Trazodone is commonly used in the treatment of major depressive disorder (MDD) in adults. This study aimed to establish consensus on the clinical scenarios and patient profiles for which trazodone treatment is considered suitable.

A two-round Delphi process was conducted across eight European countries. Statements regarding trazodone were rated by a panel of 32 experts for agreement or disagreement using a 9-point Likert scale; those with <70% agreement among panelists were revised and reassessed by the panel.

There was strong consensus agreement on 68 out of 91 statements (75%) related to trazodone. According to the panel, trazodone is well tolerated, with low anticholinergic activity, minimal impact on sexual function, weight neutrality, and low potential for clinically relevant drug–drug interactions. Consensus agreement supported trazodone use across a broad spectrum of patients with MDD, including those with insomnia, anxiety, psychomotor agitation, substance use, physical comorbidities, neurological conditions, and treatment-resistant depression; consensus agreement was also achieved for trazodone use in elderly patients, and those experiencing adverse effects with other antidepressants.

This study suggests that trazodone is useful in the treatment of MDD across multiple patient profiles. These findings offer practical guidance to support individualized and evidence-based decision-making in clinical practice.