Trazodone as a first-line treatment for depression. The importance of TED study, randomized data, and contemporary guideline Review article

Abstract

Trazodone, a serotonin antagonists and reuptake inhibitors (SARI) class antidepressant, is gaining increasing importance in the treatment of major depressive episodes, particularly following the introduction of the modern extended-release (XR) formulation. Its multimodal mechanism of action–combining 5-HT_2A/2C receptor antagonism with serotonin reuptake inhibition–allows it to target multiple key domains of depression simultaneously, including low mood, frequently co-occurring anxiety, sleep disturbances, anhedonia, and functional impairment. Evidence from randomized clinical trials, as well as numerous naturalistic studies and data from the TED programme, confirms the antidepressant efficacy of trazodone, its rapid onset of action, and favourable tolerability profile. Trazodone is especially effective in improving sleep and reducing anhedonia and anxiety symptoms, which enhances the likelihood of achieving full remission and improves quality of life. Compared with selective serotonin reuptake inhibitors (SSRI), it carries a lower risk of sexual dysfunction and less early-treatment activation or insomnia. The modern XR formulation, enabling once-daily dosing, provides a stable pharmacokinetic profile and supports better adherence. According to current Polish treatment guidelines, trazodone is recognised as a first-line option for depression and is particularly useful in patients with insomnia, prominent anxiety, anhedonia, or intolerance to SSRI therapy.