Repurposing Low-Dose Clonidine for PTSD in Veterans

Military veterans with Posttraumatic Stress Disorder (PTSD) suffer emotionally, physically, and socially. They have higher rates of suicide,1 issues with anger/aggression,2 substance use disorder,3 or other life difficulties (e.g., mental health disorders, marriage instability, unemployment).4 However, current first-line treatments are only effective for around half of patients receiving treatment.5,6 This is problematic given that PTSD is relatively common with a lifetime prevalence in US veterans of 10 - 31%3,7 meaning that many military veterans and their families are suffering for lack of effective treatments. PTSD symptoms can be categorized into four clusters: re-experiencing, avoidance, cognitive or mood disturbances, and hyperarousal/reactivity.8 Symptoms may occur during the day or at night, thus disrupting sleep. Many symptoms are thought to be mediated through noradrenergic pathways. Specifically, noradrenergic overactivity may directly or indirectly affect irritability/aggression, hypervigilance, ability to concentrate, startle reactions, and sleep or other nighttime symptoms.9 These nighttime disruptions are especially problematic given that lack of sleep can exacerbate other PTSD symptoms directly or through associations with increased depression, heightened anxiety, and unstable mood/affect.10-12 Selective serotonin reuptake inhibitors (SSRI) are a first-line pharmacotherapy for PTSD, yet SSRIs do not target noradrenergic pathways, have reduced efficacy in veterans,13 and only weakly impact nighttime symptoms.11,14,15 To directly address hyperarousal and sleep, previous studies have tested medications targeting the noradrenergic pathway or sleep interventions, resulting in promising outcomes for a subpopulation of veterans with PTSD.16-27 Studies on prazosin, an antagonist of post-synaptic α1 noradrenergic receptors, have shown promise for veterans with PTSD.16,18 Clonidine is similar to prazosin and is proposed to have similar effects on PTSD; however, whereas prazosin and blocks the effects of norepinephrine, clonidine decreases norepinephrine release 28 and could therefore have greater effects on hyperarousal. Retrospective, open-label studies have suggested that clonidine use is associated with improvement in PTSD.16,17 However, no prospective studies have been published testing the effects of clonidine on PTSD, either in veterans or any other population. Hypothesis: Veterans prescribed clonidine will demonstrate improvements in PTSD symptoms, including daytime, nighttime, and sleep-related behaviors.