A narrative review on trazodone as a multimodal and multifunctional antidepressant: clinical relevance of formulations, dosing, and pharmacokinetic/pharmacodynamic targets

BACKGROUND: Trazodone, an antidepressant, has only been approved for use in major depressive disorder (MDD), but has demonstrated potent therapeutic potential in various conditions, such as insomnia and anxiety. It targets multiple serotonergic, adrenergic, and histaminergic receptors. Given this multimodal and multifunctional profile, we aimed to provide a comprehensive overview of the pharmacodynamic and pharmacokinetic properties of trazodone and its clinical applications across various conditions. MAIN TEXT: Trazodone demonstrates sedative and anxiolytic effects even at a low dose (25-75 mg) and a full antidepressant effect at higher doses (150-300 mg). The availability of trazodone in immediate-release, extended-release, intravenous, and intramuscular formulations enables flexible and personalized treatment based on the patient's symptoms, medical history, tolerability, and clinical settings. Clinical evidence also demonstrates that trazodone is effective and well-tolerated across various conditions, including MDD, treatment-resistant depression, insomnia (off-label), neurological disorders, dementia, and delirium, highlighting its versatility. Additionally, the low risk of sexual dysfunction, limited withdrawal symptoms, and weight-neutral effects make it suitable for use in patients with comorbid conditions. CONCLUSION: Trazodone is a multimodal and multifunctional antidepressant that exhibits a broad range of therapeutic effects in MDD and other comorbid conditions. Further research on the pharmacokinetic and pharmacodynamic relationship of trazodone, its parenteral use in acute settings, and the development of prescribing algorithms for predicting treatment responses may enhance its therapeutic outcomes in patients with MDD.