Propranolol for the Treatment of Acute Stress Disorder

The effects of exposure to severe stress differ between individuals. Still, a typical response pattern consisting of increased anxiety and arousal, sleep difficulties, preoccupation with and re-experiencing of the traumatic event is the rule. In most trauma survivors the severity of this condition diminishes within days or weeks. Still, in some cases psychopathology persists, and can lead to severe and chronic PTSD. The diagnosis of "Acute Stress Disorder" (ASD) was introduced in DSM-IV, addressing psychopathology between 2 days and 1 month of exposure to trauma. It has been shown that 60%-80% of patients who meet criteria for ASD will go on and suffer from PTSD. Nevertheless, pharmacological trials in PTSD have only been performed, with few exceptions, in chronic populations. Chronic PTSD has emerged as a treatment resistant condition, with only partial response to treatment with antidepressant and anxiolytic agents. Therefore, the potential benefits of early treatment intervention in this condition could be immeasurable. A principal model proposed to explain the initiation and perpetuation of PTSD is the fear-conditioning model. It assumes that intrusive, involuntary, repetitive, vivid emotionally laden memories of the trauma are pivotal to the development of the disorder. Although such memories are a part of the early trauma response, in healthy trauma survivors these memories gradually lose their intrusive quality and much of their emotional charge, allowing recovery. In PTSD this process does not occur. The impediment to recovery may result from deeper encoding and consolidation of the traumatic memories inhibiting the normal process of extinction that is part of the healthy processing of the traumatic event. Animal and human research has conclusively shown that emotionally charged stimulation is remembered better than less emotionally arousing information. Animal and human data show that catecholamines, particularly norepinephrine, augment consolidation of emotional memory. Furthermore, administration of catecholamine receptor blockers cancels the enhanced memory for emotional, compared to non-emotional, information. These data suggest that administration of catecholamine receptor blockers soon after trauma may obstruct consolidation of emotional memories, thereby preventing or alleviating posttraumatic symptomatology. Treatment experience in humans is limited to the administration of propranolol in single case descriptions and a pilot prevention study that was not sufficiently powered to allow a definite inference. However, the overall impression from administration of propranolol in the early time period after trauma is positive. In light of the neurophysiology and preliminary data presented above, we propose a prospective, randomized placebo controlled study of propranolol treatment in ASD.