Reduction in the occurrence of distressing involuntary memories following propranolol or hydrocortisone in healthy women

Abstract

BackgroundPharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear.MethodUsing an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD. Eighty-eight healthy women (average age: 23.5 years) received oral propranolol (80 mg), hydrocortisone (30 mg), or matched placebo immediately after viewing a ‘trauma film’. They then completed daily, time-stamped intrusion diaries for 1 week, at the end of which, voluntary memory was tested.ResultsWhile neither drug affected voluntary memory for the trauma narrative, propranolol treatment was associated with 42% fewer, and hydrocortisone with 55% fewer intrusions across the week, relative to placebo. Additionally, propranolol reduced general trauma-like symptoms, and post-drug cortisol levels were negatively correlated with intrusion frequency in the hydrocortisone group.ConclusionsOverall, this study shows substantial reductions in intrusive memories and preserved voluntary narrative-declarative memory following either propranolol or hydrocortisone in an experimental model of psychological trauma. As such, despite some inconsistencies in clinical trials, our findings support continued investigation of propranolol and hydrocortisone as secondary preventive agents for re-experiencing symptoms of PTSD. The findings also suggest that it is critical for future research to identify the conditions governing the preventive efficacy of these drugs in PTSD.

Early Life Stress and Pediatric Posttraumatic Stress Disorder

“…Elevated catecholamine secretion has been implicated in excessive consolidation of traumatic memories, which is substantial for the development and maintenance of re-experiencing symptoms of PTSD such as intrusive memories, flashbacks, and repetitive nightmares [68,69]. Importantly, the administration of pharmacological agents such as β-blockers immediately after trauma exposure, might be helpful as secondary preventive agents for the development of specific PTSD symptoms [69,70].…”

“…Clinical symptoms of PTSD may thus be attributed to cortisol decrease that fails to shut down the catecholarminergic response in limbic structures. It has been suggested that an exaggerated catecholamine secretion is related to excessive consolidation of traumatic memories, which in turn may lead to the development and maintenance of PTSD symptoms, such as intrusive thoughts, flashbacks, and repetitive nightmares [67,68,70]. By contrast, glucocorticoids impair or have little effect on memory consolidation in the absence of arousal-induced noradrenergic activation [69,100].…”

Accelerated forgetting of a trauma-like event in healthy men and women after a single dose of hydrocortisone

“…Because synaptic consolidation is a brief (<6 hr), protein synthesis-dependent process, commonly used drugs with down-stream protein synthesis-inhibiting effects, such as beta-blockers or NMDA receptor antagonists, have theoretical potential as secondary preventive agents. However, currently, neither meta-analyses of clinical trials [ 4 , 5 ] nor experimental studies [ 6 ] (but see [ 7 ]) support use of beta-blockers, and only indirect experimental [ 8 ] or cross-sectional [ 9 ] evidence on NMDAR antagonists currently exists.…”

“…Such studies allow pathogenic memory phenomena (e.g., distressing involuntary memories [ 14 ]) to be modelled and assessed, while limiting the influence of numerous sources of statistical noise common in clinical studies. Two such translational studies have modelled preventative treatment for PTSD with hydrocortisone administered before [ 15 ] or shortly after [ 7 ] an analogue trauma (a distressing film). Only the latter study demonstrated a reduction in the number of intrusions relative to placebo.…”

“…Given the conflicting previous findings [ 7 , 15 ] and the need to determine whether men and women are differentially responsive to hydrocortisone treatment, the current pre-registered study tested the time- and sex-dependent effects of hydrocortisone on intrusive memories following an analogue trauma. We also explored the drug- and sex-dependent influence of progesterone and estradiol on intrusions, although this analysis was not pre-registered.…”