Targeting heterogeneous depression with trazodone prolonged release: from neuropharmacology to clinical application

Abstract

Aim: This paper evaluates the clinical efficacy, safety, and practical implications of Trazodone Prolonged Release (PR) in managing depression, anxiety, and sleep disorders, with a focus on its multimodal mechanism of action and advantages over traditional therapies. Methodology: A critical review of recent literature (2020–2024) [1, 2–3] was conducted, analyzing data from clinical trials, real-world studies, and European treatment guidelines to assess the pharmacodynamics, pharmacokinetics, and therapeutic outcomes of Trazodone PR. Results: Trazodone PR demonstrates efficacy in addressing complex symptoms of depression, anxiety, and sleep disturbances, with a favorable safety profile and reduced risk of sexual dysfunction and weight gain compared to other antidepressants. Its ability to modulate serotonin, norepinephrine, dopamine, and histamine systems enhances mood, sleep quality, and cognitive recovery. Conclusion: Trazodone PR is a versatile and well-tolerated treatment option for patients with comorbid conditions and treatment-resistant cases. Its multimodal action, combined with benefits like improved neuroplasticity through BDNF production, makes it a suitable choice for the long-term management of mood disorders and associated conditions [4, 5–6]. © The Author(s) 2025.