title: The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder.
abstract: Trazodone Contramid(R) once-a-day (TzCOAD) is a reformulation of trazodone hydrochloride that controls the release of trazodone over 24 hours. A standard effect size analysis (Cohen's d) determined which items of the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Asberg Depression Rating Scale (MADRS) showed the greatest improvement in patients with major depressive disorder (MDD), following up to 8 weeks of therapy with TzCOAD. An additional insomnia analysis assessed whether the efficacy of TzCOAD is influenced by improvements in insomnia or baseline severity of insomnia. The analyses used data from a randomized study of 412 patients receiving 150-375 mg TzCOAD (N = 206) or placebo (N = 206). The results of the Cohen's d analysis on the modified intent-to-treat population (LOCF) showed HAMD items with the greatest improvement were insomnia items (middle (-0.35), late (-0.24)), feelings of guilt (-0.24), and depressed mood (-0.23); for MADRS items they were reduced sleep (-0.31), inner tension (-0.22), reported sadness (-0.21), and suicidal thoughts (-0.21). An analysis of covariance showed no significant interaction between improvements in the HAMD Bech-6 core symptoms of depression and the baseline MADRS reduced sleep item or early changes in the HAMD-17 sleep disturbance factor. These results suggest that the antidepressant efficacy was independent of the baseline severity of insomnia and of the improvement in insomnia. Overall, the results elucidate the efficacy components and tolerability characteristics previously demonstrated for TzCOAD monotherapy for patients with MDD at the recommended daily dose of 300 mg.
authors.affiliation: University of South Florida College of Medicine, Tampa, FL, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Sheehan
authors.forename: Anna
authors.initials: A
authors.lastname: Rozova
authors.forename: E Roderich
authors.initials: ER
authors.lastname: Gossen
authors.forename: Michael
authors.initials: M
authors.lastname: Gibertini
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy / Q000209:etiology; D059020:Suicidal Ideation; D014196:Trazodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D014196:Trazodone