A randomized, double-blind, placebo-controlled trial to assess the efficacy of topiramate in the treatment of post-traumatic stress disorder

<p>Abstract</p> <p>Background</p> <p>Topiramate might be effective in the treatment of posttraumatic stress disorder (PTSD) because of its antikindling effect and its action in both inhibitory and excitatory neurotransmitters. Open-label studies and few controlled trials have suggested that this anticonvulsant may have therapeutic potential in PTSD. This 12-week randomized, double-blind, placebo-controlled clinical trial will compare the efficacy of topiramate with placebo and study the tolerability of topiramate in the treatment of PTSD.</p> <p>Methods and design</p> <p>Seventy-two adult outpatients with DSM-IV-diagnosed PTSD will be recruited from the violence program of Federal University of São Paulo Hospital (UNIFESP). After informed consent, screening, and a one week period of wash out, subjects will be randomized to either placebo or topiramate for 12 weeks. The primary efficacy endpoint will be the change in the Clinician-administered PTSD scale (CAPS) total score from baseline to the final visit at 12 weeks.</p> <p>Discussion</p> <p>The development of treatments for PTSD is challenging due to the complexity of the symptoms and psychiatric comorbidities. The selective serotonin reuptake inhibitors (SSRIs) are the mainstream treatment for PTSD, but many patients do not have a satisfactory response to antidepressants. Although there are limited clinical studies available to assess the efficacy of topiramate for PTSD, the findings of prior trials suggest this anticonvulsant may be promising in the management of these patients.</p> <p>Trial Registration</p> <p>NCT 00725920</p

Evolutionism and genetics of posttraumatic stress disorder

The authors discuss, from the evolutionary concept, how flight and fight responses and tonic immobility can lead to a new understanding of posttraumatic stress disorder. Through the analysis of symptom clusters (revivals, avoidance and hyperexcitation), neurobiological and evolutionary findings are correlated. The current discoveries on posttraumatic stress disorder genetics are summarized and analyzed in this evolutionary perspective, using concepts to understand the gene-environment interaction, such as epigenetic. The proposal is that the research of susceptibility factors in posttraumatic stress disorder must be investigated from the factorial point of view, where their interactions increase the risk of developing the disorder, preventing a unique search of the cause of this disorder. The research of candidate genes in posttraumatic stress disorder must take into consideration all the systems associated with processes of stress response, such as the hypothalamus-pituitary-adrenal and sympathetic axes, mechanisms of learning, formation and extinguishing of declarative memories, neurogenesis and apoptosis, which involve many systems of neurotransmitters, neuropeptides and neurohormones.Os autores discutem, a partir do conceito evolutivo, como a resposta de estresse, nas suas possibilidades de fuga e luta e de imobilidade tônica, pode levar a uma nova compreensão etiológica do transtorno de estresse pós-traumático. Através da análise dos agrupamentos de sintomas desse diagnóstico - revivência, evitação e hiperexcitação -, procuram correlacionar os achados neurobiológicos e evolutivos. As descobertas atuais sobre a genética do transtorno de estresse pós-traumático são resumidas e colocadas nessa perspectiva evolutiva, dentro de conceitos que possibilitam o entendimento da interação gene/ambiente, como a epigenética. Propõem que a pesquisa dos fatores de risco do transtorno de estresse pós-traumático deva ser investigada do ponto de vista fatorial, onde a somatória destes aumenta o risco de desenvolvimento do quadro, não sendo possível a procura da causa do transtorno de forma única. A pesquisa de genes candidatos no transtorno de estresse pós-traumático deve levar em consideração todos os sistemas associados aos processos de respostas ao estresse, sistemas dos eixos hipotálamo-hipofisário-adrenal e simpático, mecanismos de aprendizado, formação de memórias declarativas, de extinção e esquecimento, da neurogênese e da apoptose, que envolvem vários sistemas de neurotransmissores, neuropeptídeos e neuro-hormônios.Universidade Federal de São Paulo (UNIFESP)(UNIFESP)UNIFESP Departamento de PsiquiatriaUniversidade de São Paulo Faculdade de Medicin Hospital de ClínicasUNIFESP, Depto. de PsiquiatriaSciEL

Catechol-O-methyltransferase (COMT) val158met Polymorphism as a Risk Factor for PTSD After Urban Violence

PTSD is a psychiatric disorder that requires a traumatic event as diagnostic criteria. Brazil has high rates of violence, and it is expected that urban victims of violence would be at risk to the development of PTSD. Studies have associated the COMT val158met polymorphism with diminished stress resilience, reduced ability to extinguish conditioned fear, and the development of PTSD after multiple traumatic experiences. the aim of this study was to identify, in a case-control study, whether the val158met polymorphism (rs4860) is associated with the development of PTSD in a group of victims of urban violence. To our knowledge, this is the first study that examines the association between PTSD and urban violence. the polymorphism of COMT in PTSD patients (n = 65) as well as in victims of violence without PTSD (n = 34) and in a community control group (n = 335) were genotyped. We found a significant relationship between the met allele (p < 0.02) and PTSD among cases (PTSD+)and victims of violence without PTSD (PTSD-; OR 2.57) and between cases and community control group (p < 0.003) Further analysis with larger samples and another ethnic group should be necessary to confirm our findings.Fundacao de Amparo a Pesquisa Estado de São PauloCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Psiquiatria, Fac Med, BR-04023061 São Paulo, SP, BrazilKings Coll London, Inst Psychiat, Hlth Serv & Populat Res Dept, London WC2R 2LS, EnglandUniversidade Federal de São Paulo, Dept Psiquiatria, Fac Med, BR-04023061 São Paulo, SP, BrazilFundacao de Amparo a Pesquisa Estado de São Paulo: 2004/15039-0Web of Scienc