Posttraumatic stress disorder (PTSD) is a frequent consequence of severe physical trauma, occurring in approximately 30% of traumatized individuals. It is associated with substantial functional impairment and reduced quality of life, and is often complicated by major depression- which further adds to the burden of illness. Brief psychological therapies administered in the acute post-trauma period have not demonstrated utility to prevent the occurrence of PTSD. Furthermore, the provision of specialized psychological therapies in an acute surgical setting is impractical- even if efficacy of two different medications (propranolol or gabapentin) for the secondary prevention of PTSD following severe physical trauma. Each of these agents has a separate antagonist, is predicted to prevent PTSD on the basis of its ability in preclinical studies to block the augmentation of recall typically seen in relation to highly emotional valent or stressful events. Gabapentin, an anticonvulsant, is predicted to prevent PTSD on the basis of its neuroprotective, anti- kindling, and anxiolytic properties. We propose to pilot our pharmacological interventions in sequential phases. This planned development path will have us, if necessary, test two different dose and duration regimens. Treatment will be administered in the immediate post-trauma period. A broadly representative sample for intervention than others. Patients will be assessed at 1- and 4 months following injury. Outcomes assessed will include measures of psychiatric status, functional disability of life. The study is powered at each stage of development to detect a clinically meaningful difference between either of the interventions (i.e., propranolol or gabapentin)- or two different dose/duration regimes- and placebo on two primary measures of PTSD and depressive symptom severity. Safety and tolerability are additional outcomes of major interest. Findings will provide justification for and information about optimal parameters (e.g., subject selection; sample size; dose and duration) for a future randomized controlled trial (RCT).
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| Stein, Murray B (2002) A 46-year-old man with anxiety and nightmares after a motor vehicle collision. JAMA 288:1513-22 |
