Exercise as a complementary treatment of pharmacotherapy in patients with clinical depression
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2017-06-26
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As patologias depressivas representam um peso considerável para a sociedade,
devido ao elevado custo imposto ao sistema de saúde e elevadas perdas de produtividade,
mesmo quando sujeitas ao tratamento com farmacoterapia e intervenções psicológicas.
Tratamentos não farmacológicos para as perturbações depressivas têm sido
explorados e os efeitos antidepressivos e ansiolíticos do exercício têm sido descritos na
literatura. Apesar de existirem evidências que suportam o papel do exercício na redução da
sintomatologia depressiva, continua por clarificar a dose-resposta ótima e quais os
mecanismos subjacentes aos efeitos psicológicos e biológicos do exercício entre indivíduos
com desordens depressivas.
O propósito geral desta investigação consistiu em avaliar o papel do exercício como
terapia complementar da farmacoterapia no tratamento de pacientes que sofrem de
depressão, assim como a sua associação com variáveis psicológicas e biomarcadores
fisiológicos.
Com o intuito de estabelecer recomendações para a prática de exercício no
tratamento da depressão foi realizada uma revisão sistemática no primeiro estudo. Os
programas de exercício dos estudos randomizados que verificaram os efeitos do exercício
na sintomatologia depressiva foram conduzidos entre 2003 e 2016. Análises secundárias
foram exploradas para os dados relacionados com os níveis de aptidão física, capacidade
aeróbia e grupos placebo, com o objetivo de otimizar a prescrição. Treze estudos foram
identificados e os resultados demonstraram que há evidências que o exercício aeróbio,
realizado no mínimo por um período de nove semanas, três vezes por semana, 30-45
minutos/sessão é a dose mínima recomendada para obter uma diminuição da
sintomatologia depressiva. Definir recomendações, especificamente em relação à
intensidade, continua a ser prematuro, dado que há uma descrição inconsistente e deficitária
dos protocolos de exercício. Na verdade, as limitações e a heterogeneidade metodológica
apresentadas nos estudos, inviabilizam conclusões consistentes com o objetivo de definir a
dose-resposta ótima.
Com o objetivo de determinar o impacto do exercício como tratamento complementar
da farmacoterapia, foi conduzido um estudo controlado e randomizado (HAPPY BRAIN) no
segundo estudo. Um total de 26 pacientes foram randomizados para receber medicação
antidepressiva, ou medicação antidepressiva mais exercício. Os valores da depressão no
grupo de exercício reduziram significativamente em comparação com o grupo de controlo.
Além disso, a capacidade física no grupo de intervenção aumentou quando comparada com
o grupo de controlo. Não se verificaram diferenças significativas para as variáveis peso,
índice de massa corporal (IMC), perímetro da cintura e autoestima. A eficácia do exercício
nas desordens depressivas é classicamente atribuída ao seu impacto nos mecanismos
neurobiológicos, incluindo o metabolismo monoaminérgico.
Assim, para clarificar os mecanismos moleculares que podem estar envolvidos nos
efeitos antidepressivos do exercício, foi conduzido o terceiro estudo. A enzima catabólica
catecol-O-metilttransferase (COMT) responsável pela inativação das catecolaminas, e uma
das principais modeladoras dos níveis dopaminérgicos foi analisada antes e após a
intervenção do exercício em catorze pacientes diagnosticados com depressão clínica. Os
resultados demonstraram que no grupo de intervenção (medicação antidepressiva mais
exercício), os níveis periféricos de COMT diminuíram significativamente, comparativamente
ao grupo de controlo (medicação antidepressiva). Assim, este estudo evidencia que o
exercício interfere com os níveis periféricos de COMT. O entendimento deste mecanismo
molecular poderá ser um passo importante para clarificar os mecanismos moleculares
subjacentes à eficácia do exercício nas desordens depressivas. No entanto, estes dados
são os resultados preliminares de uma pequena amostra (n=14 pacientes) e deverão ser
replicados. Há evidência no terceiro estudo, de que o exercício pode atuar para diminuir a
atividade da COMT e levar à disponibilidade de dopamina.
Consequentemente, no quarto estudo, com o intuito de aumentar o entendimento dos
mecanismos biológicos subjacentes aos efeitos do exercício nas desordens depressivas,
foram analisados os níveis de monoaminas (dopamina, noradrenalina, adrenalina,
serotonina) e cortisol. Com este propósito, estas variáveis fisiológicas foram comparadas
entre o grupo de exercício e o grupo de controlo, antes e após o programa de exercício.
Este estudo foi desenvolvido conjuntamente com o estudo HAPPY BRAIN. No entanto, o
seu objetivo pautou-se pela análise dos parâmetros biológicos. Os resultados demonstraram
que o exercício quando combinado com a farmacoterapia não induz alterações nos
biomarcadores analisados, ou seja, nos níveis plasmáticos de monoaminas e de cortisol.
Assim sendo, as conclusões gerais desta investigação demonstraram que o exercício
poderá ser uma terapia adjuvante para pacientes com depressão clínica, que os efeitos
positivos não estão limitados à diminuição dos sintomas depressivos, mas os mecanismos
psicológicos podem mediar essa relação. Existem inúmeros mecanismos biológicos
potenciais que explicam ou estão associados aos efeitos antidepressivos. No entanto, os
resultados deverão ser explorados no futuro, dado serem controversos.
Depressive disorders represent a considerable burden for society due to increased costs imposed on the health care system and higher productivity losses, even when treated with pharmacotherapy and psychological interventions. Non-pharmacological treatments for depressive disorders have been explored and the anti-depressive and anxiolytic effects of exercise have been described in the literature. Although there is evidence supporting the role of exercise in reducing depressive symptoms, not only the optimum dose-response remains uncertain but also the mechanisms underlying the psychological and biological effects of exercise among subjects with depressive disorders. The general purpose of this research was to assess the role of exercise as a complementary therapy of pharmacotherapy on the treatment of patients who suffer from depression, as well its association with psychological variables and physiological biomarkers. In order to establish recommendations for exercise practice in the treatment of depression, a systematic review was conducted in the first study. The exercise programs of randomized controlled trials, which analyzed the effect of exercise on depressive symptoms, were studied between 2003 and 2016. Secondary analyses were explored for data relating to fitness levels, aerobic capacity and placebo groups, aiming to optimize the prescription. Thirteen trials were identified and the results have demonstrated that there is evidence that aerobic exercise performed for at least a nine-week period, of three times weekly, 30-45 minutes/session is the minimal dose required to achieve the decrease in depressive symptoms. Defining guidelines, specifically in relation to intensity, still remains to be early to establish due to inconsistent and poor description of exercise protocols. Indeed, the methodological limitations and the heterogeneity presented within trials make it unfeasible to achieve consistent conclusions with the aim to define the optimum dose-response. To address the aim of determining the impact of exercise as a complementary treatment of pharmacotherapy, a randomized controlled trial (HAPPY BRAIN) was conducted in the second study. A total of 26 patients were randomized to receive antidepressant medication, or antidepressant medication plus exercise. Depressive scores in the exercise group significantly reduced in comparison to the control group. In addition, physical capacity in the intervention group increased when compared to the control group. There were no significant differences on the variables of weight, body mass index (BMI), waist circumference and self-esteem. The efficacy of exercise in depressive disorders is classically attributed to its impact on changing neurobiological mechanisms including the monoaminergic metabolism. Thus, to clarify the molecular mechanisms, which can be involved in the antidepressant effects of exercise, a third study was carried out. The catabolic enzyme catechol-Omethyltransferase (COMT) responsible for the inactivation of catecholamines and one of the main modulators of the dopaminergic levels, was analyzed pre-post exercise intervention in fourteen patients diagnosed with clinical depression. Results demonstrated that in the intervention group (antidepressant medication plus exercise) the peripheral levels of COMT had decreased significantly comparatively to the control group (antidepressant medication). Hence, this study offers evidence that exercise interferes with peripheral levels of COMT. The understanding of this molecular mechanism could be an important step to clarify the molecular mechanisms underpinning the efficacy of exercise in depressive disorders. However, these data are preliminary results from a small sample (n=14 patients) and should be replicated. There is evidence in the third study that exercise may act to decrease COMT activity, and in turn lead to dopamine availability. Therefore, in the fourth study, in order to increase our understanding of biological mechanisms underpinning the effects of exercise on depressive disorder, levels of monoamines (dopamine, noradrenaline, adrenaline, serotonin) and cortisol were analyzed. For this purpose, these physiological variables were compared between exercise and control groups, pre and post exercise intervention. This study was developed in conjunction with the HAPPY BRAIN study. However, its goal was to assess biological parameters. Results have shown that exercise when combined with pharmacotherapy has not led to changes in the analyzed biomarkers, that is, in monoamines and cortisol plasma levels. Thus, the overall findings of this investigation demonstrated that exercise could be an adjuvant therapy for patients with clinical depression and the positive effects are not limited to the decrease of depressive symptoms, but psychological mechanisms could mediate this relationship. There are several potential biological mechanisms that explain or are linked with the antidepressant effects. Nevertheless, findings should be further explored, as they are controversial.
Depressive disorders represent a considerable burden for society due to increased costs imposed on the health care system and higher productivity losses, even when treated with pharmacotherapy and psychological interventions. Non-pharmacological treatments for depressive disorders have been explored and the anti-depressive and anxiolytic effects of exercise have been described in the literature. Although there is evidence supporting the role of exercise in reducing depressive symptoms, not only the optimum dose-response remains uncertain but also the mechanisms underlying the psychological and biological effects of exercise among subjects with depressive disorders. The general purpose of this research was to assess the role of exercise as a complementary therapy of pharmacotherapy on the treatment of patients who suffer from depression, as well its association with psychological variables and physiological biomarkers. In order to establish recommendations for exercise practice in the treatment of depression, a systematic review was conducted in the first study. The exercise programs of randomized controlled trials, which analyzed the effect of exercise on depressive symptoms, were studied between 2003 and 2016. Secondary analyses were explored for data relating to fitness levels, aerobic capacity and placebo groups, aiming to optimize the prescription. Thirteen trials were identified and the results have demonstrated that there is evidence that aerobic exercise performed for at least a nine-week period, of three times weekly, 30-45 minutes/session is the minimal dose required to achieve the decrease in depressive symptoms. Defining guidelines, specifically in relation to intensity, still remains to be early to establish due to inconsistent and poor description of exercise protocols. Indeed, the methodological limitations and the heterogeneity presented within trials make it unfeasible to achieve consistent conclusions with the aim to define the optimum dose-response. To address the aim of determining the impact of exercise as a complementary treatment of pharmacotherapy, a randomized controlled trial (HAPPY BRAIN) was conducted in the second study. A total of 26 patients were randomized to receive antidepressant medication, or antidepressant medication plus exercise. Depressive scores in the exercise group significantly reduced in comparison to the control group. In addition, physical capacity in the intervention group increased when compared to the control group. There were no significant differences on the variables of weight, body mass index (BMI), waist circumference and self-esteem. The efficacy of exercise in depressive disorders is classically attributed to its impact on changing neurobiological mechanisms including the monoaminergic metabolism. Thus, to clarify the molecular mechanisms, which can be involved in the antidepressant effects of exercise, a third study was carried out. The catabolic enzyme catechol-Omethyltransferase (COMT) responsible for the inactivation of catecholamines and one of the main modulators of the dopaminergic levels, was analyzed pre-post exercise intervention in fourteen patients diagnosed with clinical depression. Results demonstrated that in the intervention group (antidepressant medication plus exercise) the peripheral levels of COMT had decreased significantly comparatively to the control group (antidepressant medication). Hence, this study offers evidence that exercise interferes with peripheral levels of COMT. The understanding of this molecular mechanism could be an important step to clarify the molecular mechanisms underpinning the efficacy of exercise in depressive disorders. However, these data are preliminary results from a small sample (n=14 patients) and should be replicated. There is evidence in the third study that exercise may act to decrease COMT activity, and in turn lead to dopamine availability. Therefore, in the fourth study, in order to increase our understanding of biological mechanisms underpinning the effects of exercise on depressive disorder, levels of monoamines (dopamine, noradrenaline, adrenaline, serotonin) and cortisol were analyzed. For this purpose, these physiological variables were compared between exercise and control groups, pre and post exercise intervention. This study was developed in conjunction with the HAPPY BRAIN study. However, its goal was to assess biological parameters. Results have shown that exercise when combined with pharmacotherapy has not led to changes in the analyzed biomarkers, that is, in monoamines and cortisol plasma levels. Thus, the overall findings of this investigation demonstrated that exercise could be an adjuvant therapy for patients with clinical depression and the positive effects are not limited to the decrease of depressive symptoms, but psychological mechanisms could mediate this relationship. There are several potential biological mechanisms that explain or are linked with the antidepressant effects. Nevertheless, findings should be further explored, as they are controversial.
Descrição
Tese de Doutoramento em Ciências do Desporto
Palavras-chave
Exercícios físicos , Depressão , Mecanismos , Psicológico , Biológico