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Multicenter, Double-blind Comparison of Sertraline and Placebo in the Treatment of Posttraumatic Stress Disorder
Jonathan R. T. Davidson, MD;
Barbara O. Rothbaum, PhD;
Bessel A. van der Kolk, MD;
Carolyn R. Sikes, PhD;
Gail M. Farfel, PhD
Arch Gen Psychiatry. 2001;58:485-492.
ABSTRACT
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Background Posttraumatic stress disorder (PTSD) is a common illness associated
with significant disability. Few large, placebo-controlled trials have been
reported.
Methods Outpatients with a DSM-III-R diagnosis of moderate-to-severe
PTSD were randomized to 12 weeks of double-blind treatment with either sertraline
(N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo
(N = 108). Primary outcome measures consisted of the Clinician-Administered
PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event
Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement
(CGI-I) ratings.
Results Mixed-effects analyses found significantly steeper improvement slopes
for sertraline compared with placebo on the CAPS-2 (t
= 2.96, P = .003), the IES (t
= 2.26, P = .02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score
(t = 4.40, P<.001). An
intent-to-treat end-point analysis found a 60% responder rate for sertraline
and a 38% responder rate for placebo ( 21 = 8.48, P = .004). Sertraline treatment was well tolerated, with
a 9% discontinuation rate because of adverse events, compared with 5% for
placebo. Adverse events that were significantly more common in subjects given
sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea
(28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite
(12% vs 1%).
Conclusion The results of the current study suggest that sertraline is a safe,
well-tolerated, and significantly effective treatment for PTSD.
INTRODUCTION
SINCE ITS original diagnostic formulation in 1980, considerable research
has been conducted on posttraumatic stress disorder (PTSD). This research
has established that PTSD is common, with a lifetime prevalence in the range
of 7% to 12% and a 2:1 female-to-male ratio1, 2, 3;
chronic, with a median time-to-recovery in the range of 3 to 5 years1, 4; and has high comorbidity, with a 6-fold
increased risk, compared with community norms, of major depression, a 3-fold
increased risk of alcoholism or substance abuse, an approximately 4-fold increased
risk of panic disorder or agoraphobia, and an estimated suicide attempt rate
of approximately 20%.1, 5, 6
Posttraumatic stress disorder is also associated with significant functional
and psychosocial disability7, 8
and notable increases in physical symptoms and health care utilization.5, 9, 10, 11
Currently, it is estimated that the most widely used treatments for
PTSD in the community consist of counseling,12
symptomatic treatment of associated insomnia and anxiety with benzodiazepines
or low-dose antidepressants, or self-medication with alcohol.13
An increasing number of studies have been conducted in an attempt to
establish effective treatments for PTSD. Initial studies have reported promising
results for cognitive and behavioral treatments,13, 14, 15, 16
but confirmation of the efficacy of cognitive or behavior therapies for PTSD
awaits the results of additional well-designed clinical trials, with blinded
and parallel control groups, and with larger sample sizes.
Controlled trials testing the efficacy of drug therapy for PTSD are
sparse. A comprehensive review published in 199217
found few placebo-controlled clinical trials, and limited efficacy for the
few that were reported, although phenelzine, and, to a lesser extent, imipramine
and amitriptyline, were more effective than placebo in combat veterans with
PTSD.18, 19 Since that time, 2
equivocal or negative double-blind, placebo-controlled clinical trials have
been published of brofaromine (since discontinued).20, 21
Results of 2 placebo-controlled studies have also been published, each with
approximately 50 outpatients, suggesting efficacy for fluoxetine in PTSD in
civilians, but not in combat veterans.22, 23
A potential therapy for PTSD must effectively treat the core symptoms
of the disorder,24 consisting of reexperiencing
(intrusive thoughts, nightmares, flashbacks, images, or memories); phobic
avoidance of trauma-related situation; emotional numbing (flattened affect
or detachment and/or loss of interest and motivation); and hyperarousal (startle
reactions, poor concentration, irritability and jumpiness, insomnia, and hypervigilance).
Optimally, a candidate therapy should also be effective in restoring normal
functioning and improving symptoms associated with common psychiatric comorbidity.
Sertraline would seem to be such a drug, with demonstrated efficacy in the
treatment of depression25, 26, 27, 28
and panic disorder,29, 30, 31
and preliminary evidence of efficacy in alcoholism,32, 33
as well as uncontrolled pilot studies suggesting efficacy in PTSD.34, 35 We report here results of a large,
multisite, placebo-controlled, double-blind trial designed to test the efficacy
and tolerability of sertraline in the treatment of PTSD.
SUBJECTS AND METHODS
SUBJECTS
The subjects were male and female outpatients 18 years and older who
met DSM-III-R36 criteria
for a primary diagnosis of PTSD as determined by part 1 of the Clinician-Administered
PTSD Scale (CAPS-1). A minimum 6-month duration of PTSD illness was required
(exceeding the 1-month minimum required by DSM-III-R),
as well as a total score of 50 or higher on part 2 of the Clinician-Administered
PTSD Scale (CAPS-2) at the end of a 1-week placebo run-in period. All subjects
were required to be free of psychotropic medication for at least 2 weeks before
beginning treatment, or 5 weeks for fluoxetine. Female participation was contingent
on a negative ß-human chorionic gonadotropin pregnancy test and stable
use of a medically accepted form of contraception. Exclusion criteria included
(1) current or past history of bipolar, schizophrenic, or other psychotic
disorder; (2) current organic mental disorder, factitious disorder, or malingering,
or primary diagnosis of major depression; (3) alcohol or substance abuse or
dependence in the past 6 months; (4) evidence of clinically significant hepatic
or renal disease, or any other acute or unstable medical condition that might
interfere with the safe conduct of the study; (5) intolerance or hypersensitivity
to sertraline, or nonresponse to a previous adequate trial; and (6) current
use of any medication (except occasional use of chloral hydrate) with clinically
significant psychotropic properties. Subjects were not permitted to participate
in cognitive-behavioral therapy during the trial, but were permitted to attend
ongoing psychotherapy or counseling that was initiated at least 3 months before
randomization.
Subjects were recruited from current clinical populations and through
the use of flyers, newspaper advertisements, and radio advertisements. The
study was approved by the institutional review board, or by a national institutional
review board, at each of the 12 collaborating centers. The benefits and risks
of study participation were fully explained to each subject, and written informed
consent was obtained.
STUDY DESIGN
The study was a double-blind, randomized, flexible-dose comparison of
sertraline and placebo for the treatment of PTSD in outpatients. After a 1-week,
single-blind, placebo run-in period, subjects were randomized, using computer-generated
random numbers, to 12 weeks of double-blind, parallel treatment with either
matched placebo or sertraline. Sertraline treatment was initiated at 25 mg
per day for 1 week, with flexible daily dosing thereafter in the range of
50 to 200 mg, based on clinical response and tolerability.
Study visits took place at baseline and at the end of study treatment
weeks 1, 2, 3, 4, 6, 8, 10, and 12, or at the time of discontinuation if before
week 12.
ASSESSMENTS
Baseline
Subjects were evaluated for study entry by a research clinician (physician,
psychologist, or psychiatric nurse) with experience in conducting psychopharmacology
research. The current severity of PTSD symptoms was determined by a psychiatric
history and by the CAPS-1, a structured interview that includes the DSM-III-R PTSD diagnostic criteria.37, 38
A structured clinical interview based on DSM-III-R39 was performed to evaluate the presence of comorbid
psychiatric illness. A medical history, physical examination, and routine
laboratory tests were performed. Baseline PTSD symptoms was rated by the investigators
using CAPS-2 and the Clinical Global Impression-Severity Scale (CGI-S).
Efficacy and Safety
The primary outcome measures for the study consisted of the 17-item
total severity score of the CAPS-2,37, 38
which is an investigator-completed assessment instrument that rates the frequency
and intensity of PTSD symptoms on separate 5-point severity scales; the Impact
of Event Scale (IES),40, 41 a 15-item
subject-rated instrument that assesses intrusion and avoidance symptoms on
a 4-point severity scale; and the CGI-S and CGI-Improvement (CGI-I) scales.42 Assessment of primary outcome measures was performed
at baseline (except CGI-I) and at every study visit.
Secondary outcome measures consisted of (1) the 17-item Davidson Trauma
Scale (DTS),43, 44 which rates
frequency and severity of DSM-III-R–defined
PTSD symptoms on separate 5-point scales; (2) the 24-item Hamilton Depression
Rating Scale (HAM-D)45; (3) the Hamilton Anxiety
Rating Scale (HAM-A)46; (4) DSM-III-R–defined clusters of the CAPS-2, IES, and the DTS: reexperiencing/intrusion,
avoidance/numbing, and arousal; (5) individual global ratings (social functioning,
occupational functioning, overall improvement, and severity of illness) from
the CAPS-2, rated from 0 to 4; (6) CAPS-2 items that rate associated features
of PTSD in terms of frequency and intensity, including guilt and hopelessness;
and (7) the Pittsburgh Sleep Quality Index.47
The CAPS-2 and DTS were administered at every study visit, while the HAM-D,
HAM-A, and Pittsburgh Sleep Quality Index were administered at baseline and
study end point only.
Safety assessments included evaluation at each study visit of weight,
sitting blood pressure, and heart rate. Adverse effects that were spontaneously
reported or observed were recorded with regard to their time of onset, duration,
severity, action taken, and outcome. Use of concomitant medications was recorded
in terms of daily dose, stop and start dates, and reason for use. Laboratory
assessments (eg, clinical chemistry, hematology, urinalysis) were performed
initially at screen, and repeated at weeks 6 and 12 (or at the time of study
discontinuation). A physical examination and electrocardiogram were performed
at screen and at week 12 (or at the time of discontinuation if before week
12).
Compliance was monitored by pill counts of returned medication; subjects
were counseled if found to be noncompliant.
DATA ANALYSIS
Baseline characteristics were compared between the treatment groups
using analysis of variance or 2 (for sex). The main efficacy
analyses were preformed using change from baseline to end point during the
12-week treatment period. The efficacy variables were analyzed via analysis
of covariance, with the effects of site and treatment in the model and baseline
scores as the covariate. For the CGI-I scale, there is no baseline value and
therefore an analysis of variance was performed on the end-point score with
site and treatment in the model. Treatmentxsite interactions were examined
in all analyses, but none were significant and therefore interaction terms
were deleted from all further analyses. Statistical analyses were performed
on SAS, version 6.12. All statistical tests were 2-sided and performed at
the .05 level of significance.
Clinical response to treatment was defined in 2 ways: (1) a 30% or greater
decrease in the CAPS-2 scores and (2) a CGI-I rating of 1 (very much improved)
or 2 (much improved). The post hoc decision to add the CAPS-2 criteria was
based on the recommendation of an expert consensus panel (unpublished data,
Pfizer Inc, New York, NY, March 4, 1998), which suggested that a symptomatic
improvement criterion was a necessary component of determining response status.
Analysis of responder rates employed a Mantel-Haenszel 2 statistic
stratifying by site.
The incidence of adverse events, the percentage of subjects who discontinued
because of adverse events, and the incidence of clinically significant laboratory
abnormalities were compared between treatment groups using Fisher exact test.
Changes in vital signs (blood pressure, heart rate, and body weight) were
compared for the 2 treatment groups using the Wilcoxon rank-sum test.
Finally, the temporal course of response to treatment was examined using
a mixed-effects model for longitudinal data.48
For the CAPS-2 total severity score, IES, and DTS, the change from baseline
to each treatment week was fit to linear and quadratic terms of duration of
treatment. The CGI-I score at each treatment visit was fit directly to linear
and quadratic terms of duration of treatment. We examined the response curves
for each treatment group and compared the difference in curves between the
2 treatment groups.
RESULTS
SUBJECT CHARACTERISTICS
Two hundred eight subjects were randomly assigned to sertraline or placebo,
of whom 98 sertraline-treated subjects and 104 placebo-treated subjects were
available for at least 1 postbaseline efficacy assessment, and so constituted
the intent-to-treat sample.
Demographic and clinical characteristics for the subject sample are
shown in Table 1. The only significant
difference between the 2 treatment groups in any of the baseline variables
was the smaller percentage of males in the sertraline group. Women constituted
the majority of the sample. The age of subjects ranged from 18 to 69 years,
with 75% younger than 45 years. An analysis by sex revealed no significant
differences in any of the baseline variables. The difference observed in Table 1 between the duration of illness,
and the time since the traumatic event seems to be attributable to several
factors, including presence in an individual of more than 1 trauma and delayed
onset of the full diagnosis. Consistent with many other PTSD treatment studies
in civilian populations, the most common trauma category was physical/sexual
assault (Table 2).
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Table 1. Demographic and Clinical Characteristic of Study Subjects
Diagnosed as Having Posttraumatic Stress Disorder (PTSD)
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Table 2. Effect of Study Treatment on Primary and Secondary Efficacy
Measures in Subjects Diagnosed as Having Posttraumatic Stress Disorder (PTSD),
Change From Baseline to End Point*
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EFFICACY
At baseline there were no significant between-treatment group differences
on any of the efficacy variables. Treatment with sertraline resulted in significantly
greater improvement compared with placebo in all 4 primary efficacy measures
that had been defined a priori (Table 3). The benefit of sertraline on the 2 PTSD severity scales (the
CAPS-2 and the IES) was confirmed both by global (CGI) measures of severity
and improvement, as well as by the subject-rated scale, the DTS. An analysis
of completers showed similar trends in favor of the sertraline-treated group,
but failure to reach significance was probably attributable to the reduced
statistical power caused by the 22% dropout rate.
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Table 3. Effect of Study Treatment on Posttraumatic Stress Disorder
(PTSD) Symptom Cluster Subscales in Subjects Diagnosed as Having PTSD, Change
From Baseline to End Point
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Figure 1 shows the results
of a Kaplan-Meier analysis of time to response using the post hoc consensus
criteria CGI-I score of 2 or less and 30% or more reduction from baseline
in the CAPS-2 total score. As can be seen, significantly (21 = 8.48, P = .004) more sertraline-treated
subjects were classified as responders at end point compared with placebo
subjects.
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Figure 1. Kaplan-Meier time-to-response
analysis. The responder is defined by scoring 1 or 2 on the Clinical Global
Impression-Improvement Scale, and a decrease of 30% or more in the total score
from baseline on part 2 of the Clinician-Administered Posttraumatic Stress
Disorder Scale.
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Figure 2 shows the change
scores on both the clinician-rated CAPS-2 total severity measure (A), and
on the subject-rated DTS (B) estimated from mixed-effects analyses plotted
over the 12-week course of study treatment. As can be seen, a significantly
steeper improvement slope was observed with sertraline compared with placebo
on both measures (t1379 = -2.96, P = .003 for CAPS-2, and t1377 = -3.45, P<.001 for DTS). Additional
mixed-effects analyses also found significantly steeper improvement slopes
in favor of sertraline for the IES (t1375
= -2.26, P = .02), for the CGI-I score (t1178 = -3.62, P<0.001),
and for CGI-S (t1380 = -4.40, P<.001).
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Figure 2. Results of random regression analyses
comparing the effects of a 12-week treatment with sertraline and placebo.
A, Mean change score estimate from a random regression analysis on part 2
of the Clinician-Administered Posttraumatic Stress Disorder Scale (t1379 = -2.96, P = .003).
B, Mean change scores from a random regression analysis on the Impact of Event
Scale (t1377 = -3.45, P = .0006).
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Analysis of the core PTSD symptom cluster subscales showed a similar,
although less consistently significant, advantage for sertraline at study
end point on both clinician- and subject-rated measures (Table 3). The mean percentage of reduction from baseline in the
reexperiencing/intrusion symptom cluster was 50% and 53%, respectively, on
the CAPS-2 and IES, a 47% reduction in the avoidance/numbing symptom cluster
on both the CAPS-2 and IES, and a 40% reduction on the arousal symptom cluster
of the CAPS-2.
A treatment x sex analysis was performed on the CAPS-2 change
score and was not found to be significant. The number of males in the study
(46 males [22%]) was too small to perform meaningful analyses, especially
since there were other sex-related confounding factors (eg, differential trauma
type) that would have to be accounted for.
Among the secondary efficacy measures (Table 3), moderate improvement was observed on the HAM-D and HAM-A,
but there was no significant difference from placebo. Similarly, sertraline
improved sleep quality as measured by the Pittsburgh Sleep Quality Index,
but not significantly more than placebo.
EFFECT OF STUDY TREATMENT ON FUNCTIONAL AND PSYCHOSOCIAL MEASURES
Social functioning, as measured by the global rating on the CAPS-2,
showed significantly greater improvement on sertraline (2.6 ± 0.8 to
1.2 ± 1.1) compared with placebo (2.7 ± 0.9 to 1.7 ±
1.1; t = 2.48; P = .01).
Similarly, the CAPS-2 rating of occupational functioning also showed significantly
greater improvement for sertraline compared with placebo, with an adjusted
mean change score, respectively, of 0.9 vs 0.6 (t
= 2.24; P = .02). These results should be interpreted
with caution because the social and occupational ratings on CAPS-2 have been
less well validated than the symptom severity ratings.
TREATMENT AND TOLERABILITY
The mean ± SD daily dose of sertraline at study end point for
completers was 146.3 ± 49.3 mg. Sertraline was generally well tolerated.
Subjects reported the following rates of adverse events for sertraline and
placebo, respectively: insomnia (35% vs 22%, P =
.04); headache (33% vs 24%, P = .17); diarrhea (28%
vs 11%, P = .003); nausea (23% vs 11%, P = .03); drowsiness (17% vs 11%, P = .24);
nervousness (14% vs 8%, P = .27); fatigue (13% vs
5%; P = .05); decreased appetite (12% vs 1%, P = .001); dry mouth (10% vs 7%, P
= .45); and vivid dreams (10% vs 4%, P = .10).
Thirty-two subjects discontinued sertraline treatment (30%) compared
with 35 subjects who discontinued placebo treatment (27%). The primary reason
cited for discontinuation of sertraline and placebo, respectively, was as
follows: adverse events (9.1% vs 4.7%); withdrawal of consent (6.1% vs 3.8%);
lost to follow-up (5.1% vs 10.4%); protocol violation (2.0% vs 4.7%); laboratory
abnormality (2.0% vs 0%); insufficient therapeutic response (0% vs 4.7%);
and miscellaneous other reasons (2.0% vs 1.9%). Two sertraline subjects discontinued
prematurely because of mild elevations in aspartate aminotransferase and alanine
aminotransferase values. There were no serious electrocardiographic or laboratory
abnormalities during the course of the study, nor were there any significant
differences between the 2 treatment groups in the incidence of electrocardiographic
or laboratory abnormalities.
There were no significant differences between the sertraline group and
the placebo group in terms of changes in vital signs, with the exception of
sitting heart rate. Sertraline-treated subjects showed a decrease from baseline
to end point, while placebo-treated subjects showed an increase (-2.7
and 1.71 beats/min, respectively; t = 2.68; P = .007). However, no subjects in either group showed
a clinically significant change in heart rate or blood pressure.
COMMENT
The results of the present study indicate that sertraline is an effective
acute treatment for PTSD. This investigation, together with a companion study49 that was also positive on all primary outcome measures,
represent the largest randomized placebo-controlled trials published to date
on the treatment of PTSD.
Acute treatment with sertraline in the present study resulted in a clinically
significant mean reduction from baseline in the range of 45% to 50% on the
2 primary measures of overall PTSD symptom severity, the CAPS-2 and the IES
(Table 3). On both the CAPS-2
and the IES, approximately 70% of the improvement in PTSD symptoms occurred
during the first 4 weeks of treatment. The mixed-effects analysis confirmed
that the improvement observed over the 12 weeks of sertraline treatment was
consistently greater than placebo across both of these primary outcome measures
(Figure 2).
The severity of the 3 PTSD core symptom clusters also improved with
sertraline treatment, but the improvement was less consistently significant
on the clinician-rated CAPS-2 when compared with placebo. In contrast, the
subject-rated DTS and IES consistently detected significantly greater efficacy
advantage for sertraline over placebo on all 3 PTSD symptom clusters, suggesting
that subject self-rating scales may be more sensitive measures for evaluating
treatment effects in PTSD than clinician ratings.
Paralleling improvement in PTSD symptoms, global measures of social
functioning and occupational functioning also showed rapid and significant
improvement. In a similar 12-week, double-blind study of sertraline and placebo
using the Quality of Life, Enjoyment, and Satisfaction Questionnaire,49, 50 sertraline-treated subjects were
improved on measures of social relationships, leisure activities, ability
to function daily, living situation, ability to get around physically, and
ability to work after 12 weeks of treatment. The results from the CAPS-2 function
items in this study indicate similar improvements. Posttraumatic stress disorder
has been characterized as one of the most functionally debilitating disorders,
and small symptom improvements leading to resumed daily activities, such as
driving or taking elevators, can have a profound impact on family and work
life.
Although sertraline, relative to placebo, improved the symptoms of PTSD
and its associated features, no significant differences between sertraline
and placebo were found on either the HAM-A or HAM-D change scores at end point.
Subjects with primary diagnoses of major depression or most anxiety disorders
were excluded from the current trial. However, mild-to-moderate levels of
both anxiety and depression were reported by most subjects at baseline, as
evidenced by mean HAM-A and HAM-D scores near 20. The lack of differential
improvement in anxiety and depressive symptoms, therefore, was unlikely to
be a function of limited room for change on these scales because of low baseline
scores. It is possible that chronic, subsyndromic anxious and depressive symptoms
associated with PTSD may require a longer course of therapy. However, this
is speculation, and arguing against this hypothesis is the larger, and earlier-onset,
treatment effect found for sertraline treatment of subjects with dysthymic
disorder and double depression.27, 28
The relative lack of acute antidepressant effect in the current subject sample
makes it unlikely that an antidepressant response is a necessary precondition
for the efficacy of sertraline in the treatment of PTSD.
Sertraline was well tolerated, with 9% of sertraline-treated subjects,
compared with 5% of placebo-treated subjects, discontinuing treatment during
the 12-week study period because of adverse events. There were no differences
between the sertraline group and the placebo group in the incidence of laboratory
abnormalities, and no clinically significant changes in vital signs or electrocardiogram
were found for any subjects.
The study as conducted has several limitations. First, study entry criteria
excluded patients with a current history of alcohol or substance abuse. Other
study entry criteria required a moderate-or-higher level of current symptom
severity. The generalizability of our study results to patients in the community
suffering from PTSD must be made with an awareness of potential differences
between the 2 populations. Another limitation is that the study was not powered
to evaluate the influence of potentially important clinical variables, such
as sex, type of trauma, duration of illness, or presence of comorbidity on
treatment response. We plan to pool the data from the current study with data
from a study of very similar design49 to undertake
exploratory analyses of some of these issues. Another limitation of the current
study is that it provides no information on the longer-term effects of sertraline
in consolidating the improvement in PTSD symptoms obtained during acute therapy
and in sustaining this level of improvement (ie, in preventing relapse). The
results of a recently completed 12-month treatment study should provide data
on this topic (J.R.T.D., P. Londberg, MD, T. Pearlstein, MD, K. T. Brady,
MD, PhD, B.O.R., J. Bell, MD, R. Maddock, MD, M. T. Hegel, PhD, and G.M.F.,
unpublished data, 2000).
How do the results of the current study compare with previously conducted
PTSD treatment research? First, in terms of indexing the results obtained
here against previous results, it should be noted that the placebo response
rate in the current study (38%) was comparable with rates reported in previously
published placebo-controlled drug therapy studies.20, 21, 22, 23
Placebo response rates in these studies range as high as 62% (in the study
reported by Connor et al23) when no symptom
severity reduction criteria were applied. The current study joins a growing
number of well-designed studies of drug therapy20, 21, 22, 23
and cognitive or behavioral therapy13, 14, 15, 16
that have reported efficacy in the treatment of PTSD, but there are still
relatively few placebo-controlled studies with larger sample sizes available.
For example, among psychosocial treatments, cognitive-behavior therapy is
the most well established as a treatment, but the largest and most positive
recent study testing its efficacy13 had only
20 subjects at end point in the exposure-alone treatment group and 19 subjects
at end point in the exposure-plus-cognitive-therapy treatment group. Confidence
in the positive results of this study were further complicated by the fact
that subjects in each group were concurrently being treated with antidepressants
(17% in the former and 42% in the latter treatment group), as well as by other
significant between-treatment group differences, most notably a duration of
illness that ranged from 23 to 61 months.
The importance of the current study is increased by the relative dearth
of large-scale controlled treatment studies, which is surprising given the
high prevalence,1, 2, 3
chronicity,1, 4 comorbidity,1, 5, 6 and disability7, 8 associated with PTSD. The similarly
positive results of a second study49 provide
further evidence suggesting that sertraline is a safe, well-tolerated, and,
compared with placebo, significantly effective treatment for this long-neglected
public health problem.
AUTHOR INFORMATION
Accepted for publication December 21, 2000.
Financial support for this study was provided by Pfizer Inc, New York,
NY.
Presented at the American College of Neuropharmacology, Kamuela, Hawaii,
December 1997; and at the International Society for Traumatic Stress Studies,
Washington, DC, November 1998.
The investigators in this study and the corresponding sites at which
the study was conducted were Jessy Colah, MD, and Renuka Tank, MD, Adult and
Geriatric Outpatient Services, Brooklyn, NY; Kathleen Brady, PhD, MD, Institute
of Psychiatry, Charleston, SC; Paul Newhouse, MD, Fletcher Allen Healthcare,
Burlington, Vt; Barbara O. Rothbaum, PhD, The Emory Clinic, and the Department
of Psychiatry and Behavioral Sciences, Atlanta, Ga; Hisham Hafez, MD, and
Phillip Santora, MD, Charter Brookside Hospital and Research Department, C.
Brookside Hospital, Nashua, NH; Peter Londborg, MD, Seattle Clinical Research
Center, Seattle, Wash; Teri Pearlstein, MD, Butler Hospital, Providence, RI;
Bessel van der Kolk, MD, PhD, Human Resource Institute, Brookline, Mass; Wayne
Phillips, MD, PhD, Boulder PTSD Center, Boulder, Colo; Katherine Shear, MD,
University of Pittsburgh School of Medicine, Pittsburgh, Pa; Richard Weisler,
MD, Raleigh, NC; William Patterson, MD, Birmingham Research Group Inc, Birmingham,
Ala; Phebe Tucker, MD, University of Oklahoma Health Sciences Center, Oklahoma
City.
From the Anxiety and Traumatic
Stress Program, Department of Psychiatry and Behavioral Sciences, Duke
University Medical Center, Durham, NC (Dr Davidson); the Emory Clinic
and Department of Psychiatry and Behavioral Sciences, Atlanta, Ga (Dr
Rothbaum); the Human Resource Institute, Brookline, Mass (Dr van der
Kolk); and Pfizer Inc, New York, NY
(Drs Sikes and Farfel).
Corresponding author and reprints: Jonathan R.T. Davidson, MD, Department
of Psychiatry and Behavioral Sciences, Anxiety and Traumatic Stress Program,
Duke University Medical Center, Box 3812, Durham, NC 27710.
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