Norman and Olver of duloxetine in elderly patients (Davidson et al 2008). From the database there were 73 patients (45 randomly assigned to duloxetine and 28 to placebo) older than 65 years. This represented a relatively small proportion (4.9%) of the total population treated. Compared to placebo treated subjects, duloxetine treated patients had statistically signiﬁcantly greater improvements for the HAM-A total score (p 0.05) and psychic (p 0.05) but not somatic anxiety factors. Based on the reported change scores from baseline to endpoint of the total HAM-A scores Cohen’s d was calculated as 0.56 (95% CI 0.04–1.02), which is within the range of that reported for other anxiolytic agents (Hidalgo et al 2007). In this patient population there were high discontinuation rates for adverse effects (22.2% for duloxetine versus 0% for placebo). Evaluations in populations of elderly patients are of further interest, particularly given that GAD is reputedly the most common anxiety disorder in adults aged 55 years or more (Carter et al 2001). Two pooled analyses of the placebo arms of the con- trolled trials were conducted to examine duloxetine efﬁcacy and effect on functional outcomes. Patients assigned to the venlafaxine arm of the Hartford et al (2007) study were not included in the pooled analysis. The pooled analysis gave a database of 668 patients treated with duloxetine 60 to 120 mg/day and 495 patients treated with placebo for up to 10 weeks. With respect to efﬁcacy, duloxetine-treated patients improved statistically signiﬁcantly more from baseline to endpoint than did placebo treated patients (11.1 points versus 8.0 points on the HAMA-A scale; p 0.001; ANCOVA) (Allgulander et al 2007). The authors suggest that such improvements are clinically important representing a decline in baseline severity of anxiety by about a half. Remission of symptoms was attained by about a third of patients treated with duloxetine. Both psychic and somatic anxiety sub-scales of the HAM-A scale were improved. Using the data reported in this pooled analysis it was possible to calculate an effect size for baseline HAM-A scores as well as the treatment endpoint HAM-A scores. At baseline the effect size was 0.01 (Cohen’s d = 0.02). The groups were well matched and not signiﬁcantly different. At end point the effect size was 0.18 (Cohen’s d = 0.37). The effect of duloxetine in GAD can be regarded as relatively modest based on the pooled analysis particularly when compared to the effect sizes calculated in recent meta-analyses for antidepressants used in the treatment of GAD (Mitte et al 2005; Hidalgo et al 2007). Along with the improvements in anxiety symptomatol- ogy self-reported assessments of psycho-social function- ing were also signiﬁcantly improved in a pooled analysis 1176 (Endicott et al 2007). In each of the three studies the Sheehan Disability Scale (SDS), including the subscales global func- tioning, work/school life, social life and family home respon- sibility, were measured and showed a fall to mild severity in the duloxetine treated patients compared to moderate severity in the placebo treated patients. For duloxetine-treated patients 47% achieved a SDS global score 5 (indicative of a normative range) compared to 28% of placebo treated patients. Duloxetine treated patients reported a greater improvement in their quality of life, as measured with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), than did placebo treated patients (p 0.01; ANOVA). The data suggest that not only symp- tomatic improvements are achieved by patients treated with duloxetine but that these improvements impact on social function and life satisfaction. Safety and tolerability Treatment-emergent side effects Based on the pooled analysis of the three placebo controlled trials, discontinuation rates in patients receiving duloxetine due to adverse events was 15.6% compared to 4.2% for pla- cebo (p 0.001) (Allgulander et al 2007). The most common side effects ( 5% incidence and twice the rate in placebo treated patients) were nausea, dizziness, dry mouth, con- stipation, insomnia, somnolence, hyperhidrosis, decreased libido, vomiting and erectile dysfunction. For the majority of patients these side effects were rated as mild to moderate in intensity. These adverse events are similar to those reported in pooled analyses for the use of duloxetine in other conditions. For example, the tolerability of duloxetine, when used as a treatment for depression, was addressed in a pooled analysis from eight placebo controlled comparisons (Hudson et al 2005). The data base represented 1139 patients treated with doses of duloxetine ranging from 40 to 120 mg/day for up to 34 weeks in total. Nausea, dry mouth, constipation, insomnia, dizziness and fatigue were the main side effects reported in these studies and all occurred signiﬁcantly more frequently than with placebo. Cardiovascular assessments showed a slight increase in systolic and diastolic blood pressure as well as heart rate compared to placebo but were unlikely to be clinically signiﬁcant. The incidence of abnormal labora- tory parameters was generally similar between placebo and duloxetine treated patients. Most notably there were increases in liver enzyme values in patients treated with duloxetine, but the changes were not regarded as clinically important. There were 3 deaths in duloxetine-treated patients: 1 due to suicide, 1 due to cardiorespiratory arrest and the other to Neuropsychiatric Disease and Treatment 2008:4(6)