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Predictors of Early Recovery From Major Depression Among Persons Admitted to Community-Based Clinics
An Observational Study
Barnett S. Meyers, MD;
Jo Anne Sirey, PhD;
Martha Bruce, PhD;
Mimi Hamilton, PhD;
Patrick Raue, PhD;
Steven J. Friedman, MS;
Cynthia Rickey, MS;
Tatsu Kakuma, PhD;
Melissa K. Carroll;
Dimitris Kiosses, PhD;
George Alexopoulos, MD
Arch Gen Psychiatry. 2002;59:729-735.
ABSTRACT
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Background Twenty years have elapsed since the National Institute of Mental Health
Collaborative Depression Study reported on the early course and treatment
of major depression within the mental health sector. Using similar methods,
an observational study was conducted to assess relationships between initial
depression severity, personality dysfunction and other baseline characteristics,
subsequent treatment, and 3-month outcomes among persons admitted to public
and voluntary sector outpatient clinics, including 1 academic program.
Methods A 2-stage sampling technique was used to recruit subjects (N = 165)
diagnosed by the Structured Clinical Interview for DSM-IV, Patient Version, as having a major depression episode. Sociodemographic
and clinical characteristics were assessed at admission. Data on treatment
and outcome were obtained at 3 months using structured instruments from the
Longitudinal Interview Follow-up Evaluation. Logistic regression was used
to assess hypothesized predictors of early recovery. Analyses were carried
out in the total sample and after dichotomizing subjects by baseline depression
severity.
Results Fifty (30.3%) of the 165 subjects met recovery criteria. Less than half
of the subjects (45%) met criteria for adequate pharmacotherapy. Less severe
depression, having received adequate antidepressant treatment, female sex,
and being married independently predicted early recovery. In the more depressed
subgroup, early recovery was associated with female sex. Among less severely
depressed subjects, high personality dysfunction scores and being married
were significant predictors.
Conclusions Initial depression severity and receiving adequate pharmacotherapy predict
early recovery in individuals with major depression seeking outpatient treatment.
A minority of persons receive intensive antidepressant treatment. Less severe
personality dysfunction and being married predicts early recovery among persons
with less severe depression.
INTRODUCTION
WE REPORT on 12-week recovery and its predictors among patients with
major depression following admission to community-based mental health clinics
and an academic outpatient program. The study builds on and extends earlier
results from the naturalistic National Institute of Mental Health (NIMH) Collaborative
Depression Study (CDS)1-4
in the following 2 principal ways: (1) Recruitment includes admissions to
nonacademic clinics. (2) The study is conducted following the widespread use
of new classes of antidepressants. The relationship between specific predictor
variables, including antidepressant treatment intensity, and recovery 12 weeks
following admission is assessed.
Evidence from randomized controlled trials has demonstrated a 65% 6-week
response rate in subjects who receive antidepressants compared with approximately
35% in those who receive placebo.5-6
Results from efficacy studies stand in contrast to observational data generated
by the CDS.1-4
The CDS demonstrated that intensive somatic treatment prior to admission to
the study's academic centers was infrequent.1
Furthermore, the intensity of pharmacotherapy following admission to participating
academic centers was both low and unrelated to either the probability of recovery
or the duration of depressive episodes.2 The
CDS also examined other factors that influenced recovery rates under naturalistic
conditions. Acute onset was found to predict early recovery, while protracted
index episodes, underlying dysthymia, lower socioeconomic status, and a comorbid
Axis I disorder were associated with chronicity.3
The NIMH Treatment of Depression Collaborative Research Program trial
indicated that depression severity influences differential responsiveness
to pharmacotherapy compared with psychotherapy or medication clinic placebo.7 This 16-week randomized trial demonstrated that 150
mg of imipramine hydrochloride treatment was superior to placebo and 2 manualized
psychotherapies among subjects with Hamilton Depression Rating Scale (HDRS)8 scores of less than 20 only. There were no significant
differences between placebo and either imipramine or the psychotherapies in
the less severely depressed subgroup. Also, subjects with a coexisting personality
disorder were less likely to achieve remission HDRS scores of 6 or less,9 a finding consistent with other studies demonstrating
that comorbid personality dysfunction worsens the course of depression.10-13
Data generated from subjects recruited at academic centers may have
limited generalizability to patients treated in community settings.14 We report the effects of baseline patient characteristics
and treatment intensity on the early course of major depression among outpatients
admitted to 1 academic center and 5 community-based mental health clinics.
We tested the hypothesis that depression severity and comorbid personality
dysfunction would decrease the likelihood of early recovery, while intensive
antidepressant therapy would increase the recovery rate. We also investigated
the effects of sociodemographic factors, functioning, and type of service
site. A secondary analysis was carried out using the HDRS cutoff of more than
20 applied in the NIMH Treatment of Depression Collaborative Research Program
trial to determine whether this level of severity influenced the effect of
identified predictor variables.
SUBJECTS AND METHODS
SITES
Sites were selected from Westchester County, New York, in consultation
with the county's commissioner of community mental health (S.J.F.) to maximize
socioeconomic and ethnic diversity. Westchester County has approximately 900 000
inhabitants residing in urban, semiurban, suburban, and semirural settings
and includes Yonkers, the third largest city in New York State. Six clinics
were selected to provide diversity of setting types and patient sociodemographic
characteristics. Sites included the outpatient department of a teaching hospital
(New York Presbyterian Hospital–Westchester Division), a second voluntary
sector hospital-based clinic (Phelps Memorial Hospital Center, Sleepy Hollow),
3 county clinics, and a freestanding voluntary sector clinic. Two county clinics
were selected from urban settings with 1 in downtown Yonkers. Clinic administrators
assisted by coordinating the scheduling of new patient evaluations so that
a research assistant would be present when the patient arrived.
SUBJECTS
Patients 18 years and older admitted consecutively to participating
clinics during the 2 years from October 1, 1995, through December 31, 1997,
were invited to participate in a 2-stage screening process described previously.15 Written informed consent was obtained prior to the
administration of research instruments. Patients with scores of 16 or higher
on the Center for Epidemiological Studies–Depression scale16
or meeting DSM-IV17
criteria for major depression on the Mini International Neuropsychiatric Interview18 were administered the Structured Clinical Interview
for DSM-IV, Patient Version (SCID-P),19
to establish the presence of a current unipolar major depression. Cognitive
functioning was assessed with the Mini-Mental State Examination.20
The SCID-P interviews were administered by college graduates or master's-level
students who had completed a 1-week SCID-P training course. A clinical psychologist
(P.R.) with 2-year research experience who had also completed the course reviewed
each SCID-P.
Admitted patients who met criteria for major depression without having
exclusion criteria were invited to participate in the longitudinal study.
Exclusion criteria were a Mini-Mental State Examination score of less than
24 or a history of alcohol or other substance abuse within the past month.
Patients who had episodes of mania or psychosis, had another Axis I disorder
other than comorbid dysthymia, and participated in a controlled treatment
trial were excluded.
Of the 1180 outpatient admissions approached, 1106 (94%) consented to
the initial screening. Of these, 689 (62%) screened positive for major depression
and 455 of these (66%) consented to the SCID-P interview. Twenty-seven percent
of those interviewed (n = 125) had an exclusion criterion and an additional
120 (26%) failed to meet criteria for a major depression. The remaining 210
subjects (46%) received the full battery of baseline assessments and entered
the follow-up phase.
Three-month data were obtained on 165 (79%) of the initial longitudinal
sample, with the remaining 45 (21%) refusing to participate or otherwise lost
to follow-up. Subjects without 3-month assessments did not differ significantly
on baseline sociodemographic or clinical variables from those with 3-month
data.
BASELINE ASSESSMENTS
Baseline measures for subjects with major depression included the 17-item
HDRS,8 the Global Assessment of Functioning
Scale from DSM-IV,17
the Chronic Disease Score21 to assess medical
comorbidity, the 36-Item Short-Form Health Survey,22
and the Multilevel Assessment Inventory23 to
assess social support and independent functioning, and the Duke Social Support
and Stress Scale24 to assess social support
and independent functioning. The first 3 subscales of the 47-item version
of the self-report Inventory of Interpersonal Problems25
were administered to screen for the presence of personality dysfunction. The
Inventory of Interpersonal Problems is a self-report measure that inquires
about personality attributes that are presumed to be enduring without providing
a time frame. A cutoff of greater than 1.1 on these subscales has been validated
against a semistructured interview to indicate the presence of a DSM-IV personality disorder among patients with major depression.25 Soon after the study began, the 5 general anxiety
items from the Clinical Anxiety Scale26 were
added to assess comorbid baseline anxiety as a predictor of early course.
Data on recent use of medical and mental health services were collected using
the Cornell Services Use Index27 (This scale
is available from the authors on request). Subjects were provided nominal
reimbursement for participation in each phase of the study.
FOLLOW-UP ASSESSMENTS
As in the CDS, follow-up assessments used measures from the Longitudinal
Interval Follow-up Evaluation (LIFE).28 Subjects
were interviewed by telephone to determine the course of depression, treatment
provided, and adverse effects experienced.
The LIFE's Psychiatric Status Rating (PSR) uses a 6-point scale to quantify
the severity of depressive symptoms relative to full major depression criteria.
Application of the PSR uses the LIFE method of dividing the 3-month time frame
by significant landmarks (eg, holidays, birthdays, and life events) and then
determining the subject's level of symptoms in relation to the specified dates.
Recovery was defined as being asymptomatic (PSR ratings of 1) or having 1
or more symptoms of no more than a mild degree (PSR of 2) over the preceding
2 weeks. The LIFE's 8-week PSR duration of recovery criterion was shortened
to 2 weeks for the purpose of identifying cases of recovery occurring within
the first 12 weeks. An investigator (B.S.M.) with experience using these measures
trained and supervised the research assistants.
Antidepressant intensity was quantified initially on a 5-point scale
adapted from the LIFE's Composite Antidepressant Scale, with ratings added
for newer classes of antidepressants (scale available from us on request).
In the revised scale, a score of 3 was assigned for 125 mg or more of desipramine
hydrochloride, 50 mg or more of nortriptyline hydrochloride, 150 mg or more
of venlafaxine hydrochloride, 50 mg or more of sertraline hydrochloride, 20
mg or more of fluoxetine hydrochloride, 20 mg or more of citalopram hydrobromide,
or 20 mg or more of paroxetine hydrochloride.
The LIFE's Composite Antidepressant Scale score was collapsed to assess
intensity of antidepressant treatment. Adequate treatment was defined as a
weekly mean LIFE Composite Antidepressant Scale score of 3 or more for a minimum
of 4 consecutive weeks receiving 1 or more antidepressants and inadequate
treatment defined as having received antidepressants below this dose or duration.
Subjects who did not receive any antidepressant treatment comprised a third
group.
Delineation of dose and duration of antidepressant use applied significant
anchor dates to subdivide the 3-month follow-up period.28
Patient report was used to determine the dose and duration of antidepressant
treatment and compliance with medication. The use of psychotherapy was assessed
using self-report data elicited through the Cornell Services Use Index.
STATISTICAL ANALYSES
Data analyses were carried out to construct a parsimonious and clinically
informative model describing the likelihood of recovery at 12 weeks based
on the hypothesized predictors. Bivariate analyses were also carried out for
potential associations between early recovery and both baseline sociodemographic
and clinical variables. The bivariate analyses used  2 tests
with continuity adjustment for 2-sample comparisons or the Fisher exact test
for cells with expected frequencies of fewer than 5 for categorical variables
and t tests for continuous data. Data are reported
as mean (SD). Two-tailed P values of less than .05
were considered statistically significant in the bivariate analyses.
To reduce the number of factors eligible to be used for construction
of the predictive model, we added only those variables with nominal 2-sided P values of .10 or less from the bivariate analyses into
the hierarchical logistic regression after entering the hypothesized predictors,
followed by age and sex. Adjusted odds ratios (ORs) and 95% confidence intervals
(CIs) were calculated for each predictive variable. All values are reported
as mean (SD).
RESULTS
The 165 subjects with 3-month follow-up data had a mean age of 44.6
(17.2) years and 13.4 (2.8) years of education. Sixty-four percent of the
sample was female (n = 106) and 30% were members of racial minority groups
(n = 66). One hundred eight subjects (66%) received an antidepressant.
COMPARISON OF RECOVERED AND NONRECOVERED SUBJECTS
Fifty subjects (30.3%) met criteria for recovery at 3 months. An additional
52 subjects (31.5%) had not recovered but no longer met criteria for a major
depression at the 3-month assessment. There were not significant associations
between sociodemographic or site characteristics and early recovery (Table 1). Recovery seemed to be associated
with the clinical variables of lower baseline HDRS scores (t163 = 3.38, P = .001), lower anxiety
scores (t132 = 2.45, P = .02), and having interpersonal problem scores below the cutoff
for personality dysfunction (21 = 4.81, P = .03). The 21 subjects with concurrent dysthymia constituted 13%
of the sample. Although the presence of dysthymia was associated with a lower
3-month recovery rate (8% vs 15%), this difference did not reach statistical
significance (21 = 0.90, P
= .34). Early recovery was associated with better baseline functioning as
indicated by higher scores on the Global Assessment of Functioning Scale (t163 = -2.06, P
= .04) and the 36-Item Short-Form Health Survey subscales of physical functioning
(t129.7 = -3.37, P = .001) and pain perception (t160
= 2.62, P = .01).
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Table 1. Baseline Characteristics of Recovered and Nonrecovered Subjects*
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One hundred eight (65%) of the 165 subjects received antidepressants;
74 (69%) received a new class of antidepressant. The proportions of subjects
treated with an antidepressant from a new class and those treated with a tricyclic
antidepressant that met criteria for adequacy were highly comparable (68%
vs 70%). Overall, only 74 (45%) of the 165 subjects met criteria for an adequate
dose for 4 weeks. Of these 74 subjects, 28 (38%) recovered, compared with
16 (28%) of 57 subjects who did not receive any antidepressants and only 6
(18%) of 34 who received antidepressants at inadequate doses (22 = 4.7, P = .09) (Table 2). Self-reported compliance with pharmacotherapy (21 = 3.80, P = .004) was associated
with recovery among subjects for whom antidepressants were recommended. There
were no differences between recovered and nonrecovered subjects in whether
psychotherapy had been recommended and number of therapy sessions or remaining
in treatment over the 12 weeks.
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Table 2. Treatment Characteristics of Recovered and Nonrecovered Subjects
With 3-Month Follow-up Data
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There was a significant difference between the academic and nonacademic
sites in the distribution of antidepressant treatment intensity classified
as adequate, inadequate, or none (22 = 8.92, P = .02). A greater proportion of subjects treated at the
academic site met criteria for adequate antidepressant treatment (53% vs 36%, 21 = 4.41, P = .04). Nevertheless,
type of service site was not associated with differences in early recovery
(Table 1).
PREDICTORS OF EARLY RECOVERY
Hierarchical logistic regression for the 163 subjects with complete
data sets was conducted. Hypothesized predictors of baseline depression severity,
meeting criteria for personality dysfunction, treatment adequacy, age, and
sex were entered in the model first. More severe depression (OR = 0.89; 95%
CI, 0.81-0.97; P = .01) was associated with a decreased
likelihood of early recovery (Table 3). Classifying antidepressant intensity into adequate, inadequate, or none demonstrated
that subjects who had adequate treatment were more than 3 times more likely
to recover than subjects who received inadequate treatment (OR = 3.2; 95%
CI = 1.1-9.5; P = .04). Being married (OR = 2.4;
95% CI = 1.1-5.3; P = .03) was the only other baseline
characteristic or treatment variable that remained significant in the logistic
regression. There were no significant interactions between regression terms
in the model. Because most of the 42 geriatric subjects (91%) were treated
at the academic site that emphasizes antidepressant therapy, we repeated the
model using dummy variables for site and for age 60 years and older. The resulting
model was also significantly associated with early recovery. We then compared
the 2 models and found that the addition of older age and site variables did
not change the model significantly (Wald 26 = 7.4, P = .29). The more parsimonious model is reported.
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Table 3. Hierarchical Logistic Regression of Predictive Variables for
160 Subjects
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Based on the absence of a drug-placebo difference in patients with HDRS
scores of less than 21 in the NIMH Treatment of Depression Collaborative Research
Program trial,14 we repeated the logistic regressions
after subdividing subjects into those with HDRS scores of more than 20 (n
= 72) and those with scores of 20 or less (n = 101). Of predictors in the
original model, only female sex remained a significant predictor of early
recovery in the subgroup of more severely depressed subjects (OR = 1.1; 95%
CI = 1.2-106.5; P = .04). Despite an increased OR,
adequate antidepressant treatment was not a significant predictor in the smaller
subgroup of more severely depressed subjects (OR = 4.7; 95% CI = 0.76-29.2; P = .10). In the subgroup of less depressed subjects, subjects
who met criteria for personality dysfunction had a decreased likelihood of
early recovery (OR = 0.32; 95% CI = 0.13-0.79; P
= .01) while those who were married were more likely to recover (OR = 3.6;
95% CI = 1.4-9.3; P = .01).
COMMENT
Only 30% of 165 outpatient admissions with major depression achieved
the recovery criterion of 2 weeks with no more than minor symptoms over the
subsequent 12 weeks. Despite evidence that psychiatrists are 1.6 times more
likely to write antidepressant prescriptions than a decade ago,29
only 65% of the 165 outpatients received an antidepressant during the 3 months
following a clinic admission and only 44% met criteria for 4 weeks at an adequate
dose. Of subjects who had antidepressants prescribed, most (69%) did meet
criteria for adequacy.
In contrast to CDS findings,3-4
intensive pharmacotherapy was associated with early recovery. Classifying
subjects as having received adequate antidepressant treatment, inadequate
intensity, and no antidepressants demonstrated a significant independent effect
on recovery rates. These are the first data of which we are aware demonstrating
that meeting a criterion for adequately intense antidepressant therapy predicts
early course recovery under naturalistic conditions. Follow-up observational
data from the CDS did demonstrate that remaining at the level of somatic treatment
associated with recovery reduced the rate of early recurrence.30
The naturalistic design precludes determining relationships between
dose and treatment response. Although the effect of adequate antidepressant
treatment decreased to a trend level in the more severely depressed subgroup
of 61 subjects, the smaller sample size limited power to demonstrate a significant
effect. Alternatively, patients who received higher doses would include both
subjects who had their doses raised because of nonresponse and those who recovered
as a result of having received higher doses. The possible overrepresentation
of treatment-resistance among subjects who received adequate pharmacotherapy
would decrease the likelihood of finding a treatment effect. The same selectivity
process would act among less severely depressed subjects.
The finding of decreased early recovery in men, including among the
more severely depressed subjects, adds to a conflicting literature using different
methods.31 Selection factors may contribute
to these findings in that men who seek treatment in community outpatient clinics
may do so because of a more persistent form of depression.
The finding of increased early recovery among married persons overall
and particularly among those with mild depression has not been reported previously.
In an epidemiological sample, persons who were either married or single had
lower rates of persistent depression than individuals who had had a change
in marital status due to separation, divorce, or widowhood.31
In contrast, marital status did not predict time to recovery in the clinical
sample of the CDS.4 It may be that the largely
inpatient composition of the CDS subjects (75%), including 15% who met criteria
for psychotic depression, washed out a possible effect of marital status,
particularly among persons with less severe depression.
Depression severity affected the association between screening positive
for personality dysfunction and early recovery, with the significant effect
observed only in the subgroup of mildly depressed subjects (P = .01). In the absence data on personality dysfunction data at 3
months, we are unable to assess whether this association on a self-report
measure was a function of being depressed. Other factors including negative
life events32 and the presence of anxiety disorder
symptoms33 have been demonstrated to delay
recovery from major depression under naturalistic conditions. Although bivariate
analyses suggested that subjects who recovered early had less anxiety at admission
(P = .02), severity of anxiety did not independently
predict recovery in a model using the 134 subjects with baseline anxiety scores.
Similarly, subjects who did not recover had lower baseline scores in multiple
functional domains, but baseline functioning did not have an effect in the
logistic regression that controlled for other factors. Thus, the lower baseline
36-Item Short-Form Health Survey physical functional and pain perception scores
in nonrecovered subjects may have been accounted for by a factor such as depression
severity in the regression.
This study was limited by the small sample size relative to the number
of factors that may influence early recovery. By testing for the effect of
hypothesized predictors before entering other factors identified by the bivariate
associations, the analysis limited the likelihood of a type I statistical
error. Also, the numbers of subjects in specific predictor categories (eg,
ethnic minority or having comorbid dysthymia) may have been too small to demonstrate
a significant effect. Furthermore, factors such as physical functioning that
were marginally associated with early recovery in the regression (data not
shown) require further study to more definitively investigate their predictive
effects.
Because of the numerous patient, provider, and setting factors that
might influence the administration of psychotherapy and differences in forms
of this treatment, we are unable to determine whether psychotherapy administered
alone or in combination with pharmacotherapy contributed to early recovery.
Similarly, we are unable to assess the effects of different forms of insurance
benefits on the treatments provided or early course.
Inventory of Interpersonal Problems and HDRS assessments were not repeated
at 3 months. Therefore, we are unable to determine the extent to which personality
dysfunction was a feature of the depressed state or whether identified predictors
of recovery also predicted net decreases in depression severity.
Finally, interpretation of these data must be considered in light of
the definition of recovery used. The CDS focused primarily on the longer-term
course of depression and defined recovery as 8 consecutive weeks of a PSR
of 1 or 2 rather than the 2-week criterion used in this study. The low recovery
rate identified using the less rigorous 2 consecutive weeks of no or minimal
symptoms is noteworthy.
The finding that under one third of individuals seeking treatment for
major depression within the mental health sector recover within 3 months speaks
to the need for longer and more intensive treatment. The frequency of recovery
is markedly below rates reported in efficacy trials.5-6
The higher recovery rates reported from efficacy trials than naturalistic
studies may result from screening out patients who are unlikely to respond
from controlled trials. Although the use of systematically applied inclusion
criteria suggests that the patient sample was similar clinically to subjects
recruited into controlled studies, subjects participating in antidepressant
trials are more likely to have a forced titration up to adequate dosages.
These data suggest that identifiable sociodemographic, clinical, and
treatment factors can influence the early course of depression and are consistent
with the need to improve our management of depression in community-based mental
health settings. Initiatives designed to reverse the documented undertreatment
of major depression in primary care34 will
be achieved more easily after undertreatment within the mental health sector
is corrected.14, 35
AUTHOR INFORMATION
Submitted for publication May 3, 2000; final revision received September
26, 2001; accepted October 1, 2001.
This study was supported by grant MH53816 from the National Institute
of Mental Health, Bethesda, Md.
We thank Mark Olfson, MD, for his valuable consultations during this
project. We also thank Tara DiDomenico, Claire Mackay, Brooke Myers, Lauren
Picone, and Mark Russakoff, MD, for their help.
Reprints: Barnett S. Meyers, MD, Department of Psychiatry, New York–Presbyterian
Hospital, Westchester Division, 21 Bloomingdale Rd, White Plains, NY 10605
(e-mail: bmeyers{at}med.cornell.edu).
From the Department of Psychiatry, Weill Medical College of Cornell
University, White Plains, NY. Dr Meyers is now with the Departments of Psychiatry,
Weill Medical College of Cornell University and New York–Presbyterian
Hospital, White Plains.
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