Duloxetine in the treatment of major depressive disorder: an open-label study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.</p> <p>Methods</p> <p>Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD₁₇) total score ≥18 and a Clinical Global Impression of Severity (CGI-S) score ≥4 at baseline. Efficacy measures included the HAMD₁₇total score, HAMD₁₇subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.</p> <p>Results</p> <p>The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD₁₇, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.</p> <p>Conclusion</p> <p>In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.</p> <p>Trial registration</p> <p>NCT00036309.</p

Fixed dose-combination products in psychiatry: Systematic review and meta-analysis

Despite highly prevalent use of drug combinations in psychiatry, combination products are not commonly available. We aimed to systematically review the evidence for the use and efficacy of combination products in the practice of psychiatry. Systematic search of major data bases yielded nine double-blind randomized controlled trials, which generated 15 comparisons of combination products against a single therapeutic agent, that included a placebo. All these studies included 2827 participants: 976 in their combination products arms and 1851 patients in the comparator arms. The number of combination products were identified, but all except two studies tested only one combination drug (e.g. olanzapine and fluoxetine (OFC)). All combined formulations were significantly superior to a single agent, with standardized mean distance (SMD) of − 0.29 (confidence interval (CI) = − 0.43, − 0 .14; p < 0.001) in improving depression. In the subgroup analysis, the OFC combination was significantly superior to a single therapeutic agent for bipolar depression (SMD = − 0.32; CI = − 0.45, − 0.19; p < 0.001) and for treatment-resistant depression (SMD = − 0.29; CI = − 0.49, − 0.08; p < 0.005), but not for borderline personality nor major depressive disorder (MDD). The evidence in general medicine suggests that combination products can offer significant advantage in improving efficacy and treatment adherence; but in psychiatry, research and development in fixed-dose combinations has been limited