8 research outputs found
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 SĂŁo 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
Sleep pattern and inflammatory markers assessment: longitudinal study of women victims of sexual violence with posttraumatic stress disorder
Introdução: A violĂŞncia sexual Ă© um problema de saĂşde pĂşblica e está associada Ă maior risco de desenvolvimento de transtorno de estresse pĂłs-traumático (TEPT). Os pesadelos e a insĂ´nia sĂŁo queixas frequentes e considerados sintomas centrais no TEPT. Os distĂşrbios do sono estĂŁo associados com alterações no sistema imunolĂłgico e desempenham papel fundamental no desenvolvimento e evolução deste transtorno, enfatizando a importância de estudos do sono no TEPT . Objetivos: Investigar o padrĂŁo de sono em mulheres com TEPT, vĂtimas de violĂŞncia sexual, e sua associação com marcadores inflamatĂłrios. MĂ©todos: Participaram deste estudo, longitudinal e prospectivo, setenta e quatro mulheres com TEPT (grupo TEPT) que sofreram violĂŞncia sexual, com intervalo máximo de seis meses do evento traumático, e sessenta e quatro mulheres saudáveis sem histĂłria de violĂŞncia sexual (grupo Controle). A primeira avaliação foi realizada no momento basal (T1). As participantes foram avaliadas clinicamente e as seguintes escalas foram aplicadas: Entrevista Neuropsiquiátrica Internacional (MINI), Escala de TEPT Administrada pelo ClĂnico (CAPS-5), Inventário de DepressĂŁo de Beck (BDI), Inventário de Ansiedade de Beck (BAI), ĂŤndice de Qualidade do Sono de Pittsburgh (PSQI), ĂŤndice de Qualidade do Sono de Pittsburgh addendum para TEPT (PSQI-A), ĂŤndice de Gravidade de InsĂ´nia (IGI), Escala de SonolĂŞncia de Epworth (ESE), Escala de Impacto de Fadiga Modificada (MFIS). TambĂ©m foram realizados exame de polissonografia (PSG) e dosagem sĂ©rica de IL-1β, IL-6, PCR e TNF-α. As participantes do grupo TEPT foram randomizadas para receber tratamento com sertralina ou psicoterapia interpessoal (IPT) por 14 semanas. ApĂłs o ensaio clĂnico, as participantes foram acompanhadas atĂ© completar um ano, com o tratamento usual, conforme a necessidade. A segunda avaliação do grupo TEPT foi realizada apĂłs um ano de seguimento (T2), sendo repetidas as avaliações clĂnicas, PSG e dosagens dos marcadores inflamatĂłrios. Resultados: O grupo TEPT apresentou pior qualidade do sono (p<0,001) na escala subjetiva do sono e diminuição do tempo total do sono (p=0,05) na PSG, porĂ©m, sem diferença com relação Ă sonolĂŞncia excessiva diurna (p=0,84) em comparação ao grupo Controle. ApĂłs 1 ano de estudo, o grupo TEPT apresentou melhora significativa dos sintomas do TEPT (p<0,001) e depressĂŁo (p<0,001). No entanto, apesar da melhora significativa da qualidade do sono (p=0,001) e da gravidade da insĂ´nia (p<0,001), as pacientes ainda apresentavam uma qualidade do sono ruim (PSQI=6,81), insĂ´nia (IGI=7,73) e fragmentação do sono (ID=13,44).
A melhora da gravidade dos sintomas do TEPT estava significativamente associada Ă melhora da qualidade do sono (p=0,03). AlĂ©m disso, houve aumento significativo dos nĂveis dos marcadores inflamatĂłrios IL-1β (p<0,001), PCR (p<0,001) e TNF-α (p<0,001) apĂłs um ano e esse aumento nĂŁo estava associado aos sintomas do TEPT. O aumento dos nĂveis de TNF-α, PCR e IL-6 estava associado Ă diminuição do sono de ondas lentas (p=0,018), gravidade de insĂ´nia (p=0,012) e fragmentação do sono (p=0,024) respectivamente.
Conclusão: Neste estudo, o aumento das citocinas pró-inflamatórias estava associado com a gravidade da insônia, fragmentação do sono e diminuição do sono profundo, sugerindo a associação desses imunomoduladores com os distúrbios do sono no TEPT. A restrição e a fragmentação crônica do sono no TEPT podem estar associadas à gradual e persistente alteração no sistema imune, resultando em processo inflamatório crônico. Diante disso, as mudanças que ocorrem no sistema imunológico por causa da privação de sono podem ser um fator de risco para diversas patologias como as doenças cardiovasculares e neurodegenerativas. Portanto, a restauração do sono pode, não apenas contribuir para a redução dos sintomas de TEPT, mas também, redução da resposta inflamatória sistêmica nesta amostra de mulheres com TEPT.Introduction: Sexual violence is a public health problem. It is associated with a higher risk for post-traumatic stress disorder (PTSD) development. Nightmares and insomnia are frequently reported symptoms and are considered core clinical features of PTSD. Sleep disturbances are associated with changes in the immune system and play a key role in the development and course of this disorder, emphasizing the importance of sleep studies in individuals with PTSD.
Objectives: To investigate sleep pattern in women with PTSD following sexual assault and its relationship with inflammatory markers.
Methods: Seventy-four women with PTSD (PTSD group) with history of sexual assault in the prior 6 months before enrollment and sixty-four healthy women (Control group) with no history of sexual violence participated in this longitudinal and prospective study. The first assessment was performed at baseline (T1). Participants were clinically evaluated and the following scales were applied: International Neuropsychiatric Interview (MINI), Clinician-Administered PTSD Scale-5 (CAPS-5), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), Pittsburgh Sleep Quality Index addendum for Post-Traumatic Stress Disorder (PSQI-A), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Modified Fatigue Impact Scale (MFIS). In addition, full in-lab polysomnography (PSG) and serum levels of IL-1β, IL-6, TNF-α, and CRP were performed. Participants in the PTSD group were randomized to receive either sertraline treatment or interpersonal psychotherapy (IPT) for 14 weeks. After the clinical trial, participants were followed up to one year, with standard treatment. The second assessment of the PTSD group was performed after one-year follow-up (T2): clinical assessments, PSG and inflammatory markers measurements.
Results: The PTSD group had worse sleep quality (p<0.001) on the subjective sleep assessments and a decrease in total sleep time (p=0.05) on the PSG parameters, however with no difference concerning excessive daytime sleepiness (p=0.84) compared to the Control group. After one year of follow-up, the PTSD group showed significant improvement in PTSD symptoms (p<0.001) and depression (p<0.001). However, despite the significant improvement in sleep quality (p=0.001) and insomnia severity (p<0.001), the participants with PTSD still had poor sleep quality (PSQI=6.81), insomnia (IGI=7.73), and sleep fragmentation (ID=13.44). The improvement in PTSD symptoms severity was significantly associated with improvement in sleep quality (p=0.03). Furthermore, there was a significant increase in the levels of the inflammatory markers IL-1β (p<0.001), TNF-α (p<0.001), and CRP (p<0.001) after one year, and this increase were not associated with PTSD symptoms. Increased levels of TNF-α, CRP, and IL-6 were associated with decreased slow wave sleep (p=0.018), insomnia severity (p=0.012), and sleep fragmentation (p=0,024), respectively.
Conclusions: In this study, the increase in pro-inflammatory cytokines was associated with insomnia, sleep fragmentation, and decreased slow-wave sleep, suggesting the association of these immunomodulators with sleep disturbances in PTSD. Chronic sleep restriction and fragmentation may be associated with a gradual and persistent alteration in the immune system, resulting in a progressive inflammatory process, which, in turn, may be risk factor for several pathologies such as cardiovascular and neurodegenerative diseases. Therefore, restorative sleep may not only contribute to the reduction of PTSD symptoms but also reduce the systemic inflammatory response in women with PTSD.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)303389/2016-82014/12559-