Norman and Olver advantage for the higher dose of duloxetine, in terms of remission, over the lower dose. Statistically there were no differences between the two duloxetine doses for any of the efﬁcacy measures used. In all secondary efﬁcacy variables duloxetine 60 and 120 mg were superior to placebo statisti- cally. Greater improvements in functioning were observed in both duloxetine groups compared to placebo (p 0.001) based on the change from baseline in the Sheehan Disability Scales. The data suggest that duloxetine attenuated the symptoms of GAD. A similar double-blind, placebo-controlled trial of dulox- etine was conducted in patients with a DSM-IV diagnosis of GAD over a 10-week period (Rynn et al 2007). Patients were recruited from 27 outpatient treatment centres in the US. To be eligible for the study, in addition to meeting DSM criteria, patients also had to meet certain severity criteria: Clinical Global Impression-Severity Scale (CGI-S) 4; Hospital Anxiety and Depression Scale (HADS) anxiety subscale 10; CAS 9; and CAS total Raskin Depression Scale. After a screening and washout phase of up to 30 days patients entered a single-blind, placebo phase of 1 week. An acute therapy phase of 10 weeks followed together with a 2-week discontinuation phase. The primary efﬁcacy mea- sure was the HAM-A total score administered at each visit (weeks 1, 2, 4, 7 and 10). Secondary outcomes focused on improvements in overall symptom severity and global func- tioning. A ﬂexible dosing schedule was adopted, such that a maximum of 120 mg/day of duloxetine could be attained. The primary efﬁcacy variable was the mean change from baseline to endpoint in the total HAMA-A score. Statistical differences were assessed using analysis of co-variance, while change over time was assessed with a mixed-effects repeated measures method. A total of 168 patients treated with duloxetine and 159 treated with placebo were included in the statistical analyses. A statistically signiﬁcant differ- ence between duloxetine and placebo was evident from week 2 of treatment (p 0.001). Statistically signiﬁcant differences were evident at endpoint for the change in total HAM-A scores observed in duloxetine (8.12) and placebo (5.89) treated patients (p 0.05). Similar or greater differ- ences were observed for the HAM-A factors and items. It was not possible to calculate an effect size for this study as the variance in the change scores was not reported. Based on the mean changes in the HAM-A score compared to that of the previous study, the effect of duloxetine did not appear to be as robust. Response, deﬁned as a 50% reduction in HAM-A score from baseline, was 40% for duloxetine and 32% for placebo (p 0.05). However for remission, 1174 a HAM-A score at endpoint 7, there was no statistically signiﬁcant difference between duloxetine (28%) and placebo (23%). The mean ﬁnal dose of duloxetine at endpoint was 101.9 mg/day with the majority of patients (58%) achieving 120 mg/day. Despite the opportunity in this study to examine dose response effects for duloxetine such an analysis was not undertaken. The study suggests that duloxetine may possess a modest efﬁcacy in the short term treatment of GAD. Duloxetine 60 to 120 mg/day was compared to venlafaxine XR (75–225 mg/day) and placebo over 10 weeks in adult patients meeting the DSM-IV criteria for the disorder (Hartford et al 2007). Almost 500 patients were randomly assigned to duloxetine (n = 160), venlafaxine XR (n = 164) or placebo (n = 161) and the efﬁcacy was assessed by the change in the HAM-A Rating score from baseline to end point. For the evaluation of statistical signiﬁcance of change an analysis of covariance was used. Greater improvement was observed in both the duloxetine (p 0.01) and venlafaxine (p 0.001) groups than for the placebo treated patients. There were no statistically signiﬁcant differences between the duloxetine and venlafaxine groups. Cohen’s d was used to compute an effect for this trial based on the reported mean (and standard deviation) change from baseline in the HAM-A scores for patients in the three treatment arms. For duloxetine 60 to 120 mg/day compared to placebo the Cohen’s d was 0.30 (95% conﬁdence interval [CI] 0.08 to 0.52) and for venlafaxine 72 to 225 mg/day compared to placebo Cohen’s d was calculated as 0.37 (95% CI 0.15–0.59). These effect sizes are similar to those reported in a recent meta-analysis for antidepressant treatment of GAD (Hidalgo et al 2007). For the comparison of duloxetine and venlafaxine Cohen’s d was 0.07 (95% CI –0.15 to 0.29), suggesting no difference in efﬁcacy between the two drugs. Discontinuation of treatment for adverse events was greater in the duloxetine (14.2%) and venlafaxine (11.0%) groups than for placebo group (1.9%). On the other hand the overall rate of discontinuation for any reason was not different for the three groups. Following tapering of the medication over a 2-week period at the end of the trial there were signiﬁcantly more emergent adverse events for venlafaxine treated patients (26.9%) than for either duloxetine (19.4%) or for placebo (15.8%). Duloxetine was equivalent to venlafaxine in the symptomatic relief of GAD and both provided greater relief than placebo. A further comparative study of duloxetine and venlafaxine was performed in 33 non-US sites (Nicolini et al 2008). Diagnostic criteria were substantially the same as those used in the previous trials with the HAM-A scale as the primary efﬁcacy measure. Secondary efﬁcacy measures were assessed Neuropsychiatric Disease and Treatment 2008:4(6)