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Objective: To investigate the efficacy, safety, and clinical benefit of a once-daily formulation of trazodone (Trazodone Contramid® OAD) in the treatment of major depressive disorder. Design/Participants: In this double-blind study, 412 patients with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) were randomized 1:1 to receive either Trazodone Contramid OAD (150 to 375mg) or placebo. Treatment was titrated over two weeks to each individual optimal dose. Patients then continued six weeks of treatment; further dose adjustments were allowed based on efficacy and tolerability. Measurements: The primary end point was change in the 17-item Hamilton Depression Rating Scale total score from baseline to last study visit. Secondary end points included Hamilton Depression Rating Scale responders/remitters, change in Montgomery-Åsberg Depression Rating Scale, Clinician and Patient Global Improvement Scales, and quality of sleep. Results: From the end of titration to the end of the six-week treatment period, the mean maximum daily dose of the intent-to-treat population was 310mg for the active group and 355mg for the placebo group. There was a statistically significant difference between trazodone and placebo on the mean HAMD-17 score (-11.4 vs. -9.3, P=0.012). A significant difference was present as early as Week 1 and was maintained at all subsequent study visits. Many secondary end points supported these findings, including improvements in quality of sleep. The most frequent adverse events were the same for both the treatment and placebo groups: headache and somnolence. There were no serious adverse events that were considered related to treatment. There were no clinically significant electrocardiogram or laboratory abnormalities. Conclusions: The trazodone Contramid formulation was more effective than placebo in major depressive disorder and was well tolerated. [ABSTRACT FROM AUTHOR]

Objective: Combinations of oral analgesics may offer several potential benefits compared with an individual agent. The objective of this study was to investigate the efficacy and safety of an extended-release, twice-daily fixed combination of 75 mg tramadol/650 mg paracetamol (DDS-06C) in the treatment of moderate-to-severe pain, using acute low back pain as a model., Research Design and Methods: In this phase III study, 277 patients with moderate-to-severe acute low back pain were randomized to 1-2 tablets of DDS-06C or placebo every 10-12 h for 2.5 days during the double-blind phase. Following the double-blind phase, patients had the option to continue for a 2.5-day open-label phase., Clinical Trial Registration: Clinicaltrials.gov (Identifier: NCT00643383), Main Outcome Measures: The primary end point was the sum of pain intensity differences (SPID) over the 50-h double-blind phase (SPID50). Secondary end points included total pain relief score over the 50-h double-blind phase (TOTPAR50), patient's global impression of medication, and SPID over the first 4 h., Results: A statistically significant (p = 0.038) greater decrease in pain intensity was observed in the DDS-06C group (median SPID50: -6.0) versus placebo (median SPID50: -4.0). Greater pain relief was also observed in patients randomized to DDS-06C: the median TOTPAR50 was 13.0 for the DDS-06C group and 11.0 for placebo (p = 0.026). DDS-06C demonstrated statistically significant superior efficacy compared with placebo for the majority of the other secondary end points. Overall, 38% of patients treated with DDS-06C experienced at least one adverse event; the intensity was mild-to-moderate in 81% of cases. The most commonly reported adverse events (>5% of patients receiving DDS-06C) were nausea, dizziness, vomiting, and somnolence., Conclusions: Using acute low back pain, a model with a high degree of heterogeneity and intrinsic variability, DDS-06C was superior to placebo on measures of pain intensity and relief, and was well-tolerated.