RESUMO
ABSTRACT: Burgeoning body of evidence from neuroscience is pouring in highlighting a potential association between gut microbiota with the pathophysiology of depression and anxiety. Manipulation of gut microbiota may be then useful to decode this role and to provide novel therapeutics for major depressive disorder (MDD), developing microbiota-related biomarkers to stratify patients at risk and to delineate more homogeneous biotypes of MDD.
Assuntos
Transtorno Depressivo Maior/microbiologia , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Animais , Ansiedade/microbiologia , Biomarcadores , Depressão/microbiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/dietoterapia , Humanos , Camundongos , Prebióticos , Probióticos/uso terapêutico , RatosRESUMO
BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder, closely associated with obesity. This study aimed to assess the effects of prebiotics combined with calorie restriction on clinical and metabolic response in obese women with MDD. METHODS: In an 8-week double-blind placebo-controlled randomized clinical trial, 62 obese women with MDD were equally allocated into either prebiotic (10â g/day Inulin) or placebo (10â g/day Maltodextrin) group. In addition, all the participants were also prescribed a 25% calorie-restricted diet (registration ID: IRCT20100209003320N15). Depression was assessed by Hamilton depression rating scale (HDRS) and Beck depression inventory (BDI-II) pre- and post-intervention. Anthropometric measures, fasting serum levels of glucose, insulin and lipid profile were assessed, and dietary assessments were performed pre- and post-intervention. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: 45 patients completed the trial. There were no significant between-group differences for MDD symptoms and other study outcomes, post-intervention. Weight, waist and hip circumferences, systolic blood pressure, and HDRS score significantly decreased in both groups, while fat mass and total cholesterol (TC) declined only in the prebiotic arm. Those who had ≥1.9â kg weight loss showed significantly improved HDRS score, compared to women with <1.9â kg weight reduction, irrespective of the supplement they took. CONCLUSION: Although prebiotic supplementation had some beneficial metabolic effects, calorie restriction and weight loss seem to play a more important role in improving depressive symptoms among obese women with MDD.
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Restrição Calórica , Transtorno Depressivo Maior/dietoterapia , Obesidade/dietoterapia , Prebióticos/administração & dosagem , Adulto , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/metabolismo , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Resultado do TratamentoRESUMO
CONTEXT: Zinc is an essential trace mineral required for the function of brain and neural structures. The role of zinc supplementation in the prevention and treatment of depression has been suggested in clinical studies that reported a reduction in depressive symptoms. OBJECTIVE: The aim of this review was to determine whether zinc supplementation vs placebo can prevent or improve depressive symptoms in children, adolescents, or adults. DATA SOURCES: Five electronic databases were searched, and studies published until September 2019 were included without language restriction. STUDY SELECTION: Randomized, controlled, crossover trials that evaluated the effect of zinc supplementation vs a comparator for prevention or improvement of depressive symptoms in children, adolescents, or adults were eligible for inclusion. DATA EXTRACTION: Two authors independently performed data extraction and risk-of-bias assessment. RESULTS: The initial search identified 12â 322 studies, 5 of which were eligible for meta-analysis. The standardized mean difference (SMD) showed an average reduction of 0.36 point (95%CI, -0.67 to -0.04) in the intervention group compared with the placebo group. Forstudies in which the mean age of participants was ≥â 40 years, the SMD was reduced by 0.61 point (95%CI, -1.12 to -0.09) in the intervention group vs the placebo group. The meta-analysis by sample size (<â 60 individuals and ≥ 60 individuals) did not show an effect of zinc supplementation in reducing depressive symptoms (SMD -0.28; 95%CI, -0.67 to -0.10; and SMD -0.52; 95%CI, -1.10 to 0.06). CONCLUSION: Zinc supplementation may reduce depressive symptoms in individuals treated with antidepressant drugs for clinical depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42018081691.
Assuntos
Antidepressivos/uso terapêutico , Depressão/dietoterapia , Depressão/tratamento farmacológico , Suplementos Nutricionais , Zinco/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Transtorno Depressivo Maior/dietoterapia , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Oligoelementos , Adulto JovemRESUMO
One very promising hypothesis of Major Depressive Disorder (MDD) pathogenesis is the gut-brain axis (GBA) dysfunction, which can lead to subclinical inflammation, hypothalamic-pituitary (HPA) axis dysregulation, and altered neural, metabolic and endocrine pathways. One of the most important parts of GBA is gut microbiota, which was shown to regulate different functions in the central nervous system (CNS). The purpose of this scoping review was to present the current state of research on the relationship between MDD and gut microbiota and extract causal relationships. Further, we presented the relationship between the use of probiotics and antidepressants, and the microbiota changes. We evaluated the data from 27 studies aimed to investigate microbial fingerprints associated with depression phenotype. We abstracted data from 16 and 11 observational and clinical studies, respectively; the latter was divided into trials evaluating the effects of psychiatric treatment (nâ¯=â¯3) and probiotic intervention (nâ¯=â¯9) on the microbiome composition and function. In total, the data of 1187 individuals from observational studies were assessed. In clinical studies, there were 490 individuals analysed. In probiotic studies, 220 and 218 patients with MDD received the intervention and non-active study comparator, respectively. It was concluded that in MDD, the microbiota is altered. Although the mechanism of this relationship is unknown, we hypothesise that the taxonomic changes observed in patients with MDD are associated with bacterial proinflammatory activity, reduced Schort Chain Fatty Acids (SCFAs) production, impaired intestinal barrier integrity and neurotransmitter production, impaired carbohydrates, tryptophane and glutamate metabolic pathways. However, only in few publications this effect was confirmed by metagenomic, metabolomic analysis, or by assessment of immunological parameters or intestinal permeability markers. Future research requires standardisation process starting from patient selection, material collection, DNA sequencing, and bioinformatic analysis. We did not observe whether antidepressive medications influence on gut microbiota, but the use of psychobiotics in patients with MDD has great prospects; however, this procedure requires also standardisation and thorough mechanistic research. The microbiota should be treated as an environmental element, which considers the aetiopathogenesis of the disease and provides new possibilities for monitoring and treating patients with MDD.
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Antidepressivos/uso terapêutico , Eixo Encéfalo-Intestino/fisiologia , Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Microbioma Gastrointestinal/fisiologia , Animais , Antidepressivos/efeitos adversos , Encéfalo/efeitos dos fármacos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Transtorno Depressivo Maior/dietoterapia , Transtorno Depressivo Maior/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Estudos Observacionais como Assunto/métodos , Probióticos/administração & dosagemRESUMO
The endocannabinoid system is a metabolic pathway involved in the communication between the gut microbiota and the host. In the gut, the endocannabinoid system regulates the integrity of the intestinal barrier. A compromised integrity of the intestinal barrier is associated with several disorders such as inflammatory bowel disorder, obesity and major depressive disorder. Decreasing the integrity of the intestinal barrier results in an increased translocation of bacterial metabolites, including lipopolysaccharides, across the epithelial layer of the gut, causing the subsequent inflammation. Targeting the endocannabinoid system in the gut can improve the integrity of the intestinal barrier. Currently, microbial interventions in the form of probiotics are under investigation for the treatment of diseases related to a compromised integrity of the intestinal barrier. However, the role of the endocannabinoid system in the gut is ambiguous since activity of the endocannabinoid system is increased in obesity and decreased in inflammatory bowel disease, emphasizing the need for development of personalized microbial interventions. This review discusses the role of the endocannabinoid system in regulating the gut barrier integrity and highlights current efforts to develop new endocannabinoid-targeted microbial interventions.
Assuntos
Eixo Encéfalo-Intestino/fisiologia , Transtorno Depressivo Maior/metabolismo , Endocanabinoides/metabolismo , Microbioma Gastrointestinal/fisiologia , Probióticos/administração & dosagem , Animais , Eixo Encéfalo-Intestino/efeitos dos fármacos , Transtorno Depressivo Maior/dietoterapia , Transtorno Depressivo Maior/psicologia , Endocanabinoides/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , HumanosRESUMO
The gut microbiota are being called the human "second brain," as they play a key role in the regulation of the central nervous system (CNS). Recent findings provide strong evidence for the presence of bidirectional communication networks between the gut microbiota and the CNS, and such crosstalk has been correlated with alterations in major depressive disorder (MDD) and other psychiatric disorders. Further, germ-free animal models have been used to investigate the effect of the microbiota on MDD and other psychiatric disorders, which have greatly expanded our knowledge of the role of the microbiota in the etiology of MDD and promoted causality studies of this psychiatric disorder and others as well. In this review, we first introduce the methodological approaches used for microbiota research and then provide an overview of current research progress on the modulatory function and composition of the gut microbiota in MDD and the therapeutic effect of probiotics that has been gained using data from human studies as well as animal experiments. Future research should focus on identification and characterization of specific bacterial strains involved in MDD with the hope of applying these findings in the prevention and treatment of MDD.
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Depressão/microbiologia , Transtorno Depressivo Maior/microbiologia , Microbioma Gastrointestinal , Animais , Depressão/dietoterapia , Transtorno Depressivo Maior/dietoterapia , Vida Livre de Germes , Humanos , Probióticos/uso terapêuticoRESUMO
Microorganisms can be found in virtually any environment. In humans, the largest collection of microorganisms is found in the gut ecosystem. The adult gut microbiome consists of more genes than its human host and typically spans more than 60 genera from across the taxonomic tree. In addition, the gut contains the largest number of neurons in the body, after the brain. In recent years, it has become clear that the gut microbiome is in communication with the brain, through the gut-brain axis. A growing body of literature shows that the gut microbiome plays a shaping role in a variety of psychiatric disorders, including major depressive disorder (MDD). In this review, the interplay between the microbiome and MDD is discussed in three facets. First, we discuss factors that affect the onset/development of MDD that also greatly impinge on the composition of the gut microbiota-especially diet and stressful life events. We then examine the interplay between the microbiota and MDD. We examine evidence suggesting that the microbiota is altered in MDD, and we discuss why the microbiota should be considered during MDD treatment. Finally, we look toward the future and examine how the microbiota might become a therapeutic target for MDD. This review is intended to introduce those familiar with the neurological and psychiatric aspects of MDD to the microbiome and its potential role in the disorder. Although research is in its very early days, with much yet to be the understood, the microbiome is offering new avenues for developing potentially novel strategies for managing MDD.
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Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/microbiologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Animais , Encéfalo/metabolismo , Encéfalo/microbiologia , Transtorno Depressivo Maior/dietoterapia , Trato Gastrointestinal/fisiologia , Humanos , Probióticos/uso terapêuticoRESUMO
BACKGROUND: A growing body of evidence has linked mental health outcomes to the gut microbiome. This has led to the investigation of the GI tract as a target for novel treatments and interventions for depression, including probiotic supplementation. Our recent pilot study provided the first evidence of probiotics improving symptoms of depression in treatment-naive depressed patients. To further support and expand upon this evidence, data from the pilot study were used to plan a 16-week, double-blind, randomized, placebo-controlled trial to assess the effects of probiotics on depression. Here, we report the protocol for this trial. METHODS: Participants diagnosed with depression will orally consume a probiotic supplement containing Lactobacillus helveticus and Bifidobacterium longum or placebo once daily. Participants will undergo assessments measuring clinical outcomes using a battery of validated clinical scales and questionnaires. Sleep architecture and quality will be measured using polysomnography. Neuroimaging data will be collected using magnetic resonance imaging to examine functional and structural neurophysiological changes. Molecular data will be collected from blood, stool, and urine samples to examine cytokine levels and explore potential genes and proteins that may predict outcomes in depression. RESULTS: We expect results to replicate and expand on our pilot data demonstrating that probiotics may be effective in alleviating symptoms of depression, and to find biomarkers that will predict these outcomes. CONCLUSIONS: The findings from this study will add to the growing body of research in this emerging field, which eventually may provide evidence for probiotics having a role in alleviating symptoms of depression.
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Transtorno Depressivo Maior/dietoterapia , Probióticos/farmacologia , Adolescente , Adulto , Idoso , Biomarcadores , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/administração & dosagem , Projetos de Pesquisa , Adulto JovemRESUMO
PURPOSE: Depression clinical trials are increasingly studying biomarkers to predict and monitor response to treatment. Assessment of biomarkers may reveal subsets of patients who are responsive to nutraceutical treatment, which may facilitate a personalized approach to treating depression. METHODS: This is a post hoc analysis of an 8-week, double-blind, randomized, controlled trial (n = 158) investigating a combination nutraceutical comprising Omega-3 (EPA 1 g/DHA 656 mg), SAMe, zinc, 5-HTP, folinic acid, and co-factors versus placebo for the treatment of Major Depressive Disorder. The study explored levels of polyunsaturated fatty acids, folate, vitamin B12, zinc, homocysteine, and BDNF as possible predictors and correlates of response to nutraceutical supplementation. RESULTS: Concentrations of EPA and DHA in red cell membranes increased in response to treatment and were significantly correlated with a decrease in depressive symptoms during active treatment (p = 0.003 and p = 0.029; respectively). Higher baseline levels of omega-6 fatty acid also correlated with depression reduction in the active treatment group ( p = 0.011). No other biomarkers were associated with a lessening of depressive symptoms. CONCLUSION: Changes in fatty acid levels resulting from a nutraceutical combination containing EPA and DHA provide a response biomarker in treating depression.
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Transtorno Depressivo Maior/dietoterapia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análise , Adulto , Biomarcadores/análise , Método Duplo-Cego , Membrana Eritrocítica/química , Feminino , Humanos , MasculinoRESUMO
Background/objectives: Major depression has a negative impact on quality of life, increasing the risk of premature death. It imposes social and economic costs on individuals, families and society. Mental illness is now the leading cause globally of disability/lost quality life and premature mortality. Finding cost-effective treatments for depression is a public health priority. We report an economic evaluation of a dietary intervention for treating major depression. Methods: This economic evaluation drew on the HELFIMED RCT, a 3-month group-based Mediterranean-style diet (MedDiet) intervention (including cooking workshops), against a social group-program for people with major depression. We conducted (i) a cost-utility analysis, utility scores measured at baseline, 3-months and 6-months using the AQoL8D, modelled to 2 years (base case); (ii) a cost-effectiveness analysis, differential cost/case of depression resolved (to normal/mild) measured by the DASS. Differential program costs were calculated from resources use costed in AUD2017. QALYs were discounted at 3.5%pa. Results: Best estimate differential cost/QALY gain per person, MedDiet relative to social group was AUD2775. Probabilistic sensitivity analysis, varying costs, utility gain, model period found 95% likelihood cost/QALY less than AUD20,000. Estimated cost per additional case of depression resolved, MedDiet group relative to social group was AUD2,225. Conclusions: A MedDiet group-program for treating major depression was highly cost-effective relative to a social group-program, measured in terms of cost/QALY gain and cost per case of major depression resolved. Supporting access by persons with major depression to group-based dietary programs should be a policy priority. A change to funding will be needed to realise the potential benefits.
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Transtorno Depressivo Maior/dietoterapia , Transtorno Depressivo Maior/economia , Dietoterapia/economia , Análise Custo-Benefício , Dieta Mediterrânea/economia , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
Curcumin is the principal curcuminoid found in turmeric (Curcuma longa), a spice frequently used in Asian countries. Given its anti-inflammatory and antioxidant properties, it has been hypothesized that curcumin might be effective in treating symptoms of a variety of neuropsychiatric disorders, such as depression. We conducted a systematic review following the PRISMA guidelines. In August 2019, we screened 930 articles, of which 9 were eligible for the meta-analysis. In 7 articles, participants were affected by major depressive disorder (MDD), while in other two they suffered from depression secondary to a medical condition. We found an overall significant effect of curcumin on depressive (10 studies, 531 participants, Hedge's g = -0.75, 95% CI -1.11 to -0.39, p < 0.001) and anxiety symptoms (5 studies, 284 participants, Hedge's g = -2.62, 95% CI -4.06 to -1.17, p < 0.001), with large effect size. Curcumin was generally well-tolerated by patients. Our findings suggest that curcumin, if added to standard care, might improve depressive and anxiety symptoms in people with depression. However, given the small sample size, our results should be cautiously interpreted. Further trials should be implemented, particularly in Western countries, where curcumin does not represent a usual component of dietary regimens.
Assuntos
Curcumina/uso terapêutico , Depressão/dietoterapia , Transtorno Depressivo Maior/dietoterapia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Curcuma/química , Depressão/complicações , HumanosRESUMO
INTRODUCTION: Major depressive disorder (MDD) is a common chronic mental health condition and not all patients respond to pharmacotherapy. Increasing evidence suggests that dietary choices play a role in the pathogenesis of mental illness and serve as modifiable factors with utility in the treatment of these disorders. Although many mechanisms are being explored, one area of study is the role of food hypersensitivity reactions in mental health conditions. CASE PRESENTATION: This article reports on a 34-year-old female patient with MDD whose symptoms improved in response to a dietary intervention involving the elimination of common food allergens. Reintroduction of the foods on several occasions was associated with a worsening of mood symptoms. Serum IgG testing reported results consistent with the reintroduction challenge. DISCUSSION AND CONCLUSIONS: Hypothesized mechanisms underlying the potential relationship between food hypersensitivity and MDD are presented. Further research in this area is warranted.
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Transtorno Depressivo Maior/dietoterapia , Hipersensibilidade Alimentar/dietoterapia , Adulto , Transtorno Depressivo Maior/etiologia , Feminino , Hipersensibilidade Alimentar/complicações , Humanos , Resultado do TratamentoRESUMO
A growing body of data has accumulated in the past decades about the possible role of nutritional factors in influencing the initiation and course of mental disorders as well as in the treatment of these disorders. As a result of the aggregation of this data a new field emerged - "nutritional psychiatry". In our current review paper we discuss some of those natural agents that supposedly have antidepressive properties and, accordingly, may play a role in the stand-alone and/or adjuvant treatment of major depressive disorder.
Assuntos
Transtorno Depressivo Maior/dietoterapia , Estado Nutricional , Psiquiatria/métodos , Psiquiatria/tendências , HumanosAssuntos
Transtorno Depressivo Maior/terapia , Dieta Mediterrânea , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Terapia por Exercício , Ketamina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo , Transtorno Depressivo Maior/dietoterapia , Transtorno Depressivo Maior/tratamento farmacológico , HumanosRESUMO
BACKGROUND: Interactions between the digestive system and the brain functions have become in recent years an important field of psychiatric research. These multidirectional interactions take place in the so called microbiota-gut-brain axis and emerging scientific data indicate to the significant role of microbiota in the modulation of the central nervous system (CNS) including affective and cognitive functions. OBJECTIVE: An assessment of psychobiotic and immunomodulatory effects of probiotic bacteria Lactobacillus Plantarum 299v (LP299v) by measuring affective, cognitive functions and biochemical parameters in patients with MDD undergoing treatment with selective serotonin reuptake inhibitors (SSRI). DESIGN: Seventy nine patients with MDD were randomized and allocated to a double-blind, placebo-controlled trial. Participants received either a SSRI with the probiotic LP299v (n = 40) for a period of 8 weeks or a SSRI with the placebo of the probiotic (n = 39) for the same period. The severity of psychiatric symptoms was assessed using Hamilton Depression Rating Scale (HAM-D 17), Symptom Checklist (SCL-90) and Perceived Stress Scale (PSS-10). Cognitive functions were assessed using the Attention and Perceptivity Test (APT), Stroop Test parts A and B, Ruff Figural Fluency Test (RFFT), Trail Making Test (TMT) Parts A and B and the California Verbal Learning Test (CVLT). Biochemical parameters such as tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3HKYN), anthranilic acid (AA), 3-hydroxy anthranilic acid (3HAA), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL-1b) and cortisol plasma concentrations were measured. RESULTS: Sixty participants finished the study and were analyzed: 30 participants in the LP299v group and 30 participants in the placebo group. There was an improvement in APT and in CVLT total recall of trials 1-5 in the LP299v group compared with the placebo between baseline and after 8 weeks of intervention. There was a significant decrease in KYN concentration in the LP299v group compared to the placebo group. We also observed significant increase in 3HKYN:KYN ratio in the LP299v group compared with the placebo group. Additionally, Repeated Measures ANOVA revealed a significant effect of interaction of Treatment x time for AA concentration. However, results of post hoc analysis did not reach statistical significance in neither probiotic nor placebo group. There were no significant changes of TNF-α, IL-6 and IL-1b and cortisol concentrations in neither probiotic nor placebo groups. CONCLUSIONS: Augmentation of SSRI treatment with probiotic bacteria Lactobacillus Plantarum 299v improved cognitive performance and decreased KYN concentration in MDD patients. Decreased KYN concentration could contribute to the improvement of cognitive functions in the LP299v group compared to the placebo group. To our knowledge results of this study are the first evidence of improvement of cognitive functions in MDD patients due to probiotic bacteria and this is the first evidence of decreased KYN concentration in MDD patients due to probiotic bacteria.
Assuntos
Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/dietoterapia , Cinurenina/sangue , Lactobacillus plantarum , Probióticos/uso terapêutico , Adulto , Atenção/efeitos dos fármacos , Cognição/fisiologia , Terapia Combinada , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Probióticos/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown. METHODS: To examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subjected to acute tryptophan depletion (ATD) and the balanced control condition on two separate study days within a first study phase (Phase A), and the order in which these conditions (ATD/balanced control condition) occur will be random. This phase will be followed by Phase B, where participants will receive open label pharmacological treatment as usual with the SSRI fluoxetine and followed-up over a 12-week period. DISCUSSION: ATD is a neurodietary method typically used to investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The major hypothesis of this study is that ATD will be negatively associated with mood and cognitive functioning, therefore reflecting individual serotonergic sensitivity and related depressive symptoms. Additionally, we expect the aforementioned effects of ATD administration on mood to predict clinical improvement with regard to overall depressive symptomatology 12 weeks into SSRI treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.
Assuntos
Comportamento do Adolescente/efeitos dos fármacos , Afeto/efeitos dos fármacos , Aminoácidos/administração & dosagem , Antidepressivos de Segunda Geração/uso terapêutico , Encéfalo/efeitos dos fármacos , Comportamento Infantil/efeitos dos fármacos , Transtorno Depressivo Maior/dietoterapia , Suplementos Nutricionais , Fluoxetina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Serotonina/metabolismo , Triptofano/deficiência , Adolescente , Fatores Etários , Aminoácidos/efeitos adversos , Antidepressivos de Segunda Geração/efeitos adversos , Encéfalo/metabolismo , Criança , Terapia Combinada , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/psicologia , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Fluoxetina/efeitos adversos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Austrália OcidentalRESUMO
OBJECTIVE: Reports are mixed on the efficacy of omega-3 fatty acids (O3FA) for the treatment of major depressive disorder (MDD), with only limited data in adolescents. The present trial aimed to investigate systematically the efficacy of O3FA as a monotherapy, compared to a placebo, in adolescents with MDD. Secondarily, we explored O3FA effects on anhedonia, irritability, and suicidality-all key features of adolescent MDD. METHODS: Fifty-one psychotropic medication-free adolescents with DSM-IV-TR diagnoses of MDD (aged 12-19 years; 57% female) were randomized to receive O3FA or a placebo for 10 weeks. Data were collected between January 2006 and June 2013. O3FA and a placebo were administered on a fixed-flexible dose titration schedule based on clinical response and side effects. The initial dose of 1.2 g/d was increased 0.6 g/d every 2 weeks, up to a maximum of 3.6 g/d. Clinician-rated and self-rated depression severity, along with treatment response, served as primary outcome measures. Additionally, we examined O3FA effects on depression-related symptoms, including anhedonia, irritability, and suicidality. Treatment differences were analyzed via intent-to-treat analyses. RESULTS: O3FA were not superior to a placebo on any clinical feature, including depression severity and levels of anhedonia, irritability, or suicidality. Additionally, response rates were comparable between treatment groups. Within-treatment analyses indicated that both treatments were associated with significant improvement in depression severity on self- (O3FA: t = -4.38, P < .001; placebo: t = -3.52, P = .002) and clinician (O3FA: t = -6.47, P < .001; placebo: t = -8.10, P < .001) ratings. CONCLUSIONS: In adolescents with MDD, O3FA do not appear to be superior to placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00962598.
Assuntos
Transtorno Depressivo Maior/dietoterapia , Ácidos Graxos Ômega-3/uso terapêutico , Adolescente , Anedonia/efeitos dos fármacos , Criança , Método Duplo-Cego , Feminino , Humanos , Humor Irritável/efeitos dos fármacos , Masculino , Ideação Suicida , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Major depression is a highly prevalent condition. Its pathogenesis is related to a wide variety of biological and psychosocial factors and among these is factors related to lifestyle. Lifestyle-based interventions seem to be appropriate strategies as coadjutant treatment. The objective of this study is to explore and identify expectations and experiences of both patients and healthcare professionals that can point to the main barriers and facilitators with regard to the promotion of healthy dietary and hygiene behaviours in patients suffering from major depression. METHODS: A qualitative design was used to collect information from a wide range of purposefully and theoretically guided samples of depressed patients and health professionals from Primary Care (PC). Both in-depth interviews and discussion groups were used. A standardized protocol was designed to guide the interviews and groups, including the preparation of a topic list to be addressed, with previously tested, open suggestions that could be of interest. A thematic analysis was performed from grounded theory in order to explore, develop and define until saturation the emergent categories of analysis derived from the individual interview and group data. RESULTS: Both patients as well as PC professionals noted a series of central aspects with respect to the implementation of a programme for the acquisition of healthy dietary and hygiene habits for depressive patients, which may be organized around 'personal', 'programmatic', and 'transversal' aspects. As for the personal aspects, categories regarding 'patient history', and 'disposition' were found; the programmatic aspects included categories such as 'presentation and monitoring', and modification of 'cognitive' and 'behavioural' habits; whereas the transversal aspects comprised the possibilities of 'social support' and defining categories of 'objectives'. CONCLUSION: The implementation of intervention programmes that combine dietary and hygiene-related factors in patients with depression is complex, given the nature of the disorder itself, and its symptoms such as apathy and feelings of guilt or incompetence. Key issues exist for the success of the intervention, such as the simplicity of guidelines, tailoring through motivational interviewing, prolonged and intense monitoring throughout the different stages of the disorder, and the provision of adequate feedback and social support. PC could be an appropriate level in which to implement these interventions.
Assuntos
Transtorno Depressivo Maior/dietoterapia , Dieta , Higiene , Adolescente , Adulto , Idoso , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Entrevista Motivacional/métodos , Atenção Primária à Saúde , Pesquisa Qualitativa , Apoio Social , Adulto JovemRESUMO
BACKGROUND: Recently, the efficacy of dietary improvement as a therapeutic intervention for moderate to severe depression was evaluated in a randomised controlled trial. The SMILES trial demonstrated a significant improvement in Montgomery-Åsberg Depression Rating Scale scores favouring the dietary support group compared with a control group over 12 weeks. We used data collected within the trial to evaluate the cost-effectiveness of this novel intervention. METHODS: In this prospective economic evaluation, sixty-seven adults meeting DSM-IV criteria for a major depressive episode and reporting poor dietary quality were randomised to either seven sessions with a dietitian for dietary support or to an intensity matched social support (befriending) control condition. The primary outcome was Quality Adjusted Life Years (QALYs) as measured by the AQoL-8D, completed at baseline and 12 week follow-up (endpoint) assessment. Costs were evaluated from health sector and societal perspectives. The time required for intervention delivery was costed using hourly wage rates applied to the time in counselling sessions. Food and travel costs were also included in the societal perspective. Data on medications, medical services, workplace absenteeism and presenteesim (paid and unpaid) were collected from study participants using a resource-use questionnaire. Standard Australian unit costs for 2013/2014 were applied. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in average costs between groups divided by the difference in average QALYs. Confidence intervals were calculated using a non-parametric bootstrap procedure. RESULTS: Compared with the social support condition, average total health sector costs were $856 lower (95% CI -1247 to - 160) and average societal costs were $2591 lower (95% CI -3591 to - 198) for those receiving dietary support. These differences were driven by lower costs arising from fewer allied and other health professional visits and lower costs of unpaid productivity. Significant differences in mean QALYs were not found between groups. However, 68 and 69% of bootstrap iterations showed the dietary support intervention was dominant (additional QALYs at less cost) from the health sector and societal perspectives. CONCLUSIONS: This novel dietary support intervention was found to be likely cost-effective as an adjunctive treatment for depression from both health sector and societal perspectives. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820 . Registered on 29 February 2012.
Assuntos
Transtorno Depressivo Maior/dietoterapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Adulto , Austrália , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Apoio Social , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: The SMILES trial was the first randomized controlled trial (RCT) explicitly designed to evaluate a dietary intervention, conducted by qualified dietitians, for reducing depressive symptomatology in adults with clinical depression. OBJECTIVES: Here we detail the development of the prescribed diet (modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive disorders (MDDs) that was designed specifically for the SMILES trial. We also present data demonstrating the extent to which this intervention achieved improvements in diet quality. METHODS: The ModiMedDiet was designed using a combination of existing dietary guidelines and scientific evidence from the emerging field of nutritional psychiatric epidemiology. Sixty-seven community dwelling individuals (Melbourne, Australia) aged 18 years or over, with current poor quality diets, and MDDs were enrolled into the SMILES trial. A retention rate of 93.9 and 73.5% was observed for the dietary intervention and social support control group, respectively. The dietary intervention (ModiMedDiet) consisted of seven individual nutrition counselling sessions delivered by a qualified dietitian. The control condition comprised a social support protocol matched to the same visit schedule and length. RESULTS: This manuscript details the first prescriptive individualized dietary intervention delivered by dietitians for adults with major depression. Significant improvements in dietary quality were observed among individuals randomized to the ModiMedDiet group. These dietary improvements were also found to be associated with changes in depressive symptoms. DISCUSSION/CONCLUSION: The ModiMedDiet, a novel and individually tailored intervention designed specifically for adults with major depression, can be effectively implemented in clinical practice to manage this highly prevalent and debilitating condition. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered 29 February 2012.