Trazodone (Desyrel) vs Mirtazapine (Remeron)

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

Trazodone advantages over Mirtazapine

  • Trazodone may improve sexual dysfunction induced by SSRIs.
  • Unlike mirtazapine, Trazodone has relatively low potential to promote weight gain.
  • Trazodone is helpful for patients with significant sleep disturbance, and it does not worsen sleep disorders like mirtazapine does.
  • Trazodone is very inexpensive. Trazodone has no anticholinergic effects.

Mirtazapine advantages over Trazodone

  • Mirtazapine has relatively fast onset of antidepressant effect.
  • Unlike trazodone, mirtazapine has no risk of priapism.
  • Adding mirtazapine to SNRIs or SSRIs may reverse drug-induced insomnia and agitation.
  • Mirtazapine may be used as an appetite stimulant in depressed patients with poor appetite and weight loss.


Trazodone Mirtazapine
Brand names
Remeron SolTab®
Initial approval date
• 1981 • 1994
Drug class
• Phenylpiperazine– triazolopyridine antidepressant
• Serotonin antagonist/reuptake inhibitor
• Piperazinodibenzoazepine antidepressant
• Noradrenergic and specific serotonergic antidepressant
Dose formulations
• Tablets
• Tablets, extended-release
• Tablets
• Tablets, disintegrating
Legal status
• Rx only
Labeled indications
• Depression
"Off-label" uses
• Insomnia
• Antidepressant-induced sexual dysfunction
• Dementia - trazodone improved symptoms of irritability, agitation, and depression in patients with dementia
•Panic disorder
• Generalized anxiety disorder
• Posttraumatic stress disorder
Mechanism of action
• Trazodone weakly inhibits neuronal reuptake of serotonin and has strong antagonistic action at serotonergic 5-HT2 receptors.
• Trazodone also antagonizes alpha-1 and alpha-2 adrenergic receptors, and histamine receptors2.
• Mirtazapine enhances both serotonergic and noradrenergic neurotransmission.
• Mirtazapine antagonizes of alpha 2 adrenergic receptors.
• Mirtazapine also antagonizes 5-HT2 receptors and 5-HT3 receptors, and is antihistaminic.
• 7-10 hours • 16-40 hours
Oral bioavailability
• 60–70% • ~50%
Metabolism, Elimination
• Trazodone is metabolized to its active metabolite, m-chlorophenylpiperazine, by hepatic P450 enzyme CYP3A4.
• Excretion is predominantly renal, urine 75%, feces 25%.
• Mirtazapine is metabolized by hepatic P450 enzymes CYP1A2, CYP2D6, and CYP3A4.
• Excretion is predominantly renal, urine 75%, feces 15%.
Side effects
• Orthostatic hypotension
• Priapism (painful and prolonged erection)
Mirtazapine is one of the most antihistaminic antidepressants and is most likely to cause sedation during initial treatment. The antihistaminic effect also contributes to increased appetite and weight gain.
Important problem with both antidepressants is oversedation, which limits their usefulness in many patients.
Weight gain
Mirtazapine has a greater tendency to cause weight gain2.
Trazodone may cause small weight gain over time (0.5 to 1.1 kg)1 Mirtazapine has pronounced appetite stimulant and weight gain–promoting properties. The drug may be placed between the SSRIs and the tricyclic antidepressants in terms of relative risk of weight gain.

Trazodone vs Mirtazapine for Insomnia

Neither trazodone nor mirtazapine are marketed as a hypnotic. However, both antidepressants have well-known sedative properties and are used "off label" for insomnia. Both mirtazapine and trazodone have no restrictions on long-term use unlike benzodiazepine hypnotics.

Improvement of sleep quality is particularly prominent in depressed patients with insomnia, anxiety, and agitation. Sedative antidepressants are also prescribed to people who do not suffer from depression but do have insomnia.

Antidepressants antagonizing serotonergic 5-HT2 receptors can not only increase the sleep continuity, but promote also slow wave sleep. And what's important, mirtazapine and trazodone in comparison to other antidepressants do not suppress REM sleep3.

Trazodone for insomnia

As a hypnotic trazodone works mainly via antagonistic action at serotonergic 5-HT2 receptors. Trazodone is non-addictive, well tolerated, and effective in promoting sleep and has certain advantages over traditional FDA approved hypnotics.

Trazodone is proven to be an effective sleep aid in patients with selective serotonin reuptake inhibitor-induced insomnia4. However, trazodone, like benzodiazepine hypnotics, is associated with next-day functioning impairment.

Trazodone dosage for insomnia:
25-100 mg at bedtime.
The hypnotic effect starts within 1-3 hours. So trazodone should be taken early enough before bedtime.

Mirtazapine for insomnia

Mirtazapine induces sleep mainly via antihistaminergic action and to a lesser extent via antagonism at serotonergic 5-HT2A receptors.

Mirtazapine can prolong the total sleep time, decrease nighttime awakenings, and shorten the time it takes to fall asleep5.

Mirtazapine may trigger nightmares6 or restless legs syndrome7.

Mirtazapine dosage for insomnia:
15-30 mg at bedtime.


Trazodone vs Mirtazapine for Depression

Mirtazapine has significant clinical advantages over trazodone in terms of overall efficacy 8.

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 8.

Further reading


  • 1. Nihalani N, Schwartz TL, Siddiqui UA, Megna JL. Weight gain, obesity, and psychotropic prescribing. J Obes. 2011;2011:893629.
  • 2. Jarema M, Dudek D, Landowski J, et al. Trazodon: mechanism of action and its position in the treatment of depression. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25.
  • 3. Wichniak A, Wierzbicka A. The effects of antidepressants on sleep in depressed patients with particular reference to trazodone in comparison to agomelatine, amitriptyline, doxepin, mianserine and mirtazapine. Pol MerkurLekarski. 2011 Jul;31(181):65-70.
  • 4. 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.
  • 5. Winokur A, Sateia MJ, Hayes JB, Bayles-Dazet W, MacDonald MM, Gary KA. Acute effects of mirtazapine on sleep continuity and sleep architecture in depressed patients: a pilot study. Biol Psychiatry. 2000 Jul 1;48(1):75-8.
  • 6. Buschkamp JA, Frohn C, Juckel G. Mirtazapine induces nightmares in depressed patients. Pharmacopsychiatry. 2017
  • 7. Rottach KG, Schaner BM, Kirch MH, Zivotofsky AZ, Teufel LM, Gallwitz T, Messer T. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res. 2008;43:70–75
  • 8. 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: February 03, 2018
Last updated: February 03, 2018


Some facts
  • Mirtazapine is not widely used because of high incidence of somnolence and substantial weight gain.
  • Insomnia remains an "off-label", although widely recognized, use of trazodone.
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