Context Despite the high prevalence, chronicity, and associated comorbidity
of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled
studies have evaluated the efficacy of pharmacotherapy for this disorder.
Objective To determine if treatment with sertraline hydrochloride effectively
diminishes symptoms of PTSD of moderate to marked severity.
Design Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week,
single-blind placebo lead-in period, conducted between May 1996 and June 1997.
Setting Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical
research centers.
Patients A total of 187 outpatients with a Diagnostic and Statistical
Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD
and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity
score of at least 50 at baseline (mean age, 40 years; mean duration of illness,
12 years; 73% were women; and 61.5% experienced physical or sexual assault).
Intervention Patients were randomized to acute treatment with sertraline hydrochloride
in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94);
or placebo (n=93).
Main Outcome Measures Baseline-to-end-point changes in CAPS-2 total severity score, Impact
of Event Scale total score (IES), and Clinical Global Impression–Severity
(CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo
groups.
Results Sertraline treatment yielded significantly greater improvement than
placebo on 3 of the 4 primary outcome measures (mean change from baseline
to end point for CAPS-2 total score, −33.0 vs −23.2 [P=.02], and for CGI-S, −1.2 vs −0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend
toward significance (mean change from baseline to end point, −16.2 vs −12.1; P=.07). Using a conservative last-observation-carried-forward
analysis, treatment with sertraline resulted in a responder rate of 53% at
study end point compared with 32% for placebo (P=.008,
with responder defined as >30% reduction from baseline in CAPS-2 total severity
score and a CGI-I score of 1 [very much improved], or 2 [much improved]).
Significant (P<.05) efficacy was evident for sertraline
from week 2 on the CAPS-2 total severity score. Sertraline had significant
efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing
(P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14).
Sertraline was well tolerated, with insomnia the only adverse effect reported
significantly more often than placebo (16.0% vs 4.3%; P=.01).
Conclusions Our data suggest that sertraline is a safe, well-tolerated, and effective
treatment for PTSD.
Traumatic stress is a significant public health problem1
that frequently results in a distinctive pattern of persistent and disabling
psychological and physiological symptoms.2,3
Once thought to be primarily limited to soldiers in combat, posttraumatic
stress disorder (PTSD) is now recognized in civilians, including those who
have experienced natural disasters, physical and sexual assault, fire, motor
vehicle and other serious trauma, as well as those who have witnessed inflicted
injury or death. Exposure to a traumatic event is common, estimated in the
range of 5% to 35% annually, with a lifetime exposure to 1 or more traumatic
events occurring in more than 50% of the US population.1
The clinical presentation of PTSD is characterized by moderate-to-severe
symptoms in 3 separate domains: reexperiencing (intrusive thoughts, nightmares,
flashbacks, images, or memories), emotional numbing and avoidance (flattened
affect or detachment, loss of interest and motivation, and avoidance of any
activity, place, person, or topic associated with the trauma); and increased
arousal (startle reactions, poor concentration, irritability and jumpiness,
insomnia, or hypervigilance). With a minimum symptom duration of 1 month at
a level of severity necessary to impair an individual's functioning, PTSD
has been estimated to have a lifetime prevalence in the range of 5% to 12%,
based on epidemiological surveys,1,4,5
with women having twice the prevalence rate of men.
Frequently, PTSD is a chronic illness, with a median time to recovery
in the range of 3 to 5 years.1,6
The disorder is associated with unusually high rates of lifetime psychiatric
comorbidity,1,5,7
especially major depression (odds ratio relative to non-PTSD sample, approximately
4-7), alcoholism and drug abuse (odds ratio, approximately 3), and panic disorder
(odds ratio in the range of 3-20). Research has shown that previous psychiatric
history is a risk factor for development of PTSD following trauma exposure.1,8-10 Furthermore,
patients with PTSD often have subsequent onset of another psychiatric disorder.
Analysis of epidemiological data relating to age at time of trauma and onset
of PTSD diagnosis suggests that when PTSD occurs in conjunction with a mood
or anxiety illness, it constitutes the primary disorder in 41% to 58% of women
and 29% to 51% of men.1 The high chronicity,
severity, and comorbidity of PTSD are associated with high levels of functional
and psychosocial disability,11,12
as well as increased somatic complaints and health care use.13-16
An empirical review published in 199217
identified only 5 controlled trials of medication treatment,18-22
all of which were limited to men (mostly combat veterans). This review found
"modest efficacy" for pharmacological and behavioral treatments with "the
strongest efficacy favoring behavioral techniques." Only 3 double-blind, placebo-controlled
studies have been published since that review. Two reported conflicting results
for the never-marketed monoamine oxidase type A inhibitor brofaromine.23,24 A third study reported positive results
for fluoxetine (n=10) compared with placebo (n=13) in a subgroup of civilian
patients with PTSD,25 while no significant
differences between fluoxetine and placebo were found in a subgroup of patients
with combat-related PTSD treated in a Veterans Affairs clinic setting.
The selective serotonin reuptake inhibitor antidepressants appear promising
in the treatment of PTSD for various reasons. Optimally, a candidate therapy
should be well-tolerated and able to effectively treat the core clinical features
of PTSD and common affective and anxiety disorder comorbidity, as well as
to improve psychosocial functioning. Sertraline, one of the most widely prescribed
selective serotonin reuptake inhibitor antidepressants, effectively attenuates
the behavioral syndrome that occurs in animals after exposure to uncontrollable
stress,26 which has been interpreted as an
animal model of PTSD.27,28 Two
small, open-label studies29,30
have shown efficacy for sertraline, 1 in the treatment of those with PTSD
due to sexual assault and 1 in patients with comorbid alcoholism and PTSD.
The efficacy of sertraline in treating depression,31-33
panic disorder,34-36
and obsessive-compulsive disorder37,38
are well established. In light of this clinical activity, we conducted a large,
placebo-controlled study from May 1996 to June 1997 to examine the efficacy
of sertraline in the treatment of PTSD. Because of the marked impairment in
occupational, health, and psychosocial functioning associated with PTSD, quality-of-life,
psychosocial, and symptomatic outcomes were assessed.7,12
The subjects were male and female outpatients aged 18 years and older
who met Diagnostic and Statistical Manual of Mental Disorders,
Revised Third Edition (DSM-III-R) criteria
for a principal diagnosis of PTSD as determined by part 1 of the Clinician
Administered PTSD Scale.39,40
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
severity score of at least 50 (range, 0-136) on the Clinician Administered
PTSD Scale, Part 2 (CAPS-2) at the end of a 2-week placebo run-in period;
subjects were at least moderately ill. All patients were required to be free
of psychotropic medication for at least 2 weeks prior to beginning treatment.
Women's participation was contingent on negative results of a beta–human
chorionic gonadotropin pregnancy test and stable use of a medically accepted
form of contraception. Exclusion criteria were: (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, obsessive-compulsive disorder,
or other anxiety disorders; (3) alcohol or substance dependence or abuse 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; (6) current use of
any medication (except chloral hydrate, taken as needed) with clinically significant
psychotropic activity within 2 weeks of randomization (or 5 weeks for fluoxetine);
(7) any cognitive-behavioral therapy during the trial; and (8) psychotherapy
that was initiated or that ended during the trial.
The research was conducted at outpatient psychiatric clinics in 8 academic
medical centers and 6 clinical research centers. The study was approved by
the institutional review board at each of the 14 collaborating centers or
by a national institutional review board. The benefits and risks of study
participation were fully explained to each patient, and written informed consent
was obtained.
Following a 2-week, single-blind placebo run-in period, patients were
randomized to 12 weeks of double-blind parallel treatment with either sertraline
or matched placebo. To be randomized, patients had to demonstrate at baseline
a minimum level of PTSD symptom severity as indicated by a CAPS-2 severity
score of at least 50. There were no other operationally defined placebo responder
exclusion criteria. Treatment was initiated at 25 mg/d for 1 week, with flexible
daily dosing and 50 to 200 mg/d thereafter, based on clinical response and
tolerability. Dosing changes were made in 50-mg increments at no less than
weekly intervals unless required for safety. At the conclusion of 12 weeks
of double-blind treatment, patients were eligible to enroll in a 24-week open-label
sertraline treatment protocol. Entry into the open-label study was not dependent
on responder status, nor was the blinding for the acute phase broken at the
time of entry into open-label treatment.
Patients were evaluated for study entry by a semistructured psychiatric
interview and administration of Part 1 of the structured Clinician Administered
PTSD Scale,39,40 an instrument
rating lifetime history and current symptoms of PTSD as defined in DSM-III-R. A medical history was taken and a physical examination and
routine laboratory testing were performed. Severity of PTSD symptoms at baseline
was rated by the investigators using CAPS-2 and the Clinical Global Impression–Severity
scale (CGI-S).
The primary outcome measures for the study consisted of the 17-item
total severity score of the CAPS-239,40
(a 30-item investigator-completed scale that rates the frequency and intensity
of PTSD symptoms on separate 5-point scales); the Impact of Event Scale (IES)41,42 (a 15-item patient-completed scale
that rates intrusion and avoidance symptoms on a 6-point severity scale);
and the investigator-rated CGI-S and Clinical Global Impression–Improvement
scale (CGI-I).43 Primary outcome assessments
were performed at baseline and at study treatment weeks 1, 2, 3, 4, 6, 8,
10, and 12 (or at the time of discontinuation if prior to week 12). The CAPS-2
was not administered at weeks 1 and 3, and the CGI-I was not administered
at baseline.
The secondary outcome measures consisted of (1) the 17-item Davidson
Trauma Scale (DTS)44,45 that allows
patients to rate the 17 DSM-III-R–defined PTSD
symptoms on a 5-point frequency and a 5-point severity scale; (2) the investigator-rated
24-item Hamilton Depression Rating scale46;
(3) a validated short form of the patient-rated Quality of Life Enjoyment
and Satisfaction scale47; (4) subscales of
the CAPS-2, IES, and DTS that rate the severity of PTSD symptom clusters (reexperiencing/intrusion,
avoidance/numbing, and increased arousal); and (5) subscales of the CAPS-2
that measure associated features and functional impairment. Secondary outcome
assessments were performed at baseline and at the end of study treatment weeks
2, 4, 6, 8, 10, and 12 (except DTS, which was also completed at the end of
weeks 1 and 3; and the Hamilton Depression Rating scale and Quality of Life
Enjoyment and Satisfaction scale, which were completed only at baseline and
week 12).
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 dosage, stop and start dates, and reason for use. Laboratory
assessments (eg, clinical chemistry, hematology, and urinalysis) were performed
at initial screening and repeated at weeks 6 and 12 (or at the time of study
discontinuation). A physical examination and electrocardiogram were performed
at baseline and at week 12 or discontinuation. Compliance was monitored by
counts of returned medication, and patients were counseled if they were found
to be noncompliant.
Baseline characteristics were compared between treatment groups using
analysis of variance or χ2tests (for sex). Main efficacy analyses
were performed using change from baseline to end point during the 12-week
treatment period. Efficacy variables were analyzed via analysis of covariance,
using the effects of site and treatment in the model and baseline scores as
the covariates. For the CGI-I scale, there is no baseline value; therefore,
an analysis of variance was performed on the end point score with site and
treatment in the model. Treatment by site interactions were examined in all
analyses, but none were significant and interaction terms were deleted from
the analysis. All statistical tests were 2-sided and performed at the .05
level of significance.
Clinical response to treatment was defined as a 30% or greater decrease
in CAPS-2 scores and a CGI-I rating of 1 (very much improved) or 2 (much improved).
Analysis of responder rates used a Mantel-Haenszel χ2 statistic
stratified by site.
The incidence of adverse events, the proportion of patients who discontinued
treatment because of adverse events, and the incidence of clinically significant
laboratory abnormalities were compared between treatment groups using the
Fisher exact test. Changes in vital signs (blood pressure, heart rate, body
weight) were compared for the 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. 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.
Demographic and Clinical Characteristics
A total of 187 patients were randomly assigned to sertraline (n=94)
or placebo (n=93), of whom 93 (99%) sertraline-treated patients and 90 (97%)
placebo-treated patients were available for at least 1 postrandomization efficacy
assessment. Efficacy analyses were performed on the latter group, omitting
the 1 patient taking sertraline and the 3 patients taking placebo who were
unavailable for postrandomization assessment.
For the total randomized sample there were no significant differences
between the treatment groups in any of the baseline demographic and clinical
characteristics (Table 1). Women
constituted the majority of the sample. Ages ranged from 18 to 69 years, with
65% of the sample being younger than 45 years. An analysis by sex revealed
no significant differences in any of the baseline variables. There were no
significant differences between the treatment groups in the types of trauma
experienced (Table 2). Thirty-eight
percent of patients in the sertraline group and 42% of patients in the placebo
group reported having received treatment in the previous 5 years for symptoms
of PTSD, depression, anxiety, or sleep disturbance, although most had not
received a formal diagnosis of PTSD. Of those patients who received symptomatic
treatment, 80% in the sertraline group and 68% in the placebo group reported
a good response to prior symptomatic treatment (χ21=2.52, P=.11).
Figure 1 shows patient numbers
and disposition through the course of treatment.
Treatment and Tolerability
The mean (SD) daily dosage of sertraline at study end point was 133.3
(59.2) mg, while the dosage for those who completed the study was 151.3 (51.2)
mg. Sertraline was well tolerated overall. The adverse events reported by
at least 10% of patients were, for sertraline and placebo, respectively: headache,
20.2% vs 28.3% (P=.23); diarrhea, 23.4% vs 19.6%
(P=.59); malaise, 17.0% vs 15.2% (P=.84); nausea, 16.0% vs 12.0% (P=.53); insomnia,
16.0% vs 4.3% (P=.01); drowsiness, 12.8% vs 9.8%
(P=.64); and dry mouth, 11.7% vs 4.3% (P=.10).
Twenty-nine patients discontinued sertraline treatment (30.9%) compared
with 25 patients discontinuing placebo treatment (27.2%, P=.63). The primary reasons cited for discontinuation in the sertraline
and placebo groups, respectively, were: insufficient therapeutic response
(3.2% vs 2.2%; P>.99); adverse events (5.3% vs 5.4%; P>.99); laboratory abnormality (3.2% vs 0%; P=.25); protocol violation (1.1% vs 0%; P>.99);
lost to follow-up (10.6% vs 2.2%; P=.03); did not
meet entrance criteria (1.1% vs 0%; P>.99); withdrawal
of consent (4.3% vs 14.4%; P=.02); and miscellaneous
other reasons (2.1% vs 3.3%; P=.68).
Treatment-emergent laboratory abnormalities led to study discontinuation
in 2 patients receiving sertraline treatment: 1 patient at day 51 because
of decreases in hemoglobin from 92 to 81 g/L, a second patient at day 44 when
an increase was noted in alanine aminotransferase from 11 to 150 U/L and in
aspartate aminotransferase from 15 to 50 U/L. There were no statistically
significant differences between patients treated with sertraline vs placebo
in vital signs or electrocardiographic results. Mean change in body weight
during study treatment for sertraline and placebo, respectively, was –1.3
kg vs –0.3 kg (P=.01). One sertraline and 1
placebo patient had serious adverse events, but neither event was considered
treatment-related.
Treatment with sertraline yielded statistically significantly greater
efficacy than placebo at study end point (based on a last-observation-carried-forward
analysis) on 3 of the 4 a priori primary outcome measures (Table 3). The difference between the mean CAPS-2 change scores at
end point was 9.8 (95% confidence interval, 1.8-17.7; P=.02); the difference between the mean CGI-S change scores at end point
was 0.5 (95% confidence interval, 0.1-0.8; P=.01);
the difference between the mean CGI-I scores at end point was 0.4 (95% confidence
interval, 0.1-0.8; P=.02). Improvement in the IES
total score showed only a trend toward significance (P=.07),
with a difference between the mean IES change scores at end point equal to
4.1 (95% confidence interval, −0.4 to 8.7). Patients taking sertraline
also showed significantly greater improvement than placebo on all secondary
measures (Table 3, Table 4, and Table 5).
Patient ratings confirmed clinician assessments, with a significant advantage
(P=.003) found for sertraline compared with placebo
on the DTS.
Global improvement in primary and secondary outcome measures was reflected
in the significantly greater improvement observed for sertraline treatment
at study end point on both the CGI-S (P=.01) and
the CGI-I scores (P=.02). Using the conservative
last-observation-carried-forward analysis, treatment with sertraline resulted
in a responder rate of 53% at study end point compared with 32% for placebo
(P=.008 with responder defined as >30% reduction
from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very
much improved] or 2 [much improved]).
Figure 2 shows a significantly
steeper improvement slope with sertraline compared with placebo on both CAPS-2
and IES measures. Additional random regression analyses also found steeper
improvement slopes in favor of sertraline for the DTS (t1206= –4.58; P<.001)
and for the CGI-I score (t1052= –2.71; P<.001). The benefit of sertraline treatment was evident
relatively early, with a 25% reduction in the mean CAPS-2 total severity score
by week 2. A statistically significant advantage over placebo was maintained
from week 2. The time course of improvement was similar for the IES, although
the degree of statistical significance was less in comparison with the significance
for the CAPS-2 scale.
Improvement in PTSD Symptom Clusters
Table 4 provides a summary
of the effect of the 2 study interventions on the 3 core PTSD symptom clusters.
The magnitude of the treatment effect (reduction in mean symptom cluster score
as a percentage of baseline score) for sertraline was similar for all 3 symptom
clusters (40%-50%).
Effect of Study Treatment on Functional and Quality-of-Life Measures
Among those who completed the study, sertraline treatment was associated
not simply with an improvement in PTSD symptom scores but in a significant
improvement in measures of social and occupational functioning, as well as
perception of improved quality of life (Table 5). A last-observation-carried-forward analysis of the same
data found similar results with adjusted mean (SE) change scores for sertraline
and placebo, respectively, of –1.2 (0.11) vs –0.7 (0.11) (P=.001) for social functioning, measured by CAPS-2; –0.7
(0.10) vs –0.4 (0.10) (P=.02) for occupational
functioning measured by CAPS-2; and 11.7 (2.1) vs 3.3 (1.9) (P=.004) for Quality of Life Enjoyment and Satisfaction Questionnaire
total score.
This multicenter, randomized clinical trial found sertraline to be significantly
more effective than placebo in the treatment of PTSD across a spectrum of
illness-specific global and functional outcome measures. In the efficacy analysis,
53% of patients were much or very much improved at treatment end point (P=.008 vs placebo), with 70% of the reduction in PTSD symptom
severity on the CAPS-2 and IES achieved within the first 4 weeks of treatment
(Figure 2). The placebo response
rate of 32% was comparable with what has been observed in previous multicenter
PTSD clinical trials23,24 as well
as across most acute treatment studies of patients diagnosed as having affective
or anxiety disorders.
The efficacy of sertraline was significant compared with placebo in
reducing symptom severity for the DSM-III-R–defined
PTSD symptom clusters of arousal and avoidance/numbing but not for the third
symptom cluster, reexperiencing/intrusion. Nonetheless, the percentage reduction
from baseline in symptom severity was the same for this third cluster as for
the first 2 clusters (41%-45%; Table 4).
The baseline severity scores for the reexperiencing/intrusion cluster were
much lower than the baseline scores for the other 2 clusters, making statistical
significance harder to demonstrate, especially since the study was not powered
to show a significant drug vs placebo difference on PTSD symptom cluster subanalyses.
The benefits of pharmacotherapy in treating PTSD have been shown to
be moderate and less effective than cognitive and/or behavioral therapies.17 Although published studies of cognitive and/or behavioral
therapies that are rigorously designed and have sufficient power are still
limited in number, available data consistently suggest benefit in certain
types of patients with PTSD, particularly women who have experienced sexual
assault.
Since the 1992 treatment review,17 3
double-blind, placebo-controlled studies have been published that suggest
efficacy for monoamine oxidase inhibitor and selective serotonin reuptake
inhibitor antidepressants.23-25
Fluoxetine showed promise in civilians with PTSD25
but, consistent with previous findings, was not found to have efficacy in
combat-related PTSD treated in a Veterans Affairs clinic setting. The magnitude
of the treatment effect observed with fluoxetine was similar to that in the
current study, but fluoxetine was not well tolerated, with a 41% attrition
rate, 81% incidence of diarrhea, and 65% incidence of increased sweating,
suggesting the possibility of fluoxetine-induced autonomic effects. In contrast,
insomnia was the only adverse event in this trial with a significantly higher
incidence in patients taking sertraline vs placebo; the rate of treatment-emergent
adrenergic symptoms was also low and not significant compared with placebo.
The short-term results achieved in the current study are particularly
impressive, given that the mean duration of PTSD was more than 10 years (Table 1). In 1 large, community survey,1 the mean duration of illness was reported to be 3
to 5 years, and "one-third of patients never fully remitted even after many
years, and irrespective of whether they were in treatment." This degree of
chronicity is associated with pervasive adverse effects on psychosocial functioning,7,12 as well as prominent somatic complaints
and high use of health care services.7,13-15
Despite the chronicity and degree of psychosocial impairment reported by study
patients at baseline, the symptomatic improvement achieved by taking sertraline
during treatment was rapidly translated into significant improvement in social
and occupational functioning and perceived quality of life (Table 5). Whether treatment with sertraline yields a comparable
cost offset in terms of reduced health care use awaits the results of future
research.
Primary care providers underdiagnose and undertreat patients with PTSD
because of the complex clinical presentation and comorbidity common to the
illness.1,48 Comorbidity rates
observed in the current study are consistent with this complex clinical presentation,
with a 30% to 36% rate of major depression, a 14% to 18% rate of anxiety disorder,
a 22% to 30% history of alcohol dependence or abuse, and a 14% history of
substance dependence and/or abuse (current alcohol and substance abuse problems
were reasons for exclusion). The exclusion from the study of patients with
primary affective illness or anxiety disorder diagnoses may have reduced the
incidence of comorbid affective illness in the current sample compared with
what has been reported in the community.1 A
potential therapeutic advantage of sertraline as a treatment for PTSD is its
established efficacy in treating disorders commonly comorbid with PTSD, such
as depression31-33
and panic disorder.34-36
In the current study, sertraline demonstrated a significant efficacy advantage
over placebo in the treatment of PTSD (Table 3), although specific measures of panic or anxiety disorders
were not obtained.
Research for PTSD treatment is still in its infancy. The slow progress
in identifying effective drug therapies specific to PTSD may be partly due
to a residual conceptual bias that sees PTSD as an extension of a normative
stress reaction. Unease at the use of drug treatment to facilitate normal
coping is appropriate. Yet, as Yehuda and McFarlane argued,49
PTSD is very different from a typical or even intense stress reaction: the
high chronicity, comorbidity, and severity, as well as PTSD-related alterations
in underlying neurochemical and neuroendocrine substrates are quite distinct
from what are observed in normative stress reactions. In this view, trauma
may be a necessary but by no means sufficient condition for the development
of syndromic PTSD. Ongoing research is attempting to identify psychological
and neurobiological vulnerability factors that may place a person who has
experienced trauma at risk for the development of PTSD.49
This investigation and a companion study50
provide strong support for the efficacy of sertraline in the acute treatment
of PTSD. Additional research is needed to determine whether subgroups of PTSD
patients might respond preferentially to drug or behavioral treatments or
might optimally benefit from combination therapy. Finally, what constitutes
an adequate therapeutic trial and whether and when patients with PTSD might
benefit from long-term treatment are also issues that await further research.
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