Early response to trazodone once-a-day in major depressive disorder: review of the clinical data and putative mechanism for faster onset of action

Albert U, Lamba P, Stahl SM. Early response to trazodone once-a-day in major depressive disorder: review of the clinical data and putative mechanism for faster onset of action. CNS Spectr. 2021 Jun;26(3):232-242. doi: 10.1017/S1092852921000304. Epub 2021 Mar 18. PMID: 33731232.

Abstract

Background: Most antidepressants have a delayed onset of action and must be administered for several weeks to generate therapeutic effects. Trazodone is a serotonin antagonist and reuptake inhibitor approved for the treatment of major depressive disorder. The once-a-day (OAD) formulation of trazodone has an improved tolerability profile compared to its conventional formulations. In this study, we systematically reviewed the evidence available for the antidepressant efficacy and early improvement in depressive symptoms with trazodone OAD treatment.

Method: We conducted a PubMed database search for randomized controlled trials published from 2005 to 2020.

Results: Two studies, a placebo-controlled and an active-comparator (venlafaxine extended-release or XR) study were found. Both the studies demonstrated that trazodone exhibits antidepressant activity at a starting dose of 150 mg/day and results in statistically significant greater reduction in Hamilton Depression Rating Scale (HAM-D17) scores within 1 week of starting treatment compared to placebo or venlafaxine XR (P < .05). Trazodone also resulted in significant early improvement in the HAM-D17 sleep disturbance factor compared to placebo or venlafaxine XR at day 7 (P < .05). This clinical effect is supported by in vitro proprietary data for the affinity of trazodone for different target receptors. Activity at these receptors may underlie trazodone’s fast antidepressant action.

Conclusions: Trazodone, if properly dosed, can be an effective antidepressant with early onset of action and good tolerability. Future studies designed to specifically evaluate onset and timing of improvement of depressive symptoms remain necessary to confirm and extend these results.

Summary:

The first patient presented with anxiety major depressive symptoms. We treated him with Levetiracetam, Mirtazapine, and a low dose of trazodone. Although in his case, the trazodone was given mainly to help with sleep, I was interested in determining if trazodone could be a better treatment for major depressive disorder compared to more traditional medications (especially since it also has this benefit of being helpful for sleep.) 

This article discusses the strengths and benefits of treatment with trazodone. Since most common antidepressants, such as SSRI’s/ SNRI’s, have a delayed onset of action, and must be administered for a 4-6 weeks before feeling any therapeutic results, providers often like to look for other medications to treat depressive symptoms in the meantime, especially when depression is very severe. Trazodone is a serotonin antagonist and reuptake inhibitor which is approved to treat major depressive disorder. This study was a systematic review which looked at whether trazodone once a day treatment can provide faster onset of action than traditional antidepressants in relieving symptoms of MDD. Two randomized controlled trials were found for this review, both demonstrating that a 150 mg/day dose of trazodone exhibits antidepressant activity and results in a significantly greater decrease in the Hamilton Depression Rating Scale within one week of beginning treatment, compared to venlafaxine and placebo. In addition, trazodone resulted in significant early improvement in sleep disturbance based on this scale. Overall, trazodone OAD was well tolerated, and the adverse effects were mild to moderate in both studies. However, it is important to note that in both studies, more patients with trazodone OAD discontinued treatment due to adverse effects, so there is evidence that adverse effects are at least more severe with trazodone than with placebo/ venlafaxine.

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