Treatment and Management of Posttraumatic Stress Disorder

Treatment and Management of
Posttraumatic Stress Disorder
Program Faculty
Michael
Michael Van
Van Ameringen,
Ameringen, MD,
MD, FRCPC
FRCPC
Co-Director,
Co-Director, Anxiety
Anxiety Disorders
Disorders Clinic
Clinic
McMaster
McMaster University
University Medical
Medical Centre
Centre -- HHS
HHS
Associate
Associate Professor
Professor
Department
Department of
of Psychiatry
Psychiatry &
& Behavioural
Behavioural
Neurosciences
Neurosciences
McMaster
McMaster University
University
Ruth
Ruth Lanius,
Lanius, MD,
MD, PhD,
PhD, FRCPC
FRCPC
Assistant
Assistant Professor
Professor
Department
Department of
of Psychiatry
Psychiatry
University
University of
of Western
Western Ontario
Ontario
Director,
Director, Traumatic
Traumatic Stress
Stress Service
Service and
and
WSIB
Traumatic
Stress
Service
Workplace
WSIB Traumatic Stress Service Workplace
Program
Program
London
London Health
Health Sciences
Sciences Centre
Centre
Catherine
Catherine Mancini,
Mancini, MD,
MD, FRCPC
FRCPC
Co-Director,
Anxiety
Disorders
Co-Director, Anxiety Disorders Clinic
Clinic
McMaster
McMaster University
University Medical
Medical Centre
Centre -- HHS
HHS
Associate
Associate Professor
Professor
Department
Department of
of Psychiatry
Psychiatry &
& Behavioural
Behavioural
Neurosciences
Neurosciences
McMaster
McMaster University
University
Steven
Steven Taylor,
Taylor, PhD,
PhD, R
R Psych
Psych
Professor
Professor
Department
Department of
of Psychiatry
Psychiatry
University
University of
of British
British Columbia
Columbia
Program Agenda
Time
Topic
Faculty
9:15 a.m.
Welcome and Introduction
Dr. Van Ameringen
9:20 a.m.
Epidemiology - Clinical Features
Dr. Van Ameringen
9:40 a.m.
Q and A Session
9:45 a.m.
Neurobiology of PTSD
10:05 a.m.
Q and A Session
10:10 a.m.
CBT Treatment of PTSD
10:30 a.m.
Q and A Session
10:35 a.m.
Psychopharmacology of PTSD
10:55 a.m.
Q and A Session
Dr. Lanius
Dr. Taylor
Dr. Mancini
Clinical Features and
Epidemiology of Posttraumatic
Stress Disorder
1,2
Michael Van Ameringen MD, FRCPC1,2
1,2
Catherine Mancini MD, FRCPC1,2
Beth Pipe BScN, BEd11
Sandra Pinchak33
Michael Boyle, PhD22
11Anxiety Disorders Clinic, McMaster University Medical Centre, Hamilton, Ontario, Canada;
Anxiety Disorders Clinic, McMaster University Medical Centre, Hamilton, Ontario, Canada;
22Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton,
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton,
Ontario,
Ontario, Canada;
Canada;
33Goldfarb Consultants, Toronto, Ontario, Canada
Goldfarb Consultants, Toronto, Ontario, Canada
Conceptual Origins of PTSD
• PTSD has been given various names over
the years:
– Combat neurosis
– Shell-shock syndrome
– Operational fatigue
– Compensation neurosis
z Battle fatigue
z Soldier’s heart
z Traumatic neurosis
• DSM-IV
– Recognition that trauma is broadly defined and
is not necessarily outside the range of normal
human experience
– Categorize acute stress vs. PTSD
TM
DSM-IV
Diagnostic
PTSD
Criteria - Overview
A. The person has been exposed to a traumatic event
B. The traumatic event is persistently re-experienced
C. Persistent avoidance of stimuli associated with the
traumatic event and numbing of general responsiveness
D. Persistent symptoms of hyperarousal not present
before the traumatic event
E. Symptoms’ duration of criteria B, C, and D is more than
1 month
F. Symptoms cause clinically significant distress or
impairment at home, work, or in other areas of
functioning
PTSD: Core Symptoms
3 Primary Symptom Clusters:
• Re-Experiencing of Trauma
• Avoidance / Numbing
• Hyperarousal
DSM-IV-TR
PTSD: Re-Experiencing
• Trauma re-experienced in ≥ 1 ways:
–
–
–
–
Intrusive, distressing recollections
Nightmares
Flashbacks
Intense psychological distress when exposed
to triggers
– Exaggerated emotional and physical
reactions to triggers
Adapted
Adapted from
from American
American Psychiatric
Psychiatric Association
Association (APA).
(APA). Diagnostic
Diagnostic and
and Statistical
Statistical Manual
Manual of
of Mental
Mental
Disorders.
4th
ed.
(DSM-IV).
Washington,
DC:
1994:424-429
Disorders. 4th ed. (DSM-IV). Washington, DC: 1994:424-429
PTSD: Avoidance and Numbing
• Persistent avoidance of triggers and numbing
of responsiveness in ≥ 3 ways:
–
–
–
–
–
–
–
Avoiding thoughts, feelings, or talk about trauma
Avoiding activities, places, or people that recall
trauma
Amnesia for part of trauma
Less interest or participation in significant
activities
Feeling detached from others
Restricted emotions
Sense of foreshortened future
Adapted
Adapted from
from American
American Psychiatric
Psychiatric Association
Association (APA).
(APA). Diagnostic
Diagnostic and
and Statistical
Statistical Manual
Manual of
of Mental
Mental Disorders.
Disorders. 4th
4th ed.
ed.
(DSM-IV).
(DSM-IV). Washington,
Washington, DC:
DC: 1994:424-429
1994:424-429
PTSD: Increased Arousal
• Persistent increased arousal in ≥ 2 ways:
– Difficulty sleeping
– Irritability or outbursts of anger
– Difficulty concentrating
– Hypervigilance
– Exaggerated startle response
Adapted
Adapted from
from American
American Psychiatric
Psychiatric Association
Association (APA).
(APA). Diagnostic
Diagnostic and
and Statistical
Statistical Manual
Manual of
of Mental
Mental Disorders.
Disorders. 4th
4th ed.
ed.
(DSM-IV).
(DSM-IV). Washington,
Washington, DC:
DC: 1994:424-429
1994:424-429
Normal Responses After Trauma
• Intensity of response varies with severity
of trauma
• Re-experiencing symptoms
z Thoughts z Dreams z Images
• Intense emotional reactions:
z Fear z Bewilderment z Anger z
Helplessness z Despair
•
•
•
Increased vigilance and autonomic arousal
Persistent memory often with vivid imagery
Gradual adjustment over weeks to months
PTSD Symptoms:
Clinical Course
PTSD symptoms usually present within first 3 months
following the traumatic event*
• Less frequently, symptom onset may be delayed for
months or years after the traumatic event
• Symptoms of PTSD may persist for months or years
following the traumatic event
Approximately 50% of all cases of PTSD are chronic
• Acute: Duration of symptoms of less than 3 months
• Chronic: Duration of symptoms is 3 months or more
Longitudinal Course of PTSD
Symptoms
6% recovered
53% recovered
58% recovered
15-25%
UNRECOVERED
Weeks 3 months
Shalev & Yehuda, Psychological Trauma 1998
9 months
YEARS
Risk Factors for PTSD Development
PeriTrauma
PreTrauma
PostTrauma
PTSD
Pre-Trauma Risk Factors
• Female gender
• Previous trauma / younger age at time of
trauma
• Childhood abuse
• Trait neuroticism / poor coping style
• Past psychiatric history
• Family psychiatric history
• Low SES, less education
Brewin et al, J Consult Clin Psychol 2000
Peri-Traumatic Risk Factors
Influencing PTSD
•
•
•
•
•
•
Nature of trauma (personal assault)
Severity of trauma / chronicity of trauma
Severity of acute symptoms /
physiological reactivity (increased heart
rate and startle response)
Dissociation at time of trauma
Perceived helplessness / lack of control
Potential for mortality
Brewin et al, J Consult Clin Psychol 2000
Post-Trauma Risk Factors
• Lack of social support
• Lack of appropriate early treatment or
access
to services
• Shame / guilt / self-doubt
• Recovery-related secondary stressors
(secondary trauma)
• Ongoing life stressors
Yehuda et al, Biol Psychiatry1998
Psychiatric Comorbidity (Lifetime)
Alcohol
Abuse /
Dependence
39.9%
Panic
9.9%
Major Depression
48.2%
PTSD
GAD
15.9%
Social Phobia
29.9%
Agoraphobia
19.25%
Kessler et al, Arch Gen Psychiatry 1995
Clinical Presentation to the Physician
•
•
•
•
•
•
•
Sleep complaints
Somatic symptoms
Depression
Other comorbid anxiety disorders
Alcohol or chemical use
Suicidal ideation / ER visits
High rate of medical service consumption
Victims with trauma history are more likely to present to
their general physician than to mental health services
Hildalgo & Davidson, J Clin Pyschiatry 2000
Common Misdiagnoses
PTSD Symptom Misdiagnosis
Flashbacks
Hallucinations
Avoidance
Schizoid / Avoidant
Personality Disorder
Numbing
Depression
Hyperarousal
Anxiety, Bipolar
Disorder
Hypervigilance
Paranoia
Cyr & Farrar, Ann Pharmacother 2000
Why is PTSD Not Recognized?
• Patient attitudes - reluctance to discuss
trauma (fear, shame, guilt)
• Provider attitudes - failure to inquire about
trauma and PTSD
– discomfort with subject matter
– inexperience in assessment and making
diagnosis
– time constraints
• Diagnosis is masked by other
psychiatric/medical conditions
PTSD EPIDEMIOLOGY
PTSD – Prevalence Studies
STUDY
N
CURRENT PTSD
(12 Months) PTSD (%)
LIFETIME PTSD (%)
Total
Men
Women
Total
Men
Women
ECA – St. Louis, USA
Helzer et al (1987)
2493
1.0
0.5
1.3
-
-
-
ECA – North Carolina, USA
Davidson et al (1991)
2985
1.3
0.9
1.7
-
-
-
Post Hurricane Hugo, South EastNorris (1992)
USA
1000
-
Adult Women, USA
Resnick et al (1993)
4008
12.3
NCS, USA
Kessler et al (1995)
5877
7.8
Full/Partial PTSD, Winnipeg, Canada
Stein et al (1997)
1002
Detroit Area Survey, USA
Breslau et al (1998)
2181
9.2
Community Sample, Munich, Germany
Perkonigg et al (2000)
3021
1.3
National Survey Mental Health, Australia
Creamer et al (2001)
10641
Women’s Health Study, Ontario, Canada
(Frise et al., 2002)
3062
-
-
-
5.0
7.3
6.1
12.3
4.6
-
-
-
-
10.4
-
1.2*
2.7*
6.2
13.0
-
-
-
0.4
2.2
0.7
-
-
10.7
0.1
1
1.3
-
8.5
-
-
-
-
-
1.2
month prevalence
1.2
1.4
-
-
Variability in Prevalence Rates
•
•
•
•
Study Instrument: DIS, CIDI, PTSD symptom
scale, Traumatic Stress Scale
Greater number of events queried yields
higher prevalence
Diagnostic criteria: DSM-III, DSM-IIIR, DSMIV(expansion of qualifying stressors)
Community-based vs. Population-based
samples
Trauma Exposure and Lifetime
Prevalence in NCS
(n=5877, aged 15-54, DSM-III-R)
Lifetime Trauma Exposure
Lifetime Prevalence of PTSD
70
61%
60
51%
50
40
30
20
10.4%
10
5.0%
0
Women
Kessler et al, Arch Gen Psychiatry 1995
Men
Rate of PTSD is related to the
type of Trauma
40
Prevalence of T rauma
M ale
Female
30
%
20
10
0
%
70
60
50
40
30
20
10
0
Probability of PT SD
Witness
T hreat
Kessler et al. J Clin Psychiatry. 2000;61(Suppl 5):4.
Kessler et al. Arch Gen Psychiatry. 1995;52:1048.
Attack
M olestation
Combat
Rape
PTSD:
One-Month Prevalence in
Winnipeg Canada
Full Symptomatic PTSD
3.4%
Partial Symptoms of PTSD
3.5
Percent (%)
3
2.7%
2.5
2
1.2%
1.5
1
0.3%
0.5
0
Women
Stein et al, Am J Psychiatry 1997
Men
Canadian PTSD
Epidemiology Study
1,2
Michael Van Ameringen MD, FRCPC1,2
1,2
Catherine Mancini MD, FRCPC1,2
Beth Pipe BScN, BEd11
Sandra Pinchak33
Michael Boyle, PhD22
11Anxiety Disorders Clinic, McMaster University Medical Centre, Hamilton, Canada;
Anxiety Disorders Clinic, McMaster University Medical Centre, Hamilton, Canada;
22Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada;
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada;
33Goldfarb Consultants, Toronto, Canada
Goldfarb Consultants, Toronto, Canada
Study funded by an unrestricted research grant from
GlaxoSmithKline Canada
METHOD:
Sample
• A nationally representative sample of 3006
individuals aged 18 and older
• Random Digit Dialing
• Sample size and regional distribution were
based on national and provincial population
estimates.
• Computer-assisted telephone interviews
were conducted in either English or French
METHOD: Interviews
•
Interviewers made up to 7 attempts to contact a
household at varying times over a 45 day period
•
Participant eligibility was determined by the person
in the household over the age of 18, with the most
recent birthday
•
Qualifying respondents gave informed, verbal
consent after being given an explanation of the
study’s goals
•
Of the 4446 eligible households, a response rate of
83% was obtained.
METHOD: Instrument
• Lifetime exposure to trauma
• DSM-IV Lifetime and Current (one-month)
PTSD
• DSM-IV Major Depressive Disorder
• DSM-IV Alcohol and Substance Abuse and
Dependence
• Exposure to Childhood Maltreatment
PTSD Module
Instrument Design I
• PTSD component of this survey is a
modified version of the Canadian
Community Health Survey (CCHS) 1.2
module, designed to screen for DSM-IV
PTSD
• The CCHS - PTSD module was based on the
World Mental Health (WMH) 2000, a CIDIbased instrument
PTSD Module: Traumatic Events
•
•
•
•
•
•
•
•
•
•
Participation in combat
Peacekeeper or relief
worker
Refugee
Kidnapped/held captive
Exposure to a toxic
chemical
Life-threatening MVA
Work-related accident
Natural disaster
Being badly beaten
Mugged/threatened with
a weapon
•
•
•
•
•
•
•
Sexual assault
Sexual molestation
Unexpected death of
some one close
Traumatic event
experienced by some
one close
Witnessed physical
domestic violence as
a child
Witnessed atrocities
Other life-threatening
PTSD Module
Instrument Design II
• “After experiences like these, people sometimes have
problems like upsetting memories or dreams, feeling
emotionally distant or depressed, trouble sleeping or
concentrating or feeling jumpy or easily startled. Did
you ever experience any of these reactions following
any of these traumatic events?”
• “Did these symptoms persist for more than 1
month?”
• Asked to select their “worst” event
Data Analysis I
• All presented data were weighted based on
age and gender distributions within the total
Canadian population
(M/F: 48.4% : 51.6%)
• Missing data were eliminated from all
analyses
Data Analysis II
• Full PTSD was defined according to DSM-IV
criteria, including duration (Criterion E) and
impairment/distress (Criterion F)
• Partial PTSD was defined as those meeting
DSM-IV PTSD criteria, but were lacking 1 or 2
of the necessary 3 Criterion C symptoms, or
lacking 1 of the necessary 2 Criterion D
symptoms, (respondents were required to
have at least one symptom in each Criterion
category)
Characteristics of the Sample I
(N=3006)
CHARACTERISTIC
% (UNWEIGHTED)
% (WEIGHTED)
Gender
Female
Male
60.7
39.3
51.6
48.4
Age (years)
18-26
27-35
36-44
45-53
54-62
$ 63
15.9
17.2
20.5
16.7
12.3
11.2
15.3
16.1
20.0
17.4
12.2
19.0
Race
White
Black
Aboriginal
Latin American
Asian
Other
Refused to answer
87.4
1.7
1.9
0.2
3.4
4.5
0.7
87.1
1.7
1.9
0.2
3.5
5.0
0.7
Characteristics of the Sample II
(N=3006)
CHARACTERISTIC
Marital Status
Legally Married/Common-Law
Separated/Divorced/Widowed
Single (never married)
Refused to answer
% (UNWEIGHTED)
% (WEIGHTED)
54.9
20.3
24.3
0.5
55.2
20.3
23.9
0.5
Characteristics of the Sample III
(N=3006)
CHARACTERISTIC
% (UNWEIGHTED)
% (WEIGHTED)
Education (years)
Never attended
Kindergarten – Grade 8
Some high school
High school graduate
Some college or technical training
College graduate
Some university
University graduate
Graduate work
Don’t know/Refused to answer
0.1
4.0
12.0
22.7
12.5
16.9
7.1
19.3
5.1
0.5
0.1
4.3
12.2
22.6
12.4
16.3
7.1
19.3
5.1
0.5
Household Income
< $20,000
$20,000 - $39,000
$40,000 - $74,000
$75,000 - $99,000
$ $100,000
Unsure/Refused to answer
13.3
21.9
27.6
9.5
9.5
18.2
12.9
21.9
27.9
9.6
9.7
18.0
Currently Employed
58.3
58.2
Characteristics of the Sample IV
(N=3006)
% (UNWEIGHTED)
% (WEIGHTED)
Region
Atlantic Canada
Quebec
Ontario
Western Canada
Far North
8.9
24.0
37.6
29.2
0.3
8.9
23.9
37.5
29.4
0.3
Urbanicity
Urban core
Urban fringe
Rural fringe
Urban outside of CMA/CA
Rural outside of CMA/CA
Missing data
55.4
1.5
4.9
8.4
9.4
20.4
55.4
1.5
4.9
8.3
9.6
20.3
CHARACTERISTIC
P e rc e n t (% )
Lifetime Rate of Traumatic
Exposure
100
90
80
70
60
50
40
30
20
10
0
76.1
Total Population
73.8
78.6
W omen
Men
Number of Traumatic Exposures
Total
Population %
Women
%
Men
%
0
23.9
26.2
21.4
1
23.0
22.7
23.2
2
16.7
16.7
16.6
3
12.1
12.3
11.7
4
8.1
7.4
8.8
$5
16.2
14.7
18.3
All
Exposures
Mean
SD
Mean
SD
Mean
SD
3.3
2.3
3.2
2.2
3.5
2.5
t = 3.76, df = 3004, p <.001
Exposure to Traumatic Events
Trauma
Unexpected death of some one close
Witnessing some one killed, dead or badly injured
Sexual molestation
Life-threatening MVA
Trauma experienced by someone close
Mugged/threatened with a weapon
Natural disaster
Sexual assault
Exposure to toxic chemical
Witnessing physical fights at home as a child
Being badly beaten
Other trauma
Work-related accident
Participating in combat
Witnessed atrocities
Refugee
Peacekeeper/Relief worker
Kidnapped
Total
Population %
41.2
32.0
22.0
18.0
16.9
16.1
15.7
11.5
10.1
9.4
9.2
8.6
7.9
4.3
3.4
2.2
2.0
1.4
Women
%
Men
%
42.2
23.3
33.2
13.2
17.9
11.4
13.7
19.4
5.1
10.7
9.6
7.1
2.4
0.8
2.1
1.8
0.8
1.5
40.1
41.3
9.9
23.1
15.9
21.3
17.8
3.1
15.5
8.0
8.8
10.3
13.7
8.0
4.8
2.6
3.2
1.2
P e rc e n t (% )
PTSD PREVALENCE IN CANADA (N = 3006)
100
90
80
70
60
50
40
30
20
10
0
94.3
88.6
9.2
2.2
Lifetime PTSD
None
Full PTSD
2.4
Current PTSD
Partial PTSD
3.4
Lifetime Prevalence of Full and
Partial PTSD by Gender
14
12.9
Percent (%)
12
9.2
10
8
5.3
6
2.9
4
1.5
2.2
2
0
Full PTSD Lifetime
Female %
Partial PTSD Lifetime
Male %
Total % of Sample N=3006
x2=51.5, df=1, p<.001 (Full PTSD-L)
Current (1-month) Prevalence of
Full and Partial PTSD by Gender
Percent (%)
14
12
10
8
5.1
6
4
2
0
3.4
3.3
2.4
1.8
1.3
Full PTSD Current
Female %
Partial PTSD Current
Male %
Total % of Sample N=3006
x2= 13.6 , df= 2 , p <.001 (Full PTSD-C)
Traumatic Events Leading to PTSD (Lifetime)
Trauma
Total
Population %
Women %
Men %
Assaultive Violence
Sexual assault
Being badly beaten
Sexual molestation
Mugged/threatened with a weapon
Kidnapped
Participated in combat
19.7
11.9
5.0
3.3
2.5
0.5
25.6
13.6
5.5
3.5
0.5
0
3.9
7.7
2.6
2.6
7.7
1.3
Total
42.9
48.7
25.8
8.6
5.9
3.9
2.6
0.6
0.4
0.6
0
5.5
7.0
2.5
1.5
1.0
0
1.0
0
16.7
2.6
7.7
6.4
0
1.3
0
0
22.6
18.5
34.7
4.3
4.0
5.1
30.3
29.0
33.8
Other Injury or Shock
Witnessed some one killed, dead or badly injured
Witnessed physical domestic violence as a child
Life
- threatening MVA
Witnessed atrocities
Refugee
Involved in a serious work
- related accident
Involved in a major natural disaster
Peacekeeper/Relief worker
Total
Learning about others
Trauma experienced by someone else
Sudden unexpected death
PTSD Within Age Category
% o f in d v id u a ls w ith in a g e
c a te g o ry w ith P T S D -L
14
12
10
8
6
4
2
0
18-26
27-35
36-44
45-53
Age Category
x2=37.2, df=5, p<.001
54-62
63+
PTSD Prevalence: National
Distribution
11.6
12
9.7
10
8
Atlantic Canada
Quebec
Ontario
Western Canada
Far North
6.4 6.7
6
4
2.2 2.2
2
3
1.1
0
0
0
Lifetime PTSD
(% within region)
Current PTSD
(% within region)
x2=14.4, df=3, p<.002 (Full PTSD-L)
Prevalence of PTSD by Marital
Status and Household Income
Marital Status
% PTSD-L
6.1
Legally married/Common-law
Separated/Divorced/Widowed
14.8
Single (never married)
24.3
x2=48.6, df=2, p<.001
Household Income
< $20,000
$20,000 - $39,000
$40,000 - $74,000
$75,000 - $99,000
$ $100,000
x2=12.5, df=4, p<.014
% PTSD-L
14.3
11.5
8.6
9.4
7.8
Comorbid Diagnoses:
Post Qualifying Traumatic Event
Lifetime PTSD
Comorbid Diagnosis
Total
(%)
Partial Lifetime PTSD
Women
(%)
Men
(%)
Total
(%)
Women
(%)
Men
(%)
Major Depressive Disorder
72.6
77.3
59.7
35.4
40.9
23.8
Alcohol Abuse/Dependence
27.7
21.3
44.7
20.9
15.6
27.3
Substance Abuse/Dependence 25.2
19.3
40.3
13.4
8.9
21.7
P<.001
Social Support and PTSD in those
experiencing a Trauma
(N=659)
Perceived
Social Support
Lifetime PTSD
Present
Absent
Present
43.2
56.7
Absent
61.3
38.7
P<.007
Conclusion I
• Usually presents to primary care
physicians
• A common, highly debilitating, chronic
condition
• Easily missed diagnosis due to complexity
of disorder
Conclusion II
• PTSD is highly prevalent in Canada
• It affects women more commonly
• Exposure to traumatic events in the
general population is very common (76%)
• Assaultive violence followed by sudden,
unexpected death of some one close,
yielded the highest rates of PTSD
Conclusion III
• Comorbid MDD, alcohol abuse/dependence
and substance abuse/dependence are
frequent sequelae of trauma
• This study suggests that PTSD is a
significant public health issue
• It invokes serious implications on the
emotional, physical, occupational and
social functioning of afflicted Canadians,
and presents a significant cost to Canada
Traumatic Symptom Provocation and
Neuroimaging:
Heterogeneity of Response in PTSD
Ruth A. Lanius, M.D., Ph.D.
PTSD (DSM IV) Symptoms
•
•
•
•
•
Exposure to traumatic event
Re-experiencing
Avoidance / numbing
Hyperarousal
Symptoms cause functional
impairment
Heterogeneity of Response
Pilot studies in our lab have shown
that PTSD patients can have different
responses to traumatic script-driven
imagery
•
•
Flashback/reliving response
(increase in heart rate)
Dissociative response (decrease or
an increase in heart rate)
Question
What is the functional connectivity
underlying flashback/ reliving or
dissociative responses to
Traumatic scripts?
Hypotheses
• Compared to controls, PTSD subjects experiencing
a flashback/hyperarousal response will reveal
activation of neuronal networks more consistent with
a nonverbal pattern of memory recall
• Compared to controls, dissociated PTSD subjects
will exhibit activation of neuronal networks involved
in conveying bodily states to the brain
Methodology
•
•
•
23 Control Subjects
13 PTSD Subjects (flashback/reliving response)
11 PTSD Subjects (dissociative response)
•
Subjects were medication free for at least two
weeks prior to neuroimaging
All subjects who had a dissociative response to
scripts met criteria for Dissociative Disoder NOS
(SCID-D)
•
Methodology ((con’t)
con’t)
•
Script-driven imagery symptom provocation
paradigm (traumatic, sad, anxious, and neutral
scripts)
•
Responses to scripts were determined by the RSDI
(Hopper, unpublished) and the CADDS (Bremner et
al., 1999)
•
4 Tesla fMRI (BOLD response)
•
SPM99 Analyses (subtraction and functional
connectivity analyses)
Methodology ((con’t)
con’t)
• fMRI
– 4-Tesla
– BOLD (Blood
Oxygenation LevelDependent)
Robarts Research Institute 4T
Blood
Blood flow
flow
Blood flow
increases as a
function of neural
activity
Hemoglobin
Hemoglobin
Oxygen
Oxygen
The fMRI signal depends on the difference in the
magnetic properties of oxygenated and de-oxygenated
hemoglobin.
Methodology ((con’t)
con’t)
Subtraction Analyses
Assessment of specific
brain regions involved in
the recall of traumatic
events
Visual Representation of
Basis Functions
recall traumatic memory
60 s
Resting
30s
30 s
recall traumatic memory
60 s
60 s
30 s
30 s
recall traumatic memory
60 s
30
60 s
30 s
60 s
s
resting
resting
resting
Red lines represent the "implicit baseline" scans used in SPM99 analyses. Hatched boxcars represent the recall
only of neutral, traumatic, sad or anxious memory used in the basis function, lasting 30s (6 volumes).
Flashback / Reliving Responses
Flashback / Reliving
/Hyperarousal Responses
•
“I was back at the scene of the accident. I
was trying to get myself and my wife out of
the car.”
•
“I could feel being raped all over again. I
could feel him holding down my hands.”
•
“It felt like I was surrounded by smoke. I
could smell and see it.”
Functional Connectivity
Analyses
(right anterior cingulate gyrus)
(Flashback / Reliving versus Control)
Functional Connectivity Analyses [-14 -16 4]
CONTROL (n=11) versus FLASHBACK (n=13)
t
Left,
Caudate
Left,
Left,
Left,
Superior
Inferior Parietal Anterior
Frontal Gyrus
Lobule
Cingulate
BA 9
BA 40
BA 32
Control > PTSD
Lanius et al., AJP, 2004
Right,
Right,
Right,
Right,
Caudate Posterior Cingulate Cuneus Inferior Parietal
BA 30
BA 19
Lobule BA 40
PTSD > Control
Verbal versus Nonverbal
Memory
Prefrontal activations during episodic memory retrieval have
sometimes been shown to be bilateral, but show a tendency for
right-lateralization (reviewed by Cabeza and Nyberg, 1997).
Anterior cingulate activation during memory recall has been
hypothesized to be related to language processes, since activation
of this area is more frequent for verbal than nonverbal materials.
(reviewed by Cabeza and Nyberg, 1997).
Verbal versus Nonverbal
Memory (con’t)
For nonverbal episodic retrieval, occipital, right parietal, and
posterior cingulate activations have been shown to predominate
(Cabeza and Nyberg, 2000).
The posterior cingulate gyrus been shown to mediate interactions
of emotional and memory-related processes (Maddock et al.,
2003).
PTSD Neuroimaging
Literature
Lower levels of brain activation in the medial prefrontal cortex
and anterior cingulate gyrus are consistent with previous PET
studies of sexual abuse- and combat-related PTSD
(Rauch et al., 1996; Shin et al., 1997; 1999; Bremner et al., 1999ab;
Liberzon et al., 1999; Osuch et al., 2001)
Thalamic dysfunction has been less frequently reported in the
PTSD neuroimaging literature (Liberzon et al., 1996; Bremner et al.,
1999)
PTSD Functional Connectivity
Neuroimaging Literature
Abnormal functional connectivity was reported in PTSD during a
working memory task (Shaw et al., 2002)
PTSD patients showed greater connectivity in the inferior
parietal lobes and left precentral gyrus as compared to controls
PTSD patients showed less connectivity in the inferior and middle
frontal gyri and the right inferior temporal gyrus
PTSD Functional Connectivity
Neuroimaging Literature (con’t)
Gilboa et al. (2004) examined functional connectivity of the prefrontal
cortex and the amygdala in PTSD during repeated symptom
provocation (traumatic script)
PTSD subjects showed a predominance of direct influences of the
amygdala on visual cortex, subcallosal gyrus, and anterior cingulate
as compared to controls
There was little evidence for failure of inhibition of cingulate or
subcollosal gyrus over the amygdala
PTSD Functional Connectivity
Neuroimaging Literature (con’t)
Shin et al. (2004) examined the functional relationship between the
medial prefrontal cortex and the amygdala using correlation analyses
PTSD patients showed decreased medial prefrontal cortex activation
as compared to controls
rCBF changes in the PTSD group correlated with rCBF changes in
the left amygdala and the right amygdaloid complex
Dissociative Responses
Dissociative Responses
“I was outside my body looking down at
myself. It was too overwhelming to
recall the traumatic memory.”
“I was completely zoned out and could
not tell what I was feeling.”
“I was looking down at my own body
while I was back reliving the car
accident.”
Functional
ConnectivityAnalyses
(left ventromedial thalamus)
(Dissociative versus Control)
Functional Connectivity Analyses [-14 -16 4]
CONTROL (n=11) versus DISSOCIATED (n=10)
t
Right,
Superior
Occipital Gyrus
BA 19, 39
Right,
Parahippocampal
Gyrus
BA 30
Left,
Superior
Frontal Gyrus
BA 10
Control>Dissociated
Right,
Occipital
BA 19
Right,
Insula
BA 13,
34
Left,
Right,
Superior Parietal Middle Frontal
Lobule
Gyrus
BA 7
BA 8
Dissociated >Control
Insula
CO
NT
EN
T
OF
Sensations
Pain
Body temperature
Viscera
Striated Muscles
Vestibular System
FE
EL
IN
GS
Insular cortex
Conveys bodily states to the brain
Insula
…the anterior insula of the the
nondominant (right) hemisphere, possibly
uniquely to humans, constitutes a basis
for the subjective evaluation of one’s
condition, that is, ‘how you feel’
Craig,
Craig, 2002
2002
Dissociation Neuroimaging
Literature
•
Mathew et al. (1999) found increased global cerebral blood
flow in the frontal lobes and anterior cingulate gyrus
following THC-induced depersonalization
•
Simeon et al. (2000) reported increased brain glucose
metabolism in parietal (BA 7B) and occipital (BA 19)
areas as well as decreased glucose metabolism in the
superior temporal gyrus during states of depersonalization
in DSM-IV depersonalization disorder
Dissociation Neuroimaging
Literature (con’t)
Reinders et al. (2003) examined rCBF patterns in patients with
DID in two distinct mental states
Increased rCBF was found in the traumatic personality state
during the recall of an autobiographical trauma script in the left
parietal operculum and the left insula
SUMMARY / CONCLUSIONS
PTSD subjects showed different
responses to traumatic script-driven
imagery
• flashback/reliving response
• dissociative response
SUMMARY/CONCLUSIONS (con’t)
• Functional connectivity analysis for PTSD subjects
with a flashback/reliving response showed neural
networks more consistent with nonverbal, timeless
patterns of memory retrieval (i.e., occipital lobes,
right parietal lobe, and posterior cingulate gyrus) as
compared to control subjects who showed activation
patterns more consistent with
verbal/autobiographical memory retrieval
SUMMARY/CONCLUSIONS (con’t)
• Functional connectivity analysis for PTSD subjects
with dissociative responses showed activation of
neural networks involved in conveying bodily states
to the brain
• These findings may shed light on mechanisms
underlying distorted body perceptions and difficulty
identifying feelings often observed clinically during
dissociative episodes
COLLABORATORS
Peter Williamson, MD
Maria Densmore, BSc
Jim Neufeld, PhD
Joe Gati, MSc
Ravi Menon, PhD
Psychopharmacology
of PTSD
Catherine Mancini, M.D., FRCPC
Anxiety Disorders Clinic
McMaster University Medical Centre
Hamilton Health Sciences
Hamilton, Ontario, Canada
Expert Consensus Guidelines
Noncomorbid
Noncomorbid
Children,
Children, Adults,
Adults,
Geriatric
Geriatric
Patients
Patients
D
D
S
T
S
T
P
P
d
l
i
d
l
M
Mi
M
Moorree S
Seevveerree
Foa et al. J Clin Psychiatry. 1999;60(suppl 16):3
- 6
7.
Psychotherapy
Psychotherapy First
First
Psychotherapy
Psychotherapy First
First or
or
Combine
Combine
Meds/Psychotherapy
Meds/Psychotherapy
Treatment Goals
• Reduce core
symptoms
• Improve stress
resilience
• Improve quality of life
• Reduce disability
• Reduce comorbidity
• Prevent relapse
Davidson, J Clin Psychiatry 2000
Strategy Behind
Pharmacotherapy in PTSD
• Medication can suppress the activation of traumatic
memories and affects
• Over time trauma-related assumptions may be
extinguished, facilitating more adaptive experiences
• Pharmacotherapy can help reduce core symptoms,
improve stress resilience, and improve quality of life
• Limitations of Pharmacotherapy:
It cannot provide new experiences that could modify
complex schema and influence future behaviour
Assessment of PTSD
Interview-Based Scales
1 Clinician Administered PTSD Scale (CAPS)
Blake et al 1990(b)
2 Structured Interview for PTSD (SIP)
Davidson et al 1997
3 Treatment Outcome PTSD Scale (TOP-8)
Connor and Davidson 1999
4 Short PTSD Rating Interview (SPRINT)
Connor and Davidson 2001
Assessment of PTSD
Self-Rating Scales
1. Impact of Event Scale (IES)
Horowitz et al 1979
2. Mississippi Combat and Non-Combat Scales
Keane et al 1988
3. PENN Inventory
Hammerberg 1992
4. Foa PTSD Symptom Scale - Self-Report (PSS)
Foa et al 1993
5. Davidson Trauma Scale (DTS)
Davidson et al 1997
Clinician Administered
PTSD Scale (CAPS)
•
A structured clinical interview
•
Quantifies PTSD symptoms wrt.
frequency and intensity
•
Yields a continuous measure of
symptom severity
•
Requires clinical skills, judgement
and experience
•
Lengthy
•
Not ideal for routine clinical or
research use
Treatment Outcome PTSD Scale
(TOP-8)
•
A brief scale
•
Examines 8 PTSD symptoms belonging to all
3 symptom clusters and shown to respond
well to treatment
•
Good psychometric properties
•
10 minutes to complete
Impact of Events Scale
(IES)
•
Oldest and most widely used self-report scale
•
Evaluates the 3 symptom domains of PTSD
¾
¾
¾
Intrusion
Avoidance
Hyperarousal
•
Sensitive to change in symptom severity
•
Subscales can be scored separately
Davidson Trauma Scale
(DTS)
•
17 item self-report instrument
•
Measures frequency and severity of each DSMIV symptom
•
Good predictive properties for response to
treatment
SSRI: Placebo-controlled, Short Term Studies
Sertraline
Author
Brady et al
JAMA 2000
Davidson et al
Arch Gen Psych
2001
Zohar et al
J Cl Psychopharm
2002
Population
N
Duration
Outcome
73% female
61.5% - physical or
sexual assault
5.5% - combat
related trauma
187 DSM-3R
outpatients
12 weeks
Responder rate of
53% at study end for
Sertraline vs 32% for
PBO on CAPS and
CGI-I
63% female
62% - physical or
sexual assault
5% - combat
related trauma
208 DSM-3R
outpatients
12 weeks
60% responder rate
for Sertraline vs 38%
for PBO on CAPS,
IES and CGI-I
83% male
77% - combat
related trauma
42 DSM-3R
Israeli
outpatient
military
veterans
10 weeks
Trend of Sertraline
having a higher
responder rate than
PBO, but only
achieve significance
on CGI-I (not CAPS)
SSRI: Placebo-controlled, Short Term Studies
Paroxetine
Author
Tucker et al
J Clin Psych 2001
Marshall et al
Am J Psych 2001
Population
N
Duration
Outcome
65.4% female
49% - physical or
sexual assault
6.8% - combat
related trauma
307 DSM-IV
outpatients
12 weeks
A significantly
greater no. of
Paroxetine treated
patients achieved
remission than PBO
(29.4% vs 16.5%)
68% female
51% - physical or
sexual assault
5.5% - combat
related trauma
551 DSM-IV
outpatients
12 weeks
Paroxetine
responder rate was
62% (at 20 mg/day)
and 55% (at 40
mg/day) vs 37% for
PBO on CAPS and
CGI-I
SSRI: Placebo-controlled, Short Term Studies
Fluoxetine
Author
van der Kolk
et al
J Clin Psych 1994
Connor et al
Br J Psych 1999
Martenyi et al
J Clin Psych 2002
Population
N
Duration
Outcome
33% female
45% - combat
related trauma
64 DSM-3R
outpatients
5 weeks
Statistically
significant reduction
in total CAPS score
91% female
52% - physical or
sexual assault
53 DSM-3R
outpatients
12 weeks
Statistically
significant
improvements on
CGI-I for Fluoxetine
vs PBO (59% vs
19%)
19% female
> 48% - combatrelated trauma
301 DSM-IV
outpatients
12 weeks
Response rates
were 59.9% with
Fluoxetine vs 43.8%
with PBO using
Treatment Outcome
PTSD Scale (TOP-8)
SSRIs & PTSD
Effective in PTSD
Improved ALL core PTSD clusters
numbing, intrusions, hyperarousal
Both genders
Effective in
All trauma types
Co-morbid type
Tricyclic Antidepressants
Amitriptyline
Author
Davidson et al
1990
Arch Gen Psych
Population
All male
100% - combat
related trauma
N
Duration
Outcome
46 DSM-3
veteran
outpatients
8 weeks
DSM-3 criteria for
PTSD using SI-PTSD
- 64% of Amitriptyline
and 72% of PBO still
met criteria for OCD
N
Duration
Outcome
Desipramine
Author
Reist et al
1989
Am J Psych
Population
All male
18 DSM-3
Vietnam
veterans,
inpatients
4 week
double
blind
crossover
No difference on IES
Other Antidepressants
IMI vs Phenelzine vs PBO
Author
Population
Frank et al
1988
All male 100%
combat related
trauma
Am J Psych
N
34 DSM-3R
male
Duration
8 weeks
Outcome
IMI = Phenelzine >
PBO on Global
Assessment Scale &
IES
Phenelzine > IMI >
PBO on IES
SSRI: Long Term Studies
Sertraline
Author
Landborg, PD
et al
J Clin Psych 2001
Davidson et al
Am J Psych 2001
Population
N
Duration
Outcome
12 week placebo
controlled, double
blind followed by
24 wk. open label
continuation
92% of
responders
maintained the
response
54% of acute care
non-responders
became
responders on
CAPS-2 IES and
CGI-I
26 % female
64% - sexual or
physical
assault
128 DSM3R outpatients
70 % female
55% - sexual or
physical
assault
9% - combat
related trauma
96 DSM-3R 28 wks double
blind maintenance
outfollowing 12 wks
patients
of acute treatment
and 24 wks of
open-label
continuation
Lower PTSD
relapse rates
when compared to
PBO (5% vs 26%)
on CGI-I and
CAPS-2
SSRI: Long Term Studies
Fluoxetine
Author
Martenyi et al
Br J Psych 2002,
181, 315
- 3
20
Population
19% female
47% – combat
related trauma
N
Duration
Outcome
131
DSM-IV
outpatients
Following 12
weeks of acute
treatment
responders
were rerandomized to
Fluoxetine or
PBO for a
further 24
weeks
continuation
study
Fluoxetine/Fluoxetine
> Fluoxetine/PBO on
TOP-8 total score (P =
0.005) and CGI-S (P =
0.021)
↑ Completers of
relapse prevention
phase for Fluoxetine
vs PBO (82% vs
66.1%) and ↓
discontinuations
(5.8% vs 16.1% for
Fluoxetine/PBO)
SNRI Antidepressant
Treatment of PTSD
RCT Comparing Venlafaxine, Sertraline and PBO
Author
Davidson et al
CINP Congress 2004
Smajkic et al
J Traum Stress 2001
Population
N
Duration
Outcome
66% female
34% male
531 total
179 = Venlafaxine
173 = Sertraline
179 = PBO
12 weeks
Venlafaxine and
Sertraline
significantly
superior to PBO on
the CAPS
56% female
44% male
40 - Total
15 - Sertraline
12 - Paroxetine
13 - Venlafaxine
6 weeks
• PTSD severity was
significantly
decreased for all
groups on the PTSD
Symptoms Scale
• 8 dropouts in
Venlafaxine group
Novel Antidepressants
Mirtazapine
Author
Population
Davidson et al 81% female
Biol Psych 2003
34% - physical
or sexual
assault
14% - combat
related trauma
N
29 DSM-IV
outpatients
Duration
8 weeks
Outcome
Response rates of
64% for
Mirtazapine vs
20% for PBO on
the Short PTSD
Rating Interview
(SPRINT)
Benzodiazepine Treatment of PTSD
• 13 trauma survivors were treated with either
Clonazepam (mean dose = 2.7 mg/day) or Alprazolam
(mean dose = 2.5 mg/day) 1 week after the traumatic
event
• Controls were pair matched with the treatment group
• BZD treated group did not differ from controls in 1 and
6 months PTSD scores
• 9/13 (69%) BZD-treated and 2/13 (15%) controls met
PTSD criteria 6 months after trauma
Gelpin et al, J Clin Psych 1996
Benzodiazepine Treatment of PTSD
• 16 subjects meeting DSM-III criteria for PTSD
randomly assigned to treatment with Alprazolam or
placebo for 5 weeks
• Those who received placebo in the first phase of
the trial were then treated with Alprazolam and vice
versa for a further 5 weeks
• Primary outcome measures were a PTSD scale (12
items from DSM-III criteria), HAM-A, IES
• NS differences on PTSD measures
• Significant decrease in HAM-A score in Alprazolam
treated group
Braun et al, J Clin Psych 1990
Rationale for Mood Stabilizers and
Antikindling Agents
• Limbic structures including the amygdala and
hippocampus have a low threshold for sensitization
and kindling
• Hypothesized to contribute to increased physiologic
reactivity in PTSD
• Intrusive imagery and flashbacks may be
consequences of sensitization and kindling
Mood Stabilizers and
Antikindling Agents
Carbamazepine: Open-Label Study
Author
Loof et al
J Am Acad Child
Adolesc Psych 1995
Lipper et al
Psychosomatics
1986
Population
N
Duration
Outcome
12 female
16 males
8 - 17 years
100% - sexual
abuse
28
inpatients
Range 17 92 days
22/28 asymptomatic
6/28 significantly
improved
All male
All combat
related trauma
10 DSM-III
veterans,
inpatients
5 weeks
Significant difference
in scores on PTSD
checklist and patient
rated PTSD index postRx
70% reported
moderate to very much
improved on CGI
Mood Stabilizers and
Antikindling Agents
Valproate: Open-Label Study
Author
Fesler, F.A.
J Clin Psych 1991
Population
16 male
100% - combat
related trauma
N
Duration
Outcome
16 DSM-3R
Vietnam
veterans,
outpatients
Mean = 10.6
months
Range = 2-16
months
•No worsening of
symptoms
• No improvement
in re-experiencing
symptoms
11/16 improved in
hyperarousal
9/16 improved in
avoidance
Mood Stabilizers and
Antikindling Agents
Lithium Carbonate: Open-Label Study
Author
Van der Kolk et al
Hospital Comm Psych
1983
Population
100% male
N
14 Vietnam
veterans,
outpatients
Duration
Outcome
8/14 improvement
in hyperarousal
and nightmares
Mood Stabilizers and
Antikindling Agents
Topiramate: Open-Label Augmentation
Author
Population
N
Duration
Outcome
Berlaut and
van Kammen
74% female
60% - physical or
sexual assault
3% - combat
related trauma
35 DSM-IV
outpatients
Mean = 33
weeks
Range 1 - 199
weeks
79% - suppression
of nightmares
86% - suppression
of intrusive
memories/
flashbacks
J Clin Psych 2002
Mood Stabilizers and
Antikindling Agents
Lamotrigine: Placebo-Controlled Study
Author
Hertzberg et al
Biol Psychiatry 1999
Population
36% female
71% - combat
related trauma
*DGRP - Duke Global Rating for PTSD-improvement
N
14 DSM-IV
outpatients
Duration
12 weeks
Outcome
Response rate of
50% for Lamotrigine
and 25% for PBO on
DGRP*
Mood Stabilizers and
Antikindling Agents
Lamotrigine: Retrospective Review of Adjunctive Treatment
Author
Hamner et al
Annal of Clin
Psych 2001
Population
100% male
N
Duration
Outcome
30 DSM-IV
Vietnam
veterans,
outpatients
Mean - 10
months
Range - 1-36
months
• 77% showed either
moderate or target
symptoms.
Improvement including
insomnia, frequency and
intensity of nightmares
Mood Stabilizers and
Antikindling Agents
Naturalistic Levetiracetam Adjunctive Treatment
• Retrospective analysis of 23 patients with DSM-IV
diagnosed PTSD who were partial or non-responders
to SSRIs/SNRIs
• Received adjunctive Levetiracetam (mean dose=2000
mg/day) for mean duration of 10 weeks
• Significant improvement on CGI-S and CGI-I
Kinrys et al, CINP Congress, 2004
Adrenergic Inhibiting Agents
• Increased adrenergic activity is thought to increase the risk
of PTSD by initiating the process of over-consolidation of
memories of the traumatic event
• Propranolol, a nonselective ß-adrenergic antagonist, binds
to peripheral and central ß-adrenergic receptors
• Clinically it reduces tremulousness, sweating and
palpitations
• It may decrease the consolidation of emotional memories
• Treatment with Propranolol immediately following the
traumatic event may prevent the development of PTSD
symptoms
Adrenergic Inhibiting Agents
• 41 Emergency Department patients
• 80% female; 71% Motor Vehicle Accident
• Treated with Propranolol 40 mg po qid or PBO, started
no longer than 6 hours after the traumatic event
• At 1 month - PTSD rate was 30% in PBO completers
and 18% in Propranolol completers
• At 3 months - no difference in PTSD rate between the
2 groups, although 0/8 (0%) of Propranolol completers
and (44%) of PBO completers were physiologic
responders
Pitman et al, Biol Psych 2002
Adrenergic Inhibiting Agents
• 11 Emergency Department patients diagnosed by MINI
• 36% female; 36% physical assault; 64% Motor Vehicle
Accident
• Assessed and treated with 40 mg of Propranolol tid for
7 days
• At 2 months, PTSD rate was 3/8 (17%) in those who
refused Propranolol vs 1/11 (9%) in those who took
Propranolol
Vaiva et al, Biol Psych 2003
α1-Adrenergic Antagonists
Placebo-Controlled Double-Blind Crossover Study of Prazosin
Author
Population
N
Duration
Mean
Dose
Outcome
Raskind et
al
All male
all - combat
related trauma
10
20 weeks
9.5
mg/day
Prazosin superior to PBO on
3 primary outcome
measures of recurrent
dreams, sleep item on CAPS
and CGI - as well as total
CAPS, avoidance and hyperarousal subscales of CAPS
Am J Psych
2003
Antipsychotic Medications in PTSD
Risperidone: Placebo-Controlled Augmentation
Author
Bartsokis
Population
Duration
Mean
Dose
Outcome
48
inpatients
16
weeks
3
mg/day
Significant difference on
CAPS total score and
arousal subscore and
HAM-A
Hamner et All male
al
All combat
Int Cl
related
Psychopharm
trauma
2003
40 DSM-IV
Vietnam
veterans
outpatients
5 weeks
2.5
mg/day
Modestly significant
improvement in psychotic
symptoms on the PANSS and
the CAPS re-experiencing
subscale but not on total
CAPS compared to placebo
Monnelly
et al
16 DSM-IV
combat
veterans,
outpatients
6 weeks
0.57
mg/day
Significant improvement on
the Overt Aggression Scalemodified outpatients (OAS-M)
irritability subscale and the
patient checklist for PTSD
Military Version Total Score
and intrusive subscore
compound to PBO
et al
APA 2001
J Cl
Psychopharm
2003
PTSD
residential
treatment
program
N
All male
All combat
related
trauma
Antipsychotic Medications in PTSD
Olanzapine: Placebo-Controlled Study
Author
Butterfield et
al
J Cl Psych
Pharmacol 2001
SIP
SPRINT
TOP-8
DTS
SDS
Population
N
Duration
Outcome
93% female
73% - sexual
assault
15 DSMIV
outpatients
10 weeks
• NS between group
differences in relief of PTSD
symptoms on the SIP,
SPRINT, TOP-8, DTS or SDS
• NS difference on efficacy
measures
- Structured Interview for PTSD
- Short PTSD Rating Interview
- Treatment Outcome PTSD Score
- Davidson Self-Rated PTSD Scale
- Sheehan Disability Score
Antipsychotic Medications in PTSD
Olanzapine: Placebo-Controlled Study
Author
Stein et al
Am J Psych
2002
Population
N
Duration
Outcome
All male
All combat
related trauma
All on SSRI’s
19
12 weeks of
SSRI treatment
followed by 8
weeks of
Olanzapine or
PBO
Significant improvement on
PTSD symptoms, sleep and
depression as measured by
CAPS (DSM-IV), Pittsburgh
Sleep Quality Index, CES-D
scale. NS difference on CGI
responders
Antipsychotic Medications in PTSD
Quetiapine: Open-Label Augmentation
Author
Population
Sattar et al 1 male
Ann
N
1 (Case
Report)
Duration
11 days
Mean
Dose
Outcome
150
• CAPS decrease from 98
mg/day to 60 and HAM-D 40 to 11
Pharmacother
(2002)
Filtreau et
al
Can J Psych
(2003)
Hamner et
al
J Clin Psycho
pharm 2003
3 males;
combat related
trauma
2 females;
physical/
sexual assault
5 (Case
Series)
95% male
95% - combat
related trauma
45% on SSRI’s
19
100
• Gradual reduction in
mg/day flashbacks with the
addition of Quetiapine
6 weeks
100
Significant decrease in
mg/day PTSD symptoms (CAPS)
and depression (HAMD)
with 58% meeting criteria
for significant response
on CGI
Selective GABA Reuptake Inhibitors
Tiagabine Open Label Augmentation
Author
Taylor F.
et al
APA 2004
Population
All female
N
Duration
7
6 weeks
Mean
Dose
Outcome
8 mg/day Significant decrease in total
score and intrusive,
avoidance, arousal and
distressing dreams
subscale of PTSD checklist Civilian Version
• 617 patients were markedly
improved on CGI-C
Dosing Considerations
• Start low (50% of usual dose)
• Go slow
– Titrate to maximum dose over 4-8
weeks
– Titrate to side effects
• Aim sufficient (mid to upper dose
ranges)
• Wait long enough for response (812 weeks)
Predictors of Response to
Treatment of PTSD
1. There may be a significant treatment-by-trauma
interaction with a greater number of responders
in certain trauma types such as “seeing
someone dies or hurt”
2. In long term studies patients continue to
experience improvement in PTSD symptoms
after the acute treatment phase (12 weeks)
3. Longer trials of acute treatment need to be
considered.
Medication Strategy
PTSD
SNRI / SSRI
? Recovery
Remission
1 Year of Medication
followed by ???
drug-free trial
Partial / Failure
SSRI
SNRI
SARI / NASSA
MAOI
AC / Atypical
Conclusion
1. SSRIs are the most studied drug treatments for
PTSD and remain the treatment of choice
2. Paroxetine is indicated in the treatment of PTSD
in Canada while Paroxetine and Sertraline are
indicated in the U.S.
3. While SSRI treatment does improve symptoms
of PTSD, patients often remain symptomatic
4. Several new uses of psychotropic agents, alone
or as adjunct treatment, require further study
Cognitive
-Behavioural Treatment of PTSD
Cognitive-Behavioural
Steven Taylor, Ph.D., Dept of Psychiatry, UBC
Overview
Outcome dimensions
Components of CBT
Comparative Efficacy
- meta-analytic
meta-analytic findings
findings
-- gold
gold standards
standards and
and outcome
outcome
Challenges and Future Directions
Dimensions of PTSD Symptoms
FOUR DIMENSIONS
Re-experiencing
Effortful
avoidance
Numbing
Hyperarousal
Dimensions can be distinguished in terms of…
ƒƒ Conceptual
Conceptual grounds
grounds
ƒƒ Reexperiencing
Reexperiencing Æ
Æ avoidance
avoidance
ƒƒ Hyperarousal
Hyperarousal Æ
Æ numbing
numbing
ƒƒ Factor
Factor structure
structure
ƒƒ Psychopathologic
Psychopathologic correlates
correlates
ƒƒ Prognostic
Prognostic importance
importance
ƒƒ Response
Response to
to treatment
treatment
Components of CBT
•• Psychoeducation
Psychoeducation
• Cognitive restructuring
– Anger, guilt, & shame
•• Training
Training in
in coping
coping skills
skills
–– Breathing
Breathing &
& relaxation
relaxation
exercises
exercises
–– Grounding
Grounding exercises
exercises
•• Exposure
Exposure exercises
exercises
–– In
In vivo
vivo &
& imaginal
imaginal
• Interpersonal skills
training
– Used as needed
• Relapse prevention
Comparative Efficacy
of PTSD Treatments
Meta-Analysis
PTSD Meta-Analysis
Primarily combat- or assault-related PTSD
Tricyclics
MAOIs
SSRIs
Benzodiazepines
BT or CBT
EMDR
Hypnosis
Psychodynamic Rx
Placebo
% Dropout
26
36
36
38
15
14
11
11
23
Rx Effect Size
0.54
0.61
1.38
0.49
1.27
1.24
0.94
0.90
0.51
Meta-Analysis
•• Dropouts
Dropouts
ƒƒ Pharmacotherapies
Pharmacotherapies >> psychological
psychological therapies
therapies
Meta-Analysis
•• Dropouts
Dropouts
ƒƒ Pharmacotherapies
Pharmacotherapies >> psychological
psychological therapies
therapies
•• Pharmacotherapies
Pharmacotherapies
ƒƒ SSRIs
SSRIs and
and carbamazepine
carbamazepine most
most effective
effective
•• Psychological
Psychological therapies
therapies
ƒƒ BT/CBT
BT/CBT and
and EMDR
EMDR most
most effective
effective
•• (SSRIs,
(SSRIs, carbamazepine)
carbamazepine) == (BT/CBT,
(BT/CBT, EMDR)
EMDR)
Meta-Analysis
•• Dropouts
Dropouts
ƒƒ Pharmacotherapies
Pharmacotherapies >> psychological
psychological therapies
therapies
•• Pharmacotherapies
Pharmacotherapies
ƒƒ SSRIs
SSRIs and
and carbamazepine
carbamazepine most
most effective
effective
•• Psychological
Psychological therapies
therapies
ƒƒ BT/CBT
BT/CBT and
and EMDR
EMDR most
most effective
effective
•• (SSRIs,
(SSRIs, carbamazepine)
carbamazepine) == (BT/CBT,
(BT/CBT, EMDR)
EMDR)
•• Little
Little matching
matching of
of tx
tx to
to sx
sx domain,
domain, but
but SSRIs
SSRIs had
had
some
some advantage
advantage in
in treating
treating depression
depression
Meta-Analysis
•• Dropouts
Dropouts
ƒƒ Pharmacotherapies
Pharmacotherapies >> psychological
psychological therapies
therapies
•• Pharmacotherapies
Pharmacotherapies
ƒƒ SSRIs
SSRIs and
and carbamazepine
carbamazepine most
most effective
effective
•• Psychological
Psychological therapies
therapies
ƒƒ BT/CBT
BT/CBT and
and EMDR
EMDR most
most effective
effective
•• (SSRIs,
(SSRIs, carbamazepine)
carbamazepine) == (BT/CBT,
(BT/CBT, EMDR)
EMDR)
•• Little
Little matching
matching of
of tx
tx to
to sx
sx domain,
domain, but
but SSRIs
SSRIs had
had some
some
advantage
advantage in
in treating
treating depression
depression
•• BT/CBT
BT/CBT and
and EMDR
EMDR gains
gains maintained
maintained at
at FU
FU
Comparative Efficacy of PTSD Treatments
Exposure, EMDR, and Relaxation Training
Gold Standards for Methodologically
Sound Outcome Studies
(Foa & Meadows, 1997)
• Clearly defined target symptoms
– Clear inclusion/exclusion criteria (e.g., excluding
subclinical PTSD)
Gold Standards for Methodologically Sound
Outcome Studies
(Foa & Meadows, 1997)
• Clearly defined target symptoms
– Clear inclusion/exclusion criteria (e.g., excluding
subclinical PTSD)
• Reliable, valid measures
– Preferably including structured interviews instead of
relying entirely on questionnaires
• Evaluators blind to treatment condition
• Evaluators are adequately trained
• Evaluators blind to treatment condition
• Evaluators are adequately trained
• Detailed treatment manuals
– Treatments are replicable and specific
– Manual specifies what is and isn’t part of
treatment
• Evaluators blind to treatment condition
• Evaluators are adequately trained
• Detailed treatment manuals
– Treatments are replicable and specific
– Manual specifies what is and isn’t part of treatment
• Unbiased assignment to treatment
• Evaluation of treatment adherence and integrity
• More than one therapist
Method
••
••
••
••
••
••
88 individual
individual 90
90 min
min sessions
sessions
Pre,
Pre, post,
post, and
and 3-month
3-month FU
FU assessment
assessment (CAPS
(CAPS
etc.)
etc.)
Raters
Raters blind
blind to
to treatment
treatment condition
condition
Two
Two therapists,
therapists, skilled
skilled in
in all
all 33 treatments
treatments
Sessions
Sessions videotaped
videotaped
Treatment
Treatment integrity
integrity ratings
ratings
Participants (N = 60)
• Study entrants/completers
–– EMDR:
EMDR: nn == 19/15
19/15
–– Exposure:
Exposure: nn == 22/15
22/15
–– Relaxation:
Relaxation: nn == 19/15
19/15
–– No
No difference
difference in
in attrition
attrition (p
(p >> .1)
.1)
Clinical Features
•• Chronic
Chronic PTSD:
PTSD: 97%
97%
Clinical Features
•
•
Chronic PTSD: 97%
Duration of PTSD symptoms: M = 8.7 yrs
Clinical Features
••
••
••
Chronic
Chronic PTSD:
PTSD: 97%
97%
Duration
Duration of
of PTSD
PTSD symptoms:
symptoms: M
M == 8.7
8.7 yrs
yrs
Psychotropic
Psychotropic medication
medication at
at intake:
intake: 48%
48%
Clinical Features
••
••
••
••
Chronic
Chronic PTSD:
PTSD: 97%
97%
Duration
Duration of
of PTSD
PTSD symptoms:
symptoms: M
M == 8.7
8.7 yrs
yrs
Psychotropic
Psychotropic medication
medication at
at intake:
intake: 48%
48%
Mean
Mean age
age 37
37 yrs
yrs
Clinical Features
••
••
••
••
••
Chronic
Chronic PTSD:
PTSD: 97%
97%
Duration
Duration of
of PTSD
PTSD symptoms:
symptoms: M
M == 8.7
8.7 yrs
yrs
Psychotropic
Psychotropic medication
medication at
at intake:
intake: 48%
48%
Mean
Mean age
age 37
37 yrs
yrs
75%
75% female
female
Clinical Features
•• 65%
65% had
had multiple
multiple traumatic
traumatic experiences
experiences
Clinical Features
• 65% had multiple traumatic experiences
• Traumata
ƒƒ Sexual
Sexual abuse:
abuse: 45%
45%
ƒƒ Physical
Physical abuse:
abuse: 43%
43%
ƒƒ Road
Road traffic
traffic collision:
collision: 43%
43%
ƒƒ Death
Death of
of significant
significant other
other (e.g.,
(e.g., murder):
murder): 22%
22%
ƒƒ War
War exposure
exposure (civilian):
(civilian): 8%
8%
Clinical Features
• Pretreatment comorbidity
ƒƒ Major
Major depression:
depression: 42%
42%
ƒƒ Panic
Panic disorder:
disorder: 31%
31%
ƒƒ Social
Social phobia:
phobia: 12%
12%
ƒƒ Specific
Specific phobia:
phobia: 10%
10%
ƒƒ Generalized
Generalized anxiety
anxiety disorder:
disorder: 7%
7%
ƒƒ OCD:
OCD: 5%
5%
ƒƒ Eating
Eating disorder:
disorder: 5%
5%
% no Longer Meeting Criteria for PTSD
100
90
Relaxation
80
EMDR
70
Exposure
60
50
40
30
20
10
0
Post
Followup
Sustained
(Post &
Followup)
7
6
6
5
5
Avoidance
Rexperiencing
7
4
3
3
2
2
1
1
0
0
Pre
Post
Followup
Pre
7
7
6
6
5
5
Hyperarousal
Numbing
4
4
3
Post
Followup
4
3
2
2
1
1
0
0
Pre
Post
Followup
Pre
Post
Followup
Relaxation
EMDR
Exposure
Incidence of Symptom Worsening
• Pre-to-post treatment
–– EMDR:
EMDR: 0/15
0/15
–– Exposure:
Exposure: 0/15
0/15
–– Relaxation:
Relaxation: 1/15
1/15
• Pre-treatment to followup
–– EMDR:
EMDR: 1/15
1/15
–– Exposure:
Exposure: 0/15
0/15
–– Relaxation:
Relaxation: 1/15
1/15
• Worsening rare; no differences
among treatments
Heritability and Treatment Response
Re-experiencing
1
2
3
4
5
Avoidance
6
7
Numbing
8
9
10
11
12
Hyperarousal
13
14
15
16
17
Correlation between h2 & ES
h2
ESEMDR
ESEXPOSURE
ESRELAXATION
.27
.30
.00
.00
.27
1.08
0.90
1.22
1.05
0.94
1.87
1.06
0.63
1.57
1.57
2.43
1.12
0.77
1.59
0.42
.28
.00
0.89
1.19
1.89
1.95
0.64
0.56
.21
.26
.25
.17
.23
0.64
0.52
0.80
0.52
0.42
0.55
1.16
0.46
0.70
0.37
0.56
1.04
1.32
0.40
0.49
.20
.19
.15
.22
.20
0.72
0.92
0.52
1.15
1.21
0.27
0.66
0.92
1.07
0.56
0.39
0.81
1.29
0.57
0.83
-.36
-.08
.04
EMDR Study: Conclusions
•• EMDR,
EMDR, exposure,
exposure, and
and relaxation
relaxation
–– each
each associated
associated with
with symptom
symptom reduction
reduction
•• Exposure
Exposure
–– more
more effective
effective for
for reducing
reducing reexperiencing
reexperiencing and
and
avoidance
avoidance
–– faster
faster at
at reducing
reducing avoidance
avoidance
–– patients
patients more
more likely
likely to
to lose
lose diagnosis
diagnosis of
of PTSD
PTSD
•• No
No differences
differences in
in
–– attrition
attrition
–– symptom
symptom worsening
worsening
–– secondary
secondary outcome
outcome measures
measures
A Sampling of Challenges & Future
Directions
Improving accessibility
– Internet-based treatment
Improving tolerability & reducing attrition
–
–
Sequential; skills training then exposure
Motivational interviewing
Improving outcome
–
–
Adding interoceptive exposure
Adding particular medications
Special populations
–
–
–
–
PTSD & chronic pain
Battered women
Recovered memories
Posttraumatic conversion reactions
Anxiety Sensitivity across the
Anxiety Disorders
40
40
35
35
30
30
25
25
20
20
15
15
10
10
55
00
PD
PD
PTSD
PTSD
GAD
GAD OCD
OCD SocPh
SocPh SpecPh
SpecPh
NC
NC
Pre Interoceptive exp Imag exp
In vivo exp
P1
20
33 -- MM oo FF UU
30
11 -- MM oo FF UU
PP oo ss tt -- TT xx
SS 11 22 -- IInn vv iivv oo
SS 11 11 -- IInn vv iivv oo
SS 11 00 -- IInn vv iivv oo
SS 99 -- IInn vv iivv oo
SS 88 -- IInn vv iivv oo
SS 77 -- IImm aa gg
SS 66 -- IImm aa gg
SS 55 -- IImm aa gg
SS 44 -- IIEE TT
SS 33 -- IIEE TT
SS 22 -- IIEE TT
SS 11 -- IIEE TT
PP rr ee -- TT xx -- 22
PP rr ee -- TT xx -- 11
50
Participant P1: MVA-PTSD
(no comorbidity)
40
PSDS
ASI
10
0
Po FU (1,3)
PTSD and
Chronic
Pain
Mutual Maintenance
PAIN
PTSD
Mutual Maintenance
PAIN
PTSD
3.0
2.8
Reexperiencing
2.6
Avoidance
2.4
Numbing
2.2
Hyperarousal
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
Relaxation
training
Interoceptive exposure
Im ag
exp
Pain
m gt
Im aginal
exposure
POST
S17
S16
S15
S14
S13
S12
S11
S10
S9
S8
S7
S6
S5
S4
S3
S2
S1
0.0
In vivo exposure
3.0
2.8
2.6
2.4
2.2
2.0
1.8
1.6
1.4
Reexperiencing
1.2
1.0
Avoidance
0.8
Numbing
0.6
Hyperarousal
0.4
0.2
Pain management
Imaginal exposure
In vivo exposure
POST
S12
S11
S10
S9
S8
S7
S6
S5
S4
S3
S2
S1
PRE-2
PRE-1
0.0
Future Directions in Combining
CBT with Pharmacotherapy
Augmenting outcome
SSRIs
SSRIs ++ exposure
exposure
D-Cycloserine
D-Cycloserine ++ exposure
exposure
Pain & PTSD
Gabapentin
Gabapentin
Topiramate
Topiramate
Faculty Question Period