ABSTRACT
Objective: Exposure and response prevention (ERP) is effective to treat obsessive-compulsive disorder (OCD), but the lack of tolerance to the aversion nature of exposure techniques results in a high drop-out rate. There have been reports of a generic stress endurance effect of serotonin (5-HT) in the central nervous system (CNS) which might be explained by suppression of defensive fixed action patterns. Previous studies have proposed that higher baseline 5-HT concentration and slow decrease in concentration during drug treatment of OCD were predictors of good clinical response to 5-HT reuptake inhibitors. The objective of this study was to investigate whether pre-treatment platelet rich plasma (PRP) 5-HT concentration is associated with latency of treatment response and final response to an ERP protocol for obsessive-compulsive disorder (OCD). Methods: Thirty adult and treatment-free OCD patients were included in an 8-week, 16-session ERP protocol. 5-HT concentration was determined at baseline and after treatment. Patients with a reduction ≥30% on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at the end of ERP were defined as responders. Results: A positive correlation between baseline 5-HT concentration and reduction of symptoms on the Y-BOCS was observed after 4 weeks. Baseline 5-HT concentration was not correlated with clinical response after 8 weeks of ERP, possibly due to the similar though delayed clinical response of patients with lower (compared to those with higher) baseline 5-HT concentration. Patients with higher 5-HT baseline concentration also showed more improvement in depressive symptoms with treatment. Conclusion: The present results partially support the hypothesis of a stress endurance effect of 5-HT in OCD patients. According to the literature, fast onset responders possibly have more or larger 5-HT containing neurons, higher endogenous 5-HT synthesis or lower monoamine oxidase activity; all these hypotheses remain to be investigated.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Aversive Therapy , Blood Platelets/chemistry , Serotonin/blood , Cognitive Behavioral Therapy/methods , Serotonin Receptor Agonists/blood , Obsessive-Compulsive Disorder/therapy , Psychiatric Status Rating Scales , Severity of Illness Index , Biomarkers/blood , Follow-Up Studies , Treatment Outcome , Depression/diagnosis , Depression/therapy , Obsessive-Compulsive Disorder/psychology , Obsessive-Compulsive Disorder/bloodABSTRACT
OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Middle Aged , Young Adult , Citalopram/therapeutic use , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/genetics , Polymorphism, Genetic/genetics , Receptors, Serotonin/genetics , Selective Serotonin Reuptake Inhibitors/therapeutic use , Case-Control Studies , Citalopram/administration & dosage , Endocrine System/drug effects , Genetic Markers , Selective Serotonin Reuptake Inhibitors/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
Apesar de décadas de estudos sobre os antidepressivos (ADs), seus mecanismos de ação permanecem obscuros. Muitos ADs interagem com receptores sigma e evidências crescentes sugerem que estas proteínas medeiam efeitos antidepressivos em animais e humanos. Os receptores sigma são subdivididos em dois subtipos, sigma-1 e sigma-2. Em particular, uma potencial atividade antidepressiva foi postulada para agonistas do receptor sigma-1, os quais se localizam predominantemente no reticulo- endoplasmático de neurônios e oligodendrócitos. Os receptores sigma estão localizados em regiões cerebrais que são afetadas na depressão e são capazes de modular a atividade dos sistemas centrais de neurotransmissores, incluindo os sistemas noradrenérgico, serotonérgico, dopaminérgico e glutamatérgico (NMDA), que são considerados importantes no mecanismo de ação dos ADs conhecidos. O foco desta revisão é discutir a literatura relacionada aos receptores sigma e aos seus ligantes em relação às suas propriedades antidepressivas.
Subject(s)
Humans , Male , Female , Antidepressive Agents/metabolism , Depression/etiology , Selective Serotonin Reuptake Inhibitors/analysis , Receptors, sigma/agonists , Receptors, sigma/classification , Glutamic Acid/metabolism , Serotonin Agents/analysisABSTRACT
OBJECTIVE: Comorbidity with personality disorders in obsessive-compulsive patients has been widely reported. About 40 percent of obsessive-compulsive patients do not respond to first line treatments. Nevertheless, there are no direct comparisons of personality traits between treatment-responsive and non-responsive patients. This study investigates differences in personality traits based on Cloninger's Temperament and Character Inventory scores between two groups of obsessive-compulsive patients classified according to treatment outcome: responders and non-responders. METHOD: Forty-four responsive and forty-five non-responsive obsessive-compulsive patients were selected. Subjects were considered treatment-responsive (responder group) if, after having received treatment with any conventional therapy, they had presented at least a 40 percent decrease in the initial Yale-Brown Obsessive Compulsive Scale score, had rated "better" or "much better" on the Clinical Global Impressions scale; and had maintained improvement for at least one year. Non-responders were patients who did not achieve at least a 25 percent reduction in Yale-Brown Obsessive Compulsive Scale scores and had less than minimal improvement on the Clinical Global Impressions scale after having received treatment with at least three selective serotonin reuptake inhibitors (including clomipramine), and at least 20 hours of cognitive behavioral therapy. Personality traits were assessed using Temperament and Character Inventory. RESULTS: Non-responders scored lower in self-directedness and showed a trend to score higher in persistence than responders did. CONCLUSION: This study suggests that personality traits, especially self-directedness, are associated with poor treatment response in obsessive-compulsive patients.
OBJETIVO: Comorbidade com transtornos de personalidade tem sido extensamente descrita no transtorno obsessivo-compulsivo. Aproximadamente 40 por cento dos pacientes com transtorno obsessivo-compulsivo não respondem a tratamentos de primeira linha. Não obstante, não existem estudos comparando diretamente traços de personalidade entre pacientes responsivos e refratários ao tratamento do transtorno obsessivo-compulsivo. Este estudo investiga diferenças nos traços da personalidade baseados no Inventário de Temperamento e Caráter de Cloninger (TCI) entre dois grupos de pacientes com transtorno obsessivo-compulsivo classificados segundo desfecho terapêutico: responsivos e refratários. MÉTODO: Quarenta e cinco pacientes refratários e 44 responsivos foram selecionados. Os indivíduos foram considerados responsivos se, após tratamento com terapêutica convencional, apresentaram diminuição de ao menos 40 por cento no escore inicial da Yale-Brown Obsessive Compulsive Scale, foram classificados como "melhor" ou "muito melhor" na Clinical Global Impressions; e mantiveram melhora por pelo menos um ano. Os refratários eram os pacientes que não atingiram redução de ao menos 25 por cento na Yale-Brown Obsessive Compulsive Scale e tiveram a melhoria menor que "mínima" na Clinical Global Impressions após o tratamento com ao menos três inibidores seletivos da recaptura de serotonina, incluindo clomipramina, e ao menos 20 horas da terapia cognitiva-comportamental. Os traços da personalidade foram avaliados através do Temperament and Character Inventory. RESULTADOS: Refratários pontuaram menos em autodirecionamento e tenderam a pontuar mais em persistência. CONCLUSÃO: Este estudo sugere que os traços de personalidade, especialmente autodirecionamento, estão associados com a resposta pobre do tratamento em pacientes com transtorno obsessivo-compulsivo.
Subject(s)
Adult , Female , Humans , Male , Obsessive-Compulsive Disorder/psychology , Obsessive-Compulsive Disorder/therapy , Personality Disorders/therapy , Temperament/physiology , Cross-Sectional Studies , Personality Disorders/psychology , Personality Inventory , Psychiatric Status Rating Scales , Psychotherapy , Self Efficacy , Statistics, Nonparametric , Treatment OutcomeABSTRACT
Testes provocativos com drogas serotonérgicas mostraram resultados conflitantes no TOC. O objetivo deste estudo foi comparar a atividade serotonérgica em pacientes com TOC resistente e respondedor ao tratamento com inibidores de recaptura de serotonina e voluntários saudáveis. Foram estudados 30 sujeitos em cada grupo. Cada um recebeu 20 mg de citalopram intravenoso. Foram dosados: prolactina, cortisol, hormônio de crescimento e serotonina periféricos a cada 20 minutos por 180 minutos. Não houve diferenças nas concentrações de serotonina e de hormônio de crescimento. A droga induziu um pico maior de prolactina no grupo Controle do que nos grupos Resistentes e Respondedores (p<0,05). A secreção de cortisol mostrou-se atenuada apenas no grupo Resistentes (p<0,05), sugerindo maior disfunção serotonérgica neste grupo...
Serotonergic pharmacological challenge tests have conflictant results in OCD. The aim of this study was to compare the serotonergic activity in serotonin reuptake inhibitors treatment resistant and responsive OCD patients and healthy volunteers. Thirty subjects were included in each group. Each one has received 20 mg of intravenous citalopram. Prolactin, cortisol, growth hormone and serotonin were determined peripherically at 20 minutes intervals for 180 minutes. No changes were observed either in serotonin or growth hormone concentration. Citalopram has induced an increase in prolactin secretion in the Control group, not observed in Resistant and Responsive groups (p<0.05). The cortisol response to citalopram was attenuated only in the Resistants (p<0.05), suggesting a more disrupted serotonergic transmission in this group...
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Citalopram/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Obsessive-Compulsive Disorder/therapy , Hydrocortisone , Growth Hormone/therapeutic use , Prognosis , Prolactin , Serotonin/therapeutic useABSTRACT
Os autores apresentam uma revisão de literatura sobre a farmacoterapia do transtorno de estresse pós-traumático (TEPT). Poucos ensaios clínicos controlados já foram feitos nesta área, mas o interesse no transtorno é crescente. Os antidepressivos, especialmente aqueles com atividade serotonérgica, parecem ser tratamentos farmacológicos eficazes no TEPT, seja como tratamento primário ou em associação com a psicoterapia