Khan and Macaluso groups when compared to placebo (p = 0.023 for study 2 and p 0.01 for study 3).13,14 Secondary efficacy measures for study 2 showed statistically signiﬁcant improvement in HAM-A items for anxious mood (−0.98, p = 0.006), tension (−0.98, p = 0.014), fears (−0.49, p = 0.049), cognitive (−0.98, 0.001), depressed mood (−0.43, p = 0.003), and behavior (−0.66, p = 0.011) compared with placebo.13 In the second study the CGI-I endpoint (2.68) and PGI-I endpoint (2.88) also showed a statistically significant change with respect to pla- cebo (p = 0.04 and p = 0.046 respectively).13 The HAM-A psychic factor scale also showed statistically signiﬁcant improvement (−5.33, p 0.001) compared with placebo in the second study.13 The HADS anxiety subscale (−3.92, p = 0.001) also showed a statistically signiﬁcant change when compared to placebo in the second study.13 The HAM-A somatic factor, insomnia, somatic muscular, somatic sensory, cardiovascular, respiratory, gastrointestinal, genitourinary, and autonomic items did not show a statistically signiﬁcant change when compared to placebo.13 The HADS depression subscale also did not show ﬁndings that were statistically signiﬁcant.13 Secondary efficacy measures for study 3 showed signiﬁcant improvement when compared to placebo (in the duloxetine group) for the HAM-A psychic factor (−7.01), HAM-A anxious mood (–1.40), HAM-A tension (−1.37), CGI-I endpoint (2.39), PGI-I endpoint (2.60), HADS anxiety subscale (−6.22) and HADS depression subscale (−3.91).14 The above studies showed duloxetine to be an effective treatment for GAD. However, it is often difficult to extrapolate clinical trial data to “real world” patients encountered in clinical practice. Tunis et al deﬁned a practical clinical trial as “a study design that compares clinically important interventions, a diverse population of study participants representative of clinical practice, inclusion of a range of heterogeneous practice settings that are also representative of clinical practice, and measurement of a broad range of clinically relevant health outcomes.”20 Strengths of the above studies include use of standardized rating scales such as HAM-A in the evaluation of patients, large sample-size, multi-center, effective randomization, and double-blind design. However, generalizability of research findings from clinical trials is a methodological concern. Because most of the studies exclude many participants with general medical and psychiatric co-morbidities, generalizability of the results is limited. The study also excluded patients with a history of previous unresponsiveness to SSRI or benzodiazepine in the 28 treatment of GAD, therefore selecting out non-responders who may be encountered in clinical practice. Homogeneity between the sample population and the target population is necessary so that the results can be extrapolated. Other limitations of the above studies include a short time to evaluate treatment and response. Patients in clinical practice typically utilize antidepressant medications for longer than 9 to 10 weeks. Results of long-term studies could provide information on remission rates that would be clinically useful. Long-term studies would also provide clinicians with information on maintenance treatment. Davidson, et al published results of a 26 week double-blind, placebo controlled, trials looking at efﬁcacy of duloxetine in relapse prevention. Study patients ﬁrst completed a 26-week, open-label, acute-therapy phase. Patients included in the study were those that responded to this acute phase treatment, deﬁned as 50% reduction in Hamilton Anxiety Rating Scale and “much” to “very much” improved ratings for the last two visits of acute open label treatment. For study purposes, relapse was deﬁned as 2 point increase in illness severity ratings or by discontinuation for lack of efﬁcacy. 41.8% of placebo-treated patients experienced relapse of their illness based on the above criteria, compared with only 13.7% of duloxetine treated patients (p 0.001) at the end of the second 26 weeks (continuation phase).21 Pollack, et al pooled data from three clinical trials (n = 688) and showed that 100% of responders to duloxetine ( 80% improvement of HAM-A) at week 2 and 93% of responders at week 4 were responders to treatment at endpoint. Similar data is not available for SSRI’s at this time, but would be helpful in evaluating treatment options clinically.22 We have now reviewed the efﬁcacy data that lead to FDA approval for treatment of GAD. Data from these studies was also pooled to examine improvement in quality of life. Quality of life In clinical practice, improvement of an individual’s qualify of life is a sought-after result that is difﬁcult to pull from research studies. A 2008 study by Pollack et al pooled data from 3 studies to assess if duloxetine improved quality of life in patients meeting DSM-IV-TR criteria for GAD.23 By utilizing comparative norms, the analysis examined the clinical importance of the functional outcomes improvements reported in the above studies. Speciﬁcally, the study sought to examine how this data on functional outcomes would translate into real-world clinical improvement.23 Individual patient data was pooled from the above studies, with outcome criteria deﬁned as above. At baseline, 89% of patients were impaired on the Sheehan Disability Scale (SDS) Neuropsychiatric Disease and Treatment 2009:5