studies used similar diagnostic criteria (DSM-IV determined using the Mini International Neuropsychiatric Interview) to ensure that patients met criteria for GAD only. In particular patients were excluded if they met criteria for a recent (within the past 6 months) Major Depressive Disorder or substance abuse. A history within the past year of panic disorder, posttraumatic stress disorder or eating disorder was also an exclusion criterion. Thus patients who were included in the study may have had a lifetime co-morbidity of other mood disorders with GAD but not a current co-morbidity. A life- time history of psychotic, bipolar or obsessive compulsive disorders was an additional diagnostic exclusion criterion. To ensure that anxiety symptoms predominated the clinical picture patients were required to have a Covi Anxiety score (CAS) 9 and no item in the Raskin Depression Scale 3 at baseline. Furthermore patients with an Axis II diagnosis were excluded from the studies. The studies and their main ﬁndings are summarized in Table 1. Duloxetine was compared to placebo in a 9-week, double- blind, ﬂexible dose study in 513 patients meeting DSM-IV criteria for GAD (Koponen et al 2007). 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 9 weeks followed together with a 2-week discontinuation phase. Patients were randomly assigned to treatment with 60 mg once daily, 120 mg once daily duloxetine or placebo. The total HAM-A score was used in the assessment of efﬁcacy but Duloxetine for GAD did not form part of the entry criteria. However patients were stratiﬁed according to HAM-A total scores or 22 and were recruited from 42 outpatient clinics in 7 countries. Study visits were conducted at weeks 1, 2, 4, 6 and 9 of the double-blind treatment phase. Assessment of the efﬁcacy of treatments was based on the change in the total HAM-A score from baseline in addition to a number of secondary param- eters: HAM-A psychic and somatic factors; Hospital Anxiety and Depression Scale (HADS); Patient and Clinician Global Impression-Improvements scales; Sheehan Disability Scale. For continuous efﬁcacy variables an analysis of covariance was used to assess change from baseline. In addition a mixed effects repeated measures analysis was performed to assess change over time. Statistically signiﬁcantly greater differ- ences were observed for the reduction in anxiety symptoms in patients treated with either dose of duloxetine than for placebo (p 0.001). Differences in mean HAM-A scores from baseline were 4 points larger in duloxetine than in placebo treated patients. In this study the effect size could not be calculated as the variance in the HAM-A change scores was not reported. Based on a 50% reduction in HAM-A score from baseline, response rates were 58% for duloxetine 60 mg, 56% for duloxetine 120 mg and 31% for placebo (p 0.001). Remission was deﬁned as achieving a HAM-A score 7 at endpoint. Based on this criterion 31% of duloxetine 60 mg, 38% duloxetine 120 mg and 19% of placebo treated patients achieved remission. There did not appear to be any clinical Table 1 Efﬁcacy of duloxetine in the treatment of generalized anxiety disorder: double-blind, placebo-controlled studies Study Treatment Duration of Primary* Response rates** treatment outcome Koponen et al 2007 Hartford et al 2007 Rynn et al 2007 Nicolini et al 2008 *Mean change from baseline for the HAM-A score (SEM). **Reduction in the baseline HAM-A score 50%. †Variance measure not reported. Abbreviations: DUL, duloxetine; PBO, placebo;VEN, venlafaxine. Neuropsychiatric Disease and Treatment 2008:4(6) 60 mg/day DUL 120 mg/day DUL PBO 60–120 mg/day DUL 75–225 mg/day VEN PBO 60–120 mg/day DUL PBO 20 mg/day DUL 60–120 mg/day DUL 75–225 mg/day VEN PBO 9 weeks 10 weeks 10 weeks 10 weeks −12.8† −12.5 −8.4 −11.8 (0.69) −12.4 (0.67) −9.2 (0.67) −8.1† −5.9 −14.7 (1.0) −15.3 (0.7) −15.5 (0.7) −11.6 (0.7) DUL 58% 56% 47% 40% 60% 65% VEN 54% 61% PBO 31% 37% 32% 42% 1173