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2.
Lancet Neurol ; 19(8): 661-669, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702335

RESUMO

BACKGROUND: Studies have suggested that fluoxetine could improve neurological recovery after stroke. The Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS) trial aimed to assess whether administration of oral fluoxetine for 6 months after acute stroke improves functional outcome. METHODS: EFFECTS was an investigator-led, multicentre, randomised, placebo-controlled, double-blind, parallel group trial that enrolled patients aged 18 years or older between 2 and 15 days after stroke onset in 35 stroke and rehabilitation centres in Sweden. Eligible patients had a clinical diagnosis of ischaemic or intracerebral haemorrhage, brain imaging that was consistent with intracerebral haemorrhage or ischaemic stroke, and had at least one persisting focal neurological deficit. A web-based randomisation system that incorporated a minimisation algorithm was used to randomly assign (1:1) participants to receive oral fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Patients, care providers, investigators, and outcomes assessors were masked to the allocation. The primary outcome was functional status, measured with the modified Rankin Scale (mRS) at 6 months, analysed in all patients with available mRS data at the 6-month follow-up; we did an ordinal analysis adjusted for the minimisation variables used in the randomisation. This trial is registered with EudraCT, 2011-006130-16; ISRCTN, 13020412; and ClinicalTrials.gov, NCT02683213. FINDINGS: Between Oct 20, 2014, and June 28, 2019, 1500 patients were enrolled, of whom 750 were randomly assigned to fluoxetine and 750 were randomly assigned to placebo. At 6 months, mRS data were available for 737 (98%) patients in the fluoxetine group and 742 (99%) patients in the placebo group. There was no effect of fluoxetine on the primary outcome-distribution across mRS score categories-compared with placebo (adjusted common odds ratio 0·94 [95% CI 0·78 to 1·13]; p=0·42). The proportion of patients with a new diagnosis of depression was lower with fluoxetine than with placebo (54 [7%] patients vs 81 [11%] patients; difference -3·60% [-6·49 to -0·71]; p=0·015), but fluoxetine was associated with more bone fractures (28 [4%] vs 11 [2%]; difference 2·27% [0·66 to 3·87]; p=0·0058) and hyponatraemia (11 [1%] vs one [<1%]; difference 1·33% [0·43 to 2·23]; p=0·0038) at 6 months. INTERPRETATION: Functional outcome after acute stroke did not improve with oral fluoxetine 20 mg once daily for 6 months. Fluoxetine reduced the occurrence of depression but increased the risk of bone fractures and hyponatraemia. Our results do not support the use of fluoxetine after acute stroke. FUNDING: The Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Brain Foundation, the Swedish Society of Medicine, King Gustav V and Queen Victoria's Foundation of Freemasons, and the Swedish Stroke Association (STROKE-Riksförbundet).


Assuntos
Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
3.
Lancet Neurol ; 19(8): 651-660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702334

RESUMO

BACKGROUND: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. METHODS: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2-15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. FINDINGS: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76-1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. INTERPRETATION: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke. FUNDING: National Health and Medical Research Council of Australia.


Assuntos
Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(21): e20170, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481286

RESUMO

BACKGROUND: Numerous studies have reported that transcranial magnetic stimulation (TMS) and fluoxetine is used in the treatment of postpartum depression (PPD). Currently, no study has systematically investigated the efficacy and safety of TMS and fluoxetine for the treatment of patients with PPD. Thus, this study will assess the efficacy and safety of TMS and fluoxetine for treating PPD. METHODS: Relevant studies involving TMS and fluoxetine for the treatment of patients with PPD will be comprehensively searched from the electronic databases from inception to the February 1, 2020: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, WANGFANG, VIP, and CNKI databases. No language and publication time restrictions will be applied. RevMan 5.3 software will be utilized for data pooling, data analysis, and risk of bias evaluation. If necessary, we will also assess reporting bias using funnel plot and Egger test. RESULTS: This study will comprehensively summarize the existing evidence to assess the efficacy and safety of TMS and fluoxetine for treating PPD. CONCLUSION: The findings of this study may help to establish a better approach to treat PPD using TMS and fluoxetine. DISSEMINATION AND ETHICS: This study will be disseminated through a peer-reviewed journal. This study does not need ethical approval as no primary patient data will be used. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040017.


Assuntos
Depressão Pós-Parto/terapia , Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Estimulação Magnética Transcraniana/métodos , Adulto , Terapia Combinada/métodos , Depressão Pós-Parto/epidemiologia , Feminino , Fluoxetina/administração & dosagem , Humanos , Inibidores de Captação de Serotonina/administração & dosagem , Resultado do Tratamento
5.
Neuropsychopharmacol Hung ; 22(1): 4-15, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32329748

RESUMO

Discovery and development of the selective serotonin reuptake inhibitors mark a milestone in neuropharmacology. Drugs from this class alter the functioning of the serotonin system by the potentiation of serotonin through the negative allosteric modulation of its neuronal uptake by the human serotonin transporter. Selective serotonin reuptake inhibitors show few side effects compared to those caused by traditional antidepressants and they vary in the binding interactions formed during binding. Generally, their binding involves three specific regions of the drug structures, each participating in vital interactions, such as salt bridge formation and additional hydrophobic interactions with conserved residues in the central binding site of the target protein. Side effects, however, such as the initial lack of response to treatment, or drowsiness, nausea, and sexual dysfunction occasionally may arise. Additional binding studies, furthermore, highlighted the importance of enantioselectivity in the binding of these compounds, raising concerns about the beneficial application of racemate mixtures of some of these compounds. Therefore, additional characterisation of binding and further structural improvement of this class of drugs is necessary. The recently synthesized sertraline salts, and functional derivatives of fluoxetine and citalopram show promising results in delivering antidepressant activity as well as in effectively overcoming anorexigenic side-effects in rodent models. Hence, despite certain non-desired effects associated with selective serotonin reuptake inhibitor applications, this class of drugs is considered as first-line medication in the management of major depression, and is carrying an excellent potential for the development and refinement of the currently available and novel antidepressant therapies.


Assuntos
Citalopram/uso terapêutico , Depressão/tratamento farmacológico , Fluoxetina/uso terapêutico , Sertralina/uso terapêutico , Humanos , Proteínas da Membrana Plasmática de Transporte de Serotonina , Inibidores de Captação de Serotonina
6.
Actas esp. psiquiatr ; 48(2): 47-53, mar.-abr. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-191904

RESUMO

INTRODUCCIÓN: Actualmente el tratamiento de enfermedades mentales mediante antidepresivos es muy frecuente. Los inhibidores selectivos de la recaptación de serotonina son los antidepresivos más prescritos a nivel mundial y han sido asociados con alteraciones en la acomodación o la pupila. El objetivo de este estudio es evaluar los efectos de la fluoxetina sobre el reflejo pupilar y la acomodación en población joven. METODOLOGÍA: El grupo de estudio contó con siete pacientes diagnosticados de depresión y tratados con fluoxetina; como grupo control se incluyeron 22 sujetos. Se evaluaron los reflejos pupilares y el estado acomodativo mediante el pupilómetro Power Refractor II. Se midieron 5 fases de 3 segundos cada una. En la fase 2 se produjo un deslumbramiento con una luz blanca. RESULTADOS: Para el diámetro pupilar se han obtenido valores máximos y mínimos mayores en el grupo de pacientes tratados con fluoxetina que en el control en todas las fases de medida. Para el grupo control se observa una contracción pupilar máxima en la fase de deslumbramiento, sin embargo, en el grupo de estudio se observa en la fase tras el deslumbramiento. En cuanto a la acomodación no se obtuvieron diferencias significativas entre ambos grupos. CONCLUSIONES: En pacientes tratados con fluoxetina existen alteraciones pupilares observándose diámetros pupilares mayores y menor velocidad de contracción pupilar. La falta de resultados concluyentes en cuanto a la acomodación no significa que no existan cambios relacionados con esta, cuya detección requerirá de futuros estudios utilizando diferentes metodologías y con un tamaño muestral mayor


INTRODUCTION: currently the treatment of mental illness by antidepressants is very frequent. Selective serotonin re-uptake inhibitors are the most prescribed antidepressants worldwide and have been associated with alterations in accommodation or pupil. The objective of this study is to evaluate the effects of fluoxetine on the pupillary reflex and the accommodation in young population. METHODOLOGY: The study group included seven patients diagnosed with depression and treated with fluoxetine; 22 subjects were included as a control group. The pupillary reflexes and the accommodative state were evaluated using the Power Refractor II pupilometer. Five phases of 3 seconds each were measured. In phase 2 there was a glare with a white light. RESULTS: For the pupil diameter, maximum and minimum values were obtained in the group of patients treated with fluoxetine than in the control in all the measurement phases. For the control group, a maximum pupillary contraction is observed in the glare phase, however, in the study group it is observed in the phase after glare. As for the accommodation, there are no significant differences between the two groups. CONCLUSIONS: In patients treated with fluoxetine there are pupillary alterations like a bigger pupillary diameters and slower pupillary contraction. The lack of conclusive results in terms of accommodation does not mean that there are no changes related to it, whose detection requires future studies with different methodologies and with a larger sample size


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Fluoxetina/efeitos adversos , Antidepressivos de Segunda Geração/efeitos adversos , Visão Mesópica/efeitos dos fármacos , Depressão/tratamento farmacológico , Distúrbios Pupilares/induzido quimicamente , Fluoxetina/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico
7.
Biochim Biophys Acta Rev Cancer ; 1873(2): 188355, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32135169

RESUMO

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly expressed in heart and brain tissue. HERG plays critical role in cardiac repolarization, and mutations in HERG can cause long QT syndrome. More recently, evidence has emerged that HERG channels are aberrantly expressed in many kinds of cancer cells and play important roles in cancer progression. HERG could therefore be a potential biomarker for cancer and a possible molecular target for anticancer drug design. HERG affects a number of cellular processes, including cell proliferation, apoptosis, angiogenesis and migration, any of which could be affected by dysregulation of HERG. This review provides an overview of available information on HERG channel as it relates to cancer, with focus on the mechanism by which HERG influences cancer progression. Molecular docking attempts suggest two possible protein-protein interactions of HERG with the ß1-integrin receptor and the transcription factor STAT-1 as novel HERG-directed therapeutic targeting which avoids possible cardiotoxicity. The role of epigenetics in regulating HERG channel expression and activity in cancer will also be discussed. Finally, given its inherent extracellular accessibility as an ion channel, we discuss regulatory roles of this molecule in cancer physiology and therapeutic potential. Future research should be directed to explore the possibilities of therapeutic interventions targeting HERG channels while minding possible complications.


Assuntos
Carcinogênese/patologia , Canal de Potássio ERG1/metabolismo , Integrina beta1/metabolismo , Neoplasias/patologia , Fator de Transcrição STAT1/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Carcinogênese/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Canal de Potássio ERG1/antagonistas & inibidores , Canal de Potássio ERG1/química , Canal de Potássio ERG1/genética , Epigênese Genética/efeitos dos fármacos , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Síndrome do QT Longo/genética , Potenciais da Membrana/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mutação , Miócitos Cardíacos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Conformação Proteica em alfa-Hélice , Mapeamento de Interação de Proteínas , Estrutura Quaternária de Proteína , Piridinas/farmacologia , Piridinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Sulfanilamidas/farmacologia , Sulfanilamidas/uso terapêutico
8.
Lancet Psychiatry ; 7(4): 337-343, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32199509

RESUMO

BACKGROUND: Better understanding of the heterogeneity of treatment responses could help to improve care for adolescents with depression. We analysed data from a clinical trial to assess whether specific symptom clusters responded differently to various treatments. METHODS: For this secondary analysis, we used data from the Treatment for Adolescents with Depression Study (TADS), in which 439 US adolescents aged 12-17 with a DSM-IV diagnosis of major depressive disorder and a minimum score of 45 on the Children's Depression Rating Scale-Revised (CDRS-R) were randomly assigned (1:1:1:1) to treatment with fluoxetine, cognitive behavioural therapy (CBT), fluoxetine plus CBT, or pill placebo. Our analysis focuses on the acute phase of the trial (ie, the first 12 weeks). Groups of co-occurring symptoms were established by clustering scores for each CDRS-R item at baseline with Ward's method, with Euclidean distances for hierarchical agglomerative clustering. We then used a linear mixed-effects model to investigate the relationship between symptom clusters and treatment efficacy, with the sum of symptom scores within each cluster as the dependent measure. As fixed effects, we entered cluster, time, and treatment assignment, with all two-way and three-way interactions, into the model. The random effect providing better fit was established to be a by-subject random slope for cluster based on improvement in the Schwarz-Bayesian information criterion. OUTCOMES: We identified two symptom clusters: cluster 1 comprised depressed mood, difficulty having fun, irritability, social withdrawal, sleep disturbance, impaired schoolwork, excessive fatigue, and low self-esteem, and cluster 2 comprised increased appetite, physical complaints, excessive weeping, decreased appetite, excessive guilt, morbid ideation, and suicidal ideation. For cluster 1 symptoms, CDRS-R scores were reduced by 5·8 points (95% CI 2·8-8·9) in adolescents treated with fluoxetine plus CBT, and by 4·1 points (1·1-7·1) in those treated with fluoxetine, compared with those given placebo. For cluster 2 symptoms, no significant differences in improvements in CDRS-R scores were detected between the active treatment and placebo groups. INTERPRETATION: Response to fluoxetine and CBT among adolescents with depression is heterogeneous. Clinicians should consider clinical profile when selecting therapeutic modality. The contrast in response patterns between symptom clusters could provide opportunities to improve treatment efficacy by gearing the development of new therapies towards the resolution of specific symptoms. FUNDING: Conselho Nacional de Desenvolvimento Científico e Tecnológico.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/terapia , Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Adolescente , Teorema de Bayes , Criança , Terapia Combinada , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Estados Unidos
9.
Arch. Clin. Psychiatry (Impr.) ; 47(1): 7-12, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1088740

RESUMO

Abstract Objectives This study aimed to explore the effect of antidepressant treatment on the HPA axis, changes in depression score, and serum levels of TNF-α in depressed infertile women. Methods In this randomized controlled trial research, 60 infertile women who had undergone in vitro fertilization (IVF) treatment with depression scores between 16-47 were divided into two groups. The intervention group with fluoxetine capsule was under treatment for two months before the embryo transfer, while the control group was given placebo. Depression score, serum levels of tumor necrosis factor alpha (TNF-α) as well as cortisol hormone levels were measured and recorded both before and after the intervention. The data were analyzed using SPSS version 21 software. Results We analyzed the data related to 55 subjects who had undergone embryo transfer. 7 subjects in the intervention group and 3 in the control group got pregnant. We observed a significant decrease in the depression score (p < 0/001) and serum levels of cortisol (p = 0/001) in the intervention group. There was a significant increase in the serum levels of TNF-α in the intervention group (p < 0/001). There was a significant difference between the two groups in the number of pregnancies (p = 0.04). However, there was no statistical difference between them with regard to the number of harvested oocytes (p = 0.174). Discussion Decrease in depression score and cortisol level, and an increase in the levels of TNF-α in the intervention group caused any changes in the number of oocytes in comparison with the control group. However, the number of pregnancies was larger in the intervention group.


Assuntos
Humanos , Feminino , Adulto , Fator de Necrose Tumoral alfa/sangue , Depressão/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infertilidade Feminina/psicologia , Placebos/uso terapêutico , Escalas de Graduação Psiquiátrica , Psicometria/métodos , Gravidez/psicologia , Hidrocortisona/sangue , Fertilização In Vitro , Aborto Espontâneo/etiologia , Fluoxetina/uso terapêutico , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Resultado do Tratamento , Depressão/complicações , Depressão/diagnóstico , Infertilidade/etiologia
10.
Lancet Neurol ; 19(3): 214-225, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31981516

RESUMO

BACKGROUND: Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. METHODS: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressive multiple sclerosis who were not on disease-modifying treatment and who had an Expanded Disability Status Scale (EDSS) score of 4·0-6·5. Participants were randomly assigned (1:1:1:1) at baseline, by a research nurse using a centralised web-based service, to receive twice-daily oral treatment of either amiloride 5 mg, fluoxetine 20 mg, riluzole 50 mg, or placebo for 96 weeks. The randomisation procedure included minimisation based on sex, age, EDSS score at randomisation, and trial site. Capsules were identical in appearance to achieve masking. Patients, investigators, and MRI readers were unaware of treatment allocation. The primary outcome measure was volumetric MRI percentage brain volume change (PBVC) from baseline to 96 weeks, analysed using multiple regression, adjusting for baseline normalised brain volume and minimisation criteria. The primary analysis was a complete-case analysis based on the intention-to-treat population (all patients with data at week 96). This trial is registered with ClinicalTrials.gov, NCT01910259. FINDINGS: Between Jan 29, 2015, and June 22, 2016, 445 patients were randomly allocated amiloride (n=111), fluoxetine (n=111), riluzole (n=111), or placebo (n=112). The primary analysis included 393 patients who were allocated amiloride (n=99), fluoxetine (n=96), riluzole (n=99), and placebo (n=99). No difference was noted between any active treatment and placebo in PBVC (amiloride vs placebo, 0·0% [95% CI -0·4 to 0·5; p=0·99]; fluoxetine vs placebo -0·1% [-0·5 to 0·3; p=0·86]; riluzole vs placebo -0·1% [-0·6 to 0·3; p=0·77]). No emergent safety issues were reported. The incidence of serious adverse events was low and similar across study groups (ten [9%] patients in the amiloride group, seven [6%] in the fluoxetine group, 12 [11%] in the riluzole group, and 13 [12%] in the placebo group). The most common serious adverse events were infections and infestations. Three patients died during the study, from causes judged unrelated to active treatment; one patient assigned amiloride died from metastatic lung cancer, one patient assigned riluzole died from ischaemic heart disease and coronary artery thrombosis, and one patient assigned fluoxetine had a sudden death (primary cause) with multiple sclerosis and obesity listed as secondary causes. INTERPRETATION: The absence of evidence for neuroprotection in this adequately powered trial indicates that exclusively targeting these aspects of axonal pathobiology in patients with secondary progressive multiple sclerosis is insufficient to mitigate neuroaxonal loss. These findings argue for investigation of different mechanistic targets and future consideration of combination treatment trials. This trial provides a template for future simultaneous testing of multiple disease-modifying medicines in neurological medicine. FUNDING: Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership, UK Multiple Sclerosis Society, and US National Multiple Sclerosis Society.


Assuntos
Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Adulto , Amilorida/uso terapêutico , Encéfalo , Progressão da Doença , Método Duplo-Cego , Feminino , Fluoxetina/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Riluzol/uso terapêutico , Resultado do Tratamento
11.
PLoS One ; 15(1): e0226486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31931515

RESUMO

Treatment-resistant depression (TRD) occurs in many patients and causes high morbidity and mortality. Because TRD subjects are particularly difficult to study especially longitudinally, biological data remain very limited. In a preliminary study to judge feasibility and power, 25 TRD patients were referred from specialty psychiatric practices. All were severely and chronically depressed and mostly had comorbid psychiatric disorders as is typical in TRD. Nine patients were able to complete all required components of the protocol that included diagnostic interview; rating scales; clinical magnetic resonance imaging; medication washout; treatment with maximally tolerated olanzapine-fluoxetine combination for 8 weeks; and pre- and post-treatment fluorodeoxyglucose positron emission tomography. This drug combination is an accepted standard of treatment for TRD. Dropouts arose from worsening depression, insomnia, and anxiety. One patient remitted; three responded. A priori regions of interest included the amygdala and subgenual cingulate cortex (sgACC; Brodmann area BA25). Responders showed decreased metabolism with treatment in the right amygdala that correlated with clinical response; no significant changes in BA25; better response to treatment the higher the baseline BA25 metabolism; and decreased right ventromedial prefrontal metabolism (VMPFC; broader than BA25) with treatment which did not correlate with depression scores. The baseline metabolism of all individuals showed heterogeneous patterns when compared to a normative metabolic database. Although preliminary given the sample size, this study highlights several issues important for future work: marked dropout rate in this study design; need for large sample size for adequate power; baseline metabolic heterogeneity of TRD requiring careful subject characterization for future studies of interventions; relationship of amygdala activity decreases with response; and the relationship between baseline sgACC and VMPFC activity with response. Successful treatment of TRD with olanzapine-fluoxetine combination shows changes in cerebral metabolism like those seen in treatment-responsive major depression.


Assuntos
Benzodiazepinas/uso terapêutico , Encéfalo/metabolismo , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Fluoxetina/uso terapêutico , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/metabolismo , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/metabolismo , Transtorno Depressivo Resistente a Tratamento/patologia , Combinação de Medicamentos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Índice de Gravidade de Doença
12.
Int Braz J Urol ; 45(6): 1209-1215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31808410

RESUMO

PURPOSE: To compare the efficacy and safety of available selective serotonin reuptake inhibi-tors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE). MATERIALS AND METHODS: This study was a randomized clinical trial. Four hundred and eighty pati-ents with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to Fe-bruary 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory laten-cy time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch. RESULTS: Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxeti-ne 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug. CONCLUSIONS: All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.


Assuntos
Citalopram/uso terapêutico , Fluoxetina/uso terapêutico , Paroxetina/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Adulto , Idoso , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Rev. Hosp. Ital. B. Aires (2004) ; 39(4): 128-134, dic. 2019.
Artigo em Espanhol | LILACS | ID: biblio-1099754

RESUMO

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)


Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Atenção Primária à Saúde/tendências , Depressão/diagnóstico , Psiquiatria/tendências , Sinais e Sintomas , Transtornos Somatoformes/diagnóstico , Citalopram/efeitos adversos , Citalopram/uso terapêutico , Fibromialgia/complicações , Síndrome de Fadiga Crônica/complicações , Fluoxetina/efeitos adversos , Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/efeitos adversos , Dor Lombar/complicações , Antagonistas Colinérgicos/efeitos adversos , Erros Médicos , Sertralina/efeitos adversos , Sertralina/uso terapêutico , Depressão/classificação , Depressão/complicações , Depressão/terapia , Depressão/epidemiologia , Medicina Geral , Dor Crônica/complicações , Cloridrato de Venlafaxina/efeitos adversos , Cloridrato de Venlafaxina/uso terapêutico , Cloridrato de Duloxetina/efeitos adversos , Cloridrato de Duloxetina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Cefaleia/complicações , Amitriptilina/efeitos adversos , Amitriptilina/uso terapêutico , Antidepressivos/administração & dosagem
15.
Cochrane Database Syst Rev ; 2019(11)2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769878

RESUMO

BACKGROUND: Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. MAIN RESULTS: We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow-up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta-analysis of these three trials found little or no effect of SSRI on either disability score: SMD -0.01 (95% CI -0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate-quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate-quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate-quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate-quality evidence), with no evidence of heterogeneity (I2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. AUTHORS' CONCLUSIONS: We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta-analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta-analysis of large ongoing trials will be required to determine the generalisability of these findings.


Assuntos
Depressão/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/psicologia , Adulto , Antidepressivos Tricíclicos/uso terapêutico , Depressão/etiologia , Fluoxetina/uso terapêutico , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/tratamento farmacológico
16.
Psychiatry Res ; 281: 112595, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31627074

RESUMO

Depression has brought huge disease burden to the world. This systematic review aimed to compare the efficacy and safety of pharmacological and non-pharmacological treatments for major depressive disorder (MDD). We searched electronic databases with time range from 1990.1.1 to 2018.9.5. Randomized controlled trials (RCTs) including adult patients with MDD were eligible for inclusion. We conducted network meta-analyses using multivariate meta-analyses models under the frequency framework. Primary outcomes were efficacy (response rate) and safety (overall risk of adverse events). We estimated summary odds ratios (ORs) based on group-level data. 20,937 citations were identified, 91 trials comprising 10,991 participants were included in efficacy study, and 32 trials comprising 5245 participants were included in safety study. In terms of efficacy, all treatments studied (acupuncture, mirtazapine, herbal medicine, venlafaxine, physical exercise, cognitive-behavioral therapy (CBT), bupropion, fluoxetine, and vortioxetine) except for probiotics were significantly more effective than placebo. In terms of safety, bupropion, fluoxetine, venlafaxine, and vortioxetine were significantly less safe than placebo. Herbal medicine and mirtazapine had no significant difference in overall risk of adverse events compared with placebo. Acupuncture, CBT, physical exercise and probiotics were lack of eligible safety data.


Assuntos
Antidepressivos/uso terapêutico , Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Fluoxetina/uso terapêutico , Humanos , Mirtazapina/uso terapêutico , Metanálise em Rede , Resultado do Tratamento , Cloridrato de Venlafaxina/uso terapêutico , Vortioxetina/uso terapêutico
17.
JAMA ; 322(16): 1561-1569, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638682

RESUMO

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain. Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders. Design, Setting, and Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017. Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks. Main Outcomes and Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables. Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21). Conclusions and Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference. Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Fluoxetina/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adolescente , Ansiedade/diagnóstico , Transtorno do Espectro Autista/psicologia , Criança , Fatores de Confusão Epidemiológicos , Feminino , Fluoxetina/efeitos adversos , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/classificação , Gravidade do Paciente , Inibidores de Captação de Serotonina/efeitos adversos , Transtorno de Movimento Estereotipado/tratamento farmacológico , Resultado do Tratamento
18.
Medicine (Baltimore) ; 98(41): e17501, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593119

RESUMO

BACKGROUND: Traditional treatment of functional dyspepsia (FD) is unsatisfactory in a subgroup of patients with FD, and the potential role of antidepressant medications also has not been definitely clarified. To provide more evidence for future optimal practice recommendations, we reviewed a 1-year clinical database of antidepressant agents applied in outpatients with FD. METHODS: Clinical presentations, treatment course, and outcomes were determined by chart review of patients referring to the functional gastrointestinal disorders specialist clinic. One hundred thirty patients with FD were included for further analysis. RESULTS: Patients were treated with different antidepressant drugs according to individual symptoms. The most commonly used drugs were flupenthixol melitracen and fluoxetine. Improvement and complete remission occurred in 93.8% and 54.6% of patients, respectively. There was a trend toward superior outcome for citalopram compared to sulpiride and mirtazapine in overall analysis. Meanwhile, regimens containing fluoxetine had significant increased remission rate compared to any other antidepressant regimens in postprandial distress syndrome subgroup analysis. Furthermore, older patients were more likely to achieve remission. However, sex and symptom duration were not associated with symptom remission. Finally, 11.5% of patients experienced adverse events. CONCLUSIONS: This retrospective cohort study indicated that small dose antidepressant therapy, especially citalopram and fluoxetine, is an effective and well tolerated treatment option for refractory FD.


Assuntos
Antracenos/uso terapêutico , Dispepsia/tratamento farmacológico , Fluoxetina/uso terapêutico , Flupentixol/uso terapêutico , Antracenos/efeitos adversos , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , China/epidemiologia , Citalopram/uso terapêutico , Combinação de Medicamentos , Dispepsia/diagnóstico , Feminino , Fluoxetina/efeitos adversos , Flupentixol/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Período Pós-Prandial , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
19.
Turk Kardiyol Dern Ars ; 47(6): 458-465, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31483315

RESUMO

OBJECTIVE: Panic disorder (PD) is now recognized as a common and important problem in children, and particularly adolescents, and one that can negatively affect daily well-being and educational performance. The aim of this study was to investigate the relationship between heart rate variability (HRV) and the severity of symptoms before and after treatment with psychotherapy and fluoxetine. METHODS: The PD study group consisted of 23 children diagnosed with PD and the healthy control (HC) group comprised 27 healthy children. Panic-anxiety symptoms were measured using 2 assessments performed before and after treatment. HRV was evaluated with a 24-hour Holter examination. RESULTS: According to the analysis of the 24-hour, all-day Holter device recordings, the high frequency (HF) and parasympathetic (%) scores in the PD group were lower than those of the HC group (p<0.05). The low frequency (LF)/HF ratio and sympathetic (%) scores in the PD group were higher than those of the HC group (p<0.05). The analysis of daytime readings indicated that the HF values of the PD group were lower than those of the HC group (p<0.05), while the very LF/HF ratio and LF/HF ratio were higher than those of the HC group (p<0.05). Analysis of nighttime Holter results revealed that the rMSSD, pNN50, and HF readings of the PD group were lower than those of the HC group (p<0.05), while the LF/HF ratio in PD patients was higher than that seen in the HC group (p<0.05). CONCLUSION: In children and adolescents with PD, increased sympathetic activity can cause changes in some HRV parameters. Some of these changes may return to normal with treatment.


Assuntos
Ansiolíticos/uso terapêutico , Fluoxetina/uso terapêutico , Frequência Cardíaca/fisiologia , Transtorno de Pânico , Psicoterapia , Adolescente , Estudos de Casos e Controles , Criança , Eletrocardiografia Ambulatorial , Humanos , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/fisiopatologia , Transtorno de Pânico/terapia , Índice de Gravidade de Doença , Resultado do Tratamento , Turquia
20.
Transl Psychiatry ; 9(1): 222, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501410

RESUMO

BTB/POZ domain-containing 3 (BTBD3) was identified as a potential risk gene in the first genome-wide association study of obsessive-compulsive disorder (OCD). BTBD3 is a putative transcription factor implicated in dendritic pruning in developing primary sensory cortices. We assessed whether BTBD3 also regulates neural circuit formation within limbic cortico-striato-thalamo-cortical circuits and behaviors related to OCD in mice. Behavioral phenotypes associated with OCD that are measurable in animals include compulsive-like behaviors and reduced exploration. We tested Btbd3 wild-type, heterozygous, and knockout mice for compulsive-like behaviors including cage-mate barbering, excessive wheel-running, repetitive locomotor patterns, and reduced goal-directed behavior in the probabilistic learning task (PLT), and for exploratory behavior in the open field, digging, and marble-burying tests. Btbd3 heterozygous and knockout mice showed excessive barbering, wheel-running, impaired goal-directed behavior in the PLT, and reduced exploration. Further, chronic treatment with fluoxetine, but not desipramine, reduced barbering in Btbd3 wild-type and heterozygous, but not knockout mice. In contrast, Btbd3 expression did not alter anxiety-like, depression-like, or sensorimotor behaviors. We also quantified dendritic morphology within anterior cingulate cortex, mediodorsal thalamus, and hippocampus, regions of high Btbd3 expression. Surprisingly, Btbd3 knockout mice only showed modest increases in spine density in the anterior cingulate, while dendritic morphology was unaltered elsewhere. Finally, we virally knocked down Btbd3 expression in whole, or just dorsal, hippocampus during neonatal development and assessed behavior during adulthood. Whole, but not dorsal, hippocampal Btbd3 knockdown recapitulated Btbd3 knockout phenotypes. Our findings reveal that hippocampal Btbd3 expression selectively modulates compulsive-like and exploratory behavior.


Assuntos
Encéfalo/metabolismo , Comportamento Compulsivo/metabolismo , Comportamento Exploratório/fisiologia , Rede Nervosa/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Comportamento Compulsivo/tratamento farmacológico , Comportamento Compulsivo/genética , Desipramina/farmacologia , Desipramina/uso terapêutico , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/genética , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/metabolismo
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