Intravenous trazodone for the treatment of psychomotor agitation and associated symptoms in major depressive disorder patients experiencing a depressive episode with mixed features

Psychomotor agitation is a challenging symptom of major depressive disorder with mixed features (MDD-MF), often worsening outcomes and complicating treatment. This retrospective study assessed the efficacy and tolerability of intravenous trazodone in 97 hospitalized patients with MDE-MF. Symptom severity was evaluated using montgomery asberg depression rating Scale (MADRS), young mania rating scale, hamilton anxiety rating scale, GAD-7, and clinical global impression scale-severity of illness (CGI-S) scales, with significant reductions in agitation, anxiety, and irritability observed early during treatment. Correlation analyses revealed significant negative associations between intravenous (IV) trazodone dosage and improvements in MADRS (r = −0.23; P < 0.05), item 5 of GAD-7 (r = −0.27; P < 0.001), and CGI-S scores (r = −0.22; P < 0.05). Therapy duration also correlated negatively with improvements in GAD-7 item 5 (r = −0.29; P < 0.001) and CGI-S (r = −0.27; P < 0.001), indicating diminishing returns with prolonged treatment. Regression analyses showed that therapy duration, but not dosage, significantly influenced improvements in GAD-7 item 5 and CGI-S. Trazodone was well-tolerated, with only mild side effects in 11.3% of patients. These findings suggest that IV trazodone effectively reduces agitation and related symptoms in MDD-MF, particularly in the early treatment phase, emphasizing the importance of optimizing treatment duration. Future studies should investigate individualized dosing strategies and explore long-term outcomes in this population.