Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise

Detalhes bibliográficos
Autor(a) principal: Oliveira , Danielly Chierrito de
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações do UNIOESTE
Texto Completo: http://tede.unioeste.br/handle/tede/2966
Resumo: Introduction: The Attention Deficit Hyperactivity Disorder (ADHD) is considered a neurobiological disorder characterized by symptoms of inattention, disorganization, hyperactivity and impulsiveness, and is diagnosed in about 2.5% to 3.4% in adults individuals. The choice of appropriate medical treatment should be based on reliable and quality evidences. Objectives: Gather evidences of safety and tolerability of the drugs used in the treatment of ADHD in adult patients without comorbidities associated. Methodology: A systematic review was conducted in the databases Medline, Scopus, Science Direct, The Cochrane Library, Web of Science, Scielo, Psyc Info and International Pharmaceutical Abstracts and updated in June 2016. We included randomized, double-blind and parallel trials, which evaluated the safety and tolerability of the drugs used in the treatment for ADHD. The adverse events reported with the use of atomoxetine were grouped by systems, according to the changes induced in individuals in accordance with MedDRA® dictionary. For traditional meta-analysis of dichotomous outcomes were calculated effect of measures such as odds ratio (OR) with 95% confidence intervals, using the Mantel-Haenszel statistical method. Continuous outcomes were analyzed using standardized mean difference ± standard deviation, considering the statistical method Mean difference. Regarding the network meta-analysis, we used the Bayesian statistical model, adjusted chain Monte Carlo Markov. We considered effect of measures as OR with 95% credibility intervals and statistically significant p <0.05. Statistical analyzes were conducted with the assistance of Review Manager software, version 5.3 and Addis software, version 1.16.5. Results: In the first chapter, we evaluated safety and tolerability outcomes of treatment of ADHD with atomoxetine compared to placebo, from traditional meta-analysis, and chapter 2 safety outcomes related to five drugs through network meta-analysis. It was identified a total of 7487 articles and, from these, 6 (n = 2481) and 10 (n = 3006) were included for analysis in chapters 1 and 2, respectively. Considering the outcomes of the first chapter, which were grouped by system, most meta-analyzes of adverse events related to the nervous system, psychiatric, gastrointestinal, sexual, metabolic and general, as well as security considering vital signs showed difference statistically significant in favor of placebo. The tolerability outcomes showed that the highest number of abandonment of treatment by adverse events, statistically significant, occurred in the treated group (OR 0.37 [95% CI 0.23, 0.59]) and lack of efficacy in the placebo group (OR 1.86 [95% CI 1.26, 2.75]). Through the network meta-analysis, outcomes analyzed in chapter 2, statistically significant differences were observed in comparisons: Appetite decreased between atomoxetine and placebo (OR 0.15 [95% ICr 0.05; 0.38]) and mixed amphetamine salts extended-release and placebo (OR 0.06 [95% ICr 0.00; 0.51]); insomnia between atomoxetine and placebo (OR 0.48 [95% ICr 0.27; 0.88]) and mixed amphetamine salts extended-release and placebo (OR 0.23 [95% ICr 0.06, 0.76] ); somnolence between atomoxetine and methylphenidate OROS (OR 0.24 [95% ICr 0.06; 0.97]) and libido decreased between atomoxetine and placebo (OR 0.28 [95% ICr 0.08, 0.90]). Conclusions: It was possible to generate evidence on the safety and tolerability profile of drugs for ADHD, pointing out that atomoxetine compared to placebo is more associated with adverse events and therefore higher abandonment of treatment. Another aspect that evaluated the tolerability of these drugs was the abandonment for lack of efficacy, where the placebo group presents this outcome more often statistically confirmed. From meta-analysis network (chapter 2), it became clear that atomoxetine and mixed amphetamines salts extended-release are more involved with adverse events of appetite decreased and insomnia, and atomoxetine with somnolence and libido decreased. There are still some gaps to be filled and further studies involving these drugs and pharmacoeconomic analysis should be conducted to support health decision-making, directing for choosing the best treatment option.
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spelling Sanches, Andréia Cristina Conegerohttp://lattes.cnpq.br/9706216109598342Sanches, Andréia Cristina Conegerohttp://lattes.cnpq.br/9706216109598342Rotta, Inajarahttp://lattes.cnpq.br/8686022725047306Bueno, Fernanda Giacominihttp://lattes.cnpq.br/2735821835018618http://lattes.cnpq.br/2007735848876377Oliveira , Danielly Chierrito de2017-08-31T13:02:14Z2016-11-25OLIVEIRA , Danielly Chierrito de. Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise. 2016. 166 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Paraná, Cascavel, 2016.http://tede.unioeste.br/handle/tede/2966Introduction: The Attention Deficit Hyperactivity Disorder (ADHD) is considered a neurobiological disorder characterized by symptoms of inattention, disorganization, hyperactivity and impulsiveness, and is diagnosed in about 2.5% to 3.4% in adults individuals. The choice of appropriate medical treatment should be based on reliable and quality evidences. Objectives: Gather evidences of safety and tolerability of the drugs used in the treatment of ADHD in adult patients without comorbidities associated. Methodology: A systematic review was conducted in the databases Medline, Scopus, Science Direct, The Cochrane Library, Web of Science, Scielo, Psyc Info and International Pharmaceutical Abstracts and updated in June 2016. We included randomized, double-blind and parallel trials, which evaluated the safety and tolerability of the drugs used in the treatment for ADHD. The adverse events reported with the use of atomoxetine were grouped by systems, according to the changes induced in individuals in accordance with MedDRA® dictionary. For traditional meta-analysis of dichotomous outcomes were calculated effect of measures such as odds ratio (OR) with 95% confidence intervals, using the Mantel-Haenszel statistical method. Continuous outcomes were analyzed using standardized mean difference ± standard deviation, considering the statistical method Mean difference. Regarding the network meta-analysis, we used the Bayesian statistical model, adjusted chain Monte Carlo Markov. We considered effect of measures as OR with 95% credibility intervals and statistically significant p <0.05. Statistical analyzes were conducted with the assistance of Review Manager software, version 5.3 and Addis software, version 1.16.5. Results: In the first chapter, we evaluated safety and tolerability outcomes of treatment of ADHD with atomoxetine compared to placebo, from traditional meta-analysis, and chapter 2 safety outcomes related to five drugs through network meta-analysis. It was identified a total of 7487 articles and, from these, 6 (n = 2481) and 10 (n = 3006) were included for analysis in chapters 1 and 2, respectively. Considering the outcomes of the first chapter, which were grouped by system, most meta-analyzes of adverse events related to the nervous system, psychiatric, gastrointestinal, sexual, metabolic and general, as well as security considering vital signs showed difference statistically significant in favor of placebo. The tolerability outcomes showed that the highest number of abandonment of treatment by adverse events, statistically significant, occurred in the treated group (OR 0.37 [95% CI 0.23, 0.59]) and lack of efficacy in the placebo group (OR 1.86 [95% CI 1.26, 2.75]). Through the network meta-analysis, outcomes analyzed in chapter 2, statistically significant differences were observed in comparisons: Appetite decreased between atomoxetine and placebo (OR 0.15 [95% ICr 0.05; 0.38]) and mixed amphetamine salts extended-release and placebo (OR 0.06 [95% ICr 0.00; 0.51]); insomnia between atomoxetine and placebo (OR 0.48 [95% ICr 0.27; 0.88]) and mixed amphetamine salts extended-release and placebo (OR 0.23 [95% ICr 0.06, 0.76] ); somnolence between atomoxetine and methylphenidate OROS (OR 0.24 [95% ICr 0.06; 0.97]) and libido decreased between atomoxetine and placebo (OR 0.28 [95% ICr 0.08, 0.90]). Conclusions: It was possible to generate evidence on the safety and tolerability profile of drugs for ADHD, pointing out that atomoxetine compared to placebo is more associated with adverse events and therefore higher abandonment of treatment. Another aspect that evaluated the tolerability of these drugs was the abandonment for lack of efficacy, where the placebo group presents this outcome more often statistically confirmed. From meta-analysis network (chapter 2), it became clear that atomoxetine and mixed amphetamines salts extended-release are more involved with adverse events of appetite decreased and insomnia, and atomoxetine with somnolence and libido decreased. There are still some gaps to be filled and further studies involving these drugs and pharmacoeconomic analysis should be conducted to support health decision-making, directing for choosing the best treatment option.Introdução: O Transtorno de Déficit da Atenção com Hiperatividade (TDAH) é considerado um distúrbio neurobiológico, caracterizado por sintomas de desatenção, desorganização, hiperatividade e/ou impulsividade, diagnosticado em torno de 2,5% a 3,4% dos indivíduos adultos. A escolha do tratamento medicamentoso adequado deve se basear em evidências seguras e de qualidade. Objetivos: Reunir evidências de segurança e tolerabilidade dos medicamentos utilizados no tratamento do TDAH em pacientes adultos sem comorbidades associadas. Metodologia: Uma revisão sistemática foi realizada nas bases de dados Medline, Scopus, Science Direct, The Cochrane Library, Web of Science, Scielo, Psyc Info e International Pharmaceutical Abstracts e atualizada em junho de 2016. Foram incluídos ensaios clínicos randomizados, duplo-cegos, paralelos, que avaliaram a segurança e tolerabilidade de medicamentos utilizados para o tratamento do TDAH. Os eventos adversos relatados com o uso da atomoxetina foram agrupados por sistemas, de acordo com alterações provocadas nos indivíduos conforme dicionário MedDRA®. Para as meta-análises tradicionais de desfechos dicotômicos, foram calculadas medidas de efeito como odds ratio (OR), com intervalos de confiança de 95%, usando o método estatístico Mantel-Haenszel. Os desfechos contínuos foram analisados por diferença de média padronizada ± desvio padrão, considerando o método estatístico Mean difference. Em relação às meta-análises em rede, foi utilizado o modelo estatístico Bayesiano, ajustado com cadeia de Monte Carlo Markov. Foram consideradas medidas de efeito, como OR, com intervalos de credibilidade de 95%, e estatisticamente significativo p < 0,05. As análises estatísticas foram conduzidas com auxílio do software Review Manager, versão 5.3 e do software Addis, versão 1.16.5. Resultados: No primeiro capítulo, foram avaliados desfechos de segurança e tolerabilidade do tratamento do TDAH com atomoxetina comparado ao placebo, a partir de meta-análises tradicionais, e, no capítulo 2, desfechos de segurança relacionados a cinco medicamentos por meio de meta-análises em rede. Foi identificado um total de 7487 artigos e, destes, 6 (n = 2481) e 10 (n = 3006) foram incluídos para análises nos capítulos 1 e 2, respectivamente. Considerando os desfechos do primeiro capítulo, os quais foram agrupados por sistemas, a maioria das meta-análises de eventos adversos relacionados ao sistema nervoso, psiquiátrico, gastrointestinal, sexual, metabólico e gerais, assim como a de segurança considerando sinais vitais, apresentaram diferença estatisticamente significativa a favor do placebo. Os desfechos de tolerabilidade apontaram que o maior número de abandono por eventos adversos, estatisticamente significativo, ocorreu no grupo tratado (OR 0,37 [IC 95% 0,23; 0,59]) e por falta de eficácia no grupo placebo (OR 1,86 [IC 95% 1,26; 2,75]). Através das meta-análises em rede, desfechos analisados no capítulo 2, foram observadas diferenças estatisticamente significativas nas comparações: Apetite diminuído entre atomoxetina e placebo (OR 0,15 [ICr 95% 0,05; 0,38]) e sais mistos de anfetaminas de liberação prolongada e placebo (OR 0,06 [ICr 95% 0,00; 0,51]); insônia entre atomoxetina e placebo (OR 0,48 [ICr 95% 0,27; 0,88]) e sais mistos de anfetaminas de liberação prolongada e placebo (OR 0,23 [ICr 95% 0,06; 0,76]); sonolência entre atomoxetina e metilfenidato OROS (OR 0,24 [ICr 95% 0,06; 0,97]) e libido diminuída entre atomoxetina e placebo (OR 0,28 [ICr 95% 0,08; 0,90]). Conclusões: Foi possível gerar evidências sobre o perfil de segurança e tolerabilidade de medicamentos para TDAH, apontando que a atomoxetina, quando comparada ao placebo, está mais associada a eventos adversos e, por isso, há maior abandono do tratamento. Outro aspecto que avaliou a tolerabilidade do mesmo foi o abandono por falta de eficácia, em que o grupo placebo apresentou este desfecho com maior frequência, comprovado estatisticamente. A partir de meta-análise em rede (capítulo 2), foi possível evidenciar que a atomoxetina e sais mistos de anfetaminas de liberação prolongada estão mais envolvidos com os eventos adversos apetite diminuído e insônia, e atomoxetina com sonolência e libido diminuída. Ainda há algumas lacunas a serem preenchidas e mais estudos envolvendo esses medicamentos e análises farmacoeconômicas devem ser conduzidas para subsidiar tomadas de decisão em saúde, direcionando para a escolha da melhor opção terapêutica.Submitted by Rosangela Silva (rosangela.silva3@unioeste.br) on 2017-08-31T13:02:14Z No. of bitstreams: 2 Danielly Chierrito de Oliveira.pdf: 1654466 bytes, checksum: 1e641a0f50b2b80f1b9a9250eaeb58a2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2017-08-31T13:02:14Z (GMT). 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dc.title.por.fl_str_mv Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
dc.title.alternative.eng.fl_str_mv Safety and tolerability of the drug treatment of attention deficit hyperactivy disorder in adults: systematic review and meta-analysis
title Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
spellingShingle Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
Oliveira , Danielly Chierrito de
TDAH
Meta-análise direta
Tratamento de múltiplas comparações
Eventos adversos
Abandono
ADHD
Direct meta-analysis
Mixed treatment comparison
Adverse events
Abandonment
CIENCIAS DA SAUDE::FARMACIA
title_short Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
title_full Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
title_fullStr Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
title_full_unstemmed Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
title_sort Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise
author Oliveira , Danielly Chierrito de
author_facet Oliveira , Danielly Chierrito de
author_role author
dc.contributor.advisor1.fl_str_mv Sanches, Andréia Cristina Conegero
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9706216109598342
dc.contributor.referee1.fl_str_mv Sanches, Andréia Cristina Conegero
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/9706216109598342
dc.contributor.referee2.fl_str_mv Rotta, Inajara
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/8686022725047306
dc.contributor.referee3.fl_str_mv Bueno, Fernanda Giacomini
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/2735821835018618
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/2007735848876377
dc.contributor.author.fl_str_mv Oliveira , Danielly Chierrito de
contributor_str_mv Sanches, Andréia Cristina Conegero
Sanches, Andréia Cristina Conegero
Rotta, Inajara
Bueno, Fernanda Giacomini
dc.subject.por.fl_str_mv TDAH
Meta-análise direta
Tratamento de múltiplas comparações
Eventos adversos
Abandono
topic TDAH
Meta-análise direta
Tratamento de múltiplas comparações
Eventos adversos
Abandono
ADHD
Direct meta-analysis
Mixed treatment comparison
Adverse events
Abandonment
CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv ADHD
Direct meta-analysis
Mixed treatment comparison
Adverse events
Abandonment
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FARMACIA
description Introduction: The Attention Deficit Hyperactivity Disorder (ADHD) is considered a neurobiological disorder characterized by symptoms of inattention, disorganization, hyperactivity and impulsiveness, and is diagnosed in about 2.5% to 3.4% in adults individuals. The choice of appropriate medical treatment should be based on reliable and quality evidences. Objectives: Gather evidences of safety and tolerability of the drugs used in the treatment of ADHD in adult patients without comorbidities associated. Methodology: A systematic review was conducted in the databases Medline, Scopus, Science Direct, The Cochrane Library, Web of Science, Scielo, Psyc Info and International Pharmaceutical Abstracts and updated in June 2016. We included randomized, double-blind and parallel trials, which evaluated the safety and tolerability of the drugs used in the treatment for ADHD. The adverse events reported with the use of atomoxetine were grouped by systems, according to the changes induced in individuals in accordance with MedDRA® dictionary. For traditional meta-analysis of dichotomous outcomes were calculated effect of measures such as odds ratio (OR) with 95% confidence intervals, using the Mantel-Haenszel statistical method. Continuous outcomes were analyzed using standardized mean difference ± standard deviation, considering the statistical method Mean difference. Regarding the network meta-analysis, we used the Bayesian statistical model, adjusted chain Monte Carlo Markov. We considered effect of measures as OR with 95% credibility intervals and statistically significant p <0.05. Statistical analyzes were conducted with the assistance of Review Manager software, version 5.3 and Addis software, version 1.16.5. Results: In the first chapter, we evaluated safety and tolerability outcomes of treatment of ADHD with atomoxetine compared to placebo, from traditional meta-analysis, and chapter 2 safety outcomes related to five drugs through network meta-analysis. It was identified a total of 7487 articles and, from these, 6 (n = 2481) and 10 (n = 3006) were included for analysis in chapters 1 and 2, respectively. Considering the outcomes of the first chapter, which were grouped by system, most meta-analyzes of adverse events related to the nervous system, psychiatric, gastrointestinal, sexual, metabolic and general, as well as security considering vital signs showed difference statistically significant in favor of placebo. The tolerability outcomes showed that the highest number of abandonment of treatment by adverse events, statistically significant, occurred in the treated group (OR 0.37 [95% CI 0.23, 0.59]) and lack of efficacy in the placebo group (OR 1.86 [95% CI 1.26, 2.75]). Through the network meta-analysis, outcomes analyzed in chapter 2, statistically significant differences were observed in comparisons: Appetite decreased between atomoxetine and placebo (OR 0.15 [95% ICr 0.05; 0.38]) and mixed amphetamine salts extended-release and placebo (OR 0.06 [95% ICr 0.00; 0.51]); insomnia between atomoxetine and placebo (OR 0.48 [95% ICr 0.27; 0.88]) and mixed amphetamine salts extended-release and placebo (OR 0.23 [95% ICr 0.06, 0.76] ); somnolence between atomoxetine and methylphenidate OROS (OR 0.24 [95% ICr 0.06; 0.97]) and libido decreased between atomoxetine and placebo (OR 0.28 [95% ICr 0.08, 0.90]). Conclusions: It was possible to generate evidence on the safety and tolerability profile of drugs for ADHD, pointing out that atomoxetine compared to placebo is more associated with adverse events and therefore higher abandonment of treatment. Another aspect that evaluated the tolerability of these drugs was the abandonment for lack of efficacy, where the placebo group presents this outcome more often statistically confirmed. From meta-analysis network (chapter 2), it became clear that atomoxetine and mixed amphetamines salts extended-release are more involved with adverse events of appetite decreased and insomnia, and atomoxetine with somnolence and libido decreased. There are still some gaps to be filled and further studies involving these drugs and pharmacoeconomic analysis should be conducted to support health decision-making, directing for choosing the best treatment option.
publishDate 2016
dc.date.issued.fl_str_mv 2016-11-25
dc.date.accessioned.fl_str_mv 2017-08-31T13:02:14Z
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dc.identifier.citation.fl_str_mv OLIVEIRA , Danielly Chierrito de. Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise. 2016. 166 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Paraná, Cascavel, 2016.
dc.identifier.uri.fl_str_mv http://tede.unioeste.br/handle/tede/2966
identifier_str_mv OLIVEIRA , Danielly Chierrito de. Segurança e tolerabilidade do tratamento medicamentoso do transtorno de déficit da atenção com hiperatividade em adultos: revisão sistemática e meta-análise. 2016. 166 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Paraná, Cascavel, 2016.
url http://tede.unioeste.br/handle/tede/2966
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dc.publisher.none.fl_str_mv Universidade Estadual do Oeste do Paraná
Cascavel
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Ciências Farmacêuticas
dc.publisher.initials.fl_str_mv UNIOESTE
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Centro de Ciências Médicas e Farmacêuticas
publisher.none.fl_str_mv Universidade Estadual do Oeste do Paraná
Cascavel
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