E X P E R T O P I N I O N Duloxetine in the treatment of generalized anxiety disorder Trevor R Norman James S Olver Department of Psychiatry, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia Correspondence:Trevor Norman Department of Psychiatry, University of Melbourne,Austin Hospital, Heidelberg, 3084,Victoria,Australia Email trevorrn@unimelb.edu.au Abstract: Duloxetine, a medication with effects on both serotonin and noradrenaline transporter molecules, has recently been approved for the treatment of generalized anxiety disorder. The evidence for its efﬁcacy lies in a limited number of double blind, placebo controlled comparisons. Statistically signiﬁcant improvements in the Hamilton Anxiety Rating Scale from baseline were demonstrated in all studies at doses of 60 to 120 mg per day. The signiﬁcance of such changes in terms of clinical improvements compared to placebo is less certain, particularly when the effect size of the change is calculated. In comparative trials with venlafaxine, duloxetine was as effective in providing relief of anxiety symptoms. In addition to improvements in clinical symptoms duloxetine has also been associated with restitution of role function as measured by disability scales. Duloxetine use is associated with nausea, dizziness, dry mouth, constipation, insomnia, somnolence, hyperhidrosis, decreased libido and vomiting. These treatment emergent side effects were generally of mild to moderate severity and were tolerated over time. Using a tapered withdrawal schedule over two weeks in the clinical trials, duloxetine was associated with only a mild withdrawal syndrome in up to about 30% of patients compared to about 17% in placebo treated patients. Duloxetine in doses of up to 200 mg twice daily did not prolong the QTc interval in healthy volunteers. Like other agents with dual neurotransmitter actions duloxetine reduces the symptoms of generalized anxiety disorder in short term treatments. Further evidence for its efﬁcacy and safety in long term treatment is required. Keywords: duloxetine, generalized anxiety disorder, Hamilton anxiety rating scale, withdrawal syndrome, psycho-social function Introduction Generalized anxiety disorder (GAD) is a diagnosis of relatively recent origin (Tyrer and Baldwin 2006). The term anxiety neurosis, as deﬁned by Freud, was used prior to 1980 to describe a condition characterized predominantly as feelings of unattached fearfulness. With the publication of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) anxiety neurosis was abandoned and GAD was introduced and distinguished from panic disorder. Under this rubric the diagnosis required that symptoms from three of four categories (motor tension, autonomic hyperactivity, apprehensive expectation, hyper-vigilance and scanning) to be pres- ent for at least 1 month. Under DSM-III GAD was essentially a residual diagnostic category. Modiﬁcations to the diagnostic schemata as in the publication of the revised edition of DSM-III (DSM-III-R), deﬁned GAD as being characterized by chronic (more than 6 months), persistent, generalized anxiety not meeting criteria for panic disorder, phobic disorder or obsessive-compulsive disorder. Following evidence that GAD can exist independently of anxiety related to anticipation of a panic attack, exposure to a phobic stimulus or obsessional concern, DSM-III-R deﬁned GAD by positive criteria related to unrealistic/excessive anxiety or worry about 2 or more life concerns and 6 of 18 physical symptoms including 9 autonomic symptom clusters. If another Axis I anxiety disorder was present, GAD could still be diagnosed if the Neuropsychiatric Disease and Treatment 2008:4(6) 1169–1180 © 2008 Dove Medical Press Limited. All rights reserved 1169