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Research Update: PTSD Gary H. Wynn, MD, FAPA Associate Professor / Assistant Chair Department of Psychiatry Uniformed Services University of the Health.

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Presentation on theme: "Research Update: PTSD Gary H. Wynn, MD, FAPA Associate Professor / Assistant Chair Department of Psychiatry Uniformed Services University of the Health."— Presentation transcript:

1 Research Update: PTSD Gary H. Wynn, MD, FAPA Associate Professor / Assistant Chair Department of Psychiatry Uniformed Services University of the Health Sciences Bethesda, MD

2 Disclaimer The opinions and statements in this presentation are the responsibility of the author and such opinions and statements do not necessarily represent the policies or opinions of the Uniformed Services University of the Health Sciences, the United States Army, the Department of Defense, the United States or their agencies.

3 Agenda Background and Current work on PTSD Epidemiology Stigma and Barriers to Care Psychotherapy Pharmacotherapy Complementary and Alternative Medicine Future Directions for Research

4 Epidemiology

5 Individual Loved Ones First Responders Community

6 DSM-IV-TRDSM-V A: Event B: Re-experiencing (Intrusion) C: Avoidance F: Clinically Significant Distress E: Duration D: Arousal H: Not attributable to substance/medical A: Event B: Intrusion (Re-experiencing) C: Avoidance F: Duration E: Arousal D: Negative Alterations in Cognitions/Mood G: Clinically Significant Distress Broadened definition Very similar Effectively Split in Two Identical Very similar Identical

7 DSM-IV-TR DSM-V A1: experienced, witnessed, or was confronted with events that involved actual or threatened death/serious injury A2: response involved intense fear, helplessness, or horror A1: Directly experiencing the traumatic event(s) A2: Witnessing, in person, the event(s) as it occurred to others A3: Learning that the traumatic event(s) occurred to a close family member or close friend A4: Experiencing repeated or extreme exposure to aversive details of the traumatic event(s) A: The person has been exposed to a traumatic event which both of the following were present: A: Exposure to actual or threatened death, serious injury, or sexual violence in one (or more) of the following ways: EVENT

8 DSM-IV-TRDSM-V C1: Efforts to avoid thoughts, feelings, or conversations C1: Avoidance of or efforts to avoid distressing memories, thoughts, or feelings C2: Avoidance of or efforts to avoid external reminders D: Negative alterations in cognitions and mood associated with traumatic event(s) D1: Inability to remember an important aspect of the traumatic event(s) C: Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness as indicated by 3 or more of the following: C: Persistent avoidance of stimuli associated with the traumatic event as evidenced by on or both of the following: C2: Efforts to avoid activities, places, or people C3: Inability to recall an important aspect of the trauma C4: Markedly diminished interest in significant activities C5: Feeling of detachment or estrangement from others C6: Restricted range of affect C7: Sense of foreshortened future D2: Persistent exaggerated negative beliefs about oneself, others, or the world D5: Markedly diminished interest in significant activities D4: Persistent negative emotional state D3: Persistent, distorted cognitions that lead the individual to self blame D6: Feelings of detachment or estrangement from others D7: Persistent inability to experience positive emotions

9 DSM-IV-TRDSM-V Acute (<3 months)With Dissociative Symptoms With Delayed Onset - Derealization - Depersonalization Chronic (>3 months) With Delayed Expression Specifiers Subthreshold PTSD Anxiety Disorder NOS Adjustment Disorder Other Specified Trauma- and Stressor-Related Disorder Adjustment Disorder Unspecified Trauma- and Stressor-Related Disorder

10 DSM Discordance Hoge CW, Riviere L, Wilk J et al. The prevalence of post-traumatic stress disorder (PTSD) in US combat soldiers: a head-to-head comparison of DSM-V versus DSM-IV-TR symptom criteria with the PTSD checklist. Lancet Psychiatry Aug 2014

11 Pre-Stress Stress Post-Stress Extreme Stress Genetics Prior Stress And Stress Prep Subjective Response And Recovery PTSD Depression Substance Use Disorders Chronic Pain Somatic Disorders Other Psychiatric Disorders Adapted from John Krystal (APA 2013)

12 Responses to Trauma MentalHealth Health Risk Behaviors (changed behavior) Distress Responses


14 Benedek DM and Wynn GH. Clinical Manual for Management of PTSD. American Psychiatric Press, Inc 2010

15 Stigma and Barriers to Care

16 From the 2010 National Survey on Drug Use and Health

17 Stigma Kessler RC. J Clin Psychiatry. 2000;61(suppl 5):4-12. Lack of perceived need Perceived lack of effectiveness Fear of forced hospitalization 24 22 40 60 68 54 66 01020304050607080 Agree or Strongly Agree, % Men Women Want to solve on own Stigma 35 17 23 Unsure where to go 49 40

18 Lifetime Probability of Treatment Contact Dysthymic Disorder Panic Disorder Wang PS, et al. Arch Gen Psychiatry. 2005;62:603-613. Major Depression Bipolar Disorder GADPTSD 65% 94% 86% 95% Patients Making Treatment Contact, % 60 70 80 90 100 88% 90% 7% contact within year of PTSD onset and 12-year median delay to first treatment contact

19 Lu MW, Duckart JP, O’Malley JP et al. Correlates of Utilization of PTSD Specialty Treatment Among Recently Diagnosed Veterans at the VA. Psychiatric Services 2011

20 Psychotherapy

21 Psychotherapies SRSUBSTANTIALSOMEWHATUNKNOWN A Trauma-focused psychotherapy that includes components of exposure and/or cognitive restructuring; OR Stress inoculation training C Patient Education Imagery Rehearsal Therapy Psychodynamic Therapy Hypnosis Relaxation Techniques Group Therapy I Family therapy Web-Based CBT Dialectical Behavior Therapy Acceptance & Commitment Therapy From VA/DoD Clinical Practice Guideline for The Management of Post-Traumatic Stress (2010)

22 Level A Psychotherapy Choices Patients should be offered one of the evidence-based trauma- focused psychotherapeutic interventions that include components of exposure and/or cognitive restructuring; OR stress inoculation training. Choice should be based on symptom severity, clinician expertise, and patient preference, and may include: Exposure therapy (e.g., Prolonged Exposure) Cognitive therapy (e.g., Cognitive Processing Therapy) Stress management therapy (e.g., SIT) or Eye Movement Desensitization & Reprocessing (EMDR)

23 VA/DoD Guideline: Therapy Selection 1. Explain the range of available and effective therapeutic options for PTSD to all patients with PTSD 2. Patient education is recommended as an element of treatment of PTSD for all patients and family members 3. Patient and provider preferences should drive the selection of evidence-based psychotherapy and/or evidence-based pharmacotherapy as 1 st line treatment 4. Psychotherapies should be provided by practitioners who have been trained in that particular method 5. A collaborative care approach to therapy administration, with care management, may be considered

24 Adapted from Watts BV, Schnurr PP, Mayo L et al. Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. J Clin Psychiatry 2013 Meta-analysis of Individual Psychotherapy TreatmentEffect SizeNumber of Studies Prolonged Exposure1.38 (0.9-1.86)10 Cognitive Processing Therapy 1.69 (1.27-2.11)3 Stress Inoculation Therapy1.37 (0.8-1.93)2 Exposure + Cognitive1.52 (1.08-1.95)3 Virtual Reality1.01 (0.37-1.65)4 EMDR1.04 (0.44-1.65)10

25 Prolonged Exposure in Veterans Yoder M, Tuerk PW, Price M et al. Prolonged exposure therapy for combat-related posttraumatic stress disorder: comparing outcomes for veterans of different wars. Psychological Services 2012

26 Chard KM, Ricksecker EG, Healy ET et al. Dissemination and experience with cognitive processing therapy. J Rehabil Res Dev 2012 PCL Score

27 Cognitive Behavioral Conjoint Therapy for PTSD Improves PTSD Symptoms Adapted from Monson CM, Fredman SJ, Macdonald A et al. Effect of cognitive-behavioral couple therapy for PTSD: a randomized controlled trial. JAMA 2012 (Adapted with permission from Schnurr, APA 2012)

28 The Benefits of Cognitive Behavioral Therapy for PTSD Persist Long-Term 126 female sexual assault survivors with PTSD, followed 6.2 years after treatment (range = 4.5-10 years) Comparable to 171 initial participants Remission at follow up: 77.8%Cognitive Processing Therapy 82.5%Prolonged Exposure Adapted from Resick PA, Williams LF, Suvak MK et al. Long-Term Outcomes of Cognitive-Behavioral Treatments for Posttraumatic Stress Disorder Among Female Rape Survivors, J Consult Clin Psychol 2012 (Adapted with permission from Schnurr, APA 2012) CAPS PTSD Severity

29 Pharmacotherapy

30 SRSIG BENEFIT SOMEWHATUNKNOWNNONE or HARM ASSRI SNRI B Mirtazapine Atypical antipsychotics (as adjunct) Prazosin (for sleep/nightmares) TCAs Nefazodone MAOIs (phenelzine) C Prazosin (for global PTSD) D Benzodiazepines- [Harm] Tiagabine Guanfacine Valproate Topiramate Adapted from VA/DoD Clinical Practice Guideline for The Management of Post-Traumatic Stress (2010)

31 DrugStudyFindings Ongoing Trials Sertraline (Zoloft) Robb et al. (2010); 10 week double-blind RCT of sertraline (67) v placebo (62) in children and adolescents with PTSD (ages 6- 17) No significant reduction in PTSD symptoms at 10 weeks 6*6* Panahi et al. (2011); 10 week double-blind RCT of sertraline (35) v placebo (35) in Iranian vets with combat related PTSD Significant improvement in sertraline group Paroxetine (Paxil) Simon et al. (2008); Double-blind RCT of paroxetine CR (11) v placebo (12) for PE refractory PTSD No significant improvement compared to placebo 2 * - including sertraline v PEx v combination study

32 DrugStudyFindings Ongoing Trials Duloxetine (Cymbalta) Villareal et al. (2010); 12 week open label trial of duloxetine in military vets with PTSD (20) 9/20 participants classified as responders (>20% reduction on CAPS) 0 Walderhaug et al. (2010); 8 week naturalistic study of duloxetine in male vets with PTSD and co- morbid MDD (21) Improvements in both PTSD and MDD by week 8 Venlafaxine (Effexor) Davidson et al. (2012); Post-hoc analysis of pooled data from two double-blind flexible dose RCTs of venlafaxine for PTSD 10 item CD-RISC predictive of CAPS score change 1

33 Venlafaxine ER 12-week Flexible dose 538 randomized 350 completers ~10% difference in remission Davidson J, Rothbaum BO, Tucker P et al. Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study. J Clin Psychopharmacol 2006

34 DrugStudyFindings Ongoing Trial(s) Prazosin (Minipress) Raskind et al. (2007); 8 week trial of prazosin v placebo (34) for trauma nightmares and sleep disturbance Significant benefit over placebo 4 Taylor FB. (2006); Addition of daytime prazosin to nighttime prasozin for continued daytime symptoms (11) Significant benefit over placebo Thompson et al. (2008); Treatment of Non-nightmare distressed (NNDA) awakenings in combat PTSD (22) Significant improvement in NNDA and PTSD symptoms Byers et al. (2010); Long term comparative effectiveness of Prazosin (62) v quetiapine (175) for night sxs No short term differences; less discontinuation with prasozin (AE related) Germain et al. (2012); Prasozin (18) v behavioral sleep intervention (17) v placebo (15) for sleep dist. in vets Prasozin and behavioral superior for both sleep and daytime PTSD sxs Raskind et al. (2013); Twice daily Prazosin v Placebo for Combat PTSD with nightmares in US Soldiers returned from Iraq/Afganistan (67) Significant Improvement CAPS, CAPS hyperarousal, nightmares, and sleep quality

35 DrugStudyFindings Ongoing Trials Olanzapine (Zyprexa) Carey et al. (2012); 8 week double-blind flexible dose RCT of olanzapine (14) v placebo (14) in non-combat PTSD Significant reduction in CAPS score by week 8; substantial weight gain 0 Risperidone (Risperdal) Krystal et al. (2011); 6 month double-blind RCT of adjunctive risperdal (246) for antidepressant resistant chronic military PTSD No significant benefit over placebo; risperdal had more side effects 0 Aripiprazole (Abilify) Youssef et al. (2012); Open label pilot study of flexible dose aripiprazole monotherapy (10) in M/F vets with PTSD Improvements in PTSD and depression measures 1 DrugStudyFindings Ongoing Trials Eszopiclone (Lunesta) Pollack et al. (2011); 3 week double-blind RCT cross-over of eszopiclone (12) v placebo (12) Significant improvement in CAPS, SPRINT, and PSQI 1

36 DrugStudyFindings Ongoing Trial(s) Hydrocortisone Delahanty et al. (2013); Double-blind RCT of 10 days of 20mg BID hydrocortisone (32) v placebo (32) initiated within 12 hours of trauma Lower PTSD and depression symptoms; Higher quality of life measures 3 DrugStudyFindings Ongoing Trial(s) Topiramate (Topamax) Yeh et al. (2011); 12 week double- blind RCT of topiramate (35) v placebo (35) Significant improvement in PTSD symptoms (ave. dose ~100mg) 3*3*

37 Complementary and Alternative Medicine

38 What is CAM? A group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medical. NCCAM website: Natural Products Herbal medicines, dietary supplements, probiotics Mind and Body Medicine Meditation, Acupuncture, Yoga, Progressive Relaxation Manipulative and Body-Based Practices Massage therapy, Spinal Manipulation National Center for Complementary and Alternative Medicine

39 Other ways to Organize CAM Based on validity of proposed mechanism: 1) Consistent with current medical perspectives and understanding of pathophysiology 2) Unsure of mechanism for perceived benefit 3) Violates basic laws of physics/chemistry/biology Or Based on Modality Type: 1) Interventions (e.g. Acupuncture) 2) Care Delivery Method (e.g. Computer Based Therapy) 3) Personal Activities (e.g. Recreational Therapy)

40 Why is CAM Research so complicated? 1. Hypothesis development Design believable studies 2. Definition and Validation of Diagnosis Define PTSD using validated instruments Establish Chronicity of symptoms 3. Treatment Design Standardize the intervention 4. Measuring outcome Use established assessment tools to evaluate Include follow-up assessments 5. Interpreting Results Identify primary and secondary outcome measures prior to the trial

41 InterventionStudyFindings Virtual Reality (VR) Ready et al. (2010); VR v present centered therapy in Vietnam Vets with PTSD (11) No group differences; Trend towards effect for VR comparing symptom change Reger et al. (2011); VR for PTSD in military mental health clinic (24) Significant reduction in symptoms (PCL-M) McLay et al. (2011); RCT of VR for PTSD in Active Duty with combat related PTSD Significant improvement in PTSD symptoms (CAPS) Miyahira et al. (2012); VR exposure therapy vs. minimal attention over 10 sessions Significant improvement in PTSD symptoms (CAPS) McLay et al. (2012); Open-label, single group, treatment development project (20) Improvements in PTSD, depression and anxiety

42 InterventionStudyFindings Yoga Telles et al. (2010); 1 week of yoga v WLC post natural disaster (22) Decrease in sadness in treatment group compared to increased anxiety in WLC Descilo et al. (2010); Yoga breath v yoga breath + exposure v WLC for PTSD post natural disaster (183) Significant reduction in symptoms with Yoga breath and Yoga breath + exposure Stankovic L (2011); 8 week trial of Integrative Restoration Yoga for PTSD in military and veterans (11) Reductions in rage, anxiety, intrusive memories and improvement in relaxation Acupuncture Hollifield et al. (2007); Acupuncture v CBT v WLC for PTSD (58) Significant improvement in both acupuncture and CBT groups compared to WLC Wang et al. (2012); Electro- acupuncture v. paroxetine for earthquake related PTSD (138) Significant reduction in CAPS, HAMD, HAMA. Electro-acupuncture more significant than paroxetine

43 Future Directions






49 PsychotherapyIncreased OptionsBiomarkersPharm Dismantling Dissemination Best Practices Treatment Engagement Stigma Reduction Alternative Therapies Family Interventions Comorbidities New Modalities Delivery Location Neuroimaging Genetics Proteomics/Metabolomic s Repurposing New Molecular Entities Study Group Pediatrics X X Adults XXXXXXXXXXXX Geriatrics XX Disaster XXXXX Sexual Assault XXXXXXXXXXX Combat XXXXXXXXXXXXX Motor Vehicle XX X XX

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