Investigation of the co-occurrence of panic and phobic disorders with joint laxity led to the identification of various forms of interstitial duplications involving human chromosome 15q24-q26 (named "DUP25") in a Spanish population. DUP25 was observed in 68 of 70 (97%) patients assigned the diagnosis panic disorder/agoraphobia. DUP25 was also found in 14 of 189 (7%) control individuals. In the present study, we replicated the experimental conditions described by Gratacòs and colleagues in which fluorescence in situ hybridization was used to examine metaphase chromosomes of patients with panic disorder/social phobia and of control individuals from a southern region of the United Kingdom, the primary aim being to determine the prevalence of this chromosomal rearrangement in a geographically and ethnically distinct population. DUP25 was not observed in any of our 16 patients or 40 control samples or in three previously reported DUP25-positive control (Centre d'Etude du Polymorphisme Humain) cell lines, indicating a highly significant difference in the frequency of DUP25 between the study by Gratacòs and colleagues and the present investigation.

The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram, in effects on sexual function and satisfaction. The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre randomized controlled trial of acute treatment of patients with DSM-IV major depression. Patients were randomly assigned to receive reboxetine (4 mg b.d.) or paroxetine (20 mg mane) using a double-dummy technique to preserve the blind. The dosage could be increased at day 28 (to reboxetine 4 mg mane, 6 mg nocte; or paroxetine 20 mg b.d.). Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impression Scale for Severity (CGI-S) at all study visits, and the Clinical Global Impression of Improvement (CGI-I) at each visit after randomization. Sexual function and satisfaction was assessed by visual analogue scale (VAS) items of the Rush Sexual Inventory completed at baseline and days 28 and 56. There were no significant differences between groups in demographic or clinical features at baseline. There was a gradual reduction in severity of depressive symptoms (reboxetine, 14.3; paroxetine, 12.0: observed case analysis), with no significant differences between groups. There were significant differences (p 0.05), with advantages for reboxetine, at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited, and non-significant trends with advantages for reboxetine, in frequency of sexual thoughts at Week 4 (p 0.05) and Week 8 (p 0.08); and in desire to initiate sexual activity at Week 4 (p 0.09). Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study (n 10) reduced the statistical significance of the findings, although there were still numerical advantages for reboxetine. Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine, but this improvement is greater and more rapid with reboxetine.

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder. Expert Rev. Neurotherapeutics 2(5), 717-724 (2002) † Author for correspondenceUniversity Department of Mental Health, Royal South Hants Hospital, Southampton SO14 0YG, UK Tel.: +44 2380 825533 Fax: +44 2380 KEYWORDS:citalopram, escitalopram, fluoxetine, fluvoxamine, GAD, paroxetine, sertraline, SSRI Introductory overview Clinical features & epidemiology of generalized anxiety disorderGeneralized anxiety disorder (GAD) is characterized by inappropriate or excessive anxiety and worrying that is persistent and not restricted to particular circumstances. Common symptoms include:• Apprehension, with worries about future misfortune • Inner tension and difficulty in concentrating; motor tension, with restlessness • Tremor and headache • Autonomic anxiety, with excessive perspiration, dry mouth and epigastric discomfortThe lifetime prevalence in the general population is around 5-6%, the 12-month prevalence varying according to diagnostic criteriafrom 1.5% with Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) to 3.1% with DSM-III-R criteria [1]. The age of onset of GAD differs from that with other anxiety disorders, the majority of cases presenting aged around 35-45 years [2][3][4]. GAD is probably the most common anxiety disorder among the elderly population (55-85 years) [5]. Symptoms fluctuate in intensity over time, but GAD is usually a chronic condition [6]. The functional impairment is similar in magnitude to that with major depression [3,7].GAD is amongst the most common psychiatric disorders seen in general practice. The point prevalence of ICD-10 defined GAD in European primary care settings was 4.8% for GAD without other comorbid depressive or anxiety disorders and 3.7% for GAD with depression: a further 4.1% had 'subthreshold' GAD [6]. Comorbid GAD is associated with more severe symptoms, greater functional impairment, a more prolonged course, decreased productivity and higher use of health services [6][7][8][9]. Comorbid depressive symptoms improve the chances of a patient being recognized as having a psychological problem, though not necessarily GAD [6]. Pathophysiology of generalized anxiety disorderSerotonin (5-hydroxytryptamine, 5-HT) is integrally involved in the mediation of anxiety through serotonergic innervation of the limbic system, hypothalamus and thalamus. Levels of the serotonin metabolite 5-hydroxyindoleacetic acid in c...

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