Memory Dampening Drugs To Treat Trauma

Question 1

What are the current percentages (reported and not reported) of soldiers returning from Iraq with PTSD?

Answer 1

• 17 to 25% (documented)
• 20.3 to 42.4% according to some reports
• approximately 1,000 soldiers who receive care attempt suicide every month

Question 2

What is the diagnosis of PTSD from the DSM4?

Answer 2

• essential feature is the development of characteristic symptoms following exposure to an extreme traumatic stressor involving direct personal experience of an even that involves actual or threatened death or serious injury, or other threat to one’s physical integrity, or witnessing an event that involves death, injury or a threat to another person
• the person’s response to the event must involve intense fear, helplessness or horror
• the full symptom picture must be present for more than 1 month

Question 3

What are the three phases of memory?

Answer 3

1) Formation, acquisition, and encoding of the memory
2) Emotional response and consolidation of the memory
3) Reconsolidation, reinstatement, and retrieval of memory (which includes recall and the emotional responses triggered by later stimuli)

Question 4

How is the neuroendocrine system involved in memory formation and response to trauma?

Answer 4

• adrenal stress hormones (including glucocorticoids, epi, norepi) are released in response to stressful or emotionally arousing events and interact to facilitate memory FORMATION and CONSOLIDATION
• beta-adrenergic stimulation and the subsequent physiological cascade are integral part of fight-or-flight response and response to trauma in conjunction with glucocorticoids
• increased norepi leads to better memory performance/ blocking norepi attenuated for emotional information

Question 5

Propranolol affects which parts of memory depending on when it is administered?

Answer 5

1) Given before the event - influences formation, acquisition, encoding
2) Given immediately after the event - influences response and consolidation
3) Given later - influences recall, retrieval, and reconsolidation

Question 6

What were the findings of Cahill et al (1994) regarding propranolol?

Answer 6

• no differences were observed between placebo and propranolol for neutral stimulus
• recall in the placebo group was significantly higher than in the propranolol group

Question 7

What were findings regarding propranolol administer to individuals in the emergency room?

Answer 7

• Fewer individuals treated with propranolol within six hours following a traumatic event developed PTSD than those receiving placebo
• when subjected to imagery trials three months later no individuals who received propranolol experienced physiologic responses compared to 43% of controls

Question 8

What are some findings regarding the reconsolidation of memory after development of PTSD?

Answer 8

• subjects with PTSD recalled and described triggering events before receiving propranolol or placebo immediately and again two hours later
• one week later, while listening to the accounts of their trauma, physiological responses were lower in subjects who received propranolol than those who had received placebo

Question 9

What are ethical concerns and counter arguments around propranolol use from the President’s Council on Bioethics report?

Answer 9

1) that propranolol use constitutes forgetting therapy that disrupts the sense of self
- however memories are always changing and fading (there is no “static self” to be changed by drugs)
- propranolol does not actually erase memory, but dissociates emotions from that memory
2) that it would deprive people of empathy or caring about their actions
- but this is more about the general population than PTSD
- also propranolol targets fear specifically, not disgust and sadness (and neutralizing painful memories does not make all memory “happy”)
3) that it is part of overdiagnosis and treatment of disease
- however the development and triggering of PTSD should count as a diagnosis that requires treatment as it is beyond the control of the individual
4) grief and stress following trauma are normal and the use of propranolol would deprive people of the possibility of post traumatic growth
- one goal of therapy is to attempt to induce PTG instead of PTSD, but this is not always possible, and drugs may be beneficial for those who experience loss of function or self-harm
5) The obligation to remember: those who suffer traumatic events hold information that is valuable to society and such individuals should be supported by society as much as possible
- however, people eventually die, and their children may not remember the event (the memory will eventually be lost anyway), but will have suffered the intergenerational trauma of having been raised by traumatized parents, and this may have an even more unacceptable impact on society

Question 10

Why can propranolol not be given preemptively (before a possibly traumatizing event)?

Answer 10

• because it is a beta-blocker, propranolol would keep heart rate low and prevent vasoconstriction, making the fight-or-flight response less effective a dampening awareness and performance
• furthermore, it might reduce empathy prior to situations that might require it

Question 11

What are some ethical difficulties surrounding the administration of propranolol immediately following an even that might cause PTSD?

Answer 11

• individuals respond differently to events, and some might not develop PTSD
• Does the mere possibility of PTSD warrant its use?
• Are individuals capable to informed consent following a traumatic event?
• These questions could be eliminated if propranolol proves effective at the reconsolidation stage

Question 12

What are some difficulties in studying the effects of propranolol in PTSD?

Answer 12

• many soldiers don’t develop PTSD for three to five years
• can’t traumatized people/animals to see how memories work in the brain and how they respond to propranolol (so must rely on models)