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      European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

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          Abstract

          To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce.

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          Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.

          Aripiprazole is the first next-generation atypical antipsychotic with a mechanism of action that differs from currently marketed typical and atypical antipsychotics. Aripiprazole displays properties of an agonist and antagonist in animal models of dopaminergic hypoactivity and hyperactivity, respectively. This study examined the interactions of aripiprazole with a single population of human D2 receptors to clarify further its pharmacologic properties. In membranes prepared from Chinese hamster ovary cells that express recombinant D2L receptors, aripiprazole bound with high affinity to both the G protein-coupled and uncoupled states of receptors. Aripiprazole potently activated D2 receptor-mediated inhibition of cAMP accumulation. Partial receptor inactivation using the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) significantly reduced the maximum effect of aripiprazole on inhibition of cAMP accumulation. This effect was seen with concentrations of EEDQ that did not alter the maximal inhibitory effect of dopamine. Consistent with the expected effects of a partial agonist, increasing concentrations of aripiprazole blocked the action of dopamine with maximal blockade equal to the agonist effect of aripiprazole alone. The efficacy of aripiprazole relative to that of dopamine varied from 25% in cells that lacked spare receptors for dopamine to 90% in cells with receptor reserve. These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer. The receptor activity profile may underlie the unique activity of aripiprazole in animals and its antipsychotic activity in humans.
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            Tourette's syndrome.

            As our knowledge of Gilles de la Tourette's syndrome increases, so does our appreciation for the pathogenic complexity of this disorder and the challenges associated with its treatment. Advances in the neurosciences have led to new models of pathogenesis, whereas clinical studies have reinvigorated early hypotheses. The interdependent roles of genes and environment in disease formation have yet to be fully elucidated. Results of epidemiological studies have prompted debate on how best to characterise and diagnose this disorder. Absence of ideal anti-tic drugs, combined with knowledge that uncomplicated cases of childhood Tourette's syndrome frequently have a favourable outcome, has led to striking changes in care and treatment of patients. This seminar focuses on these changing views and offers a new perspective on our understanding of the pathogenesis of Tourette's syndrome and on principles for treatment of patients with this disorder.
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              A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

              As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.
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                Author and article information

                Contributors
                +49-351-4582244 , +49-351-4585754 , veit.roessner@uniklinikum-dresden.de
                Journal
                Eur Child Adolesc Psychiatry
                European Child & Adolescent Psychiatry
                Springer-Verlag (Berlin/Heidelberg )
                1018-8827
                1435-165X
                29 March 2011
                29 March 2011
                April 2011
                : 20
                : 4
                : 173-196
                Affiliations
                [1 ]Department of Child and Adolescent Psychiatry, University of Dresden Medical School, Fetscherstrasse 74, 01307 Dresden, Germany
                [2 ]Centre for Child and Adolescent Psychiatry at Bispebjerg, Capital Region Psychiatry, Copenhagen, Denmark
                [3 ]Department of Neurology, Psychiatry and Sensory Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
                [4 ]Department of Child and Adolescent Psychiatry, University of Goettingen, Goettingen, Germany
                [5 ]Department of Child and Adolescent Psychiatry, University of Ulm, Ulm, Germany
                [6 ]Renata Rizzo Child and Adolescent Neurology and Psichiatry, Maternal Infantile and Radiological Sciences Department, Catania University, Catania, Italy
                [7 ]Department of Pediatrics, Glostrup University Hospital, Copenhagen, Denmark
                [8 ]Norwegian Resource Center for AD/HD, Tourette Syndrome and Narcolepsy, Ulleval University Hospital, Oslo, Norway
                [9 ]St George’s Hospital Neurology, London, UK
                [10 ]Child Neuropsychiatry Unit, Department of Experimental Medicine, University of Insubria, Varese, Italy
                [11 ]Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
                Article
                163
                10.1007/s00787-011-0163-7
                3065650
                21445724
                78bc6977-0e0b-4e40-beb7-7267af1d26a1
                © The Author(s) 2011
                History
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                Custom metadata
                © Springer-Verlag 2011

                Clinical Psychology & Psychiatry
                guidelines,tourette,pharmacologic,tics,treatment
                Clinical Psychology & Psychiatry
                guidelines, tourette, pharmacologic, tics, treatment

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