Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
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)
OBJECTIVE: To systematically review outcomes from randomized controlled trials (RCTs) of mind–body treatments for PTSD. METHODS: Inclusion criteria based on guidelines for assessing risk of bias were used to evaluate articles identified through electronic literature searches. RESULTS: Twenty‐two RCTs met inclusion standards. In most of the nine mindfulness and six yoga studies, significant between‐group effects were found indicating moderate to large effect size advantages for these treatments. In all seven relaxation RCT's, relaxation was used as a control condition and five studies reported significant between‐group differences on relevant PTSD outcomes in favor of the target treatments. However, there were large within‐group symptom improvements in the relaxation condition for the majority of studies. CONCLUSIONS: Although many studies are limited by methodologic weaknesses, recent studies have increased rigor and, in aggregate, the results for mindfulness, yoga, and relaxation are promising. Recommendations for design of future mind–body trials are offered. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
La presente revisión tiene como objetivo evaluar la eficacia clínica y la seguridad del antagonista α-1-adrenérgico prazosin como tratamiento farmacológico primario para el trastorno de estrés postraumático (TEPT). MÉTODO: En las bases de datos PubMed / Medline (1966-mayo de 2016), Embase (1966 - mayo de 2016), se realizó una revisión sistemática utilizando palabras clave (prazosina, antagonista α-1-adrenérgico, α-1-bloqueante, trastorno de estrés postraumático) Mayo de 2016), ScienceDirect (1823-mayo de 2016), OvidSP (1946-mayo de 2016) y Nature (1845-mayo de 2016). Para ser considerados para su inclusión, los estudios tuvieron que probar la eficacia de la prazosina sola o agregada al tratamiento en curso en adultos con TEPT, utilizar herramientas validadas para evaluar y monitorear los trastornos, permitir comparaciones sobre la base de análisis univariados (p. De las pruebas t y los tamaños del efecto) y enumere las reacciones adversas identificadas. RESULTADOS: Se incluyeron 12 estudios: 5 ensayos controlados aleatorios, 4 ensayos prospectivos abiertos y 3 exámenes retrospectivos de archivos. La evaluación incluyó a 276 pacientes expuestos a trauma civil (19%) o trauma de guerra (81%). Prazosin disminuye significativamente traumas de pesadillas, evitación, hipervigilancia y mejora el estado del paciente en todos los estudios. No se observó diferencia significativa de la presión arterial al final de los ensayos. CONCLUSIONES: Además de los sesgos metodológicos y clínicos de estos estudios, la presente revisión no sólo confirma la efectividad y buena tolerabilidad de la prazosina, sino que también sugiere su posible uso como tratamiento farmacológico primario para el TEPT. Sin embargo, siguen existiendo incertidumbres en cuanto a las modalidades de prescripción y las dosis.
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.
Las intervenciones basadas en la atención plena (MBI) se han utilizado cada vez más en la gestión de las condiciones de salud mental. Esta primera revisión de una serie de dos partes evalúa la eficacia, el mecanismo y la seguridad de la meditación de atención plena para las condiciones de salud mental frecuentemente observadas después del retorno del despliegue. Las bases de datos estándar se registraron hasta el 4 de agosto de 2015. Se incluyeron 52 revisiones sistemáticas y ensayos clínicos aleatorios. Se utilizó la taxonomía de la fuerza de la recomendación (SOR) para evaluar la calidad de los estudios individuales y para calificar la fuerza de la evidencia para cada condición clínica. La terapia cognitiva complementaria basada en la atención plena es eficaz para disminuir la gravedad de los síntomas durante el episodio depresivo actual y para reducir la tasa de recaída en los pacientes recuperados durante la fase de mantenimiento del tratamiento de la depresión. La reducción de estrés asociada a la atención plena es eficaz para mejorar los síntomas, la calidad de vida relacionada con la salud mental y la atención plena en veteranos con trastorno de estrés postraumático de combate (PTSD) (SOR B). Actualmente, no hay datos suficientes para recomendar MBIs para el trastorno de ansiedad generalizada (SOR B). Los MBI son seguros, portátiles, rentables y pueden ser recomendados como un complemento de la estrategia estándar de atención o autogestión para el trastorno depresivo mayor y PTSD. Futuros ensayos clínicos aleatorios grandes y bien diseñados en miembros de servicio y veteranos pueden ayudar a planificar el anticipado aumento de la demanda de servicios de salud conductual.
El propósito de este estudio fue evaluar la aceptabilidad y eficacia de todos los tipos de agentes farmacoterapéuticos en la reducción de los síntomas del trastorno de estrés postraumático (TEPT). En este metanálisis sistemático, se compararon las tasas de abandono y respuesta de varios tratamientos de farmacoterapia y placebo informados por ensayos clínicos aleatorios. Se recuperaron y analizaron un total de 34 informes que describieron la aceptabilidad y la eficacia de las farmacoterapias de TEPT. De ellos, 30 ensayos examinaron la tasa de abandono como un índice de aceptabilidad y revelaron la superioridad de la farmacoterapia de PTSD a placebos (odds ratio, 0,75; intervalo de confianza del 95%, 0,66-0,86; n = 4313). La tasa de respuesta se determinó en 20 ensayos como un índice de eficacia, mostrando que las farmacoterapias del TEPT eran superiores a los placebos (odds ratio: 1,47; intervalo de confianza del 95%: 1,34-1,62; n = 2166). La farmacoterapia es un componente importante del cuidado de pacientes con TEPT.
Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI.: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI.: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI.: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI.: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI.: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI.: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI.: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI.: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI.: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
