Duloxetine for GAD 50% s re45% o cS40% SD35% laS30% rom25% foN20% eg15% a ten10% rec 5% P 0% SDS Score at Endpoint Q-LES-Q-SF Score at Endpoint Duloxetine Duloxetine Placebo Placebo F 35% S - -SQ 30% E -LQ 25% e v ita rse20% roNm coS15% f eog 10% a tecn 5% r e P 0% Figure 1 Quality of life data in patients with GAD treated with duloxetine. global functioning and 95% of patients were impaired on the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF).23 The study confirmed the belief that patients with GAD have impaired functioning and quality of life. Following treatment, the duloxetine group showed statistically signiﬁcant improvement when compared to placebo (p 0.001).23 The mean SDS score for the duloxetine treatment groups at completion ranged from 7.4 to 9.5 compared with a mean range of 11.4 to 12.1 for placebo-treated groups.23 47% of duloxetine treated patients achieved a normative SDS score at studies end, compared with 28% of placebo-treated patients (Figure 1).23 Duloxetine treated patients not only demonstrated improved quality of life, but improved overall satisfaction as studied by the Q-LES-Q-SF.4 Mean endpoint scores on the Q-LES-Q-SF ranged from 65.9% to 67.9% for the duloxetine group compared to 58.5% to 60.9% for the placebo group (Figure 1).23 Two of the three clinical trials demonstrated a signiﬁcant improvement of Q-LES-Q-SF compared with placebo. Duloxetine treated patients were not only able to better carry out role functioning, but were more satisﬁed with their quality of life.24,25 Over 1100 patients were included in this analysis with the improvements in quality of life being replicated in all three. While such data is useful in real-world clinical practice, studies with longer follow-up would better determine long-term maintenance of such improvements.24 TCAs and venlafaxine are often utilized clinically in patients with concomitant chronic pain issues. The mechanism of action of duloxetine lends itself to similar use, and we will examine data in this regard. Chronic pain Duloxetine received FDA approval for the treatment of diabetic peripheral neuropathic pain in 2004 and is often Neuropsychiatric Disease and Treatment 2009:5 utilized clinically in patients whose anxiety is marked by somatic symptoms or who have concomitant chronic pain. Pooled results from two studies showed that 44.4% of patients identiﬁed with GAD had visual analog scale (VAS) scores 30.26 Hartford et al conducted a post hoc evaluation of two double-blind, placebo-controlled trials examining efﬁcacy of duloxetine in GAD. Duloxetine showed reduction in pain on all 6 VAS pain scales (p 0.001).27 Russell et al also pooled data from two double-blind, placebo-controlled trials looking at efﬁcacy of duloxetine in GAD. Results of this pooled analysis also showed that patients receiving duloxetine showed improvement on all 6 VAS pain scales (p 0.001 for overall pain, p = 0.009 for headache, p = 0.003 for back pain, p 0.001 for shoulder pain, p 0.001 for daily interference due to pain, and p 0.001 for proportion of the day while awake with pain).26 As above this is of particular interest to clinicians because of the frequent overlap between pain and anxiety in GAD. Also, as further advances in neuroscience come to light, further structural and neurophysiologic links between pain and anxiety in GAD could be uncovered. Now that we have evaluated data that is pertinent to clinical practice for duloxetine, we will take a brief look at the data for venlafaxine XR, another SNRI that is FDA approved for treatment of GAD. Venlafaxine XR While no head-to-head trials comparing duloxetine with other medications for the treatment of GAD currently exist, venlafaxine XR, an SNRI, was FDA approved for the treatment of GAD in 1991. In 2000, a study published in the American Journal of Psychiatry examined the efﬁcacy of venlafaxine XR in 29