Trazodone in Brief
- Generic name : trazodone hydrochloride
- Brand names: Desyrel, Trazon, Trialodine
- Therapeutic class: Antidepressant
- Pharmacologic class: Serotonin Reuptake Inhibitor/Antagonist
- FDA Approved: 12/24/1981
- Chemical Formula: C19H22ClN5O
- Pregnancy Category: C
- Habit forming? No
- Originally discovered: 1960s, Italy
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
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.
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.
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.
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.
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"
- 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
- 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
- Trazodone does not affect driving performance or cognitive function under acute or repeated administrations 29
- 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.
- 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.
- 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.
- 8. Pope HG Jr, Keck PE Jr, McElroy SL, Hudson JI. A placebo-controlled
study of trazodone in bulimia nervosa. J Clin Psychopharmacol. 1989
- 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
- 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.
- 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.
- 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.
- 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.
- 29. Sasada K, Iwamoto K, Kawano N, Kohmura K, Yamamoto M, Aleksic B, Ebe K, Noda Y, Ozaki N. Effects of repeated dosing trazodone, or placebo on driving performance and cognitive function in healthy volunteers. Hum Psychopharmacol. 2013 May;28(3):281-6. PubMed
Published: March 31, 2008
Last updated: July 24, 2014
- 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