Efficacy and safety of duloxetine in the treatment of older adult patients with generalized anxiety disorder: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This was a flexible-dosed study to evaluate the efficacy and safety of duloxetine 30-120 mg once daily in the treatment of generalized anxiety disorder (GAD) in older adult patients. METHODS: Patients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140). The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) total score, and the primary endpoint was at week 10. Global functioning was assessed by the Sheehan Disability Scale (SDS). Safety and tolerability was assessed by the occurrence of treatment-emergent adverse events, serious adverse events, laboratory analyses, and vital signs. Analyses were conducted on an intent-to-treat basis. RESULTS: The overall baseline mean HAM-A total score was 24, and SDS global score was 14. Completion rates were 75% for placebo and 76% for duloxetine. At week 10, duloxetine was superior to placebo on mean changes from baseline in HAM-A total scores (-15.9 vs. -11.7, p < 0.001) and in SDS global scores (-8.6 vs. -5.4, p < 0.001). Treatment-emergent adverse events occurred in ≥5% of duloxetine-treated patients and twice the rate than with placebo including constipation (9% vs. 4%, p = 0.06), dry mouth (7% vs. 1%, p = 0.02), and somnolence (6% vs. 2%, p = 0.14). CONCLUSION: Duloxetine treatment was efficacious in the improvement of anxiety and functioning in older adult patients with GAD, and the safety profile was consistent with previous GAD studies.

Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial.

UNLABELLED: This randomized, double-blind, placebo-controlled study assessed efficacy and safety of duloxetine in patients with chronic low back pain (CLBP). Adults (n = 401) with a nonneuropathic CLBP and average pain intensity of ≥ 4 on an 11-point numerical scale (Brief Pain Inventory [BPI]) were treated with either duloxetine 60 mg once daily or placebo for 12 weeks. The primary measure was BPI average pain. Secondary endpoints included Patient's Global Impressions of Improvement (PGI-I), Roland Morris Disability Questionnaire (RMDQ-24), BPI-Severity (BPI-S), BPI-Interference (BPI-I), and response rates (either ≥ 30% or ≥ 50% BPI average pain reduction at endpoint). Health outcomes included Short Form-36, European Quality of Life-5 Dimensions, and the Work Productivity and Activity Impairment questionnaire. Safety and tolerability were assessed. Compared with placebo-treated patients, duloxetine-treated patients reported a significantly greater reduction in BPI average pain (P ≤ .001). Similarly, duloxetine-treated patients reported significantly greater improvements in PGI-I, BPI-S, BPI-I, 50% response rates, and some health outcomes. The RMDQ and 30% response rate showed numerical improvements with duloxetine treatment. Significantly more patients in the duloxetine group (15.2%) than patients in the placebo group (5.4%) discontinued because of adverse events (P = .002). Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in duloxetine-treated patients. PERSPECTIVE: This study provides clinical evidence of the efficacy and safety of duloxetine at a fixed dose of 60 mg once daily in the treatment of chronic low back pain (CLBP). As of December 2009, duloxetine has not received regulatory approval for the treatment of CLBP.

A double-blind, randomized, placebo-controlled trial of olanzapine in the prevention of psychotic relapse.

Sustained response to antipsychotic therapy is an important outcome measure for patients with psychotic disorders. Placebo control in studies of relapse prevention contributes valuable information yet provokes much debate. This study, using placebo as a control, evaluated olanzapine's efficacy in preventing a psychotic relapse. Participants were stable minimally symptomatic outpatients with schizophrenia or schizoaffective disorder. The study included 4 phases: (1) 4-day to 9-day screening/evaluation (N = 583), (2) 6-week conversion to open-label olanzapine (N = 493; 10-20 mg/d), (3) 8-week stabilization on olanzapine (N = 458; 10-20 mg/d), and (4) 52-week randomized (2:1), double-blind maintenance with olanzapine (N = 224; 10-20 mg/d) or placebo (N = 102). Primary relapse criteria were clinically significant changes in the Brief Psychiatric Rating Scale (BPRS) positive item cluster or rehospitalization due to positive symptoms. Statistical methodology allowed sequential real-time estimation of efficacy across blinded treatment groups and multiple interim analyses, which permitted study termination when efficacy was significantly different between treatments. A significant between-treatment difference emerged 210 days after first patient randomization to double-blind treatment. Thus, 151 (46.3%) of the randomized patients were discontinued early and 34 (10.4%) of the planned patient enrollment were not required. The olanzapine group had a significantly longer time to relapse (P < 0.0001) than the placebo group. The 6-month cumulative estimated relapse rate (Kaplan-Meier) was 5.5% for olanzapine-treated patients versus 55.2% for placebo-treated patients. The design of this study enabled appropriate statistical testing of the primary hypothesis while minimizing exposure of patients to a less effective treatment than olanzapine. In remitted stabilized patients with schizophrenia or schizoaffective disorder, olanzapine demonstrated a positive benefit-to-risk profile in relapse prevention.