Research Update:
PTSD
Gary H. Wynn, MD, FAPA
Associate Professor / Assistant Chair
Department of Psychiatry
Uniformed Services University of the Health Sciences
Bethesda, MD
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.
Agenda
 Background and Current work on PTSD





Epidemiology
Stigma and Barriers to Care
Psychotherapy
Pharmacotherapy
Complementary and Alternative Medicine
 Future Directions for Research
Epidemiology
Community
First Responders
Loved Ones
Individual
DSM-IV-TR
A: Event
Broadened definition
Very similar
B: Re-experiencing
(Intrusion)
C: Avoidance
DSM-V
Effectively Split in Two
A: Event
B: Intrusion
(Re-experiencing)
C: Avoidance
D: Negative Alterations
in Cognitions/Mood
D: Arousal
E: Duration
Very similar
E: Arousal
Identical
F: Clinically Significant
Distress
F: Duration
Identical
G: Clinically Significant
Distress
H: Not attributable to
substance/medical
DSM-IV-TR
EVENT
DSM-V
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:
A1: experienced, witnessed,
or was confronted with events
that involved actual or
threatened death/serious injury
A1: Directly experiencing the
traumatic event(s)
A2: response involved intense
fear, helplessness, or horror
A3: Learning that the traumatic
event(s) occurred to a close family
member or close friend
A2: Witnessing, in person, the
event(s) as it occurred to others
A4: Experiencing repeated or
extreme exposure to aversive
details of the traumatic event(s)
DSM-IV-TR
C: Persistent avoidance of
stimuli associated with the trauma
and numbing of general
responsiveness as indicated by
3 or more of the following:
C1: Efforts to avoid thoughts,
feelings, or conversations
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
DSM-V
C: Persistent avoidance of stimuli
associated with the traumatic event as
evidenced by on or both of the following:
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)
D2: Persistent exaggerated negative beliefs
about oneself, others, or the world
D3: Persistent, distorted cognitions that
lead the individual to self blame
D4: Persistent negative emotional state
D5: Markedly diminished interest in
significant activities
D6: Feelings of detachment or
estrangement from others
D7: Persistent inability to experience positive
emotions
DSM-IV-TR
DSM-V
Specifiers
Acute (<3 months)
Chronic (>3 months)
With Delayed Onset
With Dissociative Symptoms
- Depersonalization
- Derealization
With Delayed Expression
Subthreshold PTSD
Adjustment Disorder
Adjustment Disorder
Anxiety Disorder NOS
Other Specified Trauma- and
Stressor-Related Disorder
Unspecified Trauma- and
Stressor-Related Disorder
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
Pre-Stress
Stress
Post-Stress
PTSD
Genetics
Depression
Subjective
Response
And
Recovery
Prior Stress
And
Stress Prep
Substance Use Disorders
Chronic Pain
Somatic Disorders
Other Psychiatric Disorders
Extreme Stress
Adapted from John Krystal (APA 2013)
Responses to Trauma
Distress
Responses
Mental
Health
Health Risk
Behaviors
(changed behavior)
Benedek DM and Wynn GH. Clinical Manual for Management of PTSD.
American Psychiatric Press, Inc 2010
Stigma and Barriers to Care
From the 2010 National Survey on Drug Use and Health
Stigma
66
Lack of perceived need
60
Perceived lack of effectiveness
66
40
54
Want to solve on own
68
40
Unsure where to go
49
35
Fear of forced hospitalization
Men
Women
22
23
Stigma
24
0
17
10
20
30
40
50
Agree or Strongly Agree, %
Kessler RC. J Clin Psychiatry. 2000;61(suppl 5):4-12.
60
70
80
Patients Making Treatment Contact, %
Lifetime Probability of Treatment Contact
7% contact within year of PTSD onset and
12-year median delay to first treatment contact
100
95%
94%
90%
90
88%
86%
80
65%
70
60
Panic
Disorder
Dysthymic
Disorder
Wang PS, et al. Arch Gen Psychiatry. 2005;62:603-613.
Bipolar
Disorder
Major
Depression
GAD
PTSD
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
Psychotherapy
Psychotherapies
SR
SUBSTANTIAL
A
• Trauma-focused psychotherapy that
includes components of exposure
and/or cognitive restructuring; OR
• Stress inoculation training
SOMEWHAT
C
•
•
•
•
•
•
I
• Family therapy
UNKNOWN
Patient Education
Imagery Rehearsal Therapy
Psychodynamic Therapy
Hypnosis
Relaxation Techniques
Group Therapy
From VA/DoD Clinical Practice Guideline for The Management of Post-Traumatic Stress (2010)
• Web-Based CBT
• Dialectical
Behavior Therapy
• Acceptance &
Commitment
Therapy
Level A Psychotherapy Choices
Patients should be offered one of the evidence-based traumafocused 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)
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 1st 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
Meta-analysis of Individual Psychotherapy
Treatment
Effect Size
Number of Studies
Prolonged Exposure
1.38 (0.9-1.86)
10
Cognitive Processing
Therapy
1.69 (1.27-2.11)
3
Stress Inoculation Therapy
1.37 (0.8-1.93)
2
Exposure + Cognitive
1.52 (1.08-1.95)
3
Virtual Reality
1.01 (0.37-1.65)
4
EMDR
1.04 (0.44-1.65)
10
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
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
PCL Score
Chard KM, Ricksecker EG, Healy ET et al. Dissemination and experience
with cognitive processing therapy. J Rehabil Res Dev 2012
Cognitive Behavioral Conjoint Therapy for PTSD
Improves PTSD Symptoms
Clinician-Administered PTSD Scale
CBCT
WL
80
70
60
50
40
30
20
Baseline
Mid-Treatment/ 4Week Wait
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)
Post-Treatment/ 12Week Wait
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)
CAPS PTSD Severity
 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)
Pharmacotherapy
SR
SIG
BENEFIT
A
SSRI
SNRI
B
C
SOMEWHAT
UNKNOWN
NONE or HARM
Mirtazapine
 Atypical antipsychotics
(as adjunct)
 Prazosin (for
sleep/nightmares)
 TCAs
 Nefazodone
 MAOIs (phenelzine)

Prazosin (for
global PTSD)

D
Adapted from VA/DoD Clinical Practice Guideline for The Management of Post-Traumatic Stress (2010)
Benzodiazepines[Harm]
 Tiagabine
 Guanfacine
 Valproate
 Topiramate

Drug
Sertraline
(Zoloft)
Paroxetine
(Paxil)
*
Study
Findings
Robb et al. (2010); 10 week
No significant reduction in
double-blind RCT of sertraline
PTSD symptoms at 10
(67) v placebo (62) in children and weeks
adolescents with PTSD (ages 617)
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
Simon et al. (2008); Double-blind
RCT of paroxetine CR (11) v
placebo (12) for PE refractory
PTSD
No significant improvement
compared to placebo
- including sertraline v PEx v combination study
Ongoing
Trials
6*
2
Drug
Duloxetine
(Cymbalta)
Venlafaxine
(Effexor)
Study
Findings
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)
Walderhaug et al. (2010); 8 week
naturalistic study of duloxetine in
male vets with PTSD and comorbid MDD (21)
Improvements in both
PTSD and MDD by week 8
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
Ongoing
Trials
0
1

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
Drug
Prazosin
(Minipress)
Study
Findings
Raskind et al. (2007); 8 week trial of
prazosin v placebo (34) for trauma
nightmares and sleep disturbance
Significant benefit over
placebo
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
Ongoing
Trial(s)
4
Drug
Olanzapine
(Zyprexa)
Risperidone
(Risperdal)
Aripiprazole
(Abilify)
Drug
Eszopiclone
(Lunesta)
Study
Findings
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
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
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
Study
Pollack et al. (2011); 3 week
double-blind RCT cross-over of
eszopiclone (12) v placebo (12)
Findings
Significant improvement in
CAPS, SPRINT, and PSQI
Ongoing
Trials
0
0
1
Ongoing
Trials
1
Drug
Study
Hydrocortisone
Drug
Topiramate
(Topamax)
Delahanty et al. (2013);
Double-blind RCT of 10 days
of 20mg BID hydrocortisone
(32) v placebo (32) initiated
within 12 hours of trauma
Study
Yeh et al. (2011); 12 week doubleblind RCT of topiramate (35) v
placebo (35)
Findings
Lower PTSD and
depression symptoms;
Higher quality of life
measures
Ongoing
Trial(s)
3
Findings
Ongoing
Trial(s)
Significant improvement
in PTSD symptoms (ave.
dose ~100mg)
3*
Complementary and Alternative Medicine
What is CAM?
A group of diverse medical and health care systems, practices,
and products that are not generally considered part of
conventional medical.
National Center for Complementary and Alternative Medicine
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
NCCAM website: nccam.nih.gov
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)
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
Intervention
Virtual Reality
(VR)
Study
Findings
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
Intervention
Yoga
Acupuncture
Study
Findings
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
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); Electroacupuncture v. paroxetine for
earthquake related PTSD (138)
Significant reduction in
CAPS, HAMD, HAMA.
Electro-acupuncture more
significant than paroxetine
Future Directions
X
X
X
X
New Molecular Entities
X
X
Repurposing
X
X
Proteomics/Metabolomic
s
X
X
Genetics
X
X
Neuroimaging
X
Combat
Delivery Location
X
X
New Modalities
X
X
Comorbidities
X
X
Family Interventions
Alternative Therapies
Stigma Reduction
Treatment Engagement
Best Practices
X
X
Motor Vehicle
Dissemination
Dismantling
X
X
X
X
X
X
X
X
X
X
X
Sexual Assault
X
X
X
X
X
X
Geriatrics
X
X
Study Group
X
X
X
X
X
X
Adults
X
Disaster
X
X
X
Pediatrics
Pharm
Biomarkers
Increased Options
Psychotherapy