The efficacy of early propranolol administration at reducing PTSD symptoms in pediatric injury patients: A pilot study

Abstract

Initial research supports the use of propranolol to prevent posttraumatic stress disorder (PTSD); research has not examined pharmacological prevention for children. Twenty-nine injury patients (ages 10-18 years old) at risk for PTSD were randomized to a double-blind 10-day trial of propranolol or placebo initiated within 12 hours post admission. Six-week PTSD symptoms and heart rate were assessed. Although intent-to-treat analyses revealed no group differences, findings supported a significant interaction between gender and treatment in medication-adherent participants, ΔR 2 = .21. Whereas girls receiving propranolol reported more PTSD symptoms relative to girls receiving placebo, ΔR 2 = .44, boys receiving propranolol showed a nonsignificant trend toward fewer PTSD symptoms than boys receiving placebo, ΔR 2 = .32. Findings inform gender differences regarding pharmacological PTSD prevention in youth. Keywords PTSD; pediatric trauma; propranololThe Efficacy of Early Propranolol Administration at Reducing PTSD Symptoms in Pediatric Injury Patients: A Pilot Study To date, no randomized controlled trials have examined the efficacy of pharmacologic agents administered shortly posttrauma in the prevention of posttraumatic stress disorder (PTSD) in youth. One promising candidate, propranolol, is a centrally-acting beta-blocker that has been found to block the memory-enhancing effects of emotional arousal (Cahill et al. 1994). Pitman and colleagues (2002) tested propranolol as a secondary intervention for the prevention of PTSD in adults. Following a 10-day medication regimen, 30% (6 out of 20) of placebo recipients as compared with 10% (1 out of 10) of propranolol recipients met PTSD criteria one month post-trauma. Three months post-trauma, Method ParticipantsParticipants included 29 pediatric trauma emergency department patients (see Table 1). Eligibility criteria included a Glasgow Coma Scale score of 14 or greater and an "at-risk" child score on a screen for risk of PTSD. Medication-specific exclusion criteria included hypersensitivity to beta-blockers, bradycardia; cardiogenic or hypovolemic shock, diabetes, preexisting heart condition, or treatment for asthma (Lacy et al., 2002). Children were also excluded if their injuries or medical treatment procedures contraindicated propranolol. Figure 1 summarizes recruitment and retention. MeasuresHeart rate and blood pressure were recorded with an automated blood pressure cuff ( Parents completed a medication log. Six participants were judged to show poor adherence (> 1 missed dose or > 4 incidents of poor time adherence). Adequate adherence was equally prevalent in propranolol (n = 9) and placebo (n = 11) groups.Posttraumatic stress disorder symptom severity and diagnosis were determined via the Clinician Administered PTSD Scale for Children and Adolescents (Nader et al., 1996). The CAPS-CA has demonstrated adequate psychometric properties (Nader et al., 1996; Carrion et al., 2002;Newman & Ribbe, 1996). Each symptom is scored for frequency and intensity. Sympto...

Examining Sex and Gender Differences in Anxiety Disorders

“…However, due to an already small sample size and high drop-out rates, it is unclear whether these differences were equal for the two drugs and whether interactions between treatment and response to a prior symptom-provoking agent differed for males and females. In addition to these studies of antidepressives, a pilot study examining the effects of propranolol found promising results that this beta-blocker decreases PTSD severity in males, but may actually increase symptom levels in females [55].…”

Propranolol’s effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis

“…Propranolol's capacity to prevent the development of PTSD immediately after trauma exposure has also been examined in a few studies with conflicting findings and methodological flaws. 26,28,29,59,60 Further investigations under improved methodological conditions are underway (see clinical trials.gov) and should help elucidate this question in the near future.…”

Psychophysiology of Delayed Extinction and Reconsolidation in Humans

“…Two distinct memory consolidation mechanisms have been proposed: a short term synapticallymediated process and a longer term hipocampally-mediated one (Dudai, 2004). While the former process is potentially vulnerable to intervention within minutes to hours following the traumatic event, it has proven difficult to intervene clincially before intial consolidation occurs; studies attempting this have reported mixed results (Hoge et al, 2012;Holmes, James, Coode-Bate, & Deeprose, 2009;Krauseneck et al, 2010;Nugent et al, 2010;Pitman et al, 2002;Stein, Kerridge, Dimsdale, & Hoyt, 2007;and Vaiva et al, 2003). Research using animals has shown that reactivation of a consolidated memory returns it to a destabilized state, from which it must be restabilized (i.e.…”