Update on Pharmacological Treatment for Comorbid Major Depressive and Alcohol Use Disorders: The Role of Extended-release Trazodone

Background: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are major public health concerns because of their high prevalence and clinical and functional severity. MDD and AUD commonly co-occur, but effective therapeutic approaches for comorbidity are still scarce. Available evidence on selective serotonin reuptake inhibitors and tricyclic antidepressants held mixed results, and further pharmacological categories have been less investigated. Trazodone is an approved antidepressant drug for adults and has shown efficacy on symptoms like anxiety and insomnia observed in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazodone on clinical and functional features in MDD + AUD subjects. Methods: One hundred MDD + AUD outpatients were retrospectively evaluated at 1, 3, and 6 months of treatment with extended-release trazodone (150-300 mg/day, flexibly dosed). Improvement in depressive symptoms was the primary outcome measure. Changes in anxiety, sleep, functioning, quality of life, clinical global severity, and alcohol craving were also investigated. Results: Trazodone reduced depressive symptoms (p < 0.001) with 54.5% remission at the endpoint. Similar improvements were observed in all secondary outcomes, including anxiety, sleep alterations, and craving (p < 0.001). Only mild side effects were reported and disappeared over time. Conclusion: Extended-release trazodone displayed good antidepressant properties in MDD + AUD patients, ameliorating overall symptomatology, functioning, and quality of life, with a good safety/ tolerability profile. Further, it significantly improved sleep disturbances and craving symptoms, which are associated with drinking relapse and worse outcomes. Therefore, trazodone might represent a promising pharmacological option for MDD + AUD patients.