Norman and Olver during a two-week tapering of the medication. There was no difference in the proportion of patients experiencing any event between duloxetine and placebo groups (Allulgander et al 2007). Dizziness, headache and insomnia all occurred more frequently with duloxetine, whereas upper respiratory infection occurred more frequently with placebo. In the trials discontinuation events were noted in 19.4% to 31.1% of duloxetine-treated patients and 15.8% to 17.3% of placebo- treated patients. In none of the trials was the difference between duloxetine and placebo statistically signiﬁcant. There did not appear to be any difference in the frequency of with- drawal symptoms depending on the dose of duloxetine. Following abrupt discontinuation in depression trails there was no evidence of a severe withdrawal syndrome (Hudson et al 2005). Despite this it is recommended that the drug be tapered on withdrawal from treatment. Conclusions These studies in relatively large populations of patients provide reasonable evidence of the efﬁcacy of duloxetine as a short term treatment for GAD. There were signiﬁcant reductions in the baseline scores in the HAM-A scale during treatment for up to 10 weeks with the drug. Some 50% to 60% of patients achieved a 50% reduction in their initial scores. In addition to symptomatic relief signiﬁcant improvements in role functioning and quality of life were also attained by patients treated with duloxetine in comparison to placebo. At the doses used the drug is associated with some side effects which are generally predictable based on the known pharmacology of the agent. On the whole the side effects were of mild to moderate severity and were well tolerated, tending to diminish in intensity over time. With respect to cardiovascular safety a speciﬁc study evaluated effects on the QT interval at doses above those recommended for treatment of GAD and found no clinically signiﬁcant prolongation of the interval. However this study was conducted in otherwise healthy volunteers and does not ensure the cardiac safety in patients with an already compromised system (eg, previ- ous myocardial infarction, heart failure). Concerns about a potential withdrawal syndrome concluded that there may be a mild syndrome provided the drug is tapered during discon- tinuation. Abrupt withdrawal may also be a safe procedure, but there is little data with which to conﬁdently assert this conclusion. Clearly, further work is necessary to address the issues of duloxetine long term safety and efﬁcacy, at least for patients with a diagnosis of GAD. Of note with all of the papers reviewed here is the poten- tial for a conﬂict of interest of the authors. A recent analysis 1178 has suggested that both industry sponsorship and author conﬂict of interest affect study outcomes (Perlis et al 2005). While potential conﬂicts of interest do not imply unethical behavior or wrongdoing, the possibility of the publication of more favorable results exists. In the studies reviewed there is a noticeable involvement of employees of the manufacturer of duloxetine in the authorship of the papers. It is not clearly delineated what role these particular authors had in the ﬁnal content of the papers and whether that involvement extended beyond statistical advice and provision of the raw data. This is not to imply that papers reviewed were unsound, either from the clinical or statistical methodology used, on the contrary this was exemplary. While ideally clinical evaluations of medicines should be conducted independently of the manu- facturer it is recognized that costs of clinical trials are now beyond the scope of individual investigators. Nevertheless, for various reasons, the issues of ﬁnancial conﬂict of inter- est have been shown to inﬂuence the reporting of such trials (Healy and Cattell 2003). Furthermore, when published clini- cal trial data are compared with that held in databases which include unpublished data there is a tendency for the efﬁcacy of drugs to be inﬂated (Turner et al 2008). We are not aware of any unpublished or failed trials of duloxetine in GAD at the time of publication which might inﬂuence the conclusions about the efﬁcacy of drug. Disclosures Neither author declares any potential conﬂict of interest with respect to this publication. References Allgulander C, Hartford J, Russell J. 2007. Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment from a pooled analysis of three clinical trials. Curr Med Res Opin, 23:1245–52. Allgulander C, Nutt D, Detke M, et al. 2008. A non-inferiority comparison of duloxetine and venlafaxine in the treatment of adult patients with generalized anxiety disorder. J Psychopharmacol, 22:417–25. Anderson I. 2006. The new guidelines from the British Association for Psychopharmacology for anxiety disorders. Int J Psychiatr Clin Pract, 10:10–7. Baldwin DS. 2006. Serotonin noradrenaline reuptake inhibitors: A new generation of treatment for anxiety disorders. Int J Psychiatr Clin Pract, 10:12–5. Baldwin DS, Polkinghorn C. 2005. Evidence-based pharmacotherapy of gen- eralized anxiety disorder. Int J Neuropsychopharmacol, 8:293–302. Ballenger JC. 2001. Overview of different pharmacotherapies for attain- ing remission in generalized anxiety disorder. J Clin Psychiatry, 62:11–9. Borsini F, Podhorma J, Marazzitti D. 2002. Do animal models of anxiety predict anxiolytic-like effects of antidepressants. Psychopharmacology, 163:121–41. Bymaster FP, Dreshﬁeld-Ahmad LJ, Threlkeld PG, et al. 2001. Comparative afﬁnity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes and other neuronal receptors. Neuropsychopharmacology, 25:871–80. Neuropsychiatric Disease and Treatment 2008:4(6)