1. Post traumatic stress disorder Jeff Clothier, M.D.

2. PTSD Overview Epidemiology Diagnosis Psychiatric Comorbidity Treatment

3. PTSD DSM-IV Criteria Exposure to traumatic event with Actual or threatened death or serious injury and Response involving intense fear, helplessness, or horror American Psychiatric Association. DSM-IV. 1994.

4. PTSD DSM-IV Criteria (cont.) Re-experiencing the traumatic event Persistent avoidance of stimuli associated with event Numbing of general responsiveness Symptoms of increased arousal At least 1 month’s duration (otherwise can diagnose Acute Stress Disorder) Significant distress or impairment in social, occupational, or other functioning American Psychiatric Association. DSM-IV. 1994.

5. PTSD Associated Features Alcohol/drug problems Aggression/violence Suicidal ideation, intent, attempts Dissociation Distancing Problems at work Marital problems Homelessness

6. Lifetime Prevalence of DSM-III-R Major Psychiatric Disorders NCS Data Mood Disorders Major depressive episode17.1 Dysthymia6.4 Manic episode1.6 Anxiety Disorders Social Phobia13.3 Simple Phobia11.3 PTSD7.8 Agoraphobia without panic5.3 GAD5.1 Panic disorder3.5 Substance Use Disorders Alcohol abuse/dependence23.5 Drug abuse/dependence11.9 Adapted from Kessler et al. 1994, 1995. %

7. Function and Quality of Life In Vietnam Veterans With and Without PTSD Percent Not Working Physical Limitation Reduced Well- Being Fair or Poor Health Zatzick DF et al. Am J Psychiatry. 1997;154:1690–1695. Violent Behavior Past Year PTSDNon-PTSD

8. PTSD Risk Factors for PTSD Severity of trauma (ie, threat, duration, injury, loss) Prior traumatization Gender Prior mood and/or anxiety disorders Family history of mood or anxiety disorders Education

9. PTSD risks Epidemiologically, there are two other risk The risk of having a trauma exposure The risk for developing PTSD from that exposure Has implications for public health policies

10. Risks of Specific Traumas in the US Population Percentage Natural Disaster RapeCombatCriminal AssaultMenWomen Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060. About 30% of people exposed to trauma developed PTSD

11. PTSD Rates Related to Specific Traumas Percentage Natural Disaster RapeCombatCriminal AssaultMenWomen Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060.

12. 0 25 50 75 100 123456710 PTSD Persistence Over Time Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060. Years % Without Recovery (Untreated Group)

13. PTSD Impact of Treatment on Recovery Kessler RC et al. Arch Gen Psychiatry. 1995;52:1057. Treated Untreated Median Months to Recovery (N = 459)

14. Biological Correlates of Chronic PTSD Increased sympathetic responses to trauma reminders Normal resting catecholamines with increased responses to trauma stimuli Decreased cortisol. Excessive feedback inhibition. Increased free T3 and T4 Insomnia and increased # of rapid eye movements during REM sleep Possible reduction in hippocampal volume?

15. Epidemiology of PTSD 7.8% of adults in the U.S. (lifetime) Type of trauma most often the basis for PTSD - rape in women (46% risk) combat in men (39% risk) one third of cases have duration of many years 88% of cases have psychiatric comorbidity Kessler et al., 1995

16. Depression 48124819 Mania 12161 Panic Disorder 72134 Social Phobia 28112814 GAD 173156 Alcohol Abuse/Dependency 52342813 Substance Abuse/Dependency 3415278 Any Diagnosis 88557946 Kessler RC et al. Arch Gen Psychiatry. 1995 Lifetime Rates (%) Men Women PTSD Non-PTSD PTSD Psychiatric Comorbidity

17. PTSD comorbidity Patient usually has other psychiatric disorders “Ticks and fleas” Makes treatment difficult More deadly

18. 0 20 40 60 80 Impact of Comorbid PTSD in Subjects With Other Anxiety Disorders (%) Rates 38 48 30 6 21 Alcohol Problems HospitalizedAttempted Suicide Anxiety Disorder With PTSD Anxiety Disorder Without PTSD Warshaw MG et al. Am J Psychiatry. 1993;150:1512–1516.

19. PTSD Treatment Options Psychotherapy Pharmacotherapy Multimodal treatment

20. Expert Consensus Guidelines J Clin Psychiatry, ‘99 Noncomorbid children, adults, geriatric patients Psychotherapy first Comorbid population Psychotherapy first or combine meds/psychotherapy Mild PTSD More severe Combine meds/ psychotherapy from start

21. Considerations for psychotherapy Capacity to tolerate distress with exposure Motivation/preference Ability to participate and follow structure Problems with interpersonal adjustment

22. Treatment of PTSD by Exposure and/or Cognitive Restructuring Marks I et al. Arch Gen Psychiatry. 1998;55:317–325. IES Scores Treatment 1 mo3 mos6 mos r = relaxation c = cognitive restructuring e = prolonged exposure ec = e + c r c ec e Follow Up

23. PTSD Goals of Pharmacotherapy Reduction/amelioration of target symptoms Improve sleep Affects improvement in other symptoms (eg, irritability, preoccupation, vigilance, impaired concentration) Decreased risk for development of comorbidity Reduce re-experiencing and intrusive symptoms Improve mood and numbing Reduce phasic and tonic hyperarousal Reduce impulsivity Reduce psychotic or dissociative symptoms Davidson and van der Kolk, 1996.

24. Pharmacologic treatment Multiple conditions Medical comorbidities Side effects from one treatment may impact other symptoms and medications.

25. PTSD Medications Studied Benzodiazepines Antidepressants TCAs MAOIs SSRIs 5-HT 2 antagonists Anticonvulsants/antipsychotics Noradrenergic agents: clonidine, propranolol

26. 40 100 0 20 80 Fluoxetine Van der Kolk BA et al. Prim Care. 1993;20:417–432. CAPS Total Score Effect of Trauma Population PTSD Treatment With SSRIs Effect of Fluoxetine Placebo PrePost 60 Trauma Clinic (n = 23) PrePostPrePost VA (n = 24) PrePost

27. Sertraline Efficacy in PTSD -40 -35 -30 -25 -20 -15 -10 -5 0 Sertraline Placebo (N=187) * * † *p<0.05; † p=0.07; Brady et al, JAMA, 2000 DTSIESCAPS-2

28. PTSD and Comorbid Depression: Sertraline Studies PTSD with No Comorbid Depressive Disorder PTSD with Comorbid Depressive Disorder Percent Responders* 0 10 20 30 40 50 60 70 80 Sertraline (N=104) Placebo (N=112) Sertraline (N=87) Placebo (N=82) *Response is defined as CGI=I score of 1 (very much improved) or 2 (much improved) at end point Brady et al., 2000, Davidson et al., 1998 56.7% 40.2% 60.9% 37.8% p=0.0034p=0.011

29. Quality of Life In PTSD 0 2 4 6 8 10 12 14 Total Scores* Change in Q-LES-Q Sertraline Placebo Sertraline vs. Placebo Subscales all p  0.05 –Mood –Social relationship –Leisure time –Ability to fix –Living/housing –Physical ability –Work/hobby *p  0.004, Brady et al., 2000

30. 80 70 60 50 40 30 20 10 0 0 Baseline Sertraline in PTSD: The Effect of Continuation Treatment with Sertraline Week 12 Week 20 Week 28 Week 36 Endpoint (LOCF) Acute Phase Continuation Phase CAPS-2 Total Score Londborg, APA/CINP 2000

31. 5HT2 antagonists 1. Trazodone – commonly used for sleep, may reduce nightmares 2. Cyproheptadine – reports of improved sleep with decreased nightmares as well, appetite stimulant as well. (Pharmacologically rich compound)

32. Anti-Psychotic Agents Not first-line but often required in difficult cases Indications: –Reduce disorganizing hyperarousal, paranoid ideation, and aggressive impulsivity –Co-morbid psychotic disorder –Low doses are often effective –Atypical agents preferred

33. Mood Stabilizers Carbamazepine –Open clinical trial: decreased intrusions, flashbacks, insomnia, irritability, impulsivity, and violent behavior (Lipper et al., Psychosomatics, 1986) Valproic acid –Open trial: decreased hyperarousal and avoidance (Stein, J Clin Psych, 1995) Lamotrigine –Small controlled trial: decreased re-experiencing, numbing and avoidance (Hertzberg et al., Biol Psychiatry, 1999)

34. Immediately after exposure : Normalize distress Educate patient, family and significant others Repeated retelling of the event Provide emotional support Relieve irrational guilt Refer to peer support group or trauma counseling Consider short-term sleep medication for insomnia Foa, Davidson, Frances, J Clin Psychiatry 1999 Early Intervention and Prevention Recommendations for Early Intervention and Prevention

35. PTSD Summary PTSD is common Usually chronic Presentations vary Comorbidity is the rule Comprehensive assessment of patients is critical to develop an individualized treatment plan Treatment often involves multiple modalities