BACKGROUND: Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA).
METHODS: Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022.
RESULTS: Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score.
CONCLUSION: The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.
QUESTION: Randomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach.
STUDY SELECTION AND ANALYSIS: We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis.
FINDINGS: We analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=-1.11, 95% CI -1.22 to -1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40-0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias.
CONCLUSIONS: Placebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response.
PROSPERO REGISTRATION NUMBER: CRD42017069090.
BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.
OBJECTIVES: To assess the effects of medication for reducing PTSD symptoms in adults with PTSD.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD.
DATA COLLECTION AND ANALYSIS: Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity.
MAIN RESULTS: We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events.
AUTHORS' CONCLUSIONS: The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.
BACKGROUND: The purpose of this study was to compare efficacy and acceptability among drug treatments for adults with post-traumatic stress disorder (PTSD) through a systematic review, random-effects pairwise and network meta-analyses. METHODS: Double-blind randomized controlled trials comparing pharmacological interventions for adults with PTSD were searched from database inception through Aug. 28, 2018, on Cochrane (Central), Embase, LILACS, PILOTS, PsycINFO, PubMed, and Web of Science. Clinical trial registries and the websites of pharmaceutical companies were also searched. The GRADE system was used to assess the quality of the evidence. RESULTS: The systematic review included 58 studies comprising 6766 patients randomized to 26 different interventions. Regarding efficacy, topiramate (SMD = -0.57; 95%CrI: -1.07,-0.10), risperidone (SMD = -0.53; 95%CrI: -0.93,-0.15), quetiapine (SMD = -0.59; 95%CrI: -1.06,-0.11), paroxetine (SMD = -0.35; 95%CrI: -0.48,-0.21), venlafaxine (SMD = -0.25; 95%CrI: -0.44,-0.05), fluoxetine (SMD = -0.28; 95%CrI: -0.46,-0.08), and sertraline (SMD = -0.21; 95%CrI: -0.33,-0.09) outperformed placebo. Moreover, phenelzine (RR = 3.39; 95%CrI: 1.43,11.09), lamotrigine (RR = 4.39; 95%CrI: 1.18,26.38), and fluoxetine (RR = 1.28%CrI: 1.01,1.59) outperformed placebo in terms of acceptability. CONCLUSIONS: The NMA supports topiramate, risperidone, quetiapine, paroxetine, venlafaxine, fluoxetine and sertraline as effective pharmacological choices for the treatment of PTSD. Quetiapine and topiramate have the shortcoming of relying on a few small studies, but the clinically meaningful change in symptoms is noteworthy and merits further investigation. Among the pharmacological treatments with evidence of efficacy compared to placebo, fluoxetine achieved a relatively high rank regarding acceptability. To the best of our knowledge, this is the largest contemporary NMA on the subject and the addition of new medications is an important extension of previous meta-analyses, enabling a larger number of drug comparisons. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Las directrices actuales de práctica clínica (CPG) para el trastorno de estrés postraumático (TEPT) ofrecen recomendaciones contradictorias sobre el uso de medicamentos o psicoterapia como tratamiento de primera línea. Comparaciones directas de cabeza a cabeza carecen. MÉTODOS: Se realizó una revisión sistémica de Medline, EMBASE, PILOTS, Registro Cochrane Central de Ensayos Controlados, PsycINFO y Global Health Library sin restricciones de lenguaje. Ensayos clínicos aleatorios de ≥ 8 semanas de duración utilizando medidas de resultados clínicos basadas en entrevistas clínicas estructuradas, condiciones de control activo (por ejemplo, psicoterapia de apoyo) e análisis de intención de tratar (intention-to-treat analysis). La revisión independiente, la abstracción de datos y la evaluación de sesgo se realizaron mediante procesos estandarizados. Los resultados del estudio se agruparon en torno a los períodos de seguimiento convencionales (3, 6 y 9 meses). Los tamaños de efecto combinados se calcularon utilizando metanálisis para medicación versus control, medicación pre / post tratamiento, psicoterapia versus control, y psicoterapia pre / post tratamiento. RESULTADOS: Los tamaños de los efectos de las psicoterapias centradas en los traumatismos (PTF) versus las de control activo fueron mayores que los de los medicamentos versus el placebo y otras psicoterapias versus los controles activos. Los PTF resultaron en mayor beneficio sostenido en el tiempo que los medicamentos. Sertralina, venlafaxina y nefazodona superaron a otros medicamentos, aunque el potencial para sesgos metodológicos fue alto. La mejoría después del tratamiento con paroxetina y fluoxetina fue pequeña. Venlafaxine y el entrenamiento de la inoculación del esfuerzo (SIT) demostraron los efectos iniciales grandes que disminuyeron con el tiempo. Bupropión, citalopram, divalproex, mirtazapina, tiagabina y topiramato no se diferenciaron del placebo. El aripiprazol, el divalproex, la guanfacina y la olanzapina no se diferenciaron del placebo cuando se combinaron con un antidepresivo. Conclusiones: Los hallazgos del estudio apoyan el uso de TFPs sobre la psicoterapia o la medicación no enfocada en el trauma como intervenciones de primera línea. Las intervenciones de segunda línea incluyen SIT y potencialmente sertralina o venlafaxina, en lugar de clases completas de medicamentos, como los ISRS. Las revisiones futuras de CPGs deben dar prioridad a los estudios que utilizan controles activos sobre la lista de espera o condiciones de tratamiento como de costumbre. Se necesitan pruebas directas de TFPs frente a sertralina o venlafaxina.
Antecedentes El tratamiento farmacológico es ampliamente utilizado para el trastorno de estrés postraumático (TEPT) a pesar de las dudas sobre su eficacia. Objetivos Determinar la eficacia de todos los tipos de farmacoterapia, como monoterapia, en la reducción de síntomas de trastorno de estrés postraumático, y para evaluar la aceptabilidad. Se llevó a cabo Método Una revisión sistemática y meta-análisis de ensayos controlados aleatorios; Se incluyeron 51 estudios. Resultados Se encontraron los inhibidores selectivos de la recaptación de serotonina para ser estadísticamente superior al placebo en la reducción de los síntomas de TEPT, pero el tamaño del efecto fue pequeño (estandarizado diferencia -0,23; IC del 95%: -0,33 a -0,12 media). Para los agentes farmacológicos individuales en comparación con el placebo en dos o más ensayos, encontramos pequeña evidencia estadísticamente significativa de la eficacia de la fluoxetina, paroxetina y venlafaxina. Conclusiones Algunos medicamentos tienen un pequeño impacto positivo sobre los síntomas de TEPT y son aceptables. La fluoxetina, paroxetina y venlafaxina pueden ser considerados como posibles tratamientos para el trastorno. Para la mayoría de las drogas no hay pruebas suficientes respecto a la eficacia para el TEPT, que apunta a la necesidad de más investigación en esta área.
OBJECTIVE: Although benzodiazepines (BZDs) are commonly used in the treatment of posttraumatic stress disorder (PTSD), no systematic review or meta-analysis has specifically examined this treatment. The goal of this study was to analyze and summarize evidence concerning the efficacy of BZDs in treating PTSD.
METHODS: The review protocol was undertaken according to the principles recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and is registered with the PROSPERO international prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42014009318). Two authors independently conducted a search of all relevant articles using multiple electronic databases and independently abstracted information from studies measuring PTSD outcomes in patients using BZDs. Eighteen clinical trials and observational studies were identified, with a total of 5236 participants. Outcomes were assessed using qualitative and quantitative syntheses, including meta-analysis.
RESULTS: BZDs are ineffective for PTSD treatment and prevention, and risks associated with their use tend to outweigh potential short-term benefits. In addition to adverse effects in general populations, BZDs are associated with specific problems in patients with PTSD: worse overall severity, significantly increased risk of developing PTSD with use after recent trauma, worse psychotherapy outcomes, aggression, depression, and substance use. Potential biopsychosocial explanations for these results are proposed based on studies that have investigated BZDs, PTSD, and relevant animal models.
CONCLUSIONS: The results of this systematic review suggest that BZDs should be considered relatively contraindicated for patients with PTSD or recent trauma. Evidence-based treatments for PTSD should be favored over BZDs.
ANTECEDENTES: Se realizó el primer meta-análisis de estudios clínicos mediante la investigación de los efectos de la desensibilización de movimiento ocular y reprocesamiento (EMDR) la terapia de los síntomas del trastorno de estrés postraumático (TEPT), la depresión, la ansiedad y la angustia subjetiva en pacientes con TEPT tratadas durante las últimas 2 décadas.
MÉTODOS: Se realizó un meta-análisis cuantitativo sobre los resultados de 26 ensayos controlados aleatorios de la terapia EMDR para el TEPT publicados entre 1991 y 2013, que fueron identificados a través de la ISI Web of Science, Embase, Cochrane Library, MEDLINE, PubMed, Scopus, PsycINFO controlado , y el índice acumulado de las bases de datos electrónicas de Enfermería y Salud Aliada Literatura, entre los cuales 22, 20, 16, y 11 de los estudios evaluaron los efectos de la EMDR en los síntomas de trastorno de estrés postraumático, la depresión, la ansiedad y la angustia subjetiva, respectivamente, ya que la el resultado clínico primario.
RESULTADOS: El meta-análisis revelaron que los tratamientos EMDR redujo significativamente los síntomas de trastorno de estrés postraumático (g = -0,662; intervalo de confianza del 95% (IC): -0,887--0,436), depresión (g = -0,643; IC del 95%: - 0,864--0,422), ansiedad (g = -0,640; IC del 95%: -0,890 a -0,390), y la angustia subjetiva (g = -0,956; IC del 95%: -1,388 a -0,525) en pacientes con TEPT.
CONCLUSIÓN: Este estudio confirmó que la terapia EMDR reduce significativamente los síntomas de trastorno de estrés postraumático, la depresión, la ansiedad y la angustia subjetiva en pacientes con TEPT. El análisis de subgrupos indicó que una duración de tratamiento de más de 60 minutos por sesión fue un factor importante que contribuye a la mejora de la ansiedad y la depresión, y que un terapeuta con experiencia en la realización de la terapia de grupo TEPT fue un factor importante que contribuye a la reducción de los síntomas de TEPT .
OBJETIVO: Se revisó la literatura existente sobre la eficacia de los anticonvulsivos en el tratamiento del trastorno de estrés post-traumático.
MÉTODOS: Se realizó una búsqueda bibliográfica en PubMed, EMBASE y la base de datos Cochrane el 30 de septiembre de 2013. Estudios aleatorizados y controlados que investigaron la eficacia de los anticonvulsivantes para el trastorno de estrés post-traumático se incluyeron en esta revisión. Se excluyeron los estudios con diseños retrospectivos, informes de casos y series de casos.
RESULTADOS: Un total de siete estudios cumplieron los criterios de inclusión para esta revisión. Tres estudios utilizaron topiramato con resultados negativos en cuanto a su eficacia. Dos estudios utilizaron divalproex, los cuales no pudieron mostrar la superioridad sobre el placebo. Un estudio utilizó la lamotrigina, con resultados favorables, y un estudio utilizado tiagabina, con resultados negativos.
Se necesitan más estudios a largo plazo con muestras de mayor tamaño para investigar la utilidad clínica de los anticonvulsivantes para el tratamiento el trastorno de estrés postraumático: CONCLUSIONES.
INTRODUCCIÓN: Los antipsicóticos (AP) inducir el aumento de peso. Sin embargo, las revisiones y meta-análisis generalmente se limitan a los antipsicóticos de segunda generación (SGA) y no se estratifican mientras se use la AP. Es la hipótesis de que los pacientes ganan más peso si la duración del uso de AP es más largo.
MÉTODO: Un meta-análisis se llevó a cabo los ensayos clínicos de la AP que informaron el cambio de peso. Las medidas de resultado fueron el cambio de peso corporal, el cambio en el IMC y el cambio de peso clínicamente relevante (7% de ganancia o pérdida de peso). Duración de la AP-uso se estratificó la siguiente manera: ≤6 semanas, 6-16 semanas, 16-38 semanas y> 38 semanas. Diagramas de bosque estratificados por AP, así como por la duración de uso se generaron y los resultados se resumen en las figuras.
Resultados: 307 artículos cumplieron los criterios de inclusión. La mayoría eran AP cambiar estudios. Casi todos los AP mostró un grado de aumento de peso después de un uso prolongado, con excepción de la amisulprida, aripiprazol y ziprasidona, para los que la exposición prolongada resultó en el cambio de peso insignificante. El nivel de ganancia de peso por AP varió de discreta a grave. Contrariamente a lo esperado, el interruptor de AP no se tradujo en la pérdida de peso de la amisulprida, aripiprazol o ziprasidona. En pacientes-AP ingenuo, el aumento de peso fue mucho más pronunciada para todos AP.
CONCLUSIÓN: Teniendo en cuenta la exposición prolongada, la práctica totalidad de AP están asociados con el aumento de peso. El racional de conmutación AP para lograr la reducción de peso puede ser sobrevalorado. En pacientes-AP ingenuo, el aumento de peso es más pronunciado.
Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA).
METHODS:
Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022.
RESULTS:
Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI.: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI.: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI.: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI.: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI.: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI.: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI.: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score.
CONCLUSION:
The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.