Concomitant treatment with sertraline and social skills training improves social skills acquisition in social anxiety disorder: A double-blind, randomized controlled trial.

OBJECTIVES: To examine whether: (1) sertraline (SER) + psychotherapy is superior to psychotherapy alone; (2) group cognitive-behavioural therapy (GCBT) is superior to group psychodynamic therapy (GPT) and (3) SER+GCBT or SER+GPT is superior to Placebo (PLA)+GCBT or PLA+GPT in social anxiety disorder (SAD). METHODS: A double-blind randomized controlled trial. Participants were assigned either to: SER+GCBT (n = 34); SER+GPT (n = 36); PLA+GCBT (n = 36) or PLA+GPT (n = 41) for 20 weeks. SER (or PLA) was administered at doses from 50 to 200 mg/d. Primary measures were both categorial: remission (CGI score≤2), response of social symptoms (≥50% reduction in Scale of Avoidance and Social Discomfort (SASD)); and continuous: reduction of SASD and Multidimensional Scale of Social Expression(M-MSSE). RESULTS: SER exhibited better improvement of social anxiety symptoms rate than PLA (25.73% vs. 9.46%, P < .05). Neither GCBT differed from GPT (12.33% vs. 22.54%, P = .11) nor SER+GCBT from PLA+GCBT (17.65% vs. 7.69%, P = .20). However, SER+GPT was superior to PLA+GPT (33.33%, vs. 11.43%, P < .05). M-MSSE had superior improvement for SER+GCBT vs PLA+GCBT (P < .01) but not for SER+GPT vs. PLA+GPT (P = .80). SASD scores improvement were greater for SER than PLA (P < .01) and for SER+GCBT vs. PLA+GCBT (P < .05), but neither GCBT differed from GPT(P = .60) nor SER+GPT differed from PLA+GPT (P = .09). CONCLUSIONS: In overall, SER+psychotherapy was superior to psychotherapy alone. SER potentiated GCBT by enhancing social skills acquisition. TRIAL REGISTRATION: ISRCTN 57551461.

The putative catalytic role of higher serotonin bioavailability in the clinical response to exposure and response prevention in obsessive-compulsive disorder

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.

The putative catalytic role of higher serotonin bioavailability in the clinical response to exposure and response prevention in obsessive-compulsive disorder.

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.

Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder.

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 1Dß 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 1Dß 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.

Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder

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.

Receptores sigma1: um novo alvo para o tratamento farmacológico da depressão? / A new target for the pharmacologycal treatment of depression?

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.

Personality traits and treatment outcome in obsessive-compulsive disorder.

OBJECTIVE: Comorbidity with personality disorders in obsessive-compulsive patients has been widely reported. About 40% 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% 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% 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.

Personality traits and treatment outcome in obsessive-compulsive disorder / Traços de personalidade e resposta terapêutica no transtorno obsessivo-compulsivo

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.

Acute hormonal changes after IV citalopram and treatment response in OCD.

RATIONALE: Serotonergic pharmacological challenges have failed to produce consensual results in patients with obsessive-compulsive disorder (OCD), suggesting a heterogeneous 5-hydroxytryptamine (5-HT) activity in this disorder. OBJECTIVES: The aim of this study was to compare the neuroendocrine response to a serotonergic challenge in OCD patient responders (RP) and nonresponders (NR) to serotonin reuptake inhibitors treatment and healthy volunteers. MATERIALS AND METHODS: Thirty OCD treatment NR, 30 RP, and 30 controls (CN) matched for sex and age were included. Each subject received 20 mg of intravenous citalopram. Prolactin, cortisol, and growth hormone plasma concentration were measured at times-20, 0, 20, 40, 60, 80, 100, 120, 140, and 160 min after the onset of citalopram infusion. RESULTS: Citalopram did not induce anxiety or OCD symptoms in patients. Citalopram was associated with stronger prolactin response in the CN group (maximal percentage variation [max%Delta] = 65.76 +/- 105.1) than in NR (max%Delta = 17.41 +/- 31.06) and RP groups (max%Delta = 15.87 +/- 31.71; p = 0.032; Friedman chi (2) = 6.87; df = 2). On the other hand, cortisol response did not differ between CN and RP groups and was blunted in the NR group (NR max%Delta = 20.98 +/- 58.14 vs RP max%Delta = 47.69 +/- 66.94; CN max%Delta = 63.58 +/- 88.4; p = 0.015; Friedman chi (2) = 8.60; df = 2). CONCLUSIONS: Compared to CN, both treatment RP and NR patients showed blunted prolactin response to citalopram, but only NR patients showed an attenuated cortisol response, suggesting a more disrupted central serotonergic transmission in this group.

Resposta neuroendócrina aguda ao citalopram e resposta terapêutica no transtorno obsessivo-complusivo / Acute neuroendocrine response to citalopram and therapeutic response in obsessive-compulsive disorder

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...

[Pharmacological treatment of posttraumatic stress disorder]. / Tratamento farmacológico do transtorno de estresse pós-traumático.

The authors present a review of pharmacotherapy for posttraumatic stress disorder (PTSD). Only a few controlled clinical trials have been carried out on PTSD, but there is a growing interest on this topic. Antidepressants, specially those with serotonergic activity, appear to provide effective pharmacotherapy for PTSD, as having either a primary therapeutic effect or in association with psychotherapy.

Tratamento farmacológico do transtorno de estresse pós-traumático / Pharmacological treatment of posttraumatic stress disorder

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

Panic attacks in the differential diagnosis and treatment of resistant epilepsy.

The authors present four patients displaying panic disorder and a history of epileptic seizures to illustrate difficulties regarding differential diagnosis between epileptic seizures and panic attacks. The cases describe the aversive properties of epileptic seizures, the role of visual seizure-triggering stimuli as phobic cues, and the effectiveness and safety of clomipramine treatment of panic attacks as an adjunct to concurrent antiepileptic medication.