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      Pharmacotherapy of anxiety disorders: a critical review

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          Abstract

          Given the enormous contribution of anxiety disorders to the burden of disease, it is key to optimize their prevention and treatment. In this critical review we assess advances in the pharmacotherapy of anxiety disorders, as well as remaining challenges, in recent decades, the field has seen rigorous clinical trial methods to quantify the efficacy and safety of serendipitously discovered agents, more focused development of medications with selective mechanisms of action, and the gradual translation of insights from laboratory research into proof-of-principle clinical trials. On the positive side, a considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents. Significant challenges in the field include barriers to appropriate diagnosis and treatment of anxiety disorders, failure of a significant proportion of patients to respond to first-line pharmacotherapy agents, and a limited database of efficacy or effectiveness studies to guide treatment in such cases.

          Translated abstract

          Considerando el gran impacto de los trasiornos ansiosos en el costo de las enfermedades, es clave optimizar su preventión y tratamiento. En esta révision critica se evalúan tanto los avances en la farmacoterapia de los trastornos ansiosos como los desaffos que persisten. En las últimas décadas en este campo se ha contado con ensayos clínicos con rigurosa metodologia para cuantificar la eficacia y seguridad de agentes descubiertos casualmente, con el desarrollo más orientado a medicamentos con mecanismos de acción selectiva y con el traspaso de ideas desde la investigation de laboratorio a los ensayos clínicos de prueba de principios, Como aspecto positivo debe considerarse que existe una gran base de datos de estudios que demuestra la eficacia y la aceptable tolerabilidad de los inhibidores selectivos de la recaptura de serotonina en los principales trastornos ansiosos, y del análisis secundario de estas bases de datos han surgido preg untas relacionadas con la definitión óptima de respuesta y remisión, la dosis optima y la duration y la eficacia comparativa de diferentes fármacos, Existen importantes desaffos en este campo que incluyen las barreras para un apropiado diagnóstico y tratamiento de los trastornos ansiosos, las fallas en la respuesia a agonies farmacológicos de primera línea de una proportion significativa de patientes y una base de datos limitada sobre la eficacia y efectividad de estudios para guiar el tratamiento en estos casos.

          Translated abstract

          Du fait de l'importance de la contribution des troubles anxieux au fardeau des maladies, il est crucial d'optimiser leur prévention et leur traitement Dans cette revue critique, nous évaluons à la fois les avancées de la pharmacothérapie des troubles anxieux et les défis qui persistent. Ces 10 dernières années, des études cliniques rigoureuses ont permis de quantifier l'efficacité et la tolérance de produits découverts de manière empirique, de développer plus précisément des médicaments aux mécanismes d'action sélectifs et d'appliquer progressivement les idées de la recherche en laboratoire à des études cliniques basées sur des preuves. Du côté positif, une importante base de données des études montre une efficacité et une tolérabilité relative des inhibiteurs sélectifs de la recapture de la sérotonine dans les troubles majeurs de l'anxiété. Des analyses secondaires de ces bases de données ont répondu à des questions portant sur la définition optimale de la réponse et de la rémission, de la meilleure posologie, de la durée et de l'efficacité comparative des différents produits. Les problèmes significatifs qui persistent dans ce domaine sont: les obstacles au diagnostic et au traitement adéquats des troubles anxieux, l'absence de réponse d'un pourcentage significatif de patients aux traitements de première intention et une base de données limitée pour les études d'efficacité pour orienter le traitement dans de tels cas.

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          Most cited references199

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          Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety.

          Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.) 2008 Massachusetts Medical Society
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            Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder.

            Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.
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              Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder.

              The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n=9) or placebo (n=10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event.
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                Author and article information

                Contributors
                Department of Psychiatry and Mental Health, University of Cape Town, South Africa
                Department of Psychiatry and Mental Health, University of Cape Town, South Africa
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                December 2011
                December 2011
                : 13
                : 4
                : 423-437
                Affiliations
                Department of Psychiatry and Mental Health, University of Cape Town, South Africa
                Department of Psychiatry and Mental Health, University of Cape Town, South Africa
                Author notes
                Article
                10.31887/DCNS.2011.13.4/nkoen
                3263390
                22275848
                319de8a4-4627-4037-a778-51b0e165012c
                Copyright: © 2011 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Pharmacological Aspects

                Neurosciences
                pharmacotherapy,social anxiety disorder,medication,post-traumatic stress disorder,generaiized anxiety disorder,anxiety disorder,obsessive-compulsive disorder

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