Depress Anxiety. 2015 Aug;32(8):570-9. doi: 10.1002/da.22384. Epub 2015 Jun 26.


Background: Combined treatment with a selective serotonin reuptake inhibitor (SSRI) plus mirtazapine has shown superior efficacy in some studies of depression, but has not been studied in posttraumatic stress disorder (PTSD). This study aimed to assess acceptability of combined sertraline plus mirtazapine treatment for PTSD and to estimate its effect size relative to sertraline plus placebo.

Methods: Thirty-six adults with PTSD were randomized to 24 weeks of double-blind treatment with sertraline plus mirtazapine or sertraline plus placebo. Outcomes were analyzed with mixed effects models.

Results: The combined treatment group showed a significantly greater remission rate (P = .042) and improvement in depressive symptoms (P = .023) than the sertraline plus placebo group. There were no significant group differences in the two primary outcomes of treatment retention and PTSD severity, or in other secondary outcomes (sleep impairment, sexual functioning, quality of life, and physical and mental functioning), but the combined treatment group showed numerical advantages on all of these outcomes, and effect sizes relative to sertraline plus placebo ranged from small to moderate (d = .26-.63). Both treatments were well-tolerated, with significantly increased appetite but not weight gain in the combined treatment group.

Conclusion: Findings suggest that combined treatment of PTSD with sertraline plus mirtazapine may have clinically meaningful advantages in symptomatic improvement, relative to SSRI treatment alone, and acceptable tolerability. Combined treatment with an SSRI plus mirtazapine in PTSD deserves additional study as initial treatment or as an augmentation strategy for nonresponders to an SSRI.

Trial registration: NCT01178671.

Keywords: antidepressants; anxiety; combined treatment; norepinephrine; posttraumatic stress disorder; psychopharmacology; randomized clinical trial; serotonin.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Mianserin / administration & dosage
  • Mianserin / adverse effects
  • Mianserin / analogs & derivatives*
  • Mianserin / pharmacology
  • Middle Aged
  • Mirtazapine
  • Outcome Assessment, Health Care*
  • Placebos
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / pharmacology*
  • Sertraline / administration & dosage
  • Sertraline / adverse effects
  • Sertraline / pharmacology*
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Young Adult


  • Antidepressive Agents, Tricyclic
  • Placebos
  • Serotonin Uptake Inhibitors
  • Mianserin
  • Mirtazapine
  • Sertraline

Associated data