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J Clin Psychiatry 68:0, Month 2007
EMDR, Fluoxetine, and Placebo in PTSD
1
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xposure to traumatic experiences is ubiquitous in
our society: 60% of men and 51% of women in the
A Randomized Clinical Trial of
Eye Movement Desensitization and
Reprocessing (EMDR), Fluoxetine, and Pill Placebo
in the Treatment of Posttraumatic Stress Disorder:
Treatment Effects and Long-Term Maintenance
Bessel A. van der Kolk, M.D.; Joseph Spinazzola, Ph.D.;
Margaret E. Blaustein, Ph.D.; James W. Hopper, Ph.D.; Elizabeth K. Hopper, Ph.D.;
Deborah L. Korn, Psy.D.; and William B. Simpson, Ph.D.
Objective: The relative short-term efficacy and
long-term benefits of pharmacologic versus psycho-
therapeutic interventions have not been studied for
posttraumatic stress disorder (PTSD). This study
compared the efficacy of a selective serotonin reup-
take inhibitor (SSRI), fluoxetine, with a psychothera-
peutic treatment, eye movement desensitization and
reprocessing (EMDR), and pill placebo and measured
maintenance of treatment gains at 6-month follow-up.
Method: Eighty-eight PTSD subjects diagnosed
according to DSM-IV criteria were randomly as-
signed to EMDR, fluoxetine, or pill placebo. They
received 8 weeks of treatment and were assessed by
blind raters posttreatment and at 6-month follow-up.
The primary outcome measure was the Clinician-
Administered PTSD Scale, DSM-IV version, and
the secondary outcome measure was the Beck De-
pression Inventory-II. The study ran from July 2000
through July 2003.
Results: The psychotherapy intervention was
more successful than pharmacotherapy in achieving
sustained reductions in PTSD and depression symp-
toms, but this benefit accrued primarily for adult-
onset trauma survivors. At 6-month follow-up, 75.0%
of adult-onset versus 33.3% of child-onset trauma
subjects receiving EMDR achieved asymptomatic
end-state functioning compared with none in the
fluoxetine group. For most childhood-onset trauma
patients, neither treatment produced complete symp-
tom remission.
Conclusions: This study supports the efficacy
of brief EMDR treatment to produce substantial
and sustained reduction of PTSD and depression
in most victims of adult-onset trauma. It suggests a
role for SSRIs as a reliable first-line intervention to
achieve moderate symptom relief for adult victims of
childhood-onset trauma. Future research should as-
sess the impact of lengthier intervention, combination
treatments, and treatment sequencing on the resolu-
tion of PTSD in adults with childhood-onset trauma.
(J Clin Psychiatry 2007;68:00–00)
Received May 27, 2005; accepted May 25, 2006. From the Trauma
Center, Justice Resource Institute, Brookline (all authors); the Boston
University School of Medicine, Boston (Drs. van der Kolk, Spinazzola,
Blaustein, and E. Hopper); McLean Hospital, Belmont (Dr. J. Hopper);
and Boston Research Associates, Boston (Dr. Simpson), Mass.
Supported by grant R01MH58363 from the National Institute
of Mental Health.
Presented at the 19th annual meeting of the International Society
for Traumatic Stress Studies, October 29–November 1, 2003, Chicago,
Ill., and at the 157th annual meeting of the American Psychiatric
Association, May 1–6, 2004, New York, N.Y.
Dr. Korn has served on the speakers or advisory boards for and
received honoraria from the EMDR International Association and
the EMDR Institute, Inc. Drs. van der Kolk, Spinazzola, Blaustein,
J. Hopper, E. Hopper, and Simpson report no additional financial
affiliations or other relationships relevant to the subject of this article.
Acknowledgments appear at the end of this article.
Corresponding author and reprints: Bessel van der Kolk, M.D.,
Trauma Center, 1269 Beacon St., Brookline, MA 02446
(e-mail: bvanderk@aol.com).
E
general population report at least 1 traumatic event in
their lives.1 For men, combat and witnessing injury or
death are the most frequent precipitants for developing
posttraumatic stress disorder (PTSD), while for adult
women, physical attacks by intimate partners is the most
frequent cause. Approximately 9.8 million adult Ameri-
can women (10.3%) have histories of violent physical
assaults, and 12.1 million (12.7%) have experienced a
completed rape at some point in their lives.2 More than
twice as many women report histories of childhood sexual
abuse than of adult rape,3 which occurs in approximately
10% of the general population.1 Childhood sexual abuse
is a strong predictor of subsequent PTSD.4,5 More than
20% of returning veterans from Iraq are currently seeking
mental health services.6
A variety of psychotherapeutic approaches to PTSD,
all involving some form of exposure and “trauma process-
ing,” have been shown to be effective (e.g., see references
7–10). Pharmacologic agents, in particular the selective
serotonin reuptake inhibitors (SSRIs), have also been
2J Clin Psychiatry 68:0, Month 2007
van der Kolk et al.
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shown to be effective in civilians with PTSD, but less so in
veterans (e.g., see references 11–15). However, no study
has directly compared the efficacy of psychotherapeutic
versus pharmacologic interventions.
The relative efficacy of biological versus psychothera-
peutic interventions is an issue of great clinical and eco-
nomic relevance. Comparative studies have been done in
panic disorder,16–18 obsessive-compulsive disorder,19,20 and
depression.21,22 Most studies in those disorders conclude
that cognitive-behavioral therapy (CBT) and pharmaco-
therapy are roughly equivalent, but there continues to be
considerable controversy about the interpretation of the
data.23,24
A recent meta-analysis of a large depression sample25
found that “among those with a history of early childhood
trauma (physical or sexual abuse, neglect, or loss of par-
ents at an early age), psychotherapy alone was superior
to antidepressant monotherapy.”(p14293) Treatment with psy-
chotherapy resulted in twice the rate of remission in
patients with major depression who also had histories of
serious early adverse life events than did treatment with
antidepressants. Surprisingly, the prevalence of PTSD was
not ascertained in that sample. Given the high rate of
PTSD comorbidity with depression,1–4 the PTSD outcome
literature may make an important contribution to effective
treatment of this population.
Research suggests that PTSD patients are more respon-
sive to treatments that specifically “process” traumatic
memories than to either supportive counseling or stress
inoculation training.8 In 1 meta-analysis of 61 treatment
outcome trials for PTSD (including drug therapies, CBT,
eye movement desensitization and reprocessing [EMDR],
relaxation training, hypnotherapy, and dynamic therapy),
psychological therapies were more effective than drug
therapies, and both were more effective than controls.26
Psychological therapies had lower dropout rates than phar-
macotherapies (14% vs. 32%). Among the psychological
approaches, CBT and EMDR were the most effective,
with no demonstrable differences in treatment efficacy.
Among the drug therapies, the SSRIs had the greatest ef-
fect sizes. Another effect-size analysis of 14 treatment out-
come studies27 found that the drug therapies with the larg-
est effect sizes were fluoxetine and amitriptyline.
The present study directly compared the efficacy of a
psychopharmacologic agent, fluoxetine, with a psycho-
therapeutic, exposure-based treatment, EMDR, and a pill
placebo in PTSD. EMDR is an exposure treatment in
which patients perform saccadic eye movements while
thinking about a traumatic experience. Rather than pro-
viding a chronological narrative of the details of the trau-
matic event, as is done in CBT, EMDR patients are
encouraged to follow their own course, moving freely
backward and forward in time, attending to inner sen-
sations and cognitions, omitting verbal communication
about content if they wish. EMDR has been declared an
effective evidence-based treatment for PTSD in the profes-
sional treatment guidelines of the U.S. Department of De-
fense,28 the American Psychological Association,29 and the
American Psychiatric Association.30
Comparing the relative effectiveness of pharmacother-
apy versus exposure therapy is particularly relevant in the
treatment of PTSD, since the SSRIs are widely used to
treat PTSD, particularly in primary care and health mainte-
nance organization (HMO) settings, where little attention
may be paid to helping patients “process” their traumas.
This is reasonable as long as the question has not been
settled whether pharmacotherapy produces better or worse
results than the active processing of traumatic memories
(which many patients are reluctant to do because of want-
ing to avoid being reminded of their trauma).31 Our study
was particularly concerned with the effects of these vari-
ous treatments on clinical symptomatology over time.
METHOD
Participants
Following institutional review board approval, individ-
uals 18 to 65 years old, with current PTSD and with mixed
trauma exposure at least 1 year prior to intake, were re-
cruited via newspaper ads, the Internet, and solicitation
from medical and mental health professionals. The study
ran from July 2000 through July 2003. A total of 229 par-
ticipants were assessed at pretreatment after giving written
informed consent. Of these, 88 (38%) met study inclusion
criteria and were randomly assigned to treatment. Of the
remainder, 47 (21%) failed to meet DSM-IV diagnostic
criteria for PTSD, 30 (13%) withdrew consent prior to
randomization, and 64 (28%) met study exclusionary crite-
ria. Baseline participant information is contained in Table
1. Trauma history was obtained by self-report. The pre-
dominant index trauma involved interpersonal victimiza-
tion (71.6%); in 50% of participants, trauma onset oc-
curred prior to age 18 (Table 2).
Exclusion criteria were unstable medical condition,
contraindications to either treatment (i.e., pregnancy, glau-
coma or detached retina, or history of severe allergies or
multiple adverse drug reactions), inability to be weaned
off current psychotropic medications, psychotic or bipolar
disorder, current alcohol or substance abuse/dependence,
severe dissociation, active suicidality or life-threatening
mutilation, prior exposure to active study interventions,
concurrent trauma-focused treatment, unstable living situ-
ation, Global Assessment of Functioning32 score < 40, and
disability compensation for PTSD or pending trauma-
related lawsuit. Initial telephone screening was used to as-
sess likely presence/absence of inclusion and exclusion
criteria; potential participants were then invited for in-
person assessment. Participants were not excluded for
engagement in nontrauma-focused, supportive psycho-
therapy, provided this treatment had been ongoing for
J Clin Psychiatry 68:0, Month 2007
EMDR, Fluoxetine, and Placebo in PTSD
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at least 3 months prior to study baseline and did not in-
volve exposure to or processing of traumatic memories. A
detailed report of screening attrition and exclusion data is
available.33
Measures
Clinician-Administered PTSD Scale (CAPS), DSM-IV
Version.34 The CAPS total score was the primary
continuous outcome measure as an index of PTSD symp-
tom severity. Rating was based on a 1-week interval for
immediate pretreatment and posttreatment assessment;
a 1-month interval was used at baseline and 6-month
follow-up. Results are also presented on PTSD diagnostic
status, defined as full DSM-IV diagnostic criteria and
using the following CAPS scoring rules: (1) total severity
score > 50, (2) per-item frequency of at least 1 and inten-
sity of at least 2, and (3) per-item total severity score of
at least 4.35 Asymptomatic end-state function (i.e., PTSD
symptom remission), defined as CAPS score < 20, is also
reported.36
Structured Clinical Interview for DSM-IV Axis I and
Axis II Disorders (SCID I37 and SCID II38). This struc-
tured interview was used for determination of PTSD and
comorbid diagnoses.
Beck Depression Inventory-II (BDI-II).39 This widely
used and psychometrically sound self-report measure of
depressive symptoms was used to assess secondary study
hypotheses regarding the immediate and long-term effi-
cacy of pharmacologic versus psychological interventions
on amelioration of depressive symptoms in traumatized
individuals with PTSD.
Procedure
Assessment. Assessments were conducted at pretreat-
ment, posttreatment, and 6 months following treatment
cessation. Assessment included interview and self-report
measures, as well as psychophysiologic response to script-
driven imagery. This was a modified version of the proto-
col adapted by Pitman and colleagues40 for use with
PTSD, consisting of a series of 30-second, audio-taped
scripts in second-person, present-tense narrative, based on
participants’ recounting of the worst memory associated
with the trauma, as well as a neutral memory from the
same time period. Modifications involved use of 2 alter-
nating sets of neutral and traumatic scripts. Physiologic
responses to script-driven imagery before and after treat-
ment will be reported elsewhere.
Evaluators were primarily postdoctoral-level clinicians
who received extensive training and ongoing supervision
in administration of study measures. Interrater reliability
on the CAPS was established prior to the start of the study,
based on coding of live and videotaped interviews, and re-
assessed at regular intervals to avoid rater drift. Interrater
reliability for PTSD diagnosis, based on Cohen’s kappa,
was very good (κ=0.82, percent agreement = 0.92).
Interrater reliability for PTSD symptom severity was
excellent (intraclass correlation coefficient = 0.96). All
raters were blind to treatment condition and were never
assigned the same participant for both pretreatment and
posttreatment evaluation.
Table 2. Index Trauma Distribution (N = 88)
Index Trauma N (%)
Child sexual abuse 25 (28.4)
Child physical abuse 4 (4.5)
Child sexual and physical abuse 8 (9.1)
Adult sexual assault 8 (9.1)
Adult physical assault 5 (5.7)
Domestic violence 7 (8.0)
Other adult victimization 6 (6.8)
Traumatic loss 8 (9.1)
War/terrorism/violence 3 (3.4)
Injury/accident 14 (15.9)
Table 1. Baseline Analyses of Demographic Variables and Comorbid Diagnoses by Treatment Group
EMDR Fluoxetine Placebo Totala
Variable (N = 29) (N = 30) (N = 29) (N = 88) p Valueb
Female, % 75.9 86.7 86.2 83.0 .46
Age, mean (SD), y 38.7 (14.3) 34.1 (12.4) 35.7 (13.4) 36.1 (13.4) .41
White, % 69.0 63.3 69.0 67.0 .87
Unemployed, % 25.0 16.7 25.0 22.1 .67
College graduate, % 51.7 56.7 44.8 51.1 .66
Never married, % 82.8 86.7 86.2 85.2 .90
Concurrent supportive therapy, % 13.8 13.3 20.7 15.9 .69
Years since index trauma, mean (SD) 12.2 (13.7) 12.8 (11.2) 13.8 (10.9) 12.9 (11.9) .87
CAPS total score, 1 month, mean (SD) 71.7 (11.9) 75.9 (15.6) 74.5 (12.5) 74.0 (13.4) .48
CAPS total score, 1 week, mean (SD) 69.4 (12.7) 73.7 (13.4) 70.3 (13.0) 71.2 (13.0) .42
BDI-II total score, mean (SD) 16.2 (9.5) 18.2 (9.2) 20.7 (9.7) 18.3 (9.6) .20
No. of current comorbid Axis I/II diagnoses, mean (SD)c3.1 (3.4) 3.2 (2.4) 3.2 (2.4) 3.2 (2.7) .99
aTotal of all 3 treatments combined.
bUsed omnibus analysis of variance for continuous measures or Pearson χ2 statistic for categorical measures.
cAssessed using Structured Clinical Interview for DSM-IV Disorders.37,38
Abbreviations: BDI-II = Beck Depression Inventory-II, CAPS = Clinician-Administered PTSD Scale, EMDR = eye movement
desensitization and reprocessing, PTSD = posttraumatic stress disorder.
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Treatment. Participants were randomly assigned to 1
of 3 treatment conditions: EMDR, fluoxetine, or pill pla-
cebo. Randomization was stratified by presence/absence
of concurrent supportive psychotherapy. In order to ensure
approximately equal numbers in each treatment condition,
random assignment was blocked in groups of 12 consecu-
tive participants, so that in each block, 4 participants were
assigned to each condition. Participants in all 3 conditions
received a total of 8 weekly treatment sessions. Following
cessation of treatment, participants in the 2 active treat-
ment conditions were asked to refrain from initiating new
treatment during the 6-month follow-up period. The blind
was removed from the placebo intervention following the
posttreatment assessment, and, for ethical reasons, partici-
pants were offered the option of receiving either of the 2
active treatments. Consequently, placebo group data were
not included in follow-up analyses.
EMDR. EMDR treatment consisted of 90-minute indi-
vidual sessions. The treatment targeted memories associ-
ated with the primary trauma identified during pretreat-
ment evaluation. Treatment was administered according
to a manual developed for this study,41 based on the stan-
dard protocol.42 The 4 clinicians in the EMDR condition
were at master’s level or above, with Level II EMDR
training. They were licensed in their profession and had
a minimum of 3 years’ experience treating patients with
PTSD. Clinicians received extensive training and bi-
weekly supervision in the manualized protocol established
for the study from a certified senior EMDR instructor
(D.L.K.). An average of 6 EMDR sessions were devoted
to trauma processing. All EMDR sessions were video-
taped, and an independent evaluator assessed treatment
fidelity through videotape review from randomly sampled
sessions.
Medication. Medication treatment consisted of 20- to
30-minute individual sessions. The fluoxetine and placebo
interventions were administered in a double-blind, fixed-
flexible-dose design according to standard protocol for
double-blind pharmacologic interventions for PTSD.12–15
This study employed a manualized pharmacotherapy pro-
tocol developed and empirically supported for interven-
tion with fluoxetine.11,12 The treatment manual included
instructions for monitoring of adverse effects and compli-
ance with prescribed dosage, tracking of PTSD symptom
change, and ongoing assessment of mental status. Starting
dosage was 10 mg/day of fluoxetine (or pill placebo
equivalent). Dosage was increased in 10-mg increments
per week to a maximum of 60 mg/day, or until symptom
remission was achieved. Increases or decreases in dosage
were based on physician judgment of clinical response
and presence/absence of dose-limiting side effects. Mean
fluoxetine dose across clients/sessions was 30 mg; 19 of
26 fluoxetine-condition completers received 30 mg or
greater for the last 4 weeks of treatment. The modal fluox-
etine dose at end of treatment was 40 mg. The drug was
discontinued over a 10-day period following the 8-week
intervention period. Pharmacotherapists were licensed
psychiatrists (fourth-year residents and above) who re-
ceived extensive training on the study protocol and re-
ceived weekly supervision by the principal investigator.
Statistical Analyses
The study was designed to evaluate whether both
fluoxetine and EMDR perform equally well, and better
than placebo, after 8 weeks of treatment of PTSD and
whether EMDR differs from fluoxetine in maintaining
treatment gains over time. Secondary hypotheses ad-
dressed the impact of child- versus adult-onset trauma on
treatment outcome. The impact of treatment on depressive
symptoms was also assessed.
Study hypotheses were tested on both treatment com-
pleter and intent-to-treat (ITT) samples. Intent-to-treat
analyses were conducted using an early termination as-
sessment, when available, or a last-observation-carried-
forward (LOCF) procedure to impute missing data. Long-
term effects of active-treatment completers were assessed
at 6 months posttreatment for both follow-up completer
and intent-to-follow (ITF) samples. For the ITF sample,
missing follow-up data were also estimated using LOCF.
Baseline group differences were assessed using anal-
ysis of variance for continuous measures and Pearson χ2
statistic for categorical measures. To minimize bias, post-
treatment continuous-measure analyses were conducted
using omnibus analysis of covariance (ANCOVA) with
baseline as the covariate.43,44 These were followed by pair-
wise comparisons using 2-group ANCOVA. Baseline by
treatment-condition interactions were tested for all pri-
mary outcome analyses. No significant interactions were
found. Therefore, interaction terms were dropped from
further analyses. Follow-up analyses were conducted on
the 2 active treatments. Analyses of continuous variables
used ANCOVA, controlling for baseline score. Posttreat-
ment and follow-up categorical outcomes (i.e., PTSD
diagnosis and end-state function) were evaluated using
the Pearson χ2 statistic. Within-group and between-group
effect sizes were calculated using Cohen’s d statistic on
the primary outcome measure (i.e., CAPS total score) at
posttreatment and at 6-month follow-up.
RESULTS
Preliminary Analyses
Baseline group differences. Participants in the 3 treat-
ment conditions did not differ significantly on any demo-
graphic variable or on any baseline measure of psycho-
pathology (Table 1).
Treatment dropout. Twelve people dropped out during
the 8-week treatment phase, leaving 76 treatment com-
pleters. There were no significant differences in dropout
rates on any baseline measure of psychopathology or
J Clin Psychiatry 68:0, Month 2007
EMDR, Fluoxetine, and Placebo in PTSD
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across treatment conditions. Completers in each group
were 24 of 29 (83%) for EMDR, 26 of 30 (87%) for flu-
oxetine, and 26 of 29 (90%) for pill placebo. Dropouts
were significantly younger than completers (dropout
mean age = 27.1 years, completer mean age = 37.6 years;
F=6.785, df = 1,86; p < .05). In addition, dropouts were
more likely to have had child- versus adult-onset trauma
(χ2=6.175, df = 1,88; p = .013).
Clinician effects. Potential clinician-specific effects
were examined in 3 one-way ANCOVAs on posttreatment
CAPS total score for the ITT sample, controlling for base-
line symptom severity. Chi-square analyses were used to
compare dropout rates by clinician. Six clinicians had
each treated 5 or fewer participants and were combined
within treatment condition for comparison with the re-
maining clinicians. No significant differences were found
by clinician in posttreatment scores or dropout rates.
Concurrent supportive psychotherapy. Potential im-
pact of concurrent supportive psychotherapy at the time
of randomization was examined in the same manner for
both treatment completers and ITT sample. No significant
main or interactive effects of concurrent treatment were
found.
Treatment expectations. No group differences were
found on baseline treatment expectations for participants
randomly assigned to medication condition versus psy-
chotherapy condition, nor were any significant interac-
tions found between treatment group and expectations on
study outcome. A positive main effect of baseline treat-
ment expectations on PTSD symptom reduction at post-
treatment was observed (F = 5.8, df = 1,84; p = .018).
Postintervention treatment seeking. After cessation of
the study intervention, 4 participants (2 EMDR, 2 fluoxe-
tine) initiated nonstudy treatments. To assess the potential
impact on 6-month follow-up findings, a second set of
analyses was run in which data from these participants
were extracted (completer analyses) or carried forward
from last data point preceding onset of new treatment
(ITF analyses). Analyses revealed no changes in direction
or significance level of findings. Thus, reported findings
retain data from these participants.
Clinician treatment adherence. Videotapes of 24
EMDR sessions (over 10% of 210 total study sessions)
were randomly selected for independent fidelity rating,
with oversampling to ensure distribution across clinicians
and session type. Fifty components across the 8 phases
of treatment were included in the fidelity manual devel-
oped for this protocol. The evaluator was an experienced,
independent, certified EMDR clinician who was not per-
sonally known to the study investigators. The evaluator
reviewed videotapes and rated adherence according to a
4-point Likert-type scale: 0 = no adherence, 1 = some
adherence, 2 = adherence acceptable, and 3 = adherence
very good. The mean fidelity score across sessions was
2.57 (SD = 0.35; minimum = 1.76, maximum = 3.00).
Adherence to the pharmacotherapy protocol and dosing
schedule was monitored through weekly case review and
supervision of study pharmacotherapists.
Primary Analyses
Means and standard deviations for all primary and sec-
ondary outcome measures are reported in Table 3. At post-
treatment, the drop in total CAPS score was 59.0% for
EMDR, 46.0% for fluoxetine, and 43.6% for placebo, as
compared with 1-week pretreatment baseline assessment.
At 6-month follow-up, the CAPS total score drop was
62.2% for EMDR and 48.3% for fluoxetine.
Notably, omnibus ANCOVA analyses (ITT and compl-
eter) of the 3-condition model failed to reveal a significant
effect of treatment on the primary outcome measures.
While common practice is to refrain from further analyses
when the omnibus analyses reveal negative findings, be-
cause our study hypotheses emphasize 2-group outcomes
over omnibus outcomes, and in light of the absence of an
appropriate control group for the psychotherapy condi-
tion, pairwise comparisons of the 3 conditions were con-
ducted and their results reported below.
EMDR versus placebo. The posttreatment ITT (LOCF)
analyses revealed nonsignificant trends for greater remis-
sion of PTSD in individuals receiving EMDR versus pla-
cebo. In the completer analyses, EMDR was significantly
superior to placebo on reduction of PTSD symptoms and
showed a greater percentage of loss of diagnostic status
compared with placebo (Table 3).
Fluoxetine versus placebo. Neither posttreatment ITT
nor completer analyses revealed significant differences
between fluoxetine and placebo on any outcome measure
(Table 3). The majority of both fluoxetine and placebo
participants demonstrated loss of PTSD diagnosis;
however, few participants achieved full remission of
symptoms.
EMDR versus fluoxetine. As hypothesized, at post-
treatment, the 2 active treatments did not differ on mea-
sures of PTSD (Table 3). At 6-month follow-up, EMDR
was superior to fluoxetine on sustained reduction of post-
traumatic symptoms (Table 3) for both ITF (LOCF) and
completer analyses. EMDR was superior to fluoxetine in
attaining complete remission of symptoms at 6 months
posttreatment: 58% of EMDR subjects were asympto-
matic, compared with none in the fluoxetine group.
EMDR was also superior to fluoxetine in reduction of
self-reported depressive symptoms for both the ITF and
completer samples.
Secondary Analyses:
Impact of Trauma Onset on Treatment Outcome
In order to account for the potential impact of index
trauma onset on treatment outcome, ANCOVA analyses
were rerun for continuous outcomes with a dummy-coded
onset variable. Main and interactive effects for onset and
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treatment condition were entered into the model. “Child
onset” was defined as onset of index trauma prior to age
18; “adult onset” was defined as index trauma onset at
or after age 18. Diagnosis and asymptomatic end-state
function were examined by onset and treatment condi-
tion using χ2 analysis. Descriptives by treatment con-
dition and trauma onset are reported in Table 4.
Baseline. Equivalent numbers of patients with child-
onset (N = 45) and adult-onset (N = 43) index traumas
were randomly assigned to treatment. Treatment con-
ditions did not differ in distribution of patients by onset
(child onset: EMDR, N = 15 [51.7%]; fluoxetine, N = 13
[43.3%]; placebo, N = 17 [58.6%]). At baseline, patients
with child-onset trauma demonstrated significantly
higher PTSD symptoms on 1-month CAPS than patients
with adult-onset trauma (child onset: mean = 77.71
[SD = 13.04]; adult onset: mean = 70.26 [SD = 12.87];
F=7.281, df = 1,86; p < .01); this dropped to a trend for
1-week CAPS (child onset: mean = 73.49 [SD = 12.99];
adult onset: mean = 68.74 [SD = 12.74]; F = 2.989,
df = 1,86; p < .10).
CAPS total score. For both posttreatment and follow-
up analyses, main effects for treatment as reported above
were retained at similar levels of significance with the
addition of the index trauma onset variable. No onset-by-
treatment-condition interaction effects were observed at
any time point. Onset was found to make additional con-
tributions to outcome, as follows: immediately posttreat-
ment, across treatment conditions, patients with adult-
onset trauma showed significantly greater reduction in
PTSD symptoms than those with child-onset trauma, for
both ITT (p < .005) and completer (p = .02) samples.
These effects were maintained at 6-month follow-up (ITT,
p=.011; completer, p = .027).
The EMDR and placebo groups demonstrated larger
effect sizes for adult- than for child-onset trauma, whereas
fluoxetine exhibited the opposite pattern (Table 5).
PTSD diagnosis and asymptomatic end-state func-
tion. At posttreatment, differential effects were found by
onset of the index trauma (Table 4). Chi-square analyses
revealed that adult-onset patients were significantly more
likely to both lose PTSD diagnosis (ITT, p = .052) and
achieve asymptomatic end-state function (ITT, p = .037)
than child-onset patients (Figure 1). When probed by
treatment condition, these differential effects were found
to occur only within the EMDR condition.
At 6-month follow-up, χ2 analyses revealed that within
the EMDR group, adult-onset patients were more likely to
Table 3. Posttreatment and Follow-up Analyses for Primary and Secondary Outcome Measures by Sample and
Treatment Condition
2-Group Comparisonsa,b
EMDR vs EMDR vs Fluoxetine
Analysis EMDR Fluoxetine Placebo Totalcp Valueb,d,e Fluoxetine Placebo vs Placebo
Completers N = 24 N = 26 N = 26 N = 76
CAPS total score, mean (SD) 28.37 (19.66) 38.69 (20.30) 39.81 (18.76) 35.82 (19.98) .09* .27 .03* .67
Loss of PTSD diagnosis, % 88 81 65 78 .15 .52 .07* .21
Asymptomatic, %f29 15 12 18 .24 .24 .12 .69
BDI-II total score, mean (SD) 9.21 (6.44) 12.42 (8.08) 12.38 (6.65) 11.39 (7.18) .24 .12 .16 .72
Intent-to-treat (ITT) N = 29 N = 30 N = 29 N = 88
CAPS total score, mean (SD) 32.55 (22.50) 42.67 (22.11) 43.55 (22.60) 39.63 (22.70) .16 .13 .07* .61
Loss of PTSD diagnosis, % 76 73 59 69 .31 .82 .16 .23
Asymptomatic, %f28 13 10 17 .17 .17 .09* .72
BDI-II total score, mean (SD) 9.10 (6.02) 13.00 (8.66) 14.38 (9.74) 12.17 (8.50) .16 .08* .07* .94
Follow-up completers N = 21 N = 18 N = 39
CAPS total score, mean (SD) 25.67 (21.17) 41.22 (15.70) NA 32.85 (20.19) .05*
Loss of PTSD diagnosis, % 91 72 NA 82 .14
Asymptomatic, %f57 0 NA 31 <.001*
BDI-II total score, mean (SD) 5.24 (5.37) 12.94 (7.68) NA 8.80 (7.53) .002*
Intent-to-follow (ITF)gN=24 N=26 N = 50
CAPS total score, mean (SD) 25.79 (21.61) 42.12 (15.83) NA 34.28 (20.37) .005*
Loss of PTSD diagnosis, % 88 73 NA 80 .20
Asymptomatic, %f58 0 NA 28 <.001*
BDI-II total score, mean (SD) 5.25 (5.23) 14.00 (7.71) NA 9.80 (7.92) <.001*
aNumbers represent p values for pairwise comparisons of continuous and categorical measures.
bResults at trend level or greater are indicated by an asterisk (*); p values significant at ≤.05 are indicated with boldface.
cTotal of all 3 treatments combined.
dOmnibus analysis of continuous measures used analysis of covariance with baseline as covariate; Pearson χ2 statistic was used for
categorical measures.
eAt posttreatment, p value is for 3-group comparison; at follow-up, p value is for 2-group (active treatment) comparison.
fDefined as CAPS total score below 20.
gAll active treatment completers are included in intent-to-follow analyses.
Abbreviations: BDI-II = Beck Depression Inventory-II, CAPS = Clinician-Administered PTSD Scale, EMDR = eye movement desensitization and
reprocessing, NA = not applicable, PTSD = posttraumatic stress disorder.
J Clin Psychiatry 68:0, Month 2007
EMDR, Fluoxetine, and Placebo in PTSD
7
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achieve loss of PTSD diagnosis and achieve asympto-
matic end state (ITF, p = .045) than those with childhood-
onset trauma. None of the fluoxetine participants
achieved asymptomatic end-state function, regardless of
age of trauma (Figure 1). EMDR patients sustained high
rates of loss of diagnosis at 6-month follow-up, regardless
of age of trauma, while fluoxetine adult-onset patients
were significantly more likely to lose PTSD diagnosis
than fluoxetine child-onset patients (ITF, p = .036).
DISCUSSION
In this 8-week study that compared an exposure-based
psychotherapeutic treatment of PTSD (EMDR) with a
pharmacologic treatment (fluoxetine) and pill placebo,
participants in all 3 groups sustained considerable im-
provement. Eighty-eight percent of EMDR, 81% of fluox-
etine, and 65% of placebo completers lost their PTSD
diagnosis, and 29% of EMDR, 15% of fluoxetine, and
12% of placebo completers became asymptomatic (CAPS
scores under 20). Over the 6 months following the cessa-
Table 4. Posttreatment and Follow-Up Completer Descriptives by Treatment Condition and
Trauma Onset
Analysis EMDR Fluoxetine Placebo Totala
Posttreatment
Child-onset N = 11 N = 10 N = 14 N = 35
CAPS total score, mean (SD) 38.36 (20.73) 40.20 (14.33) 46.57 (20.18) 42.17 (18.72)
Loss of PTSD diagnosis, % 72.7 90.0 57.1 71.4
Asymptomatic, %b9.1 10.0 7.1 8.6
Adult-onset N = 13 N = 16 N = 12 N = 41
CAPS total score, mean (SD) 19.92 (14.64) 37.75 (23.69) 31.92 (13.87) 30.39 (18.72)
Loss of PTSD diagnosis, % 100.0 75.0 75.0 82.9
Asymptomatic, %b46.2 18.8 16.7 26.8
Follow-up
Child-onset N = 9 N = 7 N = 16
CAPS total score, mean (SD) 33.00 (22.34) 50.43 (8.24) N/A 40.63 (19.31)
Loss of PTSD diagnosis, % 88.9 42.9 N/A 68.8
Asymptomatic, %b33.3 0.0 N/A 18.8
Adult-onset N = 12 N = 11 N = 23
CAPS total score, mean (SD) 20.17 (19.36) 35.36 (16.76) N/A 27.43 (19.37)
Loss of PTSD diagnosis, % 91.7 90.9 N/A 91.3
Asymptomatic, %b75.0 0.0 N/A 39.1
aTotal of all 3 treatments combined.
bDefined as CAPS total score below 20.
Abbreviations: CAPS = Clinician-Administered PTSD Scale, EMDR = eye movement desensitization and
reprocessing, NA = not applicable, PTSD = posttraumatic stress disorder.
Table 5. Effect Sizes for Primary Outcome Measure (CAPS
total score) by Sample
Between-Group Effect Sizea
EMDR vs EMDR vs Fluoxetine
Analysis Fluoxetine Placebo vs Placebo
Treatment completers
Full group 0.35 0.58 0.18
Child-onset trauma 0.00 0.20 0.19
Adult-onset trauma 0.68 1.02 0.13
Intent-to-treat (ITT)
Full group 0.24 0.45 0.19
Child-onset trauma –0.01 0.24 0.25
Adult-onset trauma 0.56 0.71 0.02
Follow-up completers
Full group 0.17 NA NA
Child-onset trauma 0.09 NA NA
Adult-onset trauma 0.25 NA NA
Intent-to-follow (ITF)
Full group 0.54 NA NA
Child-onset trauma 0.47 NA NA
Adult-onset trauma 0.65 NA NA
aPositive between-group effect sizes favor first treatment condition
over second; negative between-group effect sizes favor second
treatment condition over first.
Abbreviations: CAPS = Clinician-Administered PTSD Scale,
EMDR = eye movement desensitization and reprocessing, NA = not
applicable, PTSD = posttraumatic stress disorder.
Figure 1. Asymptomatic End-State Function (CAPS
score < 20) by Treatment Type and Index Trauma Onset
aAt 6-month follow-up, none of the fluoxetine participants achieved
asymptomatic end-state function.
Abbreviations: CAPS = Clinician-Administered PTSD Scale,
EMDR = eye movement desensitization and reprocessing,
PTSD = posttraumatic stress disorder.
80
70
60
50
40
30
20
10
0
Percent
Child Adult AdultChild
EMDR Fluoxetine
a
Posttreatment
6-Month Follow-Up
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van der Kolk et al.
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tion of treatment, the EMDR group continued to mildly
improve, while the fluoxetine group lost some of its gains:
at follow-up, 57% of EMDR completers were asympto-
matic, compared with none of the fluoxetine group.
In this study, every treatment group improved substan-
tially: undergoing routine study procedures on a weekly
basis seemed to have beneficial effects on most partici-
pants, regardless of treatment condition. A positive re-
sponse to study participation is common in PTSD drug
treatment studies: participating in a study generally ac-
counts for more of the variance than the particular treat-
ment received (e.g., see references 12, 14, 15). Post-
traumatic stress disorder has been shown to be quite
responsive to pill placebo on the order of a 35% to 40%
improvement over baseline.45 There has been considerable
debate whether thorough weekly assessments themselves
entail sufficient exposure therapy to make a clinically
significant difference.45–47 The magnitude of the placebo
response in PTSD suggests that claims of treatment effi-
cacy of any particular method need to be based on com-
parisons with a placebo or inert-treatment group rather
than a wait-list control.
The effect size of the pill-placebo group in this study
was larger than that of any other placebo groups in the
PTSD treatment outcome literature—in fact, larger than
that of several active treatments that claim efficacy com-
pared with wait-list control groups. In order to study
changes in psychophysiologic reactivity among the dif-
ferent treatments, all subjects in this study were exposed
to 2 personalized trauma scripts that involved intense con-
frontation with their traumatic memories. This exposure
may have played a significant role in the positive outcome
across treatment conditions. Exposure to memories of
one’s trauma has repeatedly been identified as a critical
element in effective PTSD therapy.48,49 Exposure may also
have contributed to the large effect size in the fluoxetine
group, which was larger than those previously reported in
pharmacologic studies.27,46
The effect size of the EMDR group was comparable to
that of previous EMDR studies (e.g., see reference 50).
The EMDR responders not only maintained their treat-
ment gains after the study but continued to improve
slightly over time: at 6-month follow-up, 57% of EMDR
completers had a CAPS score below 20 (asymptomatic
end-state function), compared with none of the fluoxetine
group. It is not surprising that fluoxetine subjects lost
some of their improvement at follow-up—pharmacologic
effects cannot be expected to last over time, but the fact
that the effects of EMDR were maintained, and somewhat
improved, has important clinical and economic implica-
tions. Continued improvement after treatment cessation
has previously been reported with prolonged exposure8
and EMDR.51 This suggests that, once people deal with
their traumatic memories, they are likely to continue to
improve without further intervention.
The clinical improvement in the EMDR group at 6-
month follow-up was not confined to PTSD symptoms:
EMDR completers had significantly lower BDI-II scores
than fluoxetine completers. Once the trauma is resolved,
other domains of psychological functioning appear to im-
prove spontaneously. This may have significant implica-
tions for the treatment of depression in individuals with
comorbid PTSD.
The issue of trauma onset has not been addressed in
previous treatment outcome studies. The present study
found that participants in the EMDR condition with
adult-onset index traumas had a substantially better treat-
ment response than those with childhood-onset trauma.
Specifically, 100% of adult-onset participants lost di-
agnostic status at posttreatment, versus a significantly
lower 75% of child-onset participants. This distinction
became even more pronounced at 6-month follow-up.
Here, trauma onset significantly predicted a large dis-
tinction in end-state functioning: 75.0% of adult-onset
versus 33.3% of child-onset trauma participants receiving
EMDR were asymptomatic at 6-month follow-up (see
Figure 1). These findings support the efficacy of short-
term treatment with EMDR in the resolution of traumatic
sequelae associated with adult-onset trauma. In contrast,
for most individuals with childhood-onset trauma (all of
whom, in this study, were victims of chronic intrafamilial
physical and/or sexual abuse), 8 weeks of therapy was
not enough to resolve longstanding trauma imprints and
adaptations.
In contrast to the EMDR condition, the outcome for
participants in the fluoxetine condition did not vary as
a function of trauma onset. Whereas participants in
the fluoxetine condition exhibited a robust decrease
in PTSD symptomatology, significantly fewer were en-
tirely asymptomatic at posttreatment, and none remained
asymptomatic at 6-month follow-up. This distinction is
important, since recent research has revealed that patients
with subthreshold PTSD have similar degrees of impair-
ment in social and work functioning as those with full-
blown PTSD.52,53 This suggests that brief treatment with
an SSRI alone is insufficient to resolve posttraumatic
psychopathology for most patients with PTSD.
At 6-month follow-up, fluoxetine treatment produced
a significantly larger effect size than EMDR for the sub-
group of individuals with child-onset trauma. This was
primarily due to the smaller standard deviation within the
fluoxetine condition. Whereas EMDR participants with
child-onset trauma varied markedly in PTSD symptom-
atology at follow-up (e.g., some were completely asymp-
tomatic while others showed little progress or slight
worsening of symptoms), child-onset PTSD participants
who received fluoxetine experienced a more consistently
modestly positive response to pharmacotherapy than to
EMDR. This suggests that, while brief intervention with
fluoxetine is unlikely to resolve PTSD for adults with
J Clin Psychiatry 68:0, Month 2007
EMDR, Fluoxetine, and Placebo in PTSD
9
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child-onset trauma, it provides moderate symptom reduc-
tion, with little risk of symptom exacerbation.
In this study, fluoxetine did not do better than placebo,
not because participants receiving fluoxetine did not im-
prove but because the placebo response in this study was
so robust. Recent studies have shown that patients who
receive prolonged treatment with an SSRI (beyond the
customary 8- to 12-week studies) are likely to experience
a gradual decrease in PTSD symptomatology.54,55 In one
study,55 32 weeks of treatment with sertraline achieved an
end state comparable to that seen in the EMDR condition
in the present study. However, that long-term study did
not address the issue of whether improvement was sus-
tained after cessation of the medication.
Clearly, more data are needed to determine which
patients with chronic childhood trauma and/or multiple
comorbidities will respond best to trauma processing/
exposure-based therapies versus long-term pharmaco-
logic treatment. Studies are also needed to establish
whether there is a synergistic effect between pharmaco-
therapy and exposure therapy for PTSD, a combination
that is common in clinical practice, but whose efficacy
has not yet been documented.
CONCLUSIONS
Patients with trauma histories, PTSD, and depression
are ubiquitous in clinical practice. This study demon-
strates that the vast majority of patients with adult-onset
PTSD can recover with a short period of intense,
exposure-based treatment, with lasting positive results.
Merely paying careful attention to the patients’ symp-
toms, as was done here in the placebo condition, as well
as treating with SSRIs, can be helpful, particularly in pa-
tients with childhood-onset trauma. However, these ap-
proaches do not lead to complete symptom remission and
the benefits do not endure with time. The present study
supports the empirical literature that proposes that skilled
confrontation with traumatic memories within a safe
therapeutic setting is the treatment of choice for PTSD
with adult-onset trauma. Future research should assess
the impact of lengthier interventions, combination treat-
ments, and treatment sequencing on the resolution of
PTSD in adults with childhood-onset trauma.
Drug names: fluoxetine (Prozac and others), sertraline (Zoloft
and others).
Acknowledgments: The authors thank Jose Hidalgo, M.D.; Jeffrey
Weir, L.I.C.S.W.; Deborah Rozelle, Ph.D.; Paula Morgan-Johnson,
L.I.C.S.W.; Jelica Todosijevich, Ph.D.; Tony Luxenburg, Ph.D.; Caren
Swift, Ph.D.; Miriam Kissin, Ph.D.; Susan Rogers, Ph.D.; Kate Walsh,
Ph.D.; Elizabeth Nickrenz, M.A.; Ibrahim Dager, M.D.; Ruth Lanius,
M.D.; Terry Smith, M.D.; Isabelle Soulard, M.D.; Dan Siskind, M.D.;
Nancy Smythe, M.S.W., Ph.D.; and Richard LaDue for the administra-
tion of treatment protocols and outcome instruments or for assistance
in the data analysis. These acknowledged individuals report no con-
flicts of interest.
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