Pilot study of secondary prevention of posttraumatic stress disorder with propranolol

Pitman, Roger K.; Sanders, Kathy M.; Zusman, Randall M.; Healy, Anna R.; Cheema, Farah; Lasko, Natasha B.; Cahill, Larry; Orr, Scott P.

doi:10.1016/s0006-3223(01)01279-3

Cited by 839 publications

(481 citation statements)

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“…All of these results suggest amygdaloid glucocorticoid receptor dysfunction impairs normal fear extinction. Our results are consistent with the growing body of evidences implying that the extinction process can be enhanced by pharmacological intervention (Quartermain et al, 1994;Roscorla, 2000;Walker et al, 2002;Pitman et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Richardson et al, 2004;Yang and Lu, 2005). Our studies suggest that glucocorticoid replacement during a controlled therapy session might restore the normal extinction in PTSD patients.…”

Section: Discussionsupporting

confidence: 91%

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Yang

Chao

et al. 2006

Neuropsychopharmacol

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Recent results show that brain glucocorticoids are involved in the dysregulation of fear memory extinction in post-traumatic stress disorder patients. The present study was aimed to elucidate the possible mechanism of glucocorticoids on the conditioned fear extinction. To achieve these goals, male SD rats, fear-potentiated startle paradigm, and Western blot were used. We found that (1) systemic administration of the synthetic glucocorticoid agonist dexamethasone (DEX) facilitated extinction of conditioned fear in a dose-dependent manner (0.05, 0.1, 0.5, or 1.0 mg/kg, i.p.); (2) systemic administration of the glutamate NMDA receptor antagonist (7)-HA966 (6.0 mg/kg, i.p.) and intra-amygdala infusion of the NMDA receptor antagonists MK801 (0.5 ng/side, bilaterally) or D,L-2-amino-5-phosphonovaleric acid (AP5, 2.0 ng/side, bilaterally) blocked the DEX facilitation effect; (3) the corticosteroid synthesis inhibitor metyrapone (25 mg/kg. s.c.) blocked extinction and this was prevented by co-administration of NMDA receptor agonist D-cycloserine (DCS, 5.0 mg/kg, i.p.); (4) co-administration of DEX and DCS in subthreshold doses provided a synergistic facilitation effect on extinction (0.2 and 5 mg/kg, respectively). Control experiments indicated that co-administration of DEX and DCS did not alter the expression of conditioned fear and the effect was not due to lasting damage to the amygdala. These results suggest that glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction.

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Section: Discussionsupporting

confidence: 91%

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Yang

Chao

et al. 2006

Neuropsychopharmacol

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“…This might lead to consideration of a second possibility, namely, that the dose was too low to affect the physiological responding. In the studies by Brunet et al (2008) and Pitman et al (2002), multiple doses or longer-acting propranolol were used. These studies involved patient groups that are characterized by high blood pressure and heart rate levels overall, and therefore, larger doses of propranolol might be needed to reduce physiological responding.…”

Section: Discussionmentioning

confidence: 99%

“…In animal research, these substances are usually given after reactivation to only affect postretrieval processes. In the study by Brunet et al (2008), a similar postreactivation approach was taken, although in the clinical trials mentioned in the introduction (Aerni et al 2004;Pitman et al 2002;Soravia et al 2006;Vaiva et al 2003), cortisol and propranolol were administered during a longer time span or before retrieval as well. The fact that, in this study, drugs were active during both retrieval and postretrieval processes could potentially explain our nonresults with regard to the prolonged effects of cortisol and propranolol.…”

Section: Discussionmentioning

confidence: 99%

“…Namely, perioperative cortisol administration reduced PTSD symptoms at 6 months after cardiac surgery ) and repeated cortisol administration was found to reduce symptoms of re-experiencing and intensity of the traumatic memories in PTSD patients (Aerni et al 2004) and also to reduce phobic fears (Soravia et al 2006). Propranolol administered within hours of a traumatic experience was found to reduce subsequent physiologic responding to traumatic memories (Pitman et al 2002) and development of PTSD symptoms (Vaiva et al 2003). Although these studies show clinically relevant effects of cortisol and propranolol, the mechanisms through which these substances work are still unclear.…”

mentioning

confidence: 98%

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Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration

et al. 2009

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Rationale Propranolol is found to reduce physiological hyper-responsiveness in post traumatic stress disorder (PTSD), possibly by affecting reconsolidation after the reactivation of traumatic memories. Cortisol is found to attenuate declarative memory retrieval, but it is unknown whether it also reduces physiological responses to emotional memories. Objectives To examine whether the effects of propranolol on physiological responding to emotional memories can also be found in healthy controls and to investigate the immediate and prolonged effects of cortisol on physiological responding to emotional memories, we tested these effects in 79 healthy young men. Materials and methods After preparing a script of a negative disturbing memory, participants were instructed to imagine this event 1 week later after ingestion of either 35 mg cortisol, 80 mg propranolol, or a placebo. Physiological responding to the script-driven imagery was recorded. Another week later, after washout, the imagery was repeated again. During all three sessions as well as 8 months later, subjective emotional reactions to the memories were assessed. ResultsThe emotionality of the memories was reduced over time, which was not affected by the treatments, however. The personal emotional script did evoke higher skin conductance responses than a neutral story, which decreased 1 week later, but no effects were found of either propranolol or cortisol on this responsiveness. Conclusions Whereas healthy males do show psychophysiological responding to personal emotional scripts, the effects of cortisol and propranolol on physiological responses to emotional memories might be specific to clinical groups characterized by hyper-responsiveness, like PTSD. Future studies using longer-acting doses and more elaborate reactivation procedures in both healthy men and women could shed more light on the effects of cortisol and propranolol on psychophysiological responding to emotional memories.

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“…Shalev, Ankri, Peleg, Israeli-Shalev, & Freedman, 2011). Pharmacological interventions that target the acquisition and extinction of fear responses have generally failed to prevent PTSD (Cohen et al, 2011; Hoge et al, 2012; Pitman et al, 2002; Stein, Kerridge, Dimsdale, & Hoyt, 2007). Early cognitive behavioural interventions, although often effective (Roberts, Kitchiner, Kenardy, & Bisson, 2010), do not reach many symptomatic survivors (Hoge et al, 2004; Shalev et al, 2012, 2011), are costly, and are difficult to carry out in trauma-affected areas such as war and disaster zones.…”

Section: Introductionmentioning

confidence: 99%

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol

Fine

Achituv

Etkin

et al. 2018

European Journal of Psychotraumatology

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Background: The immediate aftermath of traumatic events is a period of enhanced neural plasticity, following which some survivors remain with post-traumatic stress disorder (PTSD) whereas others recover. Evidence points to impairments in emotional reactivity, emotion regulation, and broader executive functions as critically contributing to PTSD. Emerging evidence further suggests that the neural mechanisms underlying these functions remain plastic in adulthood and that targeted retraining of these systems may enhance their efficiency and could reduce the likelihood of developing PTSD. Administering targeted neurocognitive training shortly after trauma exposure is a daunting challenge. This work describes a study design addressing that challenge. The study evaluated the direct effects of cognitive remediation training on neurocognitive mechanisms that hypothetically underlay PTSD, and the indirect effect of this intervention on emerging PTSD symptoms. Method: We describe a study rationale, design, and methodological choices involving: (a) participants’ enrolment; (b) implementation and management of a daily self-administered, web-based intervention; (c) reliable, timely screening and assessment of treatment of eligible survivors; and (d) defining control conditions and outcome measures. We outline the rationale of choices made regarding study sample, timing of intervention, measurements, monitoring participants’ adherence, and ways to harmonize and retain interviewers’ fidelity and mitigate eventual burnout by repeated contacts with recently traumatized survivors. Conclusion: Early web-based interventions targeting causative mechanisms of PTSD can be informed by the model presented in this paper.

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Pilot study of secondary prevention of posttraumatic stress disorder with propranolol

Cited by 839 publications

References 10 publications

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol

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