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Abstract(s)
Introdução: A depressão é uma doença mental comum e debilitante, cuja prevalência tem vindo a aumentar nos últimos anos. Embora não se conheça totalmente a sua fisiopatologia, existem algumas hipóteses que permitem explicar, em parte, como é que esta doença se desenvolve. O tratamento da depressão conta com diversas alternativas, nomeadamente fármacos, os quais atuam de formas distintas, mas que têm como finalidade comum atingir a remissão da doença. A terapêutica farmacológica apresenta, muitas vezes, efeitos adversos ou falta de efetividade, o que pode culminar na não adesão à medicação por parte dos doentes ou até mesmo em toxicidade, antes de atingida a remissão. Assim, torna-se importante garantir a efetividade e a segurança da terapêutica antidepressiva em cada doente, podendo isso ser efetuado a partir da identificação de biomarcadores farmacogenómicos que permitam prever a resposta ao antidepressivo, prevenindo tanto a ocorrência de alguns efeitos adversos, como a toxicidade ou a falta de efetividade. Método: O trabalho desenvolveu-se em duas fases: i) a pesquisa de biomarcadores farmacogenómicos nos resumos das características dos medicamentos (RCM) antidepressivos com autorização de introdução no mercado em Portugal; e ii) a realização de uma revisão sistemática da literatura (RSL) com base nos dados obtidos na primeira fase, cujo o objetivo foi procurar estudos disponíveis na literatura internacional, que descrevessem e caracterizassem, tanto os biomarcadores encontrados nos RCM, como outros potencialmente relevantes. No final, procedeu-se à classificação dos níveis de evidência e dos graus de recomendação para cada estudo identificado. Resultados: Dos 26 fármacos com RCM em Portugal, apenas 16 continham informação farmacogenómica. O biomarcador farmacogenómico mais vezes identificado foi o CYP2D6, seguido do CYP3A4. Estes resultados foram apoiados, em parte, pela RSL, que apresentou um maior número de estudos para o CYP2D6, seguido do CYP2C19. A RSL revelou também a existência outros biomarcadores relevantes, especialmente no caso da fluoxetina e da venlafaxina. Por fim, quanto ao nível de evidência e grau de recomendação, concluiu-se que a maioria dos estudos apresentam um bom nível de evidência, o que assegura a confiabilidade e consequentemente um bom grau de recomendação. Quanto à base de dados, os resultados obtidos foram meramente informativos, não resultando em nenhuma recomendação específica. Conclusão: A maior parte das variantes farmacogenómicas não são estudadas ou reconhecidas pelos testes genéticos e precisam ainda de alguma investigação científica que comprove a sua utilidade. Assim, apenas um pequeno número de variantes é considerado aquando da prescrição de medicamentos antidepressivos. Além disso, a genotipagem do doente não é uma prática clínica comum, sendo por isso necessário um maior investimento na formação dos profissionais de saúde, no que a este assunto diz respeito.
Introduction: Depression is a common and debilitating mental disorder whose prevalence has steadily increased in the past few years. Although its physiopathology is not well known, there are a number of hypotheses that aim to explain, in part, how this mental disorder develops. In the treatment of depression there are several alternatives, namely drugs, which work in different ways, but generally aim to achieve remission. Pharmacological therapy often has side effects or shows a lack of effectiveness, which can lead to non-adherence to the medication by the patients or even in toxicity before the remission is achieved. Therefore, it becomes important to guaranty the effectiveness and safety of the antidepressant therapy. That can be made through the identification of pharmacogenomic biomarkers that can predict the response to the antidepressant, preventing not only the occurrence of some side effects, but also the toxicity or the lack of effectiveness. Method: The work was developed in two phases: i) the search for pharmacogenomic biomarkers in summaries of antidepressant drugs with marketing authorization in Portugal; and ii) the undertaking of a systematic literature review based on the data obtained in the first phase, with the principal objective of finding studies in international literature that could describe and characterize the biomarkers found before and possibly identifying other relevant biomarkers. Finally, the levels of evidence and recommendation grades were classified for every study. Results: Among the 26 drugs with marketing authorization in Portugal, only 16 had pharmacogenomic information. The pharmacogenomic biomarker identified more frequently was CYP2D6, followed by CYP3A4. These results were mostly supported by the systematic review, which showed a greater number of studies for CYP2D6, followed by CYP2C19. The systematic review also revealed the existence of other relevant biomarkers, especially for fluoxetine and venlafaxine. Regarding the levels of evidence and recommendation grades, most of the studies considered show a good level of evidence, which guarantees the reliability and, consequently, a good recommendation grade. As for the database, the results were merely informative, resulting in no specific recommendations. Conclusion: Most pharmacogenomic variants are not studied or acknowledged by the genetic tests and still need more scientific research that confirm their usefulness. Therefore, only a small number of variants is considered when prescribing antidepressant drugs. Besides, genotyping of patients is not common clinical practice, and a bigger investment in the education of health professionals in this area is needed.
Introduction: Depression is a common and debilitating mental disorder whose prevalence has steadily increased in the past few years. Although its physiopathology is not well known, there are a number of hypotheses that aim to explain, in part, how this mental disorder develops. In the treatment of depression there are several alternatives, namely drugs, which work in different ways, but generally aim to achieve remission. Pharmacological therapy often has side effects or shows a lack of effectiveness, which can lead to non-adherence to the medication by the patients or even in toxicity before the remission is achieved. Therefore, it becomes important to guaranty the effectiveness and safety of the antidepressant therapy. That can be made through the identification of pharmacogenomic biomarkers that can predict the response to the antidepressant, preventing not only the occurrence of some side effects, but also the toxicity or the lack of effectiveness. Method: The work was developed in two phases: i) the search for pharmacogenomic biomarkers in summaries of antidepressant drugs with marketing authorization in Portugal; and ii) the undertaking of a systematic literature review based on the data obtained in the first phase, with the principal objective of finding studies in international literature that could describe and characterize the biomarkers found before and possibly identifying other relevant biomarkers. Finally, the levels of evidence and recommendation grades were classified for every study. Results: Among the 26 drugs with marketing authorization in Portugal, only 16 had pharmacogenomic information. The pharmacogenomic biomarker identified more frequently was CYP2D6, followed by CYP3A4. These results were mostly supported by the systematic review, which showed a greater number of studies for CYP2D6, followed by CYP2C19. The systematic review also revealed the existence of other relevant biomarkers, especially for fluoxetine and venlafaxine. Regarding the levels of evidence and recommendation grades, most of the studies considered show a good level of evidence, which guarantees the reliability and, consequently, a good recommendation grade. As for the database, the results were merely informative, resulting in no specific recommendations. Conclusion: Most pharmacogenomic variants are not studied or acknowledged by the genetic tests and still need more scientific research that confirm their usefulness. Therefore, only a small number of variants is considered when prescribing antidepressant drugs. Besides, genotyping of patients is not common clinical practice, and a bigger investment in the education of health professionals in this area is needed.
Description
Keywords
Antidepressivos Biomarcadores Depressão Farmacogenómica Farmacoterapia