1. Propranolol in Prevention of PTSD A Review of Current Literature Mohammad Jafferany, MD Resident H-R Psychiatry Program

2. INTRODUCTION Actual or threatened death or injury or exposure to catastrophic event Actual or threatened death or injury or exposure to catastrophic event Persons response include fear, helplessness and horror Persons response include fear, helplessness and horror Intrusive recollections Intrusive recollections Day time fantasies, nightmares, flashbacks. Trauma related stimuli trigger recollection of the original event. Day time fantasies, nightmares, flashbacks. Trauma related stimuli trigger recollection of the original event. Avoiding and Numbness Avoiding and Numbness Reflects behavioral, cognitive or emotional strategies like avoiding thoughts, feelings, conversation, places and activities Reflects behavioral, cognitive or emotional strategies like avoiding thoughts, feelings, conversation, places and activities Hyperarousal Hyperarousal Symptoms like in panic or GAD. Difficulty in falling or staying asleep Symptoms like in panic or GAD. Difficulty in falling or staying asleep Duration Duration More than one month More than one month Clinically significant impairment in social, occupational or other areas of functions. Clinically significant impairment in social, occupational or other areas of functions.

3. Associated Comorbidity Major depression Major depression Anxiety disorder Anxiety disorder Substance abuse Substance abuse Somatization Somatization Dissociation and Amnesia Dissociation and Amnesia Suicide Suicide

4. Epidemiology National Vietnam Veterans Readjustment Survey (NVVRS) National Vietnam Veterans Readjustment Survey (NVVRS) From November 1986 to February 1988 From November 1986 to February 1988 Interviews with 3,016 Vietnam veterans Interviews with 3,016 Vietnam veterans National Comorbidity Survey (NCS) National Comorbidity Survey (NCS) From September 1990 to February 1992 From September 1990 to February 1992 Interviews with 8,098 Americans aged 15-54 years Interviews with 8,098 Americans aged 15-54 years

5. Results of NVVRS Estimated lifetime prevalence among Vietnam veterans is 30.9% for men and 26.9% for women. Estimated lifetime prevalence among Vietnam veterans is 30.9% for men and 26.9% for women. 15.2% of all male Vietnam veterans and 8.1% of all female veterans were having PTSD at time of survey (1986-1988) 15.2% of all male Vietnam veterans and 8.1% of all female veterans were having PTSD at time of survey (1986-1988) www.ncptsd.org

6. Results…….. (Cont.) 40% : divorced once 40% : divorced once 39.2% : Alcoholic abuse 39.2% : Alcoholic abuse 23.1% : High levels of parenting problems 23.1% : High levels of parenting problems 14.1% : High levels of marital problems 14.1% : High levels of marital problems 10% :Two or more divorces 10% :Two or more divorces 5.7% : Drug abuse 5.7% : Drug abuse www.ncptsd.org

7. Results of NCS Estimated lifetime prevalence among adult American is 7.8%. Estimated lifetime prevalence among adult American is 7.8%. Women (10.4%) twice as likely as men (5%) have PTSD at some point in their life. Women (10.4%) twice as likely as men (5%) have PTSD at some point in their life. Majority of people surveyed, experienced two or more types of trauma. Majority of people surveyed, experienced two or more types of trauma. More than 10% of men and 6% of women reported four or more types of trauma during their life time. More than 10% of men and 6% of women reported four or more types of trauma during their life time. www.ncptsd.org

8. Results of NCS Traumatic events associated with PTSD Traumatic events associated with PTSD TraumaMen(N=2812)Women(N=3065) Rape65%20.4% Sexual molestation 12.2%26.5% Physical attack 1.8%21.3% Physical abuse 22.3%48.5% Threat with weapon 1.9%32.6% Neglect23.9%19.7 www.ncptsd.org

9. Treatment Modalities Pharmacotherapy Pharmacotherapy SSRIs SSRIs Trazodone and Nefazodone Trazodone and Nefazodone MAOIs MAOIs TCAs TCAs Benzos Benzos Olanzapine Olanzapine Antiadrenergics Antiadrenergics Psychotherapy Psychotherapy Cognitive behavioral therapy Psychodynamic therapy Family therapy Group therapy

10. Recent Literature Pitman,RK, Sanders,KM, Zusman RM, Healy, AR, Cheema, F, Lasko, NB, Cahill, L, Orr, SP. Pilot study of secondary prevention of PTSD with Propranolol. Biologic Psychiatry. 2002. 51(2):189-92. Pitman,RK, Sanders,KM, Zusman RM, Healy, AR, Cheema, F, Lasko, NB, Cahill, L, Orr, SP. Pilot study of secondary prevention of PTSD with Propranolol. Biologic Psychiatry. 2002. 51(2):189-92. Vaiva G, Ducrocq F, Jezoquel K, Averland B, Lestavel P, Brunet A, Marmar CR. Immediate treatment with propranolol decreases PTSD two months after trauma. Biologic Psychiatry. 2003, 54(9):947-49 Vaiva G, Ducrocq F, Jezoquel K, Averland B, Lestavel P, Brunet A, Marmar CR. Immediate treatment with propranolol decreases PTSD two months after trauma. Biologic Psychiatry. 2003, 54(9):947-49

11. Recent Literature Taylor,F & Cahill,L. Propranolol for reemergent post traumatic stress disorder following an event of retraumatization: a case study. J Trauma Stress. 2002 15(5):433-37 Taylor,F & Cahill,L. Propranolol for reemergent post traumatic stress disorder following an event of retraumatization: a case study. J Trauma Stress. 2002 15(5):433-37

12. Fear Conditioning Model Animal and human research has shown that emotionally charged stimulation is remembered better than less emotionally arousing information. Animal and human research has shown that emotionally charged stimulation is remembered better than less emotionally arousing information. Catecholamine particularly Norepinephrine, augment deeper encoding and consolidation of traumatic events and emotional memories. Catecholamine particularly Norepinephrine, augment deeper encoding and consolidation of traumatic events and emotional memories. Catecholamine receptor blockers, soon after trauma, may obstruct consolidation of emotional memories, thereby preventing post traumatic symptomatology. Catecholamine receptor blockers, soon after trauma, may obstruct consolidation of emotional memories, thereby preventing post traumatic symptomatology.

13. Pitman et al. Pilot Study Methods: 41 pts. were randomized to begin a 10 day course of double blind propranolol 40 mgs qid (n=18) vs. placebo (n=23), within 6 hours of an event. Methods: 41 pts. were randomized to begin a 10 day course of double blind propranolol 40 mgs qid (n=18) vs. placebo (n=23), within 6 hours of an event. Results: At one month follow up evaluation, scores on CAPTSD scale were slightly lower in propranolol group (27.6) than in placebo group (35.5). At 3 month follow up, none of the propranolol recipient but 43% of placebo recipient were physiological responder to mental imagery. Results: At one month follow up evaluation, scores on CAPTSD scale were slightly lower in propranolol group (27.6) than in placebo group (35.5). At 3 month follow up, none of the propranolol recipient but 43% of placebo recipient were physiological responder to mental imagery. Conclusion: Although not a robust evidence of PTSD prevention, it does suggest that post exposure treatment with propranolol, may have a preventive effect on subsequent PTSD. Conclusion: Although not a robust evidence of PTSD prevention, it does suggest that post exposure treatment with propranolol, may have a preventive effect on subsequent PTSD. Pitman,RK, Sanders,KM, Zusman RM, Healy, AR, Cheema, F, Lasko, NB, Cahill, L, Orr, SP. Biologic Psychiatry. 2002. 51(2):189-92.

14. Vaiva et al (2003) Patients: 11 victims of physical assault and auto accidents, in ED of two hospitals in France. Patients: 11 victims of physical assault and auto accidents, in ED of two hospitals in France. Methods: Patients received 40 mgs of propranolol tid for seven days, followed by taper period of 8-12 days, compared with 8 patients who refused propranolol. Methods: Patients received 40 mgs of propranolol tid for seven days, followed by taper period of 8-12 days, compared with 8 patients who refused propranolol. Results: At two months follow up, severity of symptoms was twice as high among who had not taken propranolol, compared to propranolol recipients. Results: At two months follow up, severity of symptoms was twice as high among who had not taken propranolol, compared to propranolol recipients. Conclusion: Although a non randomized small study, propranolol may be useful in mitigating PTSD symptoms or perhaps even preventing the development of PTSD. Conclusion: Although a non randomized small study, propranolol may be useful in mitigating PTSD symptoms or perhaps even preventing the development of PTSD. Vaiva G, Ducrocq F, Jezoquel K, Averland B, Lestavel P, Brunet A, Marmar CR. Biologic Psychiatry. 2003, 54(9):947-49

15. Taylor & Cahill (2002) 44 year old woman experiencing 5 similar MVA, the last 3 causing severe PTSD symptoms of over 6 month each, despite multiple drug therapies. Following a 6 th accident, severe PTSD symptoms reemerged. Forty eight hours after this trauma, Propranolol 60 mgs bid was begun and the PTSD symptoms were rapidly and markedly reduced. The CAPTSD scale score reduced from 86 to 56 by 11 days post-trauma. 44 year old woman experiencing 5 similar MVA, the last 3 causing severe PTSD symptoms of over 6 month each, despite multiple drug therapies. Following a 6 th accident, severe PTSD symptoms reemerged. Forty eight hours after this trauma, Propranolol 60 mgs bid was begun and the PTSD symptoms were rapidly and markedly reduced. The CAPTSD scale score reduced from 86 to 56 by 11 days post-trauma. Taylor,F & Cahill,L J Trauma Stress. 2002 15(5):433-37 Taylor,F & Cahill,L J Trauma Stress. 2002 15(5):433-37

16. Future prospects PET study of cerebral blood flow during traumatic mental imagery in PTSD. (R.K.Pitman, MD) PET study of cerebral blood flow during traumatic mental imagery in PTSD. (R.K.Pitman, MD) Prospective psychophysiologic study of risk for PTSD (S.P.Orr, MD) Prospective psychophysiologic study of risk for PTSD (S.P.Orr, MD) Study of brain function in firefighters who suffer from PTSD (C.Savage, MD) Study of brain function in firefighters who suffer from PTSD (C.Savage, MD) www.mgh.harvard.edu/psychoneuro/ptsd.htm

17. Future Prospects Brain chemical receptor effects in patients with panic disorder and PTSD. (NIMH) Brain chemical receptor effects in patients with panic disorder and PTSD. (NIMH) Clonazepam and Paroxetine for rapid treatment of PTSD. (NIMH) Clonazepam and Paroxetine for rapid treatment of PTSD. (NIMH) Effects of hydrocortisone in patients with PTSD. (NIMH) Effects of hydrocortisone in patients with PTSD. (NIMH) Propranolol treatment of PTSD. (Margaret Altemus, MD. (New York-Presbyterian hospital) Propranolol treatment of PTSD. (Margaret Altemus, MD. (New York-Presbyterian hospital) www.nimh.nih.gov