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Doctoral Thesis
DOI
10.11606/T.5.2007.tde-27042007-141827
Document
Author
Full name
Fabio Moraes Corregiari
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Bernik, Marcio Antonini (President)
Asbahr, Fernando Ramos
Graeff, Frederico Guilherme
Lotufo Neto, Francisco
Mello, Marcelo Feijó de
Title in Portuguese
Resposta neuroendócrina aguda ao citalopram e resposta terapêutica no transtorno obsessivo-compulsivo
Keywords in Portuguese
Citalopram
Hidrocortisona
Hormônio do crescimento
Inibidores de captação de serotonina
Prognóstico
Prolactina
Serotonina
Transtorno obsessivo-compulsivo
Abstract in Portuguese
INTRODUÇÃO: Testes provocativos com drogas serotonérgicas não apresentaram resultados consensuais em pacientes com TOC, sugerindo que a atividade serotonérgica seja heterogênea neste transtorno. É possível que a disfunção serotonérgica se relacione à resistência ao tratamento com inibidores de recaptura de serotonina (IRS) neste transtorno. O objetivo deste estudo foi comparar a atividade serotonérgica em pacientes com TOC resistente e responsivo ao tratamento com IRS e voluntários normais através de teste provocativo com citalopram. MÉTODOS: Foram estudados 30 pacientes com TOC resistente a IRS (RT), 30 pacientes com TOC respondedor (RP) e 30 voluntários sem transtorno mental (CN) pareados por sexo e idade. Cada indivíduo recebeu 20 mg de citalopram intravenoso. Foram dosados: prolactina, cortisol, hormônio de crescimento no plasma e serotonina em plasma rico em plaquetas nos seguintes tempos: -20, 0, 20, 40, 60, 80, 100, 120, 140 e 160 minutos. Como medidas da variação hormonal foram comparadas a variação percentual máxima (delta%) e a área sob a curva da variação. RESULTADOS: O citalopram não induziu sintomas ansiosos ou piora dos sintomas obsessivo-compulsivos nos pacientes. Também não houve mudanças significativas na concentração periférica de serotonina e na concentração de GH. A droga induziu um pico de secreção de prolactina no grupo controle (delta%=65,76 ± 105,1) maior que nos grupos RT e RP (RT delta%=17,41 ± 31,06; RP delta%=15,87 ± 31,71; p<0,05 em relação ao grupo controle). A secreção de cortisol mostrou-se atenuada apenas no grupo RT: (RT delta%=20,98 ± 58,14; RP delta%= 47,69 ± 66,94; CN delta%= 63,58 ± 88,4; p<0,05). CONCLUSÕES: Tanto pacientes resistentes como respondedores ao tratamento com IRS apresentaram resposta atenuada de prolactina ao citalopram em comparação a voluntários saudáveis, mas apenas pacientes resistentes apresentaram também resposta atenuada de cortisol, sugerindo maior disfunção serotonérgica neste grupo.
Title in English
Acute neuroendocrine response to citalopram and therapeutic response in obsessive-compulsive disorder
Keywords in English
Citalopram
Cortisol
Growth hormone
Obsessive-compulsive disorder
Prognosis
Prolactin
Serotonin
Serotonin uptake inhibitors
Abstract in English
INTRODUCTION: Serotonergic pharmacological challenge tests have failed to produce consensual results in patients with OCD diagnosis, suggesting a heterogeneous 5-HT activity in this disorder. It is possible that serotonergic dysfunction is related with inadequate response to treatment with serotonin reuptake inhibitors (SRI). The aim of this study was to compare the neuroendocrine response to a serotonergic challenge in serotonin reuptake inhibitors treatment resistant and responders OCD patients and healthy volunteers. Methods: Thirty OCD resistant patients, 30 responders patients and 30 healthy volunteers, age and sex matched, were included. Each subject received 20 mg of intravenous citalopram. Prolactin, cortisol, growth hormone and serotonin were determined at the following times after the onset of citalopram infusion: -20, 0, 20, 40, 60, 80, 100, 120, 140 and 160 minutes. The maximal percentage variation (delta%) and area under the curve were compared as measures of hormonal variation. RESULTS: Citalopram has not induced any worsening of anxious or obsessive-compulsive symptoms among patients. No significant changes were observed either at platelet rich plasma serotonin concentration or at plasma growth hormone concentration. Citalopram has induced an increase in prolactin secretion in the control group (delta%=65.76 ± 105.1) while RT and RP groups showed blunted prolactin response (RT delta%=17.41 ± 31.06; RP delta%=15.87 ± 31.71; p<0.05). The cortisol response to citalopram was attenuated only in the RT group: (RT delta%=20.98 ± 58.14; RP delta%= 47.69 ± 66.94; CN delta%= 63.58 ±88.4; p<0.05). CONCLUSIONS: We concluded that either treatment resistant as responders patients have blunted prolactin response to citalopram, but only resistant patients also show an attenuated cortisol response, suggesting a more disrupted central serotonergic transmission in this group.
 
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Publishing Date
2007-05-17
 
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