Posttraumatic stress disorder (PTSD) is an anxiety disorder experienced by combat veterans. Nighttime symptoms are often unrelieved by selective serotonin reuptake inhibitor therapy, and increased use of prazosin or quetiapine for treatment is seen. The purpose of this study was to determine the short- and long-term effectiveness and safety of prazosin versus quetiapine for treating nighttime symptoms in veteran PTSD patients. This is a historical prospective cohort study using retrospective chart review. Three hundred twenty-four patients with a diagnosis of PTSD, based on International Classification of Diseases, Ninth Revision coding, who were initially prescribed prazosin or quetiapine for nighttime symptoms were screened for inclusion. Short-term effectiveness was determined by documentation of symptomatic improvement within 6 months, and long-term effectiveness if patients continued therapy to study end date. Safety was assessed by comparing incidence of adverse drug effects causing discontinuation of either study drug. This study included 237 patients: 62 received prazosin, and 175 received quetiapine. Short-term effectiveness was similar for prazosin (61.3%) and quetiapine (61.7%; P = 0.54). However, patients prescribed prazosin were significantly more likely to continue their therapy to study end date compared with quetiapine (48.4% vs 24%; P < 0.001; odds ratio, 3.0; 95% confidence interval, 1.62-5.45), thus achieving long-term effectiveness. Alternatively, patients in the quetiapine group were more likely to discontinue therapy because of adverse effects compared with the prazosin group (34.9% vs 17.7%; P = 0.008). Because of similar rate of short-term effectiveness, superior long-term effectiveness, and lower incidence of events leading to discontinuation, compared with quetiapine, prazosin should be used first-line for treating nighttime PTSD symptoms in a veteran population.
Twenty-two veterans with posttraumatic stress disorder (PTSD) were assessed for trauma-related nightmares and nonnightmare distressed awakenings (NNDA) before and after treatment with the alpha-1 adrenoreceptor antagonist prazosin at an average bedtime dose of 9.6 mg/day. Ratings combining frequency and intensity dimensions of trauma-related nightmares decreased from 3.6 to 2.2, NNDA from 5.2 to 2.1, and sleep difficulty from 7.2 to 4.1 per week. These results suggest that increased brain adrenergic activity may contribute to the pathophysiology of both trauma-related nightmares and NNDA in PTSD.
ANTECEDENTES: La prazosina, un sistema nervioso central (SNC) activo alfa-1 adrenérgicos antagonista, ha reducido las pesadillas y trastornos del sueño en los estudios controlados con placebo de trastorno de estrés postraumático relacionado con el combate (TEPT). Se evaluaron los parámetros del sueño objetiva y síntomas de TEPT en un ensayo controlado con placebo, prazosin para TEPT civil relacionada con el trauma.
MÉTODOS: Trece pacientes ambulatorios con trastorno de estrés postraumático crónico trauma civil, pesadillas frecuentes, y trastornos del sueño participaron en un ensayo cruzado aleatorio controlado con placebo de prazosina. Parámetros del sueño se cuantificaron en casa con la REMView (Respironics, Pittsburgh, Pensilvania). Los síntomas de TEPT se cuantificaron con el Médico Administrado TEPT Escala (CAPS) "sueños recurrentes angustiantes" y "sueño perturbado" artículos, una escala no pesadilla despertares en dificultades, el trastorno de estrés postraumático Sueño Rating Scale (PDRS), el Checklist-Civilian TEPT (PCL -C) y la Impresión Clínica Global de Mejora (CGI-I).
RESULTADOS: La prazosina comparación con el placebo aumentó significativamente el tiempo total de sueño por 94 minutos; aumento de movimientos oculares rápidos (REM) el tiempo de sueño y la media de duración del periodo REM sin alterar la latencia del inicio del sueño; reducido significativamente pesadillas relacionadas con el trauma, despertares en dificultades, y las puntuaciones totales PCL; significativamente mejores puntuaciones de la CGI-I; y cambió las puntuaciones PDRS hacia el sueño normal.
CONCLUSIONES: La reducción de los síntomas de TEPT Prazosin nocturnas en TEPT trauma civil se acompañan de un aumento del tiempo total de sueño, tiempo de sueño REM y REM duración del periodo en la ausencia de un efecto sedante como la latencia de inicio del sueño significan.
ANTECEDENTES: la capacidad de respuesta cerebral excesiva a la norepinefrina parece contribuir al trastorno por estrés postraumático (TEPT), sobre todo por la noche. Prazosina, un activo alfa-1 antagonista de los receptores adrenérgicos cerebro, reduce significativamente las pesadillas de trauma y los trastornos del sueño en 10 veteranos de combate de la guerra de Vietnam en un estudio anterior cruzado y controlado con placebo. El ensayo de grupos paralelos actual en una muestra mayor de veteranos evaluaron efectos prazosina en pesadillas de trauma, la calidad del sueño, el estado clínico global, las características de ensueño, y depresión comórbida.
MÉTODOS: Cuarenta veteranos con TEPT crónico y pesadillas angustiantes trauma y trastornos del sueño fueron asignados al azar a la prazosina noche (13,3 +/- 3 mg / día) o placebo durante 8 semanas (56 años +/- 9 significan).
Resultados: En la muestra evaluables (n = 34), las medidas de resultado primarias demostraron que prazosina fue significativamente superior al placebo para reducir las pesadillas de trauma y la mejora de la calidad del sueño y el estado clínico global con grandes tamaños del efecto. Prazosin cambió características oníricas de los típicos de pesadillas relacionadas con el trauma hacia los que son típicos de los sueños normales. Cambios en la presión arterial desde el inicio hasta el final del estudio no difirieron significativamente entre prazosina y placebo.
CONCLUSIONES: La prazosina es un tratamiento eficaz y bien tolerado para las pesadillas de trauma, trastornos del sueño y el estado clínico global en los veteranos con TEPT crónico.
OBJECTIVE: Increased central nervous system norepinephrine outflow and alpha1-adrenergic receptor responsiveness appear to be involved in the pathophysiologic processes of trauma-related nightmares in post-traumatic stress disorder. On the basis of reports that the brain-accessible alpha1-adrenergic antagonist Prazosin substantially reduced chronic combat-related nightmares among Vietnam War veterans, we evaluated Prazosin effects on combat-related nightmares among combat soldiers returning from Operation Iraqi Freedom.
METHODS: Twenty-eight soldiers who self-reported distressing combat trauma-related nightmares on a postdeployment questionnaire were prescribed low-dose Prazosin before bedtime.
RESULTS: Of the 23 soldiers for whom follow-up evaluations were available, 20 experienced marked improvement (complete elimination of nightmares), 2 experienced moderate improvement (reduced nightmare frequency or intensity), and 1 experienced no change. Prazosin was well tolerated.
CONCLUSIONS: Prazosin appeared highly beneficial for combat-related nightmares characteristic of post-traumatic stress disorder among troops recently returned from Operation Iraqi Freedom. These findings provide a rationale for a placebo-controlled trial to establish efficacy in this population.
OBJETIVO: La prazosina es un alfa central activo (1) antagonista adrenérgico. El objetivo de los autores fue evaluar la eficacia prazosina para pesadillas, trastornos del sueño y el trastorno general de estrés postraumático (TEPT) en los veteranos de guerra.
MÉTODO: Diez veteranos de guerra de Vietnam con TEPT crónico y graves relacionados con el trauma pesadillas cada prazosina recibieron placebo y en un protocolo cruzado de 20 semanas doble ciego.
RESULTADOS: Prazosin (dosis media = 9,5 mg / día al acostarse, SD = 0,5) fue superior al placebo para las tres medidas de resultado primarias: Las puntuaciones en el 1) Tema recurrente sueños angustiantes y 2 del) dificultad para quedarse / permanecer dormido tema de la Clínico-administrada TEPT Escala y 3) el cambio en la severidad global trastorno de estrés postraumático y el estado funcional de acuerdo con la Impresión Clínica Global de cambio. Total de las puntuaciones de racimo y puntuación de síntomas de reexperimentación, evitación / embotamiento e hiperexcitación en el Clínico-administrada Escala de TEPT también fueron significativamente más mejorado en la condición de prazosin y prazosina fue bien tolerado.
Conclusiones: Estos datos apoyan la eficacia de la prazosina para pesadillas, trastornos del sueño y otros síntomas de TEPT.
Trauma-related nightmares in posttraumatic stress disorder (PTSD) rarely respond to pharmacologic treatment. Neurobiologic data suggest that enhanced brain responsiveness to adrenergic stimulation may contribute to the pathophysiology of trauma-related nightmares in PTSD. Nine older men with chronic PTSD secondary to military or Holocaust physiology trauma were prescribed the lipophilic alpha-1 adrenergic antagonist prazosin for treatment-resistant trauma-related nightmares. Prazosin 2 mg to 4 mg 1 hour before bedtime substantially reduced nightmares and moderately or markedly reduced overall PTSD severity in 8 of 9 subjects. Prazosin was well tolerated. These open-label results are consistent with demonstrated therapeutic efficacy of prazosin for PTSD nightmares and sleep disturbance in a recent placebo-controlled trial in Vietnam veterans. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Notes that heightened noradrenergic reactivity may be a contributing factor in the pathophysiology of posttraumatic stress disorder (PTSD). Prazosin is an α₁ adrenoceptor antagonist commonly used as an antihypertensive agent. Five outpatients (aged 35-58 yrs) with non-combat related PTSD were consecutively identified and received prazosin in a 6-wk open-label trial. In each case, the prazosin doses were slowly increased until optimal benefit was achieved. Change was assessed with the Clinician-Administered PTSD Scale for DSM-IV, One Week Symptom Version (CAPSSX), the Clinical Global Impression of Change Scale (CGIC), and the Clinical Impression of ChangeNightmares (CIC-Nightmares) score. All 5 patients experienced moderate to marked improvement on the CGIC. The CAPS-SX PTSD nightmare and sleep PTSD categories showed at least a 4 point reduction of those symptoms. All patients reported at least moderate improvement on the CIC-Nightmare score. Optimal doses of prazosin ranged from 1 to 4 mg/day. The drug was reasonably tolerated, and there were no drug discontinuations.These preliminary findings provide a rationale for blind placebo-controlled efficacy trials of the α₁ antagonist prazosin for PTSD. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
BACKGROUND: Preclinical and clinical observations suggest that the centrally active alpha1-adrenergic antagonist prazosin might alleviate trauma content nightmares and other symptoms in combat veterans with chronic posttraumatic stress disorder (PTSD).
METHOD: In this retrospective chart review study, we analyzed data from 59 consecutive combat veterans with previously treatment-resistant chronic PTSD (DSM-IV criteria) and severe intractable trauma content nightmares to whom prazosin had been prescribed. Nightmare severity was quantified using the recurrent distressing dreams item of the Clinician Administered PTSD Scale (CAPS). Change in overall PTSD severity exclusive of nightmares was estimated by assigning a Clinical Global Impressions-Change scale (CGI-C) score based on chart review.
RESULTS: Mean +/- SEM recurrent distressing dreams item scores improved significantly (7.0 +/- 0.2 to 3.5 +/- 0.3, p <.0001) in the 36 patients who completed at least 8 weeks of prazosin treatment at their maximum titrated dose. The mean maximum prazosin dose achieved in these 36 patients was 9.6 +/- 0.9 mg/day. Recurrent distressing dreams scores also improved in the total group who filled their prazosin prescriptions (N = 51) (7.1 +/- 0.2 to 4.2 +/- 0.3, p <.0001). In a comparison group of 8 patients who did not fill their prazosin prescriptions but continued in outpatient treatment, there was no significant change in CAPS recurrent distressing dreams score (6.8 +/- 0.5 to 6.7 +/- 0.4). There also was at least some improvement in CGI-C ratings of overall PTSD severity exclusive of nightmares in a substantial majority of patients receiving prazosin, but not in the 8 comparison subjects. There were no serious adverse effects attributable to prazosin.
CONCLUSION: These observations suggest that prazosin may relieve symptomatic distress in PTSD, and they provide rationale for placebo-controlled trials of prazosin for PTSD trauma content nightmares and other PTSD symptoms.
Posttraumatic stress disorder (PTSD) is an anxiety disorder experienced by combat veterans. Nighttime symptoms are often unrelieved by selective serotonin reuptake inhibitor therapy, and increased use of prazosin or quetiapine for treatment is seen. The purpose of this study was to determine the short- and long-term effectiveness and safety of prazosin versus quetiapine for treating nighttime symptoms in veteran PTSD patients. This is a historical prospective cohort study using retrospective chart review. Three hundred twenty-four patients with a diagnosis of PTSD, based on International Classification of Diseases, Ninth Revision coding, who were initially prescribed prazosin or quetiapine for nighttime symptoms were screened for inclusion. Short-term effectiveness was determined by documentation of symptomatic improvement within 6 months, and long-term effectiveness if patients continued therapy to study end date. Safety was assessed by comparing incidence of adverse drug effects causing discontinuation of either study drug. This study included 237 patients: 62 received prazosin, and 175 received quetiapine. Short-term effectiveness was similar for prazosin (61.3%) and quetiapine (61.7%; P = 0.54). However, patients prescribed prazosin were significantly more likely to continue their therapy to study end date compared with quetiapine (48.4% vs 24%; P < 0.001; odds ratio, 3.0; 95% confidence interval, 1.62-5.45), thus achieving long-term effectiveness. Alternatively, patients in the quetiapine group were more likely to discontinue therapy because of adverse effects compared with the prazosin group (34.9% vs 17.7%; P = 0.008). Because of similar rate of short-term effectiveness, superior long-term effectiveness, and lower incidence of events leading to discontinuation, compared with quetiapine, prazosin should be used first-line for treating nighttime PTSD symptoms in a veteran population.