
  • As Trazodone has strong sedating properties it is often used at night-time as a sleep aid.
  • Approved by the U.S. FDA in 1982, Trazodone is chemically related to Serzone (Nefazodone) and shares its actions.
  • Unlike the TCAs, which can be toxic in overdose, Trazodone was the first antidepressant developed that was not lethal when overdosed.
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