Trazodone versus ...

Trazodone vs. Fluoxetine


Both medications are similarly effective for major depression. Fluoxetine appears to have a slower onset of antidepressant action than does trazodone 1, 3, 5.

Side effects and tolerability

Fluoxetine has a higher rate of rhinitis and tremor, while trazodone has higher incidence of somnolence and dizziness. More combined events suggesting activation (agitation, anxiety, nervousness, insomnia) occur with fluoxetine than with trazodone, while more combined events suggesting sedation (somnolence, asthenia) occur with trazodone than with fluoxetine 1. Also fluoxetine is associated more frequently with weight loss than trazodone 3.

Trazodone vs. Gabapentin

Insomnia in alcohol dependence

In the study alcohol-dependent outpatients with persisting insomnia were treated with either gabapentin or trazodone. Both medications were effective on the Sleep Problems Questionnaire but the gabapentin group improved significantly more than the trazodone group 2. At follow-up (4-6 weeks later) gabapentin-treated patients were less likely than trazodone-treated patients to have initial insomnia and to awaken in the morning feeling tired and worn out.

Trazodone vs. Imipramine


Trazodone and imipramine are of approximately equivalent efficacy. Some evidence suggests that trazodone may have an earlier anxiolytic effect than imipramine by day 4 and a greater antidepressant effect by day 22 of treatment in severe endogenous depression 8.

Side effects

Anticholinergic side effects are significantly more prominent with imipramine compared to trazodone. Impaired visual accommodation is significantly greater with imipramine treatment 8.


Trazodone vs. Mirtazapine

Major depressive disorder

Mirtazapine has significant clinical advantages over trazodone in terms of overall efficacy and tolerability 9.

Side effects

Both trazodone and mirtazapine in comparison to many other antidepressants do not suppress REM sleep. Somnolence is reported significantly more often with trazodone 9.

Further reading
  • 1. Beasley CM Jr, Dornseif BE, Pultz JA, Bosomworth JC, Sayler ME Fluoxetine versus trazodone: efficacy and activating-sedating effects. J Clin Psychiatry. 1991 Jul;52(7):294-9. PubMed
  • 2. Karam-Hage M, Brower KJ. Open pilot study of gabapentin versus trazodone to treat insomnia in alcoholic outpatients. Psychiatry Clin Neurosci. 2003 Oct;57(5):542-4. PubMed
  • 3. Debus JR, Rush AJ, Himmel C, Tyler D, Polatin P, Weissenburger J. Fluoxetine versus trazodone in the treatment of outpatients with major depression. J Clin Psychiatry. 1988 Nov;49(11):422-6. PubMed
  • 4. Wichniak A, Wierzbicka A. The effects of antidepressants on sleep in depressed patients with particular reference to trazodone in comparison to agomelatine, doxepin, mianserine and mirtazapine. Pol Merkur Lekarski. 2011 Jul;31(181):65-70. PubMed
  • 5. Perry PJ, Garvey MJ, Kelly MW, Cook BL, Dunner FJ, Winokur G. Comparative trial of fluoxetine versus trazodone in outpatients with major depression. J Clin Psychiatry. 1989 Aug;50(8):290-4. PubMed
  • 7. Hecht Orzack M, Cole JO, Friedman L, Bird M, McEachern J. Weight changes in antidepressants: a comparison of amitriptyline and trazodone. Neuropsychobiology. 1986;15 Suppl 1:28-30. PubMed
  • 8. Al-Yassiri MM, Ankier SI, Bridges PK. A double blind comparison of the efficacy and safety of trazodone and imipramine in endogenous depression. J Affect Disord. 1983 Nov;5(4):333-40. PubMed
  • 9. van Moffaert M, de Wilde J, Vereecken A, Dierick M, Evrard JL, Wilmotte J, Mendlewicz J. Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression. Int Clin Psychopharmacol. 1995 Mar;10(1):3-9. PubMed

Published: March 31, 2008
Last updated: February 25, 2017


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