Extended-Release Trazodone in Comorbid Major Depressive and Sedative–Hypnotic/Anxiolytic Use Disorders: A Real-World Preliminary Evaluation of Multidimensional Outcomes

Objectives: Major depressive disorder (MDD) frequently co-occurs with substance use disorders, resulting in greater clinical severity and poorer outcomes. Sedative–hypnotic/anxiolytic agents (SHA) are commonly used to manage anxiety and insomnia, also in MDD. However, their long-term intake might lead to misuse and physical and cognitive complications. Trazodone, an antidepressant with sedative and anxiolytic properties, has been proposed as an option in SHA detoxification, but data on patients with comorbid MDD and SHA use disorders (MDD+SHA-UD) are limited. This study retrospectively evaluated the effects of a three-month treatment with extended-release trazodone in this population. Methods: Seventy-four outpatients with MDD+SHA-UD treated with extended-release trazodone were evaluated at baseline and after one and three months. Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Secondary outcomes included anxiety (Hamilton Anxiety Rating Scale), sleep disturbances (Pittsburgh Sleep Quality Index), physical symptoms (Hamilton Depression–Anxiety subscales, 36-Item Short-Form Health Survey), cognitive functioning (Perceived Deficits Questionnaire–Depression, 5-item), and quality of life (World Health Organization-Five Well-Being Index). Results: Trazodone was associated with a significant reduction in depressive symptoms (p < 0.001), with 47.3% of the initial sample achieving remission at endpoint. Improvements were also observed in measures of anxiety, physical symptoms, subjective sleep quality, perceived cognitive functioning, and quality of life (all p < 0.001). Side effects were mild (25.7% at one month) and declined over time. Conclusions: In this uncontrolled preliminary study, extended-release trazodone was associated with significant improvements across multiple symptom domains in MDD+SHA-UD, warranting controlled investigation.