Khan and Macaluso the treatment of non-depressed outpatients with GAD.28 The study was an 8-week, double-blind, ﬁxed dose trial that randomized patients to placebo (n = 96) or venlafaxine XR.28 Venlafaxine XR was dosed at 75 mg/day (n = 86), 150 mg/day (n = 81), or 225 mg/day (n = 86).28 Patients included in the study scored at least an 18 on the HAM-A and at least a 2 on the anxious mood and tension factors subscale. Unlike the above studies involving duloxetine, this study utilized HAM-A score as part of the inclusions criteria. Primary efficacy measures included change in total HAM-A score (Table 2). In 2000, results of a 6-month, double blind, placebo-controlled trial showed long-term effectiveness in the use of venlafaxine XR to treat GAD.29 The study was a 28-week, double-blind, placebo-controlled, ﬂexible dose trial involving 251 non- depressed adult outpatients meeting DSM-IV criteria for GAD (Table 2).29 The goal of this article is not to compare venlafaxine XR to duloxetine for the treatment of GAD. However, clinicians may often need to choose between these two medications as an initial therapy or as an option for patients who have failed a trial of a different medication. The two studies that we discussed on venlafaxine XR used HAM-A score as an entry criteria for the study, while the studies we discussed on duloxetine did not. By not using HAM-A score as an entry criteria, the duloxetine study designs may have reduced the potential for rater bias.14 An additional study comparing venlafaxine XR with duloxetine will generate data that will be pooled with the Hartford study to provide a better powered comparison of the two agents.14 At this time venlafaxine XR and duloxetine are both safe and efﬁcacious treatment options for clinicians to consider in GAD. Similar to our discussion of duloxetine as a possibility for patients with somatic manifestations of anxiety, choosing venlafaxine XR may often be based on co-morbidities. Additional studies in this area could also be useful to clinicians. Future studies An NIMH sponsored trial (NCT00183274) is currently recruiting subjects to study “Effectiveness of Long-Term Ver- sus Short-Term Treatment of Generalized Anxiety Disorder With Venlafaxine XR.”30 The National Taiwan Hospital (NCT00491348) is currently recruiting subjects to study “Effects of Duloxetine on Pathological Worry in Patients with Generalized Anxiety Disorder: A fMRI Study.”30 Conclusion Duloxetine is an FDA approved treatment option for GAD that has been studied in acute phase 9- to 10-week double- blind, placebo-controlled clinical trials. Duloxetine has also been evaluated for relapse prevention (26-week continuation) in patients whose GAD symptoms have responded after 26 weeks of acute phase treatment. Duloxetine may also be particularly useful to clinicians treating GAD patients with concomitant chronic pain or who have signiﬁcant somatic symptoms as a part of their anxiety. The information presented is important because it forms the basis for the size and quality of the systematic database upon which physicians can form evidence based opinions about the reliability, safety, tolerability and efﬁcacy of duloxetine in patients with GAD. This article will help physicians to interpret clinical studies properly and apply that knowledge to their patients. As the evidence base with regard to maintenance therapy and treatment of speciﬁc symptoms of GAD grows, clinicians will be able to make an informed decision about which patients are the most appropriate can- didates for a trial of duloxetine. Disclosures Dr Khan is on the speaker panel for Wyeth pharmaceuticals. Dr Macaluso has no disclosures. Table 2 Efﬁcacy studies of venlafaxine XR in the treatment of GAD Study Number Average age Gender Study length Design of subjects Rickels et al28 349 39.6a 56%a ♀ 8 weeks Gelenberg et al29 251 41** 68%b ♀ 6 months Hartford et al14 487c 40.1b 62.2%b ♀ 10 weeks Dosing Change in HAM-A Statistical signiﬁcance Placebo-controlled Fixed ↓12.36 (150 mg/day) p = 0.07 Placebo-controlled Flexible ↓13.4 p 0.001 Placebo-controlled Flexible ↓12.4 p 0.01 *venlafaxine group randomized to 150 mg/day. bvenlafaxine group. cduloxetine efﬁcacy study with venlafaxine XR comparator arm [duloxetine (n = 162), venlafaxine (n = 164), and placebo groups (n = 161)]. 30 Neuropsychiatric Disease and Treatment 2009:5