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Psychotherapy for Military-Related PTSD A Review of Randomized Clinical Trials

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Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among military personnel and veterans. First-line psychotherapies most often recommended for PTSD consist mainly of "trauma-focused" psychotherapies that involve focusing on details of the trauma or associated cognitive and emotional effects. To examine the effectiveness of psychotherapies for PTSD in military and veteran populations. PubMed, PsycINFO, and PILOTS were searched for randomized clinical trials (RCTs) of individual and group psychotherapies for PTSD in military personnel and veterans, published from January 1980 to March 1, 2015. We also searched reference lists of articles, selected reviews, and meta-analyses. Of 891 publications initially identified, 36 were included. Two trauma-focused therapies, cognitive processing therapy (CPT) and prolonged exposure, have been the most frequently studied psychotherapies for military-related PTSD. Five RCTs of CPT (that included 481 patients) and 4 RCTs of prolonged exposure (that included 402 patients) met inclusion criteria. Focusing on intent-to-treat outcomes, within-group posttreatment effect sizes for CPT and prolonged exposure were large (Cohen d range, 0.78-1.10). CPT and prolonged exposure also outperformed waitlist and treatment-as-usual control conditions. Forty-nine percent to 70% of participants receiving CPT and prolonged exposure attained clinically meaningful symptom improvement (defined as a 10- to 12-point decrease in interviewer-assessed or self-reported symptoms). However, mean posttreatment scores for CPT and prolonged exposure remained at or above clinical criteria for PTSD, and approximately two-thirds of patients receiving CPT or prolonged exposure retained their PTSD diagnosis after treatment (range, 60%-72%). CPT and prolonged exposure were marginally superior compared with non-trauma-focused psychotherapy comparison conditions. In military and veteran populations, trials of the first-line trauma-focused interventions CPT and prolonged exposure have shown clinically meaningful improvements for many patients with PTSD. However, nonresponse rates have been high, many patients continue to have symptoms, and trauma-focused interventions show marginally superior results compared with active control conditions. There is a need for improvement in existing PTSD treatments and for development and testing of novel evidence-based treatments, both trauma-focused and non-trauma-focused.
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Copyright 2015 American Medical Association. All rights reserved.
Psychotherapy for Military-Related PTSD
A Review of Randomized Clinical Trials
Maria M. Steenkamp, PhD; Brett T. Litz, PhD; Charles W. Hoge, MD; Charles R. Marmar, MD
IMPORTANCE Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder
common among military personnel and veterans. First-line psychotherapies most often
recommended for PTSD consist mainly of “trauma-focused” psychotherapies that involve
focusing on details of the trauma or associated cognitive and emotional effects.
OBJECTIVE To examine the effectiveness of psychotherapies for PTSD in military and veteran
populations.
EVIDENCE REVIEW PubMed, PsycINFO, and PILOTS were searched for randomized clinical
trials (RCTs) of individual and group psychotherapies for PTSD in military personnel and
veterans, published from January 1980 to March 1, 2015. We also searched reference lists of
articles, selected reviews, and meta-analyses. Of 891 publications initially identified, 36 were
included.
FINDINGS Two trauma-focused therapies, cognitive processing therapy (CPT) and prolonged
exposure, have been the most frequently studied psychotherapies for military-related PTSD.
Five RCTs of CPT (that included 481 patients) and 4 RCTs of prolonged exposure (that
included 402 patients) met inclusion criteria. Focusing on intent-to-treat outcomes,
within-group posttreatment effect sizes for CPT and prolonged exposure were large (Cohen d
range, 0.78-1.10). CPT and prolonged exposure also outperformed waitlist and
treatment-as-usual control conditions. Forty-nine percent to 70% of participants receiving
CPT and prolonged exposure attained clinically meaningful symptom improvement (defined
as a 10- to 12-point decrease in interviewer-assessed or self-reported symptoms). However,
mean posttreatment scores for CPT and prolonged exposure remained at or above clinical
criteria for PTSD, and approximately two-thirds of patients receiving CPT or prolonged
exposure retained their PTSD diagnosis after treatment (range, 60%-72%). CPT and
prolonged exposure were marginally superior compared with non–trauma-focused
psychotherapy comparison conditions.
CONCLUSIONS AND RELEVANCE In military and veteran populations, trials of the first-line
trauma-focused interventions CPT and prolonged exposure have shown clinically meaningful
improvements for many patients with PTSD. However, nonresponse rates have been high,
many patients continue to have symptoms, and trauma-focused interventions show
marginally superior results compared with active control conditions. There is a need for
improvement in existing PTSD treatments and for development and testing of novel
evidence-based treatments, both trauma-focused and non–trauma-focused.
JAMA. 2015;314(5):489-500. doi:10.1001/jama.2015.8370
Editorial page 453
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Author Affiliations: Steven and
Alexandra Cohen Veterans Center for
Posttraumatic Stress and Traumatic
Brain Injury, New York University
Langone School of Medicine,
New York, New York (Steenkamp,
Marmar); VA Boston Healthcare
System, Massachusetts Veterans
Epidemiological Research and
Information Center (MAVERIC),
Boston University School of
Medicine, Boston (Litz); Walter Reed
Army Institute of Research,
Silver Spring, Maryland (Hoge).
Corresponding Author: Maria M.
Steenkamp, PhD, Steven and
Alexandra Cohen Veterans
Center for Posttraumatic Stress
and Traumatic BrainInjur y,
New York University Langone
School of Medicine,
One Park Ave, Room 8-107,
New York, NY 10016
(maria.steenkamp@nyumc.org).
Section Editor: Mary McGrae
McDermott, MD, Senior Editor.
Clinical Review & Education
Review
(Reprinted) 489
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Posttraumatic stress disorder (PTSD) is a disabling psychiat-
ric condition common among military personnel and vet-
erans, and consequently, a significant public health chal-
lenge. Approximately 13% of Iraq or Afghanistan veterans
1
and
10% of Gulf War veterans who experienced combat have PTSD,
2
and 11% of Vietnam veterans continue to report PTSD symptoms
that impair functioning 40 years after the war.
3
Military-related
PTSD is often accompanied by a variety of mental and physical
health conditions, particularly depression, anxiety, and substance
misuse.
4,5
War veterans with PTSD also have extensive functional
impairments such as unemployment and income disparities,
6
fam-
ily and relationship difficulties,
7
aggressive behavior,
8
and poor
quality of life.
9
Twenty-three percent of Vietnam veterans with
PTSD (compared with 4% among those without PTSD) reported
being unemployed when assessed 15 or more years after service,
33% (compared with 16%) reported perpetrating serious interper-
sonal violence in the past year, and 40% (compared with 10%)
reported low well-being.
10
Risk factors for PTSD in military popula-
tions include war zone exposure, being wounded, younger age
when deployed, less education, greater exposure to childhood
trauma, and less social support during and after deployment.
11
If
left untreated, military-related PTSD often follows a chronic
course, resulting in lifelong dysfunction.
12
Over the past 10 years, an increasing number of randomized
clinical trials (RCTs)of PTSD treatments in military personnel and vet-
erans have emerged, coinciding with a major policy shift in the De-
partments of Defense (DoD) and Veterans Affairs(VA) toward thera-
pies considered evidence-based.
13
Psychotherapy is more
consistently recommended as first-line treatment for PTSD than
medications across clinical practice guidelines and in DoD and VA
practice settings. In this review, we focuson RCTs of individual and
group psychotherapies for PTSD in military and veteran popula-
tions to examine the degree of symptom improvement and effi-
cacy relative to control conditions.
Methods
We searched PubMed, PsycINFO, and PILOTS for RCTs of psycho-
therapy for PTSD among military personnel or veterans, pub-
lished from January 1980 (the year the PTSD diagnosis was first
introduced) to March 1, 2015. PTSD was defined according to the
diagnostic criteria accepted at the time of the RCTs, which most
often followed the Diagnostic and Statistical Manual for Mental
Disorders (Fourth Edition, Text Revision).
14
This definition
included 3 clusters of symptoms following trauma, present for at
least 1 month, including reexperiencing the trauma (eg, intrusive
thoughts or nightmares), avoiding reminders of the trauma, and
hyperarousal (eg, hypervigilance, irritability, difficulty concentrat-
ing). We also manually searched reference lists of articles,
selected reviews, and meta-analyses.
We selected only English-language RCTs that (1) were con-
ducted with service members, veterans, or both; (2) reported PTSD
as an inclusion criterion; (3) reported at least pretreatment and post-
treatment total scores on standardized PTSD clinical measures;
(4) used either individual or group psychotherapy; and (5) did not
solely involve pharmacotherapies, pharmacologically augmented
psychotherapy, or other biological treatments. We did not include
trials of collaborative care models, dosing studies, trials targeting spe-
cific symptoms (eg, insomnia, anger) rather than the full syn-
drome, or trials targeting substance use disorders comorbid with
PTSD. We focused on intent-to-treat outcomes, when available.
Results
Of 891 publications initially identified, 36 were included
(Table 1
15-27,29,58
and Table 2
30-50
; eFigure in the Supplement). We
grouped trials of the most commonly studied first-line trauma-
focused therapies (ie, therapies given the highest evidence recom-
mendations in clinical guidelines) (Table 1), followed by second-line
interventions (ie, therapies for which there is less evidence sup-
porting effectiveness) (Table 2). The principal efficacy criteria,
reported variably in published trials, included degree of clinically
significant PTSD symptom improvement (typically defined as a 10-
or 12-point decline in self-reported or interviewer-assessed PTSD
symptoms),
23
mean PTSD symptom level at posttreatment and
follow-up, loss of PTSD diagnosis, degree of symptom remission,
and effect sizes (most commonly Cohen d, calculated as the differ-
ence between 2 mean PTSD severity scores divided by the pooled
SD [a dof 0.20 indicates a small effect size; a dof 0.50, a medium
effect size; and a dof 0.80, a large effect size]).
First-Line Psychotherapies
The diverse range of PTSD psychotherapies are broadly grouped
into “trauma-focused” and non–trauma-focused. Trauma-focused
therapies are cognitive-behavioral treatments that involve a range
of techniques that attend to the details of the trauma or associated
emotions or cognitive processes (beliefs, assumptions). The 3 most
widely studied trauma-focused therapies, which are considered
leading evidence-based psychotherapies by all major clinical
guidelines,
51
are cognitive processing therapy (CPT), prolonged
exposure therapy, and eye movement desensitization and repro-
cessing (EMDR) therapy (Box). All are manualized (ie, protocolized
in a session-by-session manner), delivered principally in specialty
care settings, use different techniques and theoretical rationales,
require sustained engagement (typically 12 sessions), and can be
emotionally demanding for patients. Prolonged exposure includes
asking patients to repeatedly recount the trauma to extinguish fear
responses associated with the memory (a technique known as ima-
ginal exposure) and to practice facing trauma reminders and trig-
gers in the real world (known as in vivo exposure). CPT involves
changing maladaptive beliefs related to the trauma (known as cog-
nitive restructuring), with the option of writing an account of the
trauma. EMDR also comprises exposure and cognitive restructuring
elements but asks patients to maintain dual focus on an external
stimulus (eg, eye-movement tracking of therapist hand move-
ments) while thinking about the trauma.
Meta-analyses of mostly civilian studies show large pre-post
treatment effects (within-group) and between-group effects com-
pared with control conditions for these treatments, with generally
comparable outcomes for CPT, prolonged exposure, EMDR, and
other trauma-focused modalities.
52
In contrast, non–trauma-
focused therapies attend principally to current life stressors, reac-
tions, goals, or relationships. The only non–trauma-focused therapy
that has received high-level evidence statements in PTSD clinical
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Table 1. Summary of Outcomes FromRCTs of First-Line Interventions for Military-Related PTSD
Source Participants (No.) Conditions
Longest
Follow-up, mo
No. (%)
Mean Posttreatment
Total PTSD Score
Pre-Post Decrease in
PTSD Symptoms
No. (%) Between-Group ES
(95% CI) From
Pretreatment to
PosttreatmentDrop Out
Remission at
Post-Treatment
% Attaining Clinically
Meaningful Change
at Posttreatment
% Retaining PTSD
Diagnosis at
Posttreatment
CPT
Monson et al,
15
2006
Veterans (30) CPT 1 6 (20) NR 52.14
(CAPS ITT)
24.59
(CAPS ITT)
15 (50)
(CAPS ITT)
18 (60)
(CAPS ITT) g= 1.12
(−0.58 to 1.67)
(CAPS ITT)
Veterans (30) Waitlist 1 4 (13) NR 76.03
(CAPS ITT)
3.07
(CAPS ITT)
3 (10)
(CAPS ITT)
29 (97)
(CAPS ITT)
Forbes et al,
16
2012
Australian veterans
(30)
CPT 3 9 (30) 6 (27)
(CAPS ITT)
48.03
(CAPS ITT)
27.5
(CAPS ITT)
16 (67)
(CAPS ITT)
15 (63)
(CAPS completer) d= 0.97
(0.43 to 1.51)
Australian veterans
(29)
TAU 3 9 (31) 1 (3)CAPSITT 57.73
(CAPS ITT)
6.82
(CAPS ITT)
8 (35)
(CAPS ITT)
20 (87)
(CAPS completer)
Surís et al,
17
2013
Veterans with military
sexual trauma (72)
CPT 6 18 (35) NR 64.97
(CAPS ITT)
20.1
(CAPS ITT)
66%
(CAPS ITT)
72%
(CAPS ITT) d= 0.49
(0.22 to −0.76)
(CAPS ITT)
Veterans with military
sexual trauma (57)
PCT 6 6 (18) NR 68.64
(CAPS ITT)
15.17
(CAPS ITT)
48%
(CAPS ITT)
74%
(CAPS ITT)
Morland et al,
18
2014
Veterans (61) Group CPT-C via
telemedicine
6 10 (16) NR 58.7
(CAPS ITT)
10.2
(CAPS ITT)
71 (57) overall
(CAPS ITT)
89 (71) overall
(CAPS ITT) d= 0.27
(CAPS ITT)
Veterans (64) Group CPT-C in
person
6 8 (13) NR 55.6
(CAPS ITT)
16.4
(CAPS ITT)
71 (57) overall
(CAPS ITT)
89 (71) overall
(CAPS ITT)
Resick et al,
19
2015
Active duty soldiers
(56)
Group CPT-C 12 15 (27) NR 23.0
(PSSI)
4.7
(PSSI)
15 (49)
(PCL)
NR
d= 0.21
(PSSI)
Active duty soldiers
(52)
Group PCT 12 7 (13) NR 23.9
(PSSI)
3.2
(PSSI)
14 (34)
(PCL)
NR
Prolonged Exposure, Imaginal Exposure, and Group Exposure
Cooper &
Klum,
20
1989
Veterans (8) TAU + implosive
therapy/flooding
3 6 (27)
overall
NR NR NR NR NR
NR
Veterans (8) TAU 3 6 (27)
overall
NR NR NR NR NR
Keane et al,
21
1989
Vietnam veterans
(11)
Implosive
therapy
6NRNRNRNR NRNR
NR
Vietnam veterans
(13)
Waitlist 6 NR NR NR NR NR NR
Boudewyns &
Hyer,
22
1990
Inpatient veterans
(19)
Exposure 3 13 (25)
overall
NR NR NR NR NR
NR
Inpatient veterans
(19)
TAU 3 13 (25)
overall
NR NR NR NR NR
Schnurr et al,
23
2003
Veterans (180) Group exposure 12 41 (23) NR 74.00
(CAPS ITT)
6.41
(CAPS ITT)
39%
(CAPS ITT)
NR
NR
Veterans (180) Group PCT 12 16 (9) NR 76.03
(CAPS ITT)
5.98
(CAPS ITT)
38%
(CAPS ITT)
NR
(continued)
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Table 1. Summary of Outcomes FromRCTs of First-Line Interventions for Military-Related PTSD (continued)
Source Participants (No.) Conditions
Longest
Follow-up, mo
No. (%)
Mean Posttreatment
Total PTSD Score
Pre-Post Decrease in
PTSD Symptoms
No. (%) Between-Group ES
(95% CI) From
Pretreatment to
PosttreatmentDrop Out
Remission at
Post-Treatment
% Attaining Clinically
Meaningful Change
at Posttreatment
% Retaining PTSD
Diagnosis at
Posttreatment
Schnurr et al,
24
2007
Female veterans
primarily with sexual
trauma (141)
PE 6 53 (38) 24 (17) 52.9 (47.7 to 58.0)
(CAPS ITT)
24.7
(CAPS ITT)
99 (70)
(CAPS ITT)
86 (61)
(CAPS ITT)
d= 0.27 CAPS ITT
Female veterans
primarily with sexual
trauma (143)
PCT 6 30 (21) 10 (7) 60.1 (55.3 to 64.8)
(CAPS ITT)
17.8
(CAPS ITT)
84 (59)
(CAPS ITT)
114 (80)
(CAPS ITT)
Nacasch et al,
25
2011
Israeli survivors of
combat or terrorism
(15)
PE 12 2 (13) NR 18.9
(PSSI ITT)
18.2
(PSSI ITT)
NR NR
d= 1.80 PSSI ITT
Israeli survivors of
combat or terrorism
(15)
TAU 12 2 (13) NR 35.0
(PSSI ITT)
1.8
(PSSI ITT)
NR NR
Yehuda et al,
26
2014
Veterans (37) PE 3 12 (31) NR NR 23
(CAPS)
NR 14 (56)
(CAPS completer) NR
Veterans (15) Minimal
attention
3 3 (21) NR NR 14
(CAPS)
NR 10 (83)
(CAPS completer)
Rauch et al,
27
2015
Veterans (18) PE None 7 (39) NR 30.0
(CAPS completer)
49.2
(CAPS completer)
10 (91)
(CAPS completer)
NR
d= 0.98 CAPS
completer
Veterans (18) PCT None 3 (17) NR 53.6
(CAPS completer)
23.8
(CAPS completer)
9 (60)
(CAPS completer)
NR
EMDR
Boudewyns &
Hyer,
58
1996
Veterans (21) EMDR None NR NR 50.09
(CAPS)
25.14
(CAPS)
NR NR
NR
Veterans (18) EMDR without
eye movement
None NR NR 67.50
(CAPS)
18.1
(CAPS)
NR NR
Veterans (22) TAU None NR NR 67.18
(CAPS)
14.05
(CAPS)
NR NR
Carlson et al,
29
1998
Veterans (10) EMDR 3 0 NR NR NR NR 2 (22)
NR
Veterans (13) Biofeedback
relaxation
3 1 (3) NR NR NR NR 7 (78)
Veterans (12) Routine care 3 0
12 (26)
overall prior
to group
assignment
NR NR NR NR NR
Abbreviations: CAPS, Clinician Administered PTSD Scale; completer, treatment completer sample only;
CPT,cognitive processing therapy; CPT-C, CPT cognitive-only version; EMDR, eyemovement desensitization and
reprocessing; ES, effect size; ITT,intent-to-treat; NR, not reported; PCL , PTSD Checklist; PCT, present-centered
therapy; PSSI, PTSD Symptom Scale Interview; PTSD,posttraumatic stress disorder; RCT, randomized clinical trial;
TAU,treatment as usual.
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practice guidelines is stress inoculation training, which involves stress
management skills (eg, breathing, muscle relaxation) and applying
these skills to day-to-day stressors and reminders of the trauma.
In 2008, CPT and prolonged exposure were selected by the VA
for nationwide dissemination in an attempt to better standardizecare
for veterans, and 98% of VA centers now offer both.
53,54
Initially,
neither intervention was validated sufficiently in active duty mili-
tary or veteran populations; they were originally tested largely in ci-
vilian female survivors of sexual assault. EMDR has not been dis-
seminated within the VA and DoD,and EMDR research has received
comparatively little VA or DoD funding but has strong evidence in
civilian studies and high-level endorsement from many guidelines
internationally.RCTs of stress inoculation training are lacking in vet-
erans, and it is infrequently used in the VA and DoD.
Efficacy of CPT
Five trials of CPT (that included 481 patients) met inclusion crite-
ria; 4 enrolled veterans
15-18
and 1 enrolled active-duty soldiers.
19
The first included a waitlist comparison,
15
and subsequent studies
used either a treatment-as-usual comparison or an active com-
parison condition known as present-centered therapy, a non–
trauma-focused treatment protocol focused largely on current life
problems. One noninferiority trial compared group CPT delivered
in person vs via telemedicine.
18
Treatment dropout rates ranged
from 16% to 35%.
Within-group intent-to-treat effect sizes for CPT were
reported in 3 trials and were large (d=0.78,
18
d=1.10,
19
and
d=1.02
17
). All trials reported the percentage of patients attaining
meaningful symptom change (49%-67%), and the mean posttreat-
ment PTSD scores, which remained at or above clinical cutoffs (eg,
50 on the Clinician Administered PTSD Scale [CAPS] and 20 on the
PTSD Scale-Interview [PSSI]), with a range of 48.03 to 64.97 for
CAPS and 23.00 for PSSI. Four trials reported posttreatment PTSD
diagnosis,
15-18
with approximately two-thirds of patients retaining
their diagnosis (60%-72%). Only 1 trial reported symptom remis-
sion (CAPS score <20) of 27%.
16
Concerning comparisons to control conditions, CPT outper-
formed waitlist approaches for mean PTSD symptom reduction
(g= 1.12), loss of diagnosis, and meaningful symptom change, al-
though the latter was no longer statistically significant by 1 month
posttreatment.
15
CPT produced significantly greater symptom re-
mission and clinically meaningful symptom improvement than treat-
ment as usual in a study of Australian veterans (d= 0.97). Group dif-
ferences in loss of diagnosis and meaningful symptom improvement
were nonsignificant at 3-month follow-up but remained significant
for symptom remission.
16
In a trial comparing CPT and present-
centered therapy for military sexual trauma, CPT resulted in signifi-
cantly greater reduction in self-reported PTSD symptoms at post-
treatment (d= 0.85), although group differences were no longer
significant by 2-, 4-, or 6-month follow-up.
17
There were no signifi-
cant group differences in interviewer-assessed PTSD symptoms. A
trial comparing group CPT with group present-centered therapy in
active-duty soldiers also found that self-reported PTSD symptoms
improved in both groups but statistically significantly more so in the
CPT group (d= 0.40).
19
Between-group differences were small and
not significant for interviewer-assessed PTSD symptoms at post-
treatment (d= 0.21), 6-month (d= 0.22), and 12-month (d= 0.21)
follow-up. Therewere no signif icant differences between groups in
the percentage of patients attaining clinically significant change in
self-reported symptoms at posttreatment, 6-month, or 12-month
follow-up.
In sum, trials of CPT for military-related PTSD have included both
veterans and active-duty personnel with combat or military sexual
trauma, have shown high methodological rigor (although fidelity
problems were present in 1 trial),
17
and have had large effect sizes
when compared with no treatment (waitlist) or treatment as usual.
However, CPT was marginally superior to active, non–trauma-
focused control comparisons.
Efficacy of Prolonged Exposure
Four RCTs of prolonged exposure (that included 402 patients) met
inclusion criteria.
24-27
Earlier trials examined similar exposure-
based mechanisms but not the full prolonged exposure protocol
20-22
and included a large trial of an exposure-based group therapy that
did not lead to meaningful PTSD symptom reduction or outper-
form a present-centered control.
23
The most robust trial of pro-
longed exposure compared prolonged exposure with present-
centered therapy in female veterans with sexual trauma,
24
while 3
small studies of combat veterans used minimal attention,
26
treat-
ment as usual,
25
or present-centered therapy
27
control conditions.
Two of these trials
26,27
focused primarily on glucocorticoid-related
biomarker responses associated with clinical improvement. Treat-
ment dropout rates ranged from 13% to 39%.
Within-group intent-to-treat effect size for prolonged expo-
sure was reported in 1 trial and was large (d= 0.80).
24
One trial
reported on clinically meaningful PTSD symptom reduction in the
intent-to-treat sample, which occurred in 70% of patients.
24
Mean posttreatment intent-to-treat symptom scores were
reported in 2 trials and remained at or above clinical cutoffs for
PTSD (52.9 [CAPS]
24
and 18.9 [PSSI]
25
). One trial reported loss of
diagnosis in the intent-to-treat sample and found that 61%
retained their diagnosis after treatment.
24
The only trial to report
remission (20 CAPS) found remission in 17% of the intent-to-
treat sample.
24
When compared with control conditions, both prolonged ex-
posure and present-centered therapy improved symptoms in fe-
male veterans with predominantly sexual assault trauma, with a small
intent-to-treat effect size favoring prolonged exposure (d= 0.27);
there were no significant group differences for clinically meaning-
ful improvement at any point and no significant group differences
for loss of diagnosis or symptom remission at either the 3- or 6-month
follow-up.
24
In a small sample of Israeli veterans, prolonged expo-
sure resulted in greater symptom reduction than psychodynamic
therapy (d= 1.80), and outcomes were maintained through 12-
month follow-up.
25
Prolonged exposure failed to outperform a mini-
mal-attention control that consisted of 30-minute weekly symp-
tom monitoring phone calls; both groups significantly improved, with
no significant group differences.
26
Last, a small RCT examining cor-
tisol response following prolonged exposure found no significant dif-
ferences between prolonged exposure and present-centered
therapy on interviewer-assessed PTSD outcomes in the intent-to-
treat sample, although significant differences favoring prolonged ex-
posure were found in completers (d= 3.16 for prolonged exposure
vs d= 1.08 for present-centered therapy).
27
In sum, fewer methodologically robust trials for military-
related PTSD are available for prolonged exposure than for CPT. With
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Table 2. Summary of Outcomes From RCTs of Second-Line Interventions for Military-Related PTSD
Source Participants (No.) Conditions
Longest
Follow-up, mo
No. (%)
Mean Post-Treatment
Total PTSD Score
Pre-Post Drop in
PTSD Symptoms
No. (%)
Between-Group
ES From
Pretreatment to
PosttreatmentDrop Out
Remission at
Post-Treatment
% Attaining
Clinically
Meaningful Change
At Posttreatment
% Retaining PTSD
Diagnosis at
Posttreatment
Watson
et al,
30
1997
Vietnam veterans
(30)
Relaxation None NR NR 95.0
(PTSD-I completer)
0.4
(PTSD-I completer)
NR NR
NR
Vietnam veterans
(30)
Relaxation +
deep breathing
None NR NR 97.8
(PTSD-I completer)
0.3
(PTSD-I completer)
NR NR
Vietnam veterans
(30)
Relaxation +
deep breathing +
biofeedback
None NR NR 89.4
(PTSD-I completer)
1.1
(PTSD-I completer)
NR NR
Dunn et al,
31
2007
Veterans (55) Self-management
therapy
12 17 (33) NR 73.93
(CAPS completer)
2.01
(CAPS completer)
NR NR
d= 0.23
Veterans (56) Psychoeducation
group therapy
12 6 (12) NR 77.10
(CAPS completer)
+1.05
(CAPS completer)
NR NR
Frueh et al,
32
2007
Veterans (21) In-person group CBT 3 9 (43) NR 56.58
(PCL completer)
5.8
(PCL completer)
NR NR
NR
Veterans (17) Telepsychiatry group
CBT
3 8 (47) NR 68.11
(PCL completer)
+1.11
(PCL completer)
NR NR
Litz et al,
33
2007
Active duty
personnel (24)
Internet CBT 6 12 (27) overall 7 (42.9)
(PSS-I<6)
14.86
(PSS-I completer)
9.16
(PSS completer)
NR NR
d= 0.41
Active duty
personnel (21)
Internet supportive
counseling
6 12 (27) overall 1 (6.3) (PSS-I<6) 20.00
(PSS-I completer)
11.85
(PSS-I completer)
NR NR
Bormann
et al,
34
2008
Veterans (14) Mantram repetition None 4 (12) overall NR NR 4.79
(CAPS ITT)
NR NR
d= 0.33
Veterans (15) Waitlist None NR NR 2.64
(CAPS ITT)
NR NR
Lande
et al,
35
2010
Active duty soldiers
(22)
Biofeedback + TAU None NR NR NR NR NR NR
NR
Active duty soldiers
(17)
TAU None NR NR NR NR NR NR
Ready
et al,
36
2010
Vietnam veterans (6) Vir tual reality
exposure
6 1 (17) NR 59.20
(CAPS completer)
31.8
(CAPS completer)
NR NR
d= 0.28
Vietnam veterans (5) PCT 6 1 (20) NR 75.50
(CAPS completer)
23.0
(CAPS completer)
NR NR
Beidel
et al,
37
2011
Vietnam veterans
(14)
Trauma management
therapy
None 5 (14) overall NR 69.0
(CAPS completer)
15.9
(CAPS completer)
NR NR
NR
Vietnam veterans
(16)
Exposure therapy None NR 65.5
(CAPS completer)
25.1
(CAPS completer)
NR NR
Kent et al,
38
2011
Veterans (20) Resilience-oriented
group therapy
None 1 (5) NR 23.00
(PDS ITT)
12.90
(PDS ITT)
NR NR
d= 1.40
Veterans (19) Waitlist None 2 (11) 36.90
(PDS ITT)
0.63
(PDS ITT)
NR NR
(continued)
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Table 2. Summary of Outcomes From RCTs of Second-Line Interventions for Military-Related PTSD (continued)
Source Participants (No.) Conditions
Longest
Follow-up, mo
No. (%)
Mean Post-Treatment
Total PTSD Score
Pre-Post Drop in
PTSD Symptoms
No. (%)
Between-Group
ES From
Pretreatment to
PosttreatmentDrop Out
Remission at
Post-Treatment
% Attaining
Clinically
Meaningful Change
At Posttreatment
% Retaining PTSD
Diagnosis at
Posttreatment
McLay
et al,
39
2011
Active duty service
members (10)
Virtual reality
graded exposure
therapy
None 0 NR 48.1
(CAPS ITT)
35.4
(CAPS)
7 (70) showed
improvement
of >30%
NR
NR
Active duty service
members (10)
TAU None 1 (10) NR 72.3
(CAPS ITT)
9.4
(CAPS)
1 (11%) NR
Possemato
et al,
40
2011
OEF/OIF veterans
(15)
Written emotional
disclosure
30NRNR NRNRNR
η
2
p
= .03
OEF/OIF veterans
(16)
Writing control 3 5 (31) NR NR NR NR NR
Jain et al,
41
2013
Active duty Marines
(68)
HT + GI + TAU None 6 (9) NR 40.7 (37.0-44.2)
(PCL ITT)
13.3
(PCL ITT)
NR NR
d= 0.85
(PCL ITT)
Active duty Marines
(55)
TAU None 15 (27) NR 52.0 (48.0-56.0)
(PCL ITT)
3.6
(PCL ITT)
NR NR
Kearney
et al,
42
2012
Veterans (22) MBSR + TAU 4 2 (8) NR 52.45
(PCL ITT)
7.43
(PCL ITT)
8 (36) NR
d= 0.51
(0.11-1.12)
Veterans (25) TAU 4 1 (5) NR 58.5
(PCL ITT)
4.41
(PCL ITT)
5 (25) NR
Niles et al,
43
2012
Veterans (17) Mindfulness 6 wk 4 (24) NR 47.46
(CAPS completer)
13.46
(CAPS completer)
5 (38.5) (20 points
on CAPS)
NR
NR
Veterans (16) Psychoeducation 6 wk 2 (13) NR 74.00
(CAPS completer)
+1.5
(CAPS completer)
1 (7.1) (20 points
on CAPS)
Strachan
et al,
44
2012
OEF/OIF veterans
and active duty
service members
(20)
BA-TE in person None 5 (25) NR 47.9
(PCL completer)
11.1
(PCL completer)
NR NR
d= 0.33
OEF/OIF veterans
and active duty
service members
(20)
BA-TE telehealth None 4 (20) NR 41.4
(PCL completer)
15.8
(PCL completer)
NR NR
Bormann
et al,
45
2013
Veterans (71) Mantram
repetition + TAU
6 wk 5 (7) η
2
p
= .03 66.16
(CAPS ITT)
16.92
(CAPS ITT)
18 (24) NR
NR
Veterans (75) TAU 6 wk 5 (7) 72.59
(CAPS ITT)
10.24
(CAPS ITT)
9 (12) NR
Church
et al,
46
2013
Veterans (30) EFT + TAU 6 1 (3) 39 (80) overall
(including the
waitlist that
received EFT)
39.41
(PCL completer)
22.6
(PCL completer)
NR 3 (10)
NR
Veterans (29) TAU/waitlist 6 4 (14) 39 (80) overall
(including the
waitlist that
received EFT)
63.23
(PCL completer)
+ 0.52
(PCL completer)
NR 28 (96)
(continued)
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1 notable exception,
24
sample sizes have tended to be
smaller,and no large methodologically robust trials of pro-
longed exposure have been published in US male veter-
ans with combat trauma. The only available data on pro-
longed exposure in US combat-exposed male veterans
come from 2 small trials that studied biomarkers associ-
ated with clinical outcomes.
26,27
Efficacy of EMDR
RCTsof EMDR for military-related PTSD (all conducted prior
to the wars in Iraq and Afghanistan)involved small samples,
tested only brief interventions (1-3 sessions),
28,55,56
or in-
volved dismantling comparisons (eliminating eye
movements).
57
They also generally did not use methodol-
ogy consistent with modern trials. In the 2 trials testing ad-
equate doses of EMDR there were large symptom
reductions,
58
and 78% of completers no longer met crite-
ria for PTSD.
29
EMDR performed comparably to variants in
which the eye tracking was removed or when compared
with an active non–trauma-focused therapy.
58
EMDR out-
performed waitlisting (ie, no treatment) and biofeedback-
assisted relaxation, with results maintained at 9-month
follow-up.
29
In sum, the efficacy of EMDR remains largely
based on civilian studies
59
; additional studies in military
populations are needed.
Second-Line Interventions
Given high dropout and nonresponse rates from first-line
therapies, an increasing number of trials have examined an
array of alternatives, including variations of cognitive-
behavioral therapy
38,44
or novel delivery modalities, such
as virtual reality
36,39
or web-based content.
33
A variant of
EMDR, accelerated resolution therapy, demonstrated large
effects (d= 1.25)compared with an educational control con-
dition similar to waitlisting in a preliminary RCT of veter-
ans with PTSD.
47
Other trials have tested complementary and alterna-
tive therapies that are theoretically and mechanistically
distinct. Acupuncture combined with usual care outper-
formed usual care alone (d=1.7)
48
; small trials have
shown some evidence of efficacy for mindfulness-based
interventions,
43
mantram repetition (ie, silent repetition
of a word or phrase with spiritual significance),
34,45
atten-
tion bias modification,
49
and memory specificity
training.
50
Healing touch therapy, involving tapping body
points while engaging in non–exposure-based guided
imagery, also demonstrated efficacy over treatment as
usual (d= 0.85).
41
These findings suggest that a variety of
disparate treatment mechanisms are associated with
reduced PTSD symptoms.
In contrast, treatments that have failed to demon-
strate efficacy among veterans include relaxation, deep
breathing, biofeedback, and mindfulness-based stress
reduction.
30,35,42
A brief 3-session intervention consist-
ing of writing about combat traumas produced little mean-
ingful PTSD improvement and did not outperform writing
about one’s use of time.
40
Cognitive-behavioral group
therapy aimed at comorbid PTSD and depression,
31
and
Table 2. Summary of Outcomes From RCTs of Second-Line Interventions for Military-Related PTSD (continued)
Source Participants (No.) Conditions
Longest
Follow-up, mo
No. (%)
Mean Post-Treatment
Total PTSD Score
Pre-Post Drop in
PTSD Symptoms
No. (%)
Between-Group
ES From
Pretreatment to
PosttreatmentDrop Out
Remission at
Post-Treatment
% Attaining
Clinically
Meaningful Change
At Posttreatment
% Retaining PTSD
Diagnosis at
Posttreatment
Kip et al,
47
2013
Service members
and veterans (29)
ART 3 3 (10) NR 42.00
(PCL ITT)
15.4
(PCL ITT)
17 (65)
(PCL completer)
NR
d= 1.25
Service members
and veterans (28)
Attention control 3 NR NR 54.3
(PCL ITT)
2.1
(PCL ITT)
3 (13)
(PCL completer)
NR
Engel et al,
48
2014
Active duty soldiers
(28)
Acupuncture + TAU 12 wk 1 (4) NR 38.8
(PCL ITT)
19.3
(PCL ITT)
NR NR
NR
Active duty soldiers
(27)
TAU 12 wk 0 NR 51.5
(PCL ITT)
3.9
(PCL ITT)
NR NR
Kuckertz
et al,
49
2014
Inpatient active duty
personnel (20)
Attention bias
modification
None 8 (40) NR 42.83
(PCL completer)
20.25
(PCL completer)
NR NR
NR
Inpatient active duty
personnel (17)
Attention control
condition
None 0 NR 51.65
(PCL completer)
10.06
(PCL completer)
NR NR
Moradi
et al,
50
2014
Iranian veterans (12) MEST 3 0 NR 50.17
(IES-R ITT)
30.91
(IES-R ITT)
NR NR
d= 4.79
Iranian veterans (12) Waitlist 3 0 NR 75.34
(IES-R ITT)
+ 0.01
(IES-R ITT)
NR NR
Abbreviations: ART, accelerated resolution therapy; BA-TE, behavioral activationand therapeutic exposure;
CAPS, Clinician Administered PTSD Scale; CBT, cognitive behavioral therapy; completer, treatment completer
sample only; EFT, emotional freedom techniques; ES, effect size; HT + GI, healing touch with guided imagery;
IES-R, Impact of Event Scale–Revised; ITT, intent-to-treat; MBSR, mindfulness-based stress reduction;
MEST, memory specificity training; η
2p
, partial eta-squared; NR, not reported; PCL, PTSD Checklist;
PCT,pre sent-centeredtherapy; PSSI, PTSD Symptom Scale Interview; PTSD, posttraumatic stress disorder;
TAU,treatment as usual.
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comorbid PTSD and substance dependence, did not substantially
improve symptoms and was equivalent to controls.
Discussion
The past 10 years has seen unprecedented interest in identifying ef-
fective PTSD treatments for service members and veterans. Find-
ings from RCTs indicate a significant need for further treatment de-
velopment and improvement. CPT and prolonged exposure, the 2
most widely used first-line (ie, recommended) therapies, show large
within-group (pretreatment to posttreatment) effect sizes. How-
ever,effect sizes, which are more commonly used in psychology lit-
erature than in medical literature, reflect mean outcomes and do not
adequately capture heterogeneity in patient outcomes; between
one-third and one-half of patients receiving CPT or prolonged ex-
posure did not demonstrate clinically meaningful symptom change
(when this outcome was reported). Approximately two-thirds of pa-
tients receiving CPT or prolonged exposure retained their diagno-
sis posttreatment. Mean PTSD scores have tended to remain at or
above diagnostic thresholds after treatment, and the 2 studies re-
porting remission rates suggest that symptom remission is rela-
tively uncommon. Most importantly, many trials of CPT and pro-
longed exposure have compared patients receiving the intervention
with patients not receiving any standardized intervention (waitlist)
or with patients receiving treatment as usual. When CPT and pro-
longed exposure were compared with non–trauma-focused psy-
chotherapies, such as present-centered therapy, similar levels of
symptom improvement were often observed, particularly at
follow-up intervals.
Approximately one-fourth of patients enrolled in clinical trials
and receiving CPT and prolonged exposure dropped out during treat-
ment. These proportions are broadly comparable to the propor-
tions of dropouts in studies of trauma-focused therapies in civilians
60
and trials of depression in veterans.
61
Treatment nonretention has
been a significant problem in military-related PTSD care more gen-
erally; several large observational studies in both the VA and DoD
found that only a small proportion of individuals receive a mini-
mally adequate number of mental health encounters after PTSD
diagnosis.
62
Reasons for not seeking treatment and dropout are com-
plex and include stigma, confidentiality concerns, time demands, per-
ceived treatment inefficacy, and discomfort with the therapist.
62
Current VA policies emphasize CPT and prolongedexposure as
treatments of choice. Clinical practice guidelines (including the VA/
DoD guideline
52
), based largely on studies in civilians, also include
CPT and prolonged exposure as first-line recommendations for adults
with PTSD, although EMDR and other trauma-focused therapiesare
given at least equal standing (separate recommendations for ser-
vice members and veterans are not made). Some evidence sug-
gests that outcomes for PTSD treatment tend to be better among
civilians than among veterans,
63,64
although this has not been con-
sistent and remains an empirical question. Potential reasons why
treatment outcomes may be worse among military and veteran
populations include the extended, repeated, and intense nature of
deployment trauma
65
and the fact that service members are ex-
posed not only to life threats but to traumatic losses and morally com-
promising experiences that may require different treatment
approaches.
66-68
A recent meta-analysis comparing trauma-
focused and non–trauma-focused therapies (both civilian and mili-
tary trauma) found that, in populations with more complex trauma,
such as veterans and refugees, there was little difference in effi-
cacy; moderate differences favoringtrauma-focused therapies were
only present for less complex traumas.
69
Additional likely reasons
for worse outcomes in veterans include comorbidities (eg, 87% of
veterans with PTSD presenting to VAprimary care clinics have at least
1 psychiatric comorbidity, with the mode being 3-4 disorders
70
) and
disability compensation incentives. To contextualize these find-
ings, a recent narrative review of cognitive-behavioral therapy for
depression in veterans similarly showed that relatively few trials are
available, cognitive-behavioral therapy often does not outperform
controls, and results compare unfavorably with civilian outcomes.
61
One unresolved issue is whether focusing on the trauma, either
through exposure or cognitive reframing, is necessary for recovery.
The findings that interventions such as present-centered therapy
and, in civilians, interpersonal psychotherapy
71
are associated with
efficacy similar to that of trauma-focused therapy needs to be rec-
onciled with the common assumption in the field that fidelity to a
trauma-focused approach is essential for symptom improvement.
VA/DoDtreatment guideline s, and other guidelines, specify that pa-
tient preference should be a guiding factor in treatment selection.
Yetlittle research has been conducted on patient preferences or on
other behavioral and biological predictors of dropping out of care,
clearly the strongest influence on treatment effectiveness.
62
Several large-scale military-related PTSD trials are currently on-
going, including trials with active-duty service members, a popula-
tion rarely studied but an important target for early interventions.
Box. Descriptions of First-Line Interventions
Cognitive therapy. Focuses on modifying dysfunctional thoughts,
beliefs, and expectations by identifying, challenging, and replacing
maladaptive cognitions. Cognitive processing therapy (CPT) is the
most widely used example of cognitive therapy in the
Departments of Defense and Veterans Affairs.
Exposure therapy. Comprises psychoeducation, imaginal or
narrative exposure (targeting trauma memories), in vivo exposure
(targeting external stimuli or situations that the patient avoids
because of the trauma), and processing of thoughts and emotions,
with the aim of confronting, rather than avoiding, feared
memories and stimuli. Prolonged exposure therapy (PE) is the
most widely used example of exposure therapy in the
Departments of Defense and Veterans Affairs.
Eye movement desensitization and reprocessing (EMDR). Asks
patients to attend to emotionally disturbing material in brief
sequential doses while focusing on an external stimulus, typically
therapist-directed lateral eye movements. Additionally, treatment
involves identifying bodily sensations associated with the image,
identifying an aversive cognition associated with the trauma, and
identifying an alternative positive cognition to replace the aversive
cognition.
Stress inoculation training (SIT). Teachesanxie ty-management
skills including relaxation training, breathing retraining, positive
thinking and self-talk, assertiveness training, and thought
stopping. It may also include cognitive restructuring and exposure,
although these are optional elements.
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A large (N = 900) multisite trial is directly comparing CPT and pro-
longed exposure in veterans,
72
although it remains to be seen to what
extent continued focus on efficacy comparisons will improve care,
particularly since equivalency between leading interventions has con-
sistently been demonstrated in civilians.
59,73
Ongoing trials focus al-
most exclusively on 2 trauma-focused interventions, despite these
therapies being rarely used in actual VAand DoD clinical practice (less
than 10% of the time, in one estimate of New England region VA
centers
74
). The effectiveness of psychotherapies for PTSD as actu-
ally delivered in the VA and DoD has received little empirical
attention.
75
Limitations of this descriptive review (which did not use for-
mal meta-analytic techniques or access all international data-
bases) include the relatively small number of studies and sample
sizes, limiting generalizability. Studies often did not report key
outcomes, such as symptom remission, loss of diagnosis, or clini-
cally important subthreshold PTSD
76,77
(which would include
individuals who met previous diagnostic criteria but no longer
meet the latest criteria).
78
It is also noteworthy that the metrics
of meaningful symptom improvement (typically a 10- or 12-point
decrease in PTSD scores) are researcher-defined, not patient-
defined; patient perspectives and preferences have not been a
primary focus of research. Likewise, most trials have reported
only total PTSD symptom scores, and the potential for differential
treatment effects across symptom clusters remains unexamined.
Trials also have not reported the need for continued care follow-
ing CPT or prolonged exposure; for many patients, 12 sessions of
manualized trauma- or non–trauma-focused treatment is insuffi-
cient. Definitions of treatment dropout also differ between stud-
ies, and studies often fail to delineate why patients dropped out.
Moreover, military personnel and veterans participating in PTSD
trials are often taking psychotropic medications concurrently (ap-
proximately three-fourths of participants in CPT and prolonged
exposure trials), creating potential confounding. Data are lacking
on the relative efficacy of psychotherapy compared with medica-
tion or the synergistic effects of combined treatments.
79
Last,
although we considered group and individual therapy together,
these 2 modalities are practically and mechanistically distinct. A
recent meta-analysis of civilian and veteran group therapies
found smaller effect sizes in combat samples; although group
therapy outperformed waitlist controls, it did not outperform
active-comparison conditions.
80
Conclusions
PTSD in military and veteran populations is a complex and difficult-
to-treat disorder for which first-line trauma-focused psycho-
therapy approaches are not optimal. Although efficacious for some
patients, first-line treatments have high nonresponse and dropout
rates, and patients often remain symptomatic. Two principal clini-
cal conclusions can be drawn from this review. First, the available
evidence supports the use of either trauma-focused or structured
non–trauma-focused therapies, depending on patient preferences
or other factors that might promote treatment retention. Second,
there is a need for improvement in existing PTSD treatments as well
as the development and testing of novel evidence-based treat-
ment strategies, whether trauma-focused or non–trauma-focused.
An increasing number of novel therapeutic approaches have been
shown efficacious to varying degrees, but progress in the field is un-
likely without better understanding of treatment mechanisms, pa-
tient preferences, factors influencing treatment engagement and re-
tention, and behavioral and biomarker prediction of differential
treatment responses.
ARTICLE INFORMATION
Author Contributions: Dr Steenkamp had full
access to all of the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Steenkamp, Litz.
Acquisition, analysis, or interpretation of data:
Steenkamp, Litz, Hoge, Marmar.
Drafting of the manuscript: Steenkamp, Litz,
Marmar.
Critical revision of the manuscript for important
intellectual content: Hoge, Marmar.
Administrative, technical, or material support: Litz.
Study supervision: Litz, Marmar.
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
Disclaimer: The views of this article are those of
the authors and do not represent an official
position of the US Army,Depar tment of Defense,or
listed institutions.
Additional Contributions: We thank Carol
Hundert, BS (VA Boston Healthcare System), and
Amelia Tankersley, BA (VA Boston Healthcare
System), for assistance with manuscript
preparation. They received no compensation for
their contributions.
Submissions: We encourage authors to submit
papers for consideration as a Review.Please
contact Mary McGrae McDermott, MD, at
mdm608@northwestern.edu.
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... Regardless, a focus on effect size can overshadow other important factors such as non-response rates which can leave up to two-thirds of patients with a PTSD diagnosis after CPT treatment. 7 By this metric, the CPT nonresponse rate of 65% reported here was typical of CPT treatment. 7 SKY was effective (and non-inferior to CPT) at reducing symptoms of depression in the presence of symptoms of PTSD. ...
... 7 By this metric, the CPT nonresponse rate of 65% reported here was typical of CPT treatment. 7 SKY was effective (and non-inferior to CPT) at reducing symptoms of depression in the presence of symptoms of PTSD. Moderate depression at baseline improved by end of treatment to mild-moderate depression and remained stable at 1 month. ...
Article
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Objective Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial. Setting Outpatient Veterans Affairs healthcare centre. Participants 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study. Interventions SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks. Measures The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS). Results Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, −5.6, d= 0.41, n=41: CPT, −6.8, d= 0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (−1.2, 95% CI −5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT–SKY: −2.1, 95% CI −6.9 to 2.8) and 1-year (CPT–SKY: −1.8, 95% CI −6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54). Conclusions SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD. Trial registration number NCT02366403 .
... Among RCTs in active duty and Veteran populations, PTSD symptom effect sizes from pre-to posttreatment range from d = 0.78 to 1.02 and 35-40% of participants fail to experience clinically meaningful improvement. 69,70 Premature attrition from treatment for all trauma survivors suffering from PTSD is also problematic. For example, at least 35% of all Veterans who initiate a course of CPT in VA clinics fail to complete therapy, resulting in suboptimal doses of treatment which contributes to poor outcomes. ...
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Despite substantial efforts to counter sexual assault and harassment in the military, both remain persistent in the Armed Services. In February 2021, President Biden directed the U.S. Department of Defense to establish a 90-day Independent Review Commission on Sexual Assault in the Military (IRC) to assess the department’s efforts and make actionable recommendations. As servicemembers discharge from the military, effects of military sexual trauma (MST) are often seen in the Veterans Health Administration (VA). In response to an IRC inquiry about VA MST research, we organized an overview on prevalence, adverse consequences, and evidence-based treatments targeting the sequelae of MST. Women are significantly more likely to experience MST than their male counterparts. Other groups with low societal and institutional power (e.g., lower rank) are also at increased risk. Although not all MST survivors experience long-term adverse consequences, for many, they can be significant, chronic, and enduring and span mental and physical health outcomes, as well as cumulative impairments in functioning. Adverse consequences of MST come with commonalities shared with sexual trauma in other settings (e.g., interpersonal betrayal, victim-blaming) as well as unique aspects of the military context, where experiences of interpersonal betrayal may be compounded by perceptions of institutional betrayal (e.g., fear of reprisal or ostracism, having to work/live alongside a perpetrator). MST’s most common mental health impact is posttraumatic stress disorder, which rarely occurs in isolation, and may coincide with major depression, anxiety, eating disorders, substance use disorders, and increased suicidality. Physical health impacts include greater chronic disease burden (e.g., hypertension), and impaired reproductive health and sexual functioning. Advances in treatment include evidence-based psychotherapies and novel approaches relying on mind-body interventions and peer support. Nonetheless, much work is needed to enhance detection, access, care, and support or even the best interventions will not be effective.
... The trauma-focused therapies have demonstrated efficacy at reducing symptoms, but with high dropout and nonresponse rates, they fail to be a viable pathway to recovery for most people with PTSD. 1 Two selective serotonin reuptake inhibitors (SSRIs), sertraline and paroxetine, are the only medications United States Food and Drug Administration (FDA) approved for the treatment of PTSD. The SSRI fluoxetine and serotonin norepinephrine reuptake inhibitor venlafaxine have also been studied and, along with sertraline and paroxetine, are recommended as first-line pharmacotherapy in existing guidelines for the management of PTSD. ...
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Background: Among the renewed applications of psychedelic medicines in psychiatry, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder (PTSD) has demonstrated the most promise in early small-scale studies. Recent exploratory analyses from prior clinical trials of MDMA-assisted therapy for PTSD have suggested that recent use of selective serotonin reuptake inhibitors (SSRIs)-the only medication class with United States Food and Drug Administration (FDA) approval to treat PTSD-can significantly dampen the efficacy of this novel therapy. Although psychedelic medicines are not yet FDA approved, MDMA is very likely to be the first to achieve FDA approval-perhaps within the next 2 years. Given this timeline, the field would benefit from more knowledge about potential interactions between this novel therapy and our current treatments. Methods: This brief report reviews selected literature in the basic and clinical neurosciences relevant to the interaction of SSRIs and MDMA. Findings: The possibility that SSRI use could dampen future responses to MDMA-assisted therapy for PTSD raises many important questions about the biological mechanisms as well as ethical implications around the most appropriate way to counsel patients. In this brief report, we compare the evidence for SSRIs and MDMA-assisted therapy in the treatment of PTSD and discuss what is known about the neurobiological interactions between these 2 medicines. Conclusions: There is strong neurobiological plausibility for the hypothesis that chronic SSRI use dampens response to MDMA-assisted therapy, although current knowledge in the field is limited and primarily relates to acute pharmacodynamic interactions. Our commentary highlights the urgent need for future work dedicated to addressing this important clinical topic.
... Pregnancy itself is a complex psychological process, there are many factors to form the source of stress, which results in highly maternal stress state, causing many psychological barriers but at present the causes and treatment of repetitive abortion research mainly from the Angle of biology [3], this special group of patients with repetitive abortion the psychosocial characteristics and their influence on abortion, There are few studies at home and abroad, and they are not systematic and comprehensive [4]. This study explored the relationship between psychological stress and BDNF (rs6265) gene polymorphism in patients with unexplained habitual abortion and scientific psychological nursing intervention, systematically explored the psychosomatic symptoms, psychosocial influencing factors and genetic factors of patients with recurrent spontaneous abortion [5] [6]. From the perspective of psychology and genetics, the pathogenesis of unexplained habitual abortion high-risk groups was studied [7] [8] [9] [10], in order to provide a theoretical basis for the psychological nursing intervention of patients with habitual abortion, and to find out the method of individualized prevention and treatment of unexplained habitual abortion. ...
... Results show promising efficacy in managing irritability, depressive symptoms, aggressiveness, and anger (Davidson et al., 2002). However, after SSRI administration, symptoms improvement depends on the type of traumatic event, gender, or previous exposure to other stressful situations (Kessler et al., 1995(Kessler et al., , 2017Steenkamp et al., 2015). ...
Article
Post-traumatic stress disorder (PTSD) is a disabling psychiatric condition with a critical familiar, personal, and social impact. Patients diagnosed with PTSD show various symptoms, including anxiety, depression, psychotic episodes, and sleep disturbances, complicating their therapeutic management. Only sertraline and paroxetine, two selective serotonin reuptake inhibitors, are approved by different international agencies to treat PTSD. In addition, these drugs are generally combined with psychotherapy to achieve positive results. However, these pharmacological strategies present limited efficacy. Nearly half of the PTSD patients do not experience remission of symptoms, possibly due to the high prevalence of psychiatric comorbidities. Therefore, in clinical practice, other off-label medications are common, even though the effectiveness of these drugs needs to be further investigated. In this line, antipsychotics, antiepileptics, adrenergic blockers, benzodiazepines, and other emerging pharmacological agents have aroused interest as potential therapeutic tools to improve some specific symptoms of PTSD. Thus, this review is focused on the most widely used drugs for the pharmacological treatment of PTSD with a translational approach, including clinical and preclinical studies, to emphasize the need to develop safer and more effective medications.
Article
Background Although most veterans with posttraumatic stress disorder (PTSD) benefit from evidence-based treatments, questions persist concerning the profiles of those at risk for poor outcomes. To help address these gaps, this study analyzed a large clinical cohort of veterans receiving prolonged exposure (PE) or cognitive processing therapy (CPT). Methods Cluster analysis using Ward's method with Euclidian distances identified clinically meaningful subgroups of veterans in a national cohort (n = 20,848) using variables maintained in the electronic medical record. The clusters were then compared via one-way analysis of variance and Tukey's HSD on indicators of treatment progress including PTSD symptom change, clinical recovery, clinically significant change, remission, and treatment completion. Results Effect size differences on clinical outcome measures for PE and CPT were negligible. Less than half of veterans achieved at least a 15-point reduction in PCL-5 score and half completed treatment. We identified 10 distinct clusters. Higher rates of PTSD service-connected disability were linked to poorer outcomes across multiple clusters, especially when combined with Post-Vietnam service era. Non-White race was also linked with poorer clinical outcomes. Factors associated with better outcomes included a greater proportion of female veterans, especially when combined with recent service era, and longer PTSD diagnosis duration. Conclusions This study suggests the need to improve PTSD treatment outcomes for non-White and male veterans, examine treatment response in Post-Vietnam era veterans, and consider ways in which the service connection process could hinder treatment response. The results from this study also indicate the benefits of integrating elements of clinical complexity into an analytic approach.
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A special thank you to Drs. William Hohl, Jeffrey Sugar, and John Briere. I would also like to thank Soul Quest Ayahuasca Church of Mother Earth, Chris and Verena Young, Lance Supernaw and Daniel Murray, Jesse Gould, and everyone else who helped in bringing this research and story to fruition.
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Emotion dysregulation is considered a core component of posttraumatic stress disorder (PTSD). Cognitive reappraisal is one therapeutic emotion regulation strategy that has been widely studied among individuals with mood and anxiety disorders, and numerous differences in brain activation patterns have been shown between individuals with and without PTSD during tasks of cognitive reappraisal. Prior research among healthy subjects suggests that an acute, low dose of Δ9-tetrahydrocannabinol (THC) could attenuate the neurophysiological discrepancies that exist between individuals with and without PTSD during tasks of emotional processing; however, the effect of an acute, low dose of THC on corticolimbic activity during emotion regulation among individuals with PTSD has not yet been studied. The present study aimed to investigate the effect of THC on negative affect and brain activation in a priori regions of interest during cognitive reappraisal among trauma-exposed individuals with and without PTSD. Using a double-blind design, 51 individuals were randomized to receive THC or placebo (PBO) before participating in a well-established emotion regulation task during functional magnetic resonance imaging (fMRI). THC but not PBO reduced negative affect during reappraisal, and THC increased dorsomedial prefrontal cortex (dmPFC) activation in response to neutral images. Individuals with PTSD displayed less activation in the angular gyrus, overall, compared to the trauma-exposed control (TEC) group, however THC increased angular gyrus activation in the PTSD group so that there was no significant difference in angular gyrus activation between the TEC and PTSD groups that received THC. Compared to PBO, THC also increased cerebellar activation during exposure to neutral images in individuals with PTSD. Lastly, in participants that received THC, greater posterior cingulate cortex (PCC)/precuneus activation during reappraisal was associated with less self-reported negative affect following reappraisal blocks. Together these findings suggest that THC may prove to be a beneficial pharmacological adjunct to cognitive reappraisal therapy in the treatment of PTSD.
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Background Understanding cognitive and biological mechanisms of PTSD treatment can help refine treatments and increase rates of response.Methods Thirty-six veterans with PTSD were randomly assigned to receive Prolonged exposure therapy (PE) or Present-Centered therapy (PCT). We examined symptoms, trauma-related cognitions, and two indices of HPA axis function (cortisol awakening response and cortisol response to a script-driven imagery task).ResultsThirty veterans started treatment and 26 completed. PE resulted in significantly more symptom reduction than PCT (P = .008). High treatment responders collapsed across treatments showed nominally higher cortisol levels measured at pretreatment 30 min after trauma script exposure compared to low responders (P = .08). At midtreatment, high treatment responders showed higher cortisol levels throughout the imagery task (Ps = .03–.04). There were no differences between high and low treatment responders at posttreatment. Thoughts of incompetence (F (1.6, 35.8) = 16.8, P = .000) and a dangerous world (F (1.3, 29.9) = 8.2, P = .004) significantly improved over time in high treatment responders but showed no change in low responders. Script-associated cortisol response prior to treatment and reductions in thoughts of incompetence accounted for 83% of the variance in reductions in PTSD severity with PE.Conclusions Both increased cortisol response to personal trauma script prior to PTSD therapy and reductions in cognitive symptoms of PTSD were significantly and uniquely related to reductions in the core symptoms of PTSD in PE. However, contrary to our hypotheses, cortisol measures were not related to cognitive changes.
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The identification of biomarkers for post-traumatic stress disorder (PTSD) and resilience/recovery is critical for advancing knowledge about pathophysiology and treatment in trauma-exposed persons. This study examined a series of glucocorticoid-related biomarkers prior to and in response to psychotherapy. Fifty-two male and female veterans with PTSD were randomized 2 : 1 to receive either prolonged exposure (PE) therapy or a weekly minimal attention (MA) intervention for 12 consecutive weeks. Psychological and biological assessments were obtained prior to and following treatment and after a 12-week naturalistic follow-up. Response was defined dichotomously as no longer meeting criteria for PTSD at post-treatment based on the Clinician Administered PTSD Scale for DSM-IV (CAPS). Clinical improvement on the CAPS was apparent for both PE and MA, with no significant difference according to treatment condition. Biomarkers predictive of treatment gains included the BCLI polymorphism of the glucocorticoid receptor gene. Additional predictors of treatment response were higher bedtime salivary cortisol and 24 h urinary cortisol excretion. Pre-treatment plasma dehydroepiandrosterone/cortisol ratio and neuropetide Y (NPY) levels were predictors of reductions in PTSD symptoms, and, for NPY only, of other secondary outcomes as well, including anxiety and depression ratings. Glucocorticoid sensitivity changed in association with symptom change, reflecting clinical state. It is possible to distinguish prognostic and state biomarkers of PTSD using a longitudinal approach in the context of treatment. Identified markers may also be relevant to understanding mechanisms of action of symptom reduction.