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Epidemiologia, etiopatogenia, diagnóstico e tratamento farmacológico da depressão em Portugal
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Abstract(s)
Portugal apresenta uma prevalência elevada de perturbações depressivas, em que cerca de um quinto dos portugueses apresenta ou já apresentou algum episódio depressivo ao longo da vida. Estas perturbações, ao se associarem a elevados e prolongados gastos com medicamentos, procura dos serviços de saúde e queda de produtividade representam um elevado custo humano e financeiro para o país.
Devido à elevada relevância que esta patologia tem no país e, consequentemente, na prática da profissão farmacêutica, este trabalho tem como objectivo explorar a sua prevalência atual, etiopatogenia, classificação, diagnóstico e fármacos mais relevantes utilizados no seu tratamento.
As perturbações depressivas fazem parte das perturbações do humor e incluem as perturbações depressivas (e.g. depressão major e distimia) e perturbações bipolares (e.g. perturbação bipolar tipo I e tipo II, ciclotímia). A diferença entre ambas está na unidirecionalidade das perturbações depressivas e a alternância de estados de humor característica das perturbações bipolares. É mais correto falarmos em síndromes depressivas do que em depressão, o que salienta a diversidade de apresentações possíveis, variando quanto à sua génese, gravidade, duração, resposta aos tratamentos e prognóstico. O que une todas as variantes é o sintoma de humor deprimido, vazio ou irritável, acompanhado por alterações cognitivas e somáticas que afetam significativamente a capacidade de funcionamento do indivíduo.
A depressão é uma doença multifactorial com condicionantes biológicas (e.g. genéticas, epigenéticas, nutricionais) e sociais que produzem alterações neuroquímicas e estruturais do sistema nervoso central, mais ou menos estáveis, que condicionam as repostas ao meio e se caracterizam por comportamentos específicos.
O tratamento de perturbações depressivas envolve abordagens farmacológicas e psicoterapêuticas, tendo ambas efeitos cumulativos. Em depressões menos graves pode ser suficiente o tratamento psicoterapêutico. Porém, em casos moderados a graves a utilização de fármacos é fundamental, quer como agente terapêutico em si, quer por estabilizar psicologicamente o doente e permitir uma melhor intervenção psicológica.
Os fármacos utilizados no tratamento da depressão são os chamados antidepressivos. A farmacodinâmica destes medicamentos baseia-se no aumento da disponibilidade de alguns neurotransmissores específicos a nível cerebral. As diversas classes de antidepressivos assentam nas diferentes estratégias utilizadas para modular a concentração daqueles neurotransmissores e incluem: a inibição da recaptação dos neurotransmissores da fenda sináptica (e.g. antidepressivos tricíclicos (ADT), inibidores seletivos da recaptação da serotonina (ISRS), inibidores da recaptação da noradrenalina (IRN), inibidores da recaptação da serotonina e da noradrenalina (IRSN), inibidores da recaptação da noradrenalina e da dopamina); a ativação direta de receptores (agonistas dos recetores da serotonina, agonista dos receptores da melatonina); o bloqueio de receptores pré-sinápticos ou pós-sinápticos (efeito partilhado pelas classes anteriores) e a inibição das enzimas metabolizadoras dos neurotransmissores (inibidores da monoamina oxidase (IMAO)).
Os diversos antidepressivos podem ser classificados em de 1ª geração (IMAO e ADT) e 2ª geração. Os de 1ª geração são antidepressivos eficazes mas bastante inespecíficos, estando associados a efeitos secundários mais frequentes e graves e, por isso, reservados a casos mais graves ou resistentes à terapêutica. Contudo, o seu baixo preço faz com que ainda gozem de alguma penetração no mercado português. Por outro lado, os fármacos de 2ª geração estão associados a uma menor incidência de efeitos adversos e são, actualmente, os mais utilizados em Portugal. De fato, tem sido notório um aumento consistente de toda este grupo com particular destaque para os ISRS (e.g. fluoxetina, fluvoxamina, paroxetina e sertralina) e para os IRSN (e.g. duloxetina e velafaxina). Este aumento terá sido impulsionado pela diminuição dos custos associado a entrada no mercado dos medicamentos genéricos e faz de Portugal um dos países com a maior taxa de utilização de antidepressivos.
Em conclusão, as perturbações depressivas, pela sua incidência e prevalência, têm uma marcada relevância em Portugal e representam elevados custos, sendo responsáveis por uma fatia considerável dos gastos com saúde. Um conhecimento abrangente desta patologia, das suas manifestações e dos tratamentos são uma mais-valia para qualquer profissional de saúde, em especial para farmacêuticos, devido à proximidade que têm com os doentes e o papel ativo que exercem no tratamento e acompanhamento destes. Um farmacêutico bem informado é uma peça-chave para o sucesso terapêutico.
Portugal has a high prevalence of depressive disorders; in fact about one-fifth of the Portuguese has or has had some depressive episode throughout life. These disorders associate with high and prolonged medical treatment, increased use of health services and reduction of productivity leading to a high human and financial cost to the country. Due to the high relevance of this disease in Portugal, and consequently in the practice of the pharmaceutical profession, this paper aims to explore the depressive syndromes current prevalence, pathogenesis, classification, diagnosis, and the most relevant drug options for treating them. Depressive disorders are part of the mood disorders and include depressive disorders (e.g. major depressive disorder and dysthymia) and bipolar disorders (e.g. bipolar disorder type I and type II and cyclothymia). The difference between them lies in the unidirectional nature of depressive disorders and the alternation of humor that is characteristic of bipolar disorders. Actually, it is more correct to talk about depressive syndromes than about depression, highlighting the different presentations and the diversity of possible causes, severity, duration, response to treatment and prognosis. What unites all the possible variants of depression is the characteristic depressed, empty or irritable mood, accompanied by cognitive and somatic changes, which significantly affect the individual functional capacity. Depression is a multifactorial disease linked to biological (e.g. genetic, epigenetic, and nutritional) and social factors that produce more or less stable neurochemical and structural changes in the central nervous system which determine specific behaviors and ways of interacting with the environment. The treatment of depressive disorders involves pharmacological and psychotherapeutic approaches, presenting both cumulative effects. In mild depressions psychotherapeutic treatment may be sufficient. However, in moderate to severe cases the use of drugs is critical, either as a therapeutic agent itself, or for psychologically stabilizing the patient, allowing a more effective psychological intervention. Drugs used to treat depression are called antidepressants. The pharmacodynamics of these drugs is based on increasing the availability of certain neurotransmitters in the brain. The various strategies used to modulate the concentrations of the neurotransmitters define the different classes of antidepressants and include: inhibiting the reuptake of synaptic cleft neurotransmitters (e.g. tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI)); direct activation of receptors (e.g. agonists of serotonin receptors); blocking presynaptic or postsynaptic receptors (effect shared by the already referred classes) and inhibition of enzymes that metabolizes the neurotransmitters (monoamine oxidase inhibitors (MAOI)). The various antidepressants can be classified into 1st generation (MAOI and TCA) and 2nd generation. The 1st generation drugs are effective antidepressants but rather unspecific, being associated with more frequent and severe side effects. Therefore they are used in more severe forms or when is present a resistance to the therapy. However, theirs low prices still allows them to keep some part of the Portuguese market. On the other hand, 2nd generation drugs present a lower incidence of adverse effects, being the most widely used in Portugal. In fact, it has been notorious a consistent increase in the consumption of this class, with particular emphasis on SSRI (e.g. fluoxetine, fluvoxamine, paroxetine and sertraline) and the SNRI (e.g. duloxetine and venlafaxine). This increase might be driven by the lower costs associated with generic drugs and makes Portugal one of the countries with the highest rate of antidepressants use. In conclusion, the incidence and prevalence of depressive disorders are high in Portugal, accounting for a considerable share of the money spent in health. A comprehensive knowledge of this disease, its manifestations and treatments, are important to any health professional, especially for pharmacists, due to the proximity they share with patients and the active role they play in patient treatment and monitoring. A well informed pharmacist is a key player for therapeutic success.
Portugal has a high prevalence of depressive disorders; in fact about one-fifth of the Portuguese has or has had some depressive episode throughout life. These disorders associate with high and prolonged medical treatment, increased use of health services and reduction of productivity leading to a high human and financial cost to the country. Due to the high relevance of this disease in Portugal, and consequently in the practice of the pharmaceutical profession, this paper aims to explore the depressive syndromes current prevalence, pathogenesis, classification, diagnosis, and the most relevant drug options for treating them. Depressive disorders are part of the mood disorders and include depressive disorders (e.g. major depressive disorder and dysthymia) and bipolar disorders (e.g. bipolar disorder type I and type II and cyclothymia). The difference between them lies in the unidirectional nature of depressive disorders and the alternation of humor that is characteristic of bipolar disorders. Actually, it is more correct to talk about depressive syndromes than about depression, highlighting the different presentations and the diversity of possible causes, severity, duration, response to treatment and prognosis. What unites all the possible variants of depression is the characteristic depressed, empty or irritable mood, accompanied by cognitive and somatic changes, which significantly affect the individual functional capacity. Depression is a multifactorial disease linked to biological (e.g. genetic, epigenetic, and nutritional) and social factors that produce more or less stable neurochemical and structural changes in the central nervous system which determine specific behaviors and ways of interacting with the environment. The treatment of depressive disorders involves pharmacological and psychotherapeutic approaches, presenting both cumulative effects. In mild depressions psychotherapeutic treatment may be sufficient. However, in moderate to severe cases the use of drugs is critical, either as a therapeutic agent itself, or for psychologically stabilizing the patient, allowing a more effective psychological intervention. Drugs used to treat depression are called antidepressants. The pharmacodynamics of these drugs is based on increasing the availability of certain neurotransmitters in the brain. The various strategies used to modulate the concentrations of the neurotransmitters define the different classes of antidepressants and include: inhibiting the reuptake of synaptic cleft neurotransmitters (e.g. tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI)); direct activation of receptors (e.g. agonists of serotonin receptors); blocking presynaptic or postsynaptic receptors (effect shared by the already referred classes) and inhibition of enzymes that metabolizes the neurotransmitters (monoamine oxidase inhibitors (MAOI)). The various antidepressants can be classified into 1st generation (MAOI and TCA) and 2nd generation. The 1st generation drugs are effective antidepressants but rather unspecific, being associated with more frequent and severe side effects. Therefore they are used in more severe forms or when is present a resistance to the therapy. However, theirs low prices still allows them to keep some part of the Portuguese market. On the other hand, 2nd generation drugs present a lower incidence of adverse effects, being the most widely used in Portugal. In fact, it has been notorious a consistent increase in the consumption of this class, with particular emphasis on SSRI (e.g. fluoxetine, fluvoxamine, paroxetine and sertraline) and the SNRI (e.g. duloxetine and venlafaxine). This increase might be driven by the lower costs associated with generic drugs and makes Portugal one of the countries with the highest rate of antidepressants use. In conclusion, the incidence and prevalence of depressive disorders are high in Portugal, accounting for a considerable share of the money spent in health. A comprehensive knowledge of this disease, its manifestations and treatments, are important to any health professional, especially for pharmacists, due to the proximity they share with patients and the active role they play in patient treatment and monitoring. A well informed pharmacist is a key player for therapeutic success.
Description
Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas