Adjunctive Trazodone Effects on Sleep, Mood, and Circulating 5-HT and BDNF in Depression

This retrospective study evaluated the association of adjunctive trazodone with sleep architecture, sleep quality, depressive and anxiety symptoms, and circulating 5-HT and BDNF levels in patients with depression. A total of 156 propensity-score-matched patients were included in the final analysis, including 78 who received conventional antidepressant therapy (fluvoxamine monotherapy; control group) and 78 who received combined trazodone and fluvoxamine therapy (observation group). Both treatment regimens were continued for 8 consecutive weeks. Propensity score matching (PSM) was used to balance baseline characteristics between the groups. Sleep architecture, sleep quality, depressive and anxiety symptoms, and circulating 5-HT and BDNF levels were assessed at the prespecified clinical time points. Compared with the control group, the observation group demonstrated significantly reduced awake time, prolonged rapid eye movement (REM) sleep and slow-wave sleep (SWS) duration, improved sleep quality, and lower depression and anxiety scores at week 4 (HAMD: 8.23 ± 1.25 vs. 11.88 ± 2.50; HAMA: 4.35 ± 1.32 vs. 7.89 ± 2.17; both P < 0.001), together with higher circulating 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) levels at week 8. Furthermore, the overall clinical response rate was significantly higher in the observation group than in the control group. These findings suggest that adjunctive trazodone was associated with better sleep-related and clinical outcomes, as well as higher circulating 5-HT and BDNF levels, than fluvoxamine monotherapy.