Clonidine for post-traumatic stress disorder: a systematic review of the current evidence

Background: Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep.Objective: In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD.Method: PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented.Results: Ten reports, accounting for N = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications.Conclusions: Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.Post-traumatic stress disorder (PTSD) is associated with hyperarousal and sleep disorders, reflecting adrenergic nervous system involvement.The use of anti-adrenergic drugs to target the sympathetic activation in PTSD is rational. However, previous reports on prazosin, a peripherally acting agent, yielded weak evidence.Clonidine, a central adrenergic antagonist, shows promise in improving sleep, nightmares, and PTSD symptoms, but further research is needed because the quality of the current evidence is low.Antecedentes: La clonidina es un agente antiadren & eacute;rgico de acci & oacute;n central que podr & iacute;a tener aplicaciones en el trastorno de estr & eacute;s postraum & aacute;tico (TEPT), particularmente para el sue & ntilde;o.Objetivo: En esta revisi & oacute;n sistem & aacute;tica el objetivo fue resumir el efecto de la clonidina sobre la calidad y duraci & oacute;n del sue & ntilde;o, las pesadillas y la gravedad de los s & iacute;ntomas de TEPT en adultos con TEPT.M & eacute;todo: Se realizaron b & uacute;squedas en PubMed (Medline), Embase, PsycINFO, CINAHL y Clinicaltrials.gov hasta abril de 2023. Se incluyeron estudios sobre el uso de clonidina en pacientes adultos con TEPT informando datos sobre el efecto en el sue & ntilde;o, pesadillas y s & iacute;ntomas de TEPT. Se presenta un resumen narrativo y un metan & aacute;lisis de los hallazgos del estudio.Resultados: En la selecci & oacute;n final se incluyeron diez comunicaciones, que representaban N = 569 pacientes con TEPT (145 con clonidina y 436 controles). Hubo 4 informes de casos, 4 estudios observacionales, 1 ensayo cl & iacute;nico no ciego y 1 ensayo cl & iacute;nico aleatorizado (ECA) cruzado. La dosis mediana de clonidina fue de 0,15 mg/d & iacute;a (rango: 0,1-0,5 mg/d & iacute;a). La mediana del tiempo de seguimiento fue de 31 d & iacute;as (entre 3 d & iacute;as y 19 meses). La calidad de la evidencia se calific & oacute; de muy baja a baja. Hubo una marcada heterogeneidad entre los estudios y un poder estad & iacute;stico bajo en los estudios individuales, pero muchos informaron una mejor calidad del sue & ntilde;o, una reducci & oacute;n de las pesadillas y una mejor & iacute;a de los s & iacute;ntomas de TEPT en los pacientes tratados con clonidina. El metan & aacute;lisis solo fue posible para dos estudios que informaron el efecto de la clonidina sobre las pesadillas y no mostr & oacute; diferencias con el comparador (es decir, prazosina o terazosina) (OR: 1,16; IC del 95 %: 0,66; 2,05), potencialmente apuntando hacia una no inferioridad entre estos medicamentos.Conclusiones: Se necesitan investigaciones futuras, como ECA de suficiente poder, para identificar la eficacia en el rango de dosis m & aacute;s bajo, el grupo de tratamiento m & aacute;s adecuado y obtener buena evidencia de los efectos de la clonidina para el tratamiento de los trastornos del sue & ntilde;o relacionados con el TEPT.