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Psychosocial Outcomes Following Long-term, Double-blind Treatment of Chronic Depression With Sertraline vs Placebo
James H. Kocsis, MD;
Alan Schatzberg, MD;
A. John Rush, MD;
Daniel N. Klein, PhD;
Robert Howland, MD;
Leah Gniwesch, PhD;
Sonia M. Davis, DrPH;
Wilma Harrison, MD
Arch Gen Psychiatry. 2002;59:723-728.
ABSTRACT
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Background Chronic forms of depression are associated with significant functional
and psychosocial impairments. To date, no study has measured psychosocial
functioning in this population during long-term maintenance antidepressant
treatment or following the double-blind discontinuation of treatment.
Methods Patients with chronic major or double depression completed 12 weeks
of short-term treatment followed by 16 weeks of continuation treatment with
sertraline hydrochloride. Responders at the end of the continuation phase
were randomized, double-blind, to 18 months of maintenance therapy with either
sertraline (n = 77) or placebo (n = 84). Multiple domains of psychosocial
functioning were assessed during double-blind therapy.
Results Substantial worsening in psychosocial function measures occurred in
patients taking placebo compared with sertraline during maintenance. Patients
with reemergence of depression lost psychosocial gains regardless of treatment.
In the subsample of patients who remained in remission throughout maintenance,
most of the observed improvement in psychosocial functioning occurred during
short-term treatment. By maintenance end point, normalization of functioning
was achieved by 58% to 84% of remitters, depending on the outcome measure
used.
Conclusions These results indicate that long-term treatment of chronic forms of
depression can result in sustained psychosocial benefits. Discontinuation
of treatment results in frequent reemergence of symptoms and loss of psychosocial
gains. Long-term treatment resulted in only modest further improvement of
psychosocial measures over that achieved in the short-term phase.
INTRODUCTION
THREE FORMS of chronic unipolar depression have been described: dysthymic
disorder, chronic major depression, and double depression, in which dysthymia
is punctuated by episodes of major depression. All 3 forms of chronic depression
are frequently associated with a significant degree of social and vocational
role impairment and academic and vocational underachievement, leading to lost
human capital.1-7
Surprisingly, in light of the chronicity of the illness, successful
short-term treatment with antidepressant medications results in rapid and
marked improvement in social and vocational functioning after only 6 to 12
weeks.5-7 Such findings
suggest that the social and vocational role deficits experienced by chronically
depressed patients result from treatment-responsive depressive symptoms rather
than from ingrained personality traits.
A previous report6 focused on the effect
of short-term treatment on psychosocial functioning. This article reports
the effect of maintenance-phase treatment on psychosocial outcomes in the
same chronically depressed patient sample. The following specific questions
are addressed: (1) Is sertraline hydrochloride associated with better psychosocial
outcomes than placebo during maintenance treatment of remitted patients with
chronic depression? (2) When depression recurs, how extensive is the loss
of improvement in psychosocial functioning? (3) Is impairment in psychosocial
functioning at maintenance baseline a predictor of subsequent relapse? (4)
Are further improvements in psychosocial functioning, beyond those occurring
during the short-term phase of treatment, evident during 18 months of maintenance
treatment in remitted, depressed patients? (5) To what extent does psychosocial
functioning achieve "normal" levels by the end of maintenance treatment in
those who remain in remission?
PATIENTS AND METHODS
PATIENTS
Details of inclusion and exclusion criteria and study design are provided
in a previous publication.8 Outpatients meeting DSM-III-R criteria for a current episode of chronic major
depression (of at least 2 years' duration) or dysthymic disorder co-occurring
with major depression (double depression) were enrolled in this maintenance
treatment study if they successfully completed both a 12-week, double-blind
short-term phase of treatment and a 16-week, double-blind continuation phase.
Patients were eligible for the maintenance phase of the study if they had
achieved and sustained at least a satisfactory antidepressant response as
operationally defined by the following criteria: (1) not meeting DSM-III-R criteria for major depression; (2) 24-item Hamilton Depression
Scale (HAM-D) total score of 15 or less; (3) Clinical Global Impression (CGI)
severity score of 3 or less; (4) CGI improvement score of 2 or less; and (5)
successful completion and compliance with 28 weeks of short-term and continuation
treatment.
STUDY DESIGN
The maintenance study was approved by the institutional review boards
at each of the 12 collaborating centers. The benefits and risks of study participation
were reviewed with each patient. A separate, written informed consent was
obtained for the maintenance phase of the study. The design of the maintenance
phase of the study consisted of random, double-blind assignment to parallel
groups for 76 weeks of treatment with either sertraline hydrochloride (flexible
dose of 50-200 mg/d) or placebo. Patients randomized to placebo were tapered
off sertraline via placebo substitution at a 50-mg/wk rate of reduction.
Randomization was stratified by high and low probability of recurrence
based on 2 variables hypothesized to predict increased probability of recurrence:
presence of residual depressive symptoms (defined as a HAM-D score of  10
and a CGI severity score of 3 at the end of the continuation treatment) and
history of 2 or more prior major depressive episodes. Note that the 24-item
HAM-D scale was used to be consistent with previous chronicdepression studies
and because it more fully captures the range of symptoms often associated
with chronic forms of depressive illness. Patients were evaluated and rated
every 2 weeks for the first 12 weeks and then monthly thereafter. If patients'
depression worsened, visit frequency could be increased to once per week.
DEFINITION OF EXACERBATIONS AND RECURRENCES
Definition and management of depression exacerbations and recurrences
are detailed in previous reports.8-9
Briefly, patients were considered to have an impending recurrence if, at either
a scheduled or unscheduled assessment visit, they met the following criteria:
(1) DSM-III-R criteria for major depression for at
least 3 weeks; (2) CGI severity score of 4 or higher (at least moderate severity);
(3) CGI improvement score of 3 or higher (minimally improved or less); and
(4) an increase in HAM-D score of 4 or more points over maintenance-phase
study baseline. Such patients were rescheduled for a second visit within 1
week (total duration of clinical worsening criteria of at least 4 weeks) and
were declared to have had a recurrence if they continued to meet these criteria
and a senior investigator who interviewed the patient judged the patient to
be in a major depressive episode.
Three time-to-event variables were primary end points of the maintenance
treatment study8-9: time to recurrence
of a major depressive episode, time to reemergence of clinically significant
depression, and time to reemergence of first symptoms of depression. Time
to reemergence of clinically significant depression and time to reemergence
of first symptoms of depression were determined by a blinded review by a panel
of 6 senior investigators of the HAM-D, CGI, and overall clinical picture
of all patients who discontinued the study prematurely. Agreement among 6
of the 8 senior investigators (75%) was required for a patient to be categorized
as having met either of these 2 clinical end points.
PSYCHOSOCIAL FUNCTION ASSESSMENTS
Scales to assess psychosocial function included the Social Adjustment
Scale–Self Report (SAS-SR), the Medical Outcomes Study 36-Item Short-Form
Health Survey (SF-36), and the Longitudinal Interval Follow-up Evaluation
(LIFE). The SAS-SR, developed by Weissman and Bothwell,10
is the most widely used measure of social adjustment in depressed patients.
The scale is composed of 8 subscales and a total adjustment score. For this
study, we evaluated changes on the composite total of all 8 subscales. In
the maintenance phase of the study, the SAS-SR was administered at the maintenance
baseline (which consisted of the last visit of the continuation phase) and
weeks 24, 52, and 76 or when a patient discontinued the study if before week
76.
The SF-3611 is a self-report, health-related,
quality-of-life measure designed to assess overall health status and functioning.
Its 8 subscales assess physical functioning, role limitations owing to physical
health problems, bodily pain, general health, energy and fatigue, social functioning,
role limitations owing to emotional problems, and mental health. The SF-36
has been used extensively in general population surveys and in the Medical
Outcomes Study.4 In assessing psychosocial outcomes,
we focused on the social function and role limitations subscales. The SF-36
was administered at the maintenance baseline and at weeks 8, 24, 52, and 76
or when a patient discontinued the study if before week 76.
The LIFE12 is an assessment of symptoms
and psychosocial functioning with demonstrated reliability and validity. It
has been used in several large-scale, prospective, longitudinal studies of
psychiatric patients. We report results on items from the LIFE that assessed
overall psychosocial functioning (interviewer and patient rated) and life
satisfaction. Raters from all sites were trained to administer the LIFE by
the developers of the scale before beginning the study. The LIFE was administered
at maintenance baseline and at weeks 16, 32, 48, 64, and 76 or when a patient
discontinued the study if before week 76. The source of data on employment
was the SAS-SR, and the source of data on time worked per week is the LIFE.
GENERAL POPULATION SAMPLES
To provide a normative reference for the level of psychosocial function,
we compared SAS-SR and SF-36 scores of our sample with previously reported
community samples of the general population.13-14
Although these "between-study" comparisons are necessarily limited by differences
in time, location, demographics, and methods of administration, they provide
an approximate frame of normative reference that is useful for gauging psychosocial
function. The demographic characteristics of our chronically depressed sample
approximated the normative samples reported previously.14-15
STATISTICAL ANALYSES
The treatment sample analyzed in this report consists of the patients
originally randomized to sertraline in the short-term study and rerandomized
to sertraline or placebo in the maintenance study. Descriptive statistics
are presented for psychosocial measures at short-term baseline, short-term
end point (week 12), maintenance baseline, and maintenance end point. Maintenance
end point is defined as the last available measure for patients who discontinued
the study early or week 76 for completers. In the event of early discontinuation,
the last observed value is carried forward. Group comparisons at maintenance
baseline for psychosocial measures are from an analysis of variance model
with adjustments for 3 stratification variables: study site (pooled into 4
groups), depression type, and probability of recurrence. Because of the small
number of patients at some study sites, the 12 sites were pooled into 4 groups
based on size. Similar comparisons for change from maintenance baseline to
maintenance end point are from an analysis of covariance model with adjustments
for study site, depression type, probability of recurrence, and maintenance
baseline value. Change from maintenance baseline to maintenance end point
within groups was assessed with a 1-sample t test
for continuous data and the McNemar test for categorical data. Comparisons
of psychological measures vs the normative community sample were performed
using a 2-sample t test. The relationships between
the HAM-D and SAS-SR total scores were estimated with the Pearson correlation
coefficient.
All tests are 2-sided. P .05 was considered
statistically significant. The evaluation of psychosocial outcomes in the
maintenance protocol is a secondary analysis and is largely exploratory in
nature. Therefore, P values are best interpreted
as descriptive statistics that identify differences between groups rather
than confirm hypotheses that such differences exist. Given this exploratory
framework, P values were not adjusted for multiple
comparisons.
RESULTS
DEFINITIONS OF SAMPLES FOR THE CURRENT ANALYSES
Of the 635 patients who were enrolled in the original short-term phase
of the study, 426 were randomized to sertraline and 209 to imipramine hydrochloride.
Among the 209 sertraline responders in the short-term phase who began the
4-month continuation phase, 179 patients completed the continuation phase,
169 completed and met criteria for remission or satisfactory response in the
opinion of the investigator, and 161 (95%) enrolled in the maintenance treatment
trial. These 161 patients, randomly assigned at maintenance baseline to receive
either sertraline (n = 77) or placebo (n = 84), constitute the intent-to-treat
sample for comparative assessment of psychosocial outcomes. Fifty-seven percent
were identified as having a high probability of recurrence. Of the 161 randomized
patients, 55 patients completed 76 weeks of maintenance treatment and remained
in remission based on consensus criteria (sertraline, n = 33; placebo, n =
22). Reasons for discontinuation included, for sertraline and placebo, respectively,
insufficient response (11 vs 34), adverse events or intercurrent illness (8
vs 3), and protocol violation or lost to follow-up (23 vs 23).
DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF THE SAMPLES
The demographic and clinical characteristics of the maintenance-phase
study patients have been detailed in previous publications.9
Briefly, 66% were women, with a mean ± SD age of 41.6 ± 9.4
years, and 53% had double depression, with a mean ± SD age of onset
of 24.7 ± 12.1 years. The mean ± SD age of onset of dysthymia
was 16.2 ± 13.2 years. Compared with the original cohort undergoing
the short-term treatment, maintenance patients tended to be better educated
(40% college graduates) and more likely to be married (45% married) than those
originally randomized to sertraline and not entering maintenance treatment.13
PSYCHOSOCIAL OUTCOMES DURING MAINTENANCE TREATMENT
As reported previously,9 maintenance-phase
sertraline treatment resulted in significantly better outcome than placebo
by all criteria used, including depression recurrence (6% vs 23%; P = .004) and reemergence of depressive symptoms (26% vs 50%; P = .001). In the current analysis, no significant differences
in psychosocial measures were found at maintenance baseline for either treatment
group (Table 1). Consistent with
the significantly higher depression recurrence rates for placebo noted herein,9 psychosocial measures exhibited statistically significant
worsening in patients who had been randomized to placebo compared with patients
maintained with sertraline.
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Table 1. Effect of Maintenance-Phase Treatment With Sertraline vs Placebo
on Psychosocial Measures Among All Randomized Maintenance-Phase Patients*
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One of the most surprising findings from the short-term phase of the
current study was the speed with which psychosocial functioning improved during
short-term treatment in patients with a mean current major depression duration
of 6 years.6 In the current analysis (Table 2), patients who had a depression
reemergence during the maintenance phase of the study had a significant worsening
in their psychosocial functioning (except for the SF-36 physical role factor),
losing essentially all of the improvement they had gained in response to treatment.
The magnitude of the loss of psychosocial functioning in patients with reemergence
was similar whether the treatment was sertraline or placebo.
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Table 2. Psychosocial Measures From Maintenance Baseline to End Point
Based on Depression Outcome for All Randomized Maintenance-Phase Patients*
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There was no significant difference in psychosocial functioning from
maintenance baseline to end point for patients who remained healthy (Table 2). However, patients taking sertraline
who remained healthy showed sustained or modest improvement in the LIFE scores,
whereas patients taking placebo showed some decline in their LIFE scores.
As a result (Table 2), there was
a significant difference at maintenance end point for sertraline vs placebo
in the groups that remained healthy. The correlation between depression severity
and psychosocial functioning was high for sertraline (week 76 correlation
between HAM-D total and SAS-SR total, 0.72; P = .001),
but it was weaker for patients taking placebo (week 76 correlation between
HAM-D total and SAS-SR total, 0.24; P = .31).
We were interested to know whether there were differences in psychosocial
functioning at maintenance baseline for the subset of sertraline-treated patients
who had a depression reemergence (n = 20) vs sertraline-treated patients who
remained depression-free (n = 57). The results of this exploratory analysis
(Table 2) found significantly worse
maintenance baseline LIFE scores (by interviewer assessment) for patients
who eventually relapsed (2.25 ± 0.91) compared with patients who remained
healthy (1.65 ± 0.84; P = .02). There were
no significant maintenance baseline differences between the 2 outcome groups
on the other measures we evaluated.
An analysis of the subgroup of sertraline-treated patients whose depressions
remained in remission throughout the maintenance phase of the study revealed
that less than 5% of the overall improvement (from short-term baseline) in
SAS-SR total and LIFE interviewer assessment scores occurred during the maintenance
phase of the study. There was no statistically significant further improvement
on any psychosocial measure from maintenance baseline to maintenance end point.
We compared scores for the sertraline-treated patients who remained
in remission at maintenance end point with community samples for the SAS-SR
and the social functioning, emotional role, and physical role subscales of
the SF-36 (Table 3). Patients were
considered to have achieved normative levels of functioning on a measure if
they were no more than 10% worse than community means (ie, no more than 10% of community norms for the SAS-SR total score and no less than 10% of the mean for the SF-36 scores). Most remitted
patients were at or above community levels of functioning at the baseline
of the maintenance phase of the study, and they maintained this level of functioning
through the end of the maintenance phase.
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Table 3. Course of Psychosocial Improvement Among Subgroup of 55 Patients
Treated With Sertraline Who Remained in Remission During the Entire Maintenance
Phase*
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For sertraline-treated patients, the SAS-SR total score remained significantly
higher (worse) when compared with the community sample throughout all phases
of study treatment. The SF-36 emotional role and physical role were not significantly
different from the community sample at the end point of the short-term phase
and at the baseline and end point of the maintenance phase of the study. However,
the SF-36 social functioning was significantly better than the community sample
at these 3 time points.
An analysis of the subset of sertraline-treated patients who remained
in remission throughout the maintenance phase of the study (Table 4) revealed that improvements in psychosocial measures were
paralleled by improvements in work-related functioning, with most of the improvement
also occurring during the short-term phase, including reductions in unemployment
and improvements in work attendance.
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Table 4. Course of Improvement in Work-Related Indexes During Long-term
Sertraline Use in Subgroup of 55 Patients Who Remained in Remission During
the Entire Maintenance Phase*
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COMMENT
To our knowledge, this is the first report of the effects of long-term
treatment on the psychosocial functioning of patients with chronic depression.
We found only modest additional improvement in psychosocial measures compared
with the rapid improvement noted at the completion of the short-term treatment
phase.6 Nonetheless, maintenance treatment ensured
that initial gains were sustained. In contrast, discontinuation of sertraline
use, by double-blind substitution of placebo, resulted in a rapid decline
in psychosocial function back to pretreatment levels.
There has been some suggestion in the literature16
that patients who achieve normative levels of psychosocial functioning may
be at lower risk for depression relapse than patients who do not achieve comparable
psychosocial recovery. The results of the current study provide only weak
support for an association between lack of psychosocial recovery and relapse
(Table 2). In fact, the only psychosocial
measure that was significantly less improved at maintenance
baseline among patients who progressed to depression reemergence during the
maintenance phase of the study was the LIFE interviewer assessment score.
Similarly, the LIFE (Table 2)
detects a small but significant difference in favor of sertraline among the
subgroup of patients who remained healthy in terms of symptom criteria. This
result parallels data from a recent report17
that found placebo responders in a panic study to have significantly reduced
quality-of-life improvement than responders treated with sertraline who achieved
equivalent levels of improvement.
If there is only modest incremental improvement in psychosocial indices
during long-term treatment, to what extent is this because patients have already
achieved normative levels of functioning compared with individuals in the
community? Using psychosocial functioning scores within 10% of established
community norms as a criterion level, this was only partially true. Normative
levels of psychosocial functioning had been achieved at maintenance baseline
(Table 3) by between 60% and 92%
of patients, depending on the psychosocial measure that was examined. In fact,
some scales (eg, SF-36 role physical and social functioning; Table 3) show modest declines during maintenance treatment. The
presence of persistent psychosocial impairments, despite symptomatic improvement
and long-term therapy, suggests that this subset of patients might benefit
from specific psychosocial interventions designed to foster more complete
rehabilitation.
Perhaps the most notable limitation of the current study consists of
the reliance on subjective psychosocial and functional outcome measures. In
the current study, there is a relatively high correlation at end point between
psychosocial measures and the HAM-D score. Correlations between symptom-based
psychosocial scales tend to be lower at baseline, and (as noted herein) there
have been reports17 that placebo responders
(based on symptom criteria) show significantly less improvement on psychosocial
measures than do responders to active drug. Both of these findings suggest
that psychosocial measures are tapping an outcome domain that is, to a certain
extent, independent of depression symptom severity as measured by the HAM-D.
Nonetheless, more "objective" measures of functioning might be preferable
and attempts should be made to include them in future studies. These might
include both systematic ratings from significant others and actual measures
of behavioral activity (eg, acetometers), job attendance, and productivity.
Use of in vivo behavioral and work measures in place of current surrogate
markers (such as the LIFE and the SAS-SR) may be ideal but is often impractical
and may raise confidentiality and other issues relating to the Americans With
Disabilities Act.
Another limitation of the study consists of the significant degree of
attrition during the treatment. Even though the rate of attrition was what
was expected during such a long study, it may have introduced some unspecified
bias that might serve to reduce the generalizability of the results.
Finally, the magnitude of the treatment effect observed on the one clinician-rated
psychosocial measure (the LIFE) was higher than for the patient-rated measures
(the SAS-SR and the SF-36). This parallels the results for depression symptom
ratings across most treatment studies and raises the issue of whether adverse
effect cueing may have partially abrogated the blind. In our estimation, this
is less likely in the current study since the adverse event rate was relatively
low at this stage of long-term treatment. In conclusion, this study provides
evidence that long-term treatment of chronic forms of depression can result
in sustained psychosocial benefits that lead to normalized psychosocial functioning
in approximately two thirds of remitted patients.
AUTHOR INFORMATION
Submitted for publication August 13, 1999; final revision received September
26, 2001; accepted October 1, 2001.
This study was supported by a grant from Pfizer Inc.
Drs Howland, Kocsis, and Rush are on the Speaker's Bureau of Pfizer
Inc. Drs Schatzberg and Kocsis are consultants for Pfizer Inc. Dr Schatzberg
owns stock in Pfizer Inc. Drs Rush and Kocsis have received research grants
from Pfizer Inc.
Corresponding author and reprints: James H. Kocsis, MD, New York
Hospital-Cornell Medical Center, Box 140, 525 E 68th St, New York, NY 10021
(e-mail: jhk2002{at}med.cornell.edu).
From the Cornell University School of Medicine, New York, NY (Drs Kocsis
and Gniwesch); Stanford University School of Medicine, Stanford, Calif (Dr
Schatzberg); University of Texas Southwestern Medical Center, Dallas (Dr Rush);
State University of New York at Stony Brook (Dr Klein); University of Pittsburgh
Medical Center and Western Psychiatric Institute and Clinic, Pittsburgh, Pa
(Dr Howland); Quintiles, Research Triangle Park, NC (Dr Davis); and Pfizer
Inc and College of Physicians and Surgeons, Columbia University, New York
(Dr Harrison).
REFERENCES
| |
1. Wells K, Stewart A, Hays R, Burnam A, Rogers W, Daniels M, Berry S, Greenfield S, Ware J. The functioning and well-being of depressed patients: results from
the Medical Outcomes Study. JAMA. 1989;262:914-919.
ABSTRACT
2. Spitzer RL, Williams JB, Kroenke K, Linzer M, deGruy FV, Hahn SR, Brody D, Johnson JG. Utility of a new procedure for diagnosing mental disorders in primary
care: the PRIME-MD 1000 Study. JAMA. 1994;272:1749-1756.
ABSTRACT
3. Markowitz JC. Comorbidity of dysthymic disorder. In: Kocsis JH, Klein DN, eds. Diagnosis and Treatment of Chronic
Depression. New York, NY: Guilford Press; 1995:41-57.
4. Berndt ER, Koran LM, Finkelstein SN, Gelenberg AJ, Kornstein SG, Miller IM, Thase ME, Trapp GA, Keller MB. Lost human capital from early-onset chronic depression. Am J Psychiatry. 2000;157:940-947.
FREE FULL TEXT
5. Kocsis JH, Frances AJ, Voss C, Mason BJ, Mann JJ, Sweeney J. Imipramine and social-vocational adjustment in chronic depression. Am J Psychiatry. 1988;145:997-999.
FREE FULL TEXT
6. Miller IW, Keitner GI, Schatzberg AF, Klein DN, Thase ME, Rush AJ, Markowitz JC, Schlager DS, Kornstein SG, Davis SM, Harrison WM, Keller MB. The treatment of chronic depression, part 3: psychosocial functioning
before and after treatment with sertraline or imipramine. J Clin Psychiatry. 1998;59:608-619.
ISI
| PUBMED
7. Kocsis JH, Zisook S, Davidson J, Shelton R, Yonkers K, Hellerstein DJ, Rosenbaum J, Halbreich U. Double-blind comparison of sertraline, imipramine, and placebo in the
treatment of dysthymia: psychosocial outcomes. Am J Psychiatry. 1997;154:390-395.
ABSTRACT
8. Rush AJ, Koran LM, Keller MB, et al. The treatment of chronic depression: study design and rationale for
evaluating the comparative efficacy of sertraline and imipramine as acute,
crossover, continuation, and maintenance phase therapies. J Clin Psychiatry. 1998;59:589-597.
PUBMED
9. Keller MB, Kocsis JH, Thase ME, Gelenberg AJ, Rush AJ, Koran L, Schatzberg A, Russell J, Hirschfeld R, Klein D, McCullough JP, Fawcett JA, Kornstein S, LaVange L, Harrison W. Maintenance phase efficacy of sertraline for chronic depression: a
randomized controlled trial. JAMA. 1998;280:1665-1672.
FREE FULL TEXT
10. Weissman MM, Bothwell S. Assessment of social adjustment by patient self-report. Arch Gen Psychiatry. 1976;33:1111-1115.
ABSTRACT
11. Ware J, Sherbourne C. The MOS 36-Item Short-Form Health Survey (SF-36). Med Care. 1992;30:473-481.
ISI
| PUBMED
12. Keller M, Lavori P, Friedman B, Nielsen E, Endicott J, McDonald-Scott P, Andreasen N. The Longitudinal Follow-up Evaluation. Arch Gen Psychiatry. 1987;44:540-548.
ABSTRACT
13. Keller MB, Gelenberg AJ, Hirschfeld RM, Rush AJ, Thase ME, Kocsis JH, Markowitz JC, Fawcett JA, Koran LM, Klein DN, Russell JM, Kornstein SG, McCullough JP, Davis SM, Harrison WM. The treatment of chronic depression, part 2: a double-blind, randomized
trial of sertraline and imipramine. J Clin Psychiatry. 1998;59:598-607.
ISI
| PUBMED
14. McHorney C, Kosinski M, Ware J. Comparisons of the costs and quality of norms for the SF-36 Health
Survey collected by mail versus telephone interview: results from a national
survey. Med Care. 1994;32:551-567.
ISI
| PUBMED
15. Weissman MM, Prusoff BA, Thompson WD, Harding PS, Myers JK. Social adjustment by self-report in a community sample and in psychiatric
outpatients. J Nerv Ment Dis. 1978;166:317-326.
ISI
| PUBMED
16. Keitner GI, Ryan CE, Miller IW, Zlotnick C. Psychosocial factors and the long-term course of major depression. J Affect Disord. 1997;44:57-67.
PUBMED
17. Rapaport MH, Pollack M, Wolkow R, Mardekian J, Clary C. Is placebo response the same as drug response in panic disorder? Am J Psychiatry. 2000;157:1014-1016.
FREE FULL TEXT
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