A Pilot Trial of Prazosin, an Alpha‐1 Adrenergic Antagonist, for Comorbid Alcohol Dependence and Posttraumatic Stress Disorder

Abstract

Background Posttraumatic Stress Disorder (PTSD) and alcohol dependence (AD) commonly co-occur and are associated with greater symptom severity and costs than either disorder alone. No pharmacologic interventions have been found to decrease both alcohol use and PTSD symptom severity relative to matched placebo. Prazosin, an alpha-1 adrenoreceptor antagonist, has demonstrated efficacy reducing PTSD and AD symptoms among individuals with one or the other disorder and may be useful in addressing comorbid PTSD/AD. Methods Prazosin and matched placebo were compared in the context of an outpatient 6-week double-blind randomized controlled pilot trial involving 30 individuals with comorbid PTSD/AD. Medication was titrated to 4mg q AM, 4mg q PM and 8mg qhs by the end of week 2. Participants in both conditions received five Medical Management sessions. Information regarding alcohol use, craving, and PTSD was gathered daily using a telephone Interactive Voice Response (IVR) system. Results Participants randomized to prazosin had a greater reduction in percent days drinking per week and percent days heavy drinking per week between baseline and week 6 than did placebo participants. No significant differences were detected within or between groups in change from weeks 1 to 6 in total PTSD symptoms. Participants in the prazosin condition reported drowsiness on significantly more days than those in the placebo condition. Conclusions Consistent with the extant research evaluating medications for comorbid PTSD/AD, the current evaluation of prazosin also found decreased alcohol consumption but no medication effect on PTSD symptomatology.

The Corticotropin Releasing Factor Receptor 1 in Alcohol Use Disorder: Still a Valid Drug Target?

“…In one outpatient, DBPC pilot study of 17 men with alcohol dependence, prazosin dramatically reduced the number of drinks consumed by 88% and the number of drinking days by 84% during the final 3 weeks of the 6-week study (Simpson et al, 2009). This finding was confirmed in a second outpatient pilot study by the same group that involved 20 men and women with alcohol dependence and PTSD, though 6 in the prazosin group required dose reductions for side effects (Simpson et al, 2015). However, a more extensive, outpatient, DBPC trial of 96 veterans with alcohol dependence and PTSD found no significant effect of prazosin over placebo on drinking measures during 13 weeks of treatment (Petrakis et al, 2016).…”

Doxazosin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in military veterans

“…Several RCTs with varying sample sizes of veterans and civilians demonstrate safety, tolerability and efficacy of prazosin to reduce nightmares, sleep impairment, and overall PTSD symptom severity [1,18,51–53,59,68], as well as AUD severity [59,60]. However, the largest RCT to date examining prazosin in the treatment of PTSD ( N = 304) [49] resulted in null findings.…”

“…Previous studies have examined the use of prazosin, an alpha-1 noradrenergic blocker approved by the U.S. Food and Drug Administration (FDA) for hypertension and benign prostatic hyperplasia, in the treatment of PTSD, AUD and comorbid AUD/PTSD. The findings have been mixed with some studies showing significant reduction in AUD symptoms [15,59,60] and reduction in PTSD symptoms, particularly nightmares, sleep disruption and daytime hyperarousal symptoms [18,50,52], while other studies find no significant differences in prazosin vs. placebo for AUD or PTSD symptoms [41,49]. Several studies suggest that pre-treatment blood pressure may represent a biomarker to help identify who will respond favorably to prazosin, or potentially other alpha-1 blockers [48,74].…”

Pharmacological treatment options for alcohol use disorder

“…It is believed that prazosin is effective especially in the presence of post-traumatic stress disorder comorbidity (140,141).…”