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discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/21301973

Sotsky SM, Glass D, Shea MT, Pilkonis PA, Collins

JF, Elkin I et al. Patient predictors of response to
psychotherapy and pharmacotherapy: findings
in the NIMH treatment of depressi...
ARTICLE in AMERICAN JOURNAL OF PSYCHIATRY SEPTEMBER 1991
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Regular

and

Articles

Patient
Predictors
of Response
to Psychotherapy
Pharmacotherapy:
Findings
in the NIMH
Treatment
of Depression
Collaborative
Research
Program

Stuart

M. Sotsky,
M.D., M.P.H.,
David R. Glass, Ph.D., M. Tracie Shea, Ph.D.,
Paul A. Pilkonis,
Ph.D., Joseph F. Collins,
Sc.D., Irene Elkin, Ph.D.,
John T. Watkins,
Ph.D., Stanley D. Imber, Ph.D., William
R. Leber, Ph.D.,
Janet Moyer,
M.S., and Mary Ellen Oliveri,
Ph.D.

Objective:
The authors
investigated
patient
characteristics
predictive
of treatment
response
in the National
Institute
of Mental
Health
(NIMH)
Treatment
of Depression
Collaborative
Research
Program.
Method:
Two hundred
thirty-nine
outpatients
with major
depressive
disorder
according
to the Research
Diagnostic
Criteria
entered
a 1 6-week
multicenter clinical
trial and were randomly
assigned
to interpersonal
psychotherapy,
cognitivebehavior
therapy,
imipramine
with clinical
management,
or placebo
with clinical
management.
Pretreatment
sociodemographic
features,
diagnosis,
course
of illness,
function,
personality,
and symptoms
were studied
to identify
patient
predictors
of depression
severity
(measured
with the Hamilton
Rating Scale for Depression)
and complete
response
(measured
with the Hamilton
scale and the Beck Depression
Inventory).
Results:
One hundred
sixtytwo patients
completed
the entire 1 6-week
trial. Six patient
characteristics,
in addition
to
depression
severity
previously
reported,
predicted
outcome
across all treatments:
social dysf unction,
cognitive
dysfunction,
expectation
of improvement,
endogenous
depression,
double depression,
and duration
of current
episode.
Significant
patient
predictors
of differential
treatment
outcome
were identified.
1) Low social dysfunction
predicted
superior
response
to
interpersonal
psychotherapy.
2) Low cognitive
dysfunction
predicted
superior
response
to
cognitive-behavior
therapy
and to irniprarnine.
3) High work dysfunction
predicted
superior
response
to irnipramine.
4) High depression
severity
and impairment
of function
predicted
superior
response
to imipramine
and to interpersonal
psychotherapy.
Conclusions:
The resuits demonstrate
the relevance
of patient
characteristics,
including
social,
cognitive,
and
work function,
for prediction
of the outcome
of major depressive
disorder.
They provide
indirect
evidence
of treatment
specificity
by identifying
characteristics
responsive
to different
modalities,
which may be of value in the selection
of patients
for alternative
treatments.
(Am J Psychiatry
1991;
148:997-1008)

Presented
in part at the 139th annual
meeting
of the American
Psychiatric
Association,
Washington,
D.C., May 10-16,
1986. Received Aug. 13, 1990; revision
received
Feb. 20, 1991; accepted
March 20, 1991. From the Department
of Psychiatry
and Behavioral
Sciences, George Washington
University
Medical
Center;
the Mood,
Anxiety
and Personality
Disorders
Research
Branch,
NIMH,
Rockville, Md.; Western
Psychiatric
Institute
and Clinics, Pittsburgh,
Pa.;
the VA Medical
Center,
Perry Point, Md.; the University
of Chicago
School of Social Service Administration;
and the Department
of Psy-

Am

J Psychiatry

1 48:8,

August

1991

chiatny and Behavioral

Sciences,
University
of Oklahoma
Health
Sciences
Center,
Oklahoma
City. Address
reprint
requests
to Dr.
Sotsky, Department
of Psychiatry
and Behavioral
Sciences,
George
Washington
University
Medical
Center,
2150 Pennsylvania
Ave.,
N.W., Washington,
DC 20037.
The authors
thank David Reiss, M.D., for scientific
consultation
and manuscript
review, Samuel Simmens,
Ph.D., for statistical
consultation,
Victoria
L. Herzberg
for administrative
assistance,
and the
clinical evaluators
and therapists
at the three research
sites.

997

PATIENT

PREDICTORS

OF RESPONSE

n the effort to understand

the variability
of response
to treatments
for depression,
the relevance
of patient characteristics
has received
much attention.
Nevertheless,
relatively
little systematic
research
has exammed the predictive
value
of these characteristics
in
studies
comparing
different
forms
of psychotherapy
and pharmacotherapy.
Certain
characteristics
of the
patient
and the nature
of the depression
may be general indicators
of prognosis
irrespective
of treatment,
while others
may be indicators
of response
to individual treatments
alone or of differential
treatment
outcome,
that is, preferential
response
to one or more
treatments
compared
to others. The elucidation
of predictors
of response
addresses
an important
aspect
of
treatment
specificity
by characterizing
the type of patients for whom
a treatment
is most or least effective;
it could
also have direct
clinical
applicability
in the
selection
of patients
for the most appropriate
treatment
modality.
In addition,
some predictors
of response
to treatment
may provide
indirect
evidence
about
the putative
specific
mechanism
of a particular
modality

by indicating

patient

characteristics

that

are

especially
responsive
to it, such as functional
and relational
capacities
or type of depression.
This may be
especially
important
because
only limited
evidence
about differential
treatment
effects on measures
of outcome hypothesized
to be specific to each modality
has
emerged
from this study (1, 2). Although
we chose to
consider
patient
characteristics
initially,
since there is
some indication
from the literature
(3, 4) that they
have greater
influence
on outcome,
we plan to address
therapist,
relationship,
and process
variables
in future
analyses.
Comprehensive
reviews
of general
predictors
of response to psychotherapy
(5, 6) and to tricyclic
antidepressants
(7-9) reveal that the literature
is characterized by lack of consensus
about or replication
of many
findings.
The general
predictors
of response
to psychotherapy
that have emerged
have been derived
from
many studies
based on various
psychotherapies,
often
in small and heterogeneous
samples
of patients
with
diverse
disorders.
Other
major
reasons
for the inconsistent
findings
among
studies
include
lack of specification
of the treatment,
variability
of inclusion
and
diagnostic
criteria,
lack of standardization
of outcome
measures,
variability
of criteria
for improvement,
and
differences
in selection
of patient
variables
and measures investigated.
The purpose
of this article
is to report
the patient
characteristics
that predicted
treatment
response
in the
National
Institute
of Mental
Health
(NIMH)
Treatment of Depression
Collaborative
Research
Program
(10), which was the first multicenter,
comparative
dinical treatment
trial in the field of psychotherapy
research
initiated
by NIMH.
This study compared
the
efficacy
of interpersonal
psychotherapy,
cognitive-behavior
therapy,
imipramine
with clinical
management
(as a standard
reference
condition),
and placebo
with
clinical
management
(as a control
condition)
for out-

998

patients
with nonbipolar,
nonpsychotic
major
depressive disorder.
Several
features
of the Collaborative
Research
Program
clinical
trial
design
were
considered
advantageous
for the study
of the relation
of patient
predictors

to treatment

outcome.

First,

the

multisite,

common

protocol
design
permitted
study
of a larger
sample
than do most single-site
studies,
but with uniformity
of
diagnosis
and severity
of depression
across
sites. Second,
the extraordinary
standardization
of the thera-

pies-with

treatment

manuals,

therapist

training,

and

monitoring
of the quality
of performance-would
enhance
the prediction
of response
to specific
treatments
by reducing
the variability
of the treatments
themselves.
Third,
the use of a control
condition,
placebo
with
clinical
management,
would
help
differentiate
predictors
of response
to specific
treatments
from predictors
of general
response
or response
to nonspecific
treatment.
Fourth,
the use of standard
outcome
measures and response
criteria
would
permit
better
comparison
with the results
of other
studies.
We examined
predictors
in two groups
of patients:
1) those
who
completed
the course
of treatment,
in order
to search

for predictors

of outcome

sure to the
all of those

specific
ingredients
who entered
the

those

who

search

for

withdrew

of the

was

full expo-

therapies,
trial,

completion,
full

range

and 2)
including

in order

to

of outcomes.

single-site
comparative
treatment
studies
psychotherapy
and cognitive-behavior

therapy
whose
results
would
those
of the NIMH
Treatment

orative

there

of the
treatment

before

predictors

In previous
of interpersonal

when

Research

Program,

be

most
comparable
to
of Depression
Collab-

some

patient

predictors

of

response
to psychotherapy
and
tricyclic
antidepressants
were
reported.
Among
the six studies
that
reported
patient
predictors
of response
to cognitive-behavior
therapy,
one
(1 1) found
that
pretreatment
symptom
severity
was
significantly
associated
with
negative
outcome
at termination,
while
another
(12)
reported
an association
with positive
outcome.
Inconsistent
findings
were reported
for endogenous
depression (13, 14). Learned
resourcefulness,
assessed
by the

Self-Control
itive

ured
poor

Schedule,
,

by the
response

havior

Dysfunctional
at termination

therapy

follow-up,

(16)

though

and

not

cognitive-behavior

Among

was

found

to be related
to posdysfunction,
as measAttitude
Scale, predicted
for group
cognitive-be-

( 1 1 1 5). Cognitive

outcome

negative

therapy

studies

of patient

interpersonal

psychotherapy,

on the Social

Adjustment

outcome

at termination,

Am

1-year

individual

(17).

predictors
initial

Scale

of outcome
social

and

interpersonal
(19).

J Psychiatry

of emo-

predicted
not depreswas associpsychotreatment
with favor-

psychotherapy

148:8,

in

adjustment

an index

tional
freedom,
education,
and occupation
positive
outcome
in social
adjustment
but
sion severity
(4). Endogenous
depression
ated with
poorer
outcome
for interpersonal
therapy
than
for tricyclic
or combination
(18). Situational
depression
was associated

able response
to either
a tricyclic
antidepressant

at

for

August

or

1991

SOTSKY,

Among
these
studies,
there
were
several
patient
characteristics
that predicted
response
to tricyclic
antidepressants.
Endogenous
depression
was associated
with
favorable
outcome
with an antidepressant
alone
or in combination
with
interpersonal
psychotherapy
(18), as well as good
outcome
for patients
who completed
treatment,
but poor
outcome
for those
who
dropped
out (14).
Depression
severity
was related
to
negative
outcome
( 1 1 ), and
learned
resourcefulness
was related
to poor
response
(15).

METHOD

A common

protocol

was

conducted

at three

clinical

research
sites with a prospective,
random-assignment,
placebo-controlled
design,
double-blind
for pharmacotherapy
and with
independent,
blind
clinical
evaluation. A detailed
description
of the background
and design of the main treatment
study
and the pilot training
study
has been previously
published
(10).
The subjects
were
male and female
outpatients
between
the ages of 21 and 60 years
who met the Research
Diagnostic
Criteria
(RDC)
for a current,
definite episode
of major
depressive
disorder
on the basis
of the Schedule
for Affective
Disorders
and Schizophrenia
(SADS)
(20) structured
interview
and who had

a score

of 14 or more

on the 17-item

modified

version

of the Hamilton
Rating
Scale for Depression
(2 1) for at
least 2 weeks
before
initial
screening
and again
at rescreening
after
a 1- to 2-week
wait or drug washout
period.
Exclusion
criteria
consisted
of other
specific
psychiatric
disorders,
medical
contraindications
for
the use of imipramine,
concurrent
psychiatric
treatment,
current
active
suicide
potential,
and need
for
immediate
treatment.
Patients
were clinically
referred,
voluntary
research
subjects
who gave written
informed
consent
to participate.

All 28 therapists

were

experienced

psychiatrists

and

psychologists
who
had received
further
clinical
training by independent
expert
trainers
and had met competence
criteria
in order
to participate.
Their
performance
was monitored
throughout
the study
(10, 2224). Treatments
were conducted
in accord
with detailed
manuals
that specified
the theoretical
rationale,
strategies, techniques,
and boundaries
of each modality
(2527). All treatments
were
planned
to be 16 weeks
in
duration
and to consist
of 16-20
sessions.
The pharmacotherapy
dosage
schedule
was flexible,
with a goal

of 200 mg
management

and

a maximum
component

for

of 300 mg. The clinical

the pharmacotherapy

conditions
provided
not only guidelines
for medication
monitoring
and management
but also support,
encouragement,
and
advice
as necessary,
although
specific
psychotherapy
interventions
were proscribed.

The total
who actually

sample
entered

(N=239)
treatment

comprised
all patients
from among
the 250

patients
assigned.

who met inclusion

The
completer

criteria
sample

and were
comprised

patients

who

at least

12 sessions

Am

J Psychiatry

completed

148:8,

August

1991

randomly
only
the

and

15

GLASS,

SHEA,

ET AL.

weeks
of treatment
and had clinical
evaluations
at termination.
Clinical
evaluations
were available
for 155
patients
on the Hamilton
depression
scale for analyses
of depression
severity
and for 156 patients
for analyses
of complete
response
(because
of the inclusion
of an
additional
patient
for whom
the Beck inventory
score
only
was
available).
There
were
no statistically
significant
differences
between
treatments
in overall
attrition,
treatment-related
attrition,
or symptomatic
failure.
Seven
patients
did not have termination
evaluations
(1). The findings
on comparative
treatment
efficacy with regard
to depressive
symptoms
and general
functioning,
modality-specific
measures
of change,
and
the temporal
course
of treatment
effect
have been reported
elsewhere
(1, 2, and manuscript
by J.T. Watkins et al., submitted
for publication).

A comprehensive

review

of the literature

was

under-

taken
to identify
patient
predictors
of response
to cognitive-behavior
therapy,
interpersonal
psychotherapy,
and psychotherapy
in general,
as well as to tricyclic
antidepressants
and imipramine
in particular.
Among
the predictor
variables
for which
there was evidence
of
stability
and replication,
a limited
set of independent
variables
for the multivariate
analyses
was selected
on
the basis of the distribution,
intercorrelation,
reliability, and face validity
of the relevant
measures.
Personality disorders
were added
on the basis of experience
in
the pilot study.
Because
of the potential
importance
of
a cognitive
function
predictor
for cognitive-behavior
therapy,
the Dysfunctional
Attitude
Scale
total
score
was selected
on an exploratory
basis.
Two subsequent
reports
suggesting
its relationship
to outcome
(see the
beginning
of this article)
confirmed
that decision.
The 26 independent
variables
were grouped
within
three
domains:
1) sociodemographic
variables-age,

sex,

marital

status,

social

class;

2)

diagnostic

and

course
variables-endogenous,
recurrent,
primary,
situational,
and double
depression,
melancholia,
family
history
of affective
disorder,
age at onset
of first episode, duration
of current
episode,
acuteness
of onset
of
current
episode,
and number
of previous
episodes;
and
3) function,
personality,
and symptom
variables-social dysfunction,
work
dysfunction,
cognitive
dysfunction,
social
satisfaction,
expectation
of improvement,
number
of personality
disorders,
dramatic
personality
disorder,
odd personality
disorder,
anxiety,
somatization/hypochondriasis,
and interpersonal
sensitivity.
The dependent
measures
of depression
outcome
at
termination
were 1) complete
response,
a stringent
categorical
measure
based
on the combination
of a 17item Hamilton
depression
scale score less than or equal
to 6 and a Beck Depression
Inventory
(28) score
less
than or equal
to 9, and 2) depression
severity,
a continuous
measure
based
on the 23-item
Hamilton
depression
scale
score,
which
included
cognitive
and
atypical
vegetative
symptom
items.
Two
dependent
variables
were selected
to examine
predictors
of complete response
or remission
and change
in the severity
of depression,
which
would
reflect
partial
response
as
well. One measure
was based
solely
on clinical
evalu-

999

OF RESPONSE

PREDICTORS

PATIENT

ator ratings,
while the other also incorporated
patient
self-reports.
Scores were based on ratings
at termination of treatment
for completers
and on the last rating
obtained
for patients
who were withdrawn
or dropped
out (generally,
at either
interim
or early termination
evaluation,
but for 20 early dropouts,
at rescreening
evaluation).
The interrater
reliability,
as assessed
by
intraclass
correlation
coefficients,
for the Hamilton
17item scale score ranged
from 0.92 to 0.96 across sites
and from 0.90 to 0.98 within
sites; for the Hamilton
23-item
scale score it ranged
from 0.93 to 0.96 across
sites and from 0.89 to 0.98 within
sites. The Beck
inventory
total
score
showed
good
internal
consistency,
with an alpha coefficient
equal to 0.78. The percentages
of patients
achieving
complete
response
were
43.6%
(N=68)
and 31.4%
(N=7S)
in the completer
and total samples,
respectively.
The meanSD
depression severity
scores
at termination
were 9.43 7.33
and 13.9210.19
in the completer
and total samples,
respectively.

Data

Analysis

To reduce

further

the number

of independent

pa-

tient variables
from the initial set of 26 for the main
predictor
analyses
across treatments,
preliminary
multiple regression
analyses
were conducted
within
each
individual
treatment
condition,
and only the most consistent
predictors
of outcome
within
individual
treatments were selected
for the main analyses.
In both the
total sample
and the completer
sample,
initial analyses

were conducted
the three

single

of predictor

for independent
domains,

variables

and

within

variables
then

in each of

the best

each domain

subsets

were corn-

bined,
with
the pretreatment
Hamilton
depression
score included,
in final analyses
conducted
for each
outcome
measure.
For these preliminary
analyses
we
used the method
of all possible
subsets regression
(29),
which examines
all possible
models
containing
the independent
variables
and selects the best
subsets
on
the basis of an algorithm
that uses the criterion
of
minimal
Mallows
C (30) to select
the regression

model

which

minimizes

the total mean squared

the relative

however,
importance

that the results do not identify

of any single

variable,

since

the

effect of each variable on outcome variance takes into

account the partial effects of all of the other variables
in the

model.

We

recognize

that,

given

the

number

of

initial patient
variables
and the size of the groups in the
individual
treatment
conditions,
there is an increased
risk of chance
findings
because
of the inherent
limita-

1000

of the regression

analytic

approach.

We therefore

consider
these
analyses
exploratory
in nature.
While
certain
predictor
relationships
replicated
earlier
findings, other
predictors
will require
further
attempts
to
replicate.

The main data analyses

examined
the evidence
for
possible
predictors
of outcome
across
all treatments
and of differential
outcome
among
treatments.
Only
13 variables
were selected
for these analyses,
which
were the most consistent
predictors
of outcome
in the
final

regression

having

been

analyses

within

predictors

individual

in at least

treatments,

two

of the four analyses and at a level of significance

of p<O.OSin at least
one. For depression
severity
as a continuous
measure
of outcome,
analyses
of covariance
(ANCOVAs)
were
performed,
with treatment
(four levels) and predictors
(two or more levels) as factors
in the design and with
pretreatment
depression
severity
and marital
status as
covariates.
Marital
status was included
because
it was
significantly
related
to outcome
and unevenly
distributed among
treatment
conditions.
For continuous
predictor
variables,
patients
were divided
into two groups
by using
a median
split in score.
Significant
main
effects
identified
patient
variables
that
predicted
out-

come across treatments.

Significant
Predictor
by Treatment interactions
identified
differential
treatment
effects
of patient
variables
on outcome.
For complete
response as a categorical
measure
of outcome,
log linear
analyses

(Treatment

by

Predictor

by

Response)

were

performed,
and the best fit models
were examined
for predictor
main effects as well as Predictor
by Treatment interactions.
A significance
level of p<O.lO
was
chosen
for the overall
difference
among
treatments.
The Bonferroni
correction
for multiple
comparisons
was used, so for any individual
treatment
comparison
the obtained
probability
level had to be <0.017
to be
considered
significant
at an adjusted
alpha
level of
<0.10.

RESULTS

error

and bias. Each variable

in the model
contributed
a
minimum
of 2% of the variance
to the adjusted
R2
value
and had a regression
coefficient
significant
at
p<0. 10.
The subsets of predictor
variables
that emerged
from
these multiple
regression
analyses
together
constitute
a
model which best predicts
outcome
and are indicators
of the relative
likelihood
of favorable
or unfavorable
outcome
for each individual
treatment.
It should
be

emphasized,

tions

Preliminary

Predictors

Within

Individual

Treatments

Cognitive-behavior
therapy.
The most
consistent
predictor
findings
indicated
that patients
were relatively more responsive
to cognitive-behavior
therapy
if
there was lower
initial
cognitive
dysfunction,
briefer
duration
of the current
episode
of depression,
absence
of a family
history
of affective
disorder,
later age at
onset, and a history
of more previous
episodes
of depression.
Furthermore,
among
completers,
married
patients were relatively
more responsive
to this therapy.
Interpersonal
psychotherapy.
Less
social
dysfunction was associated
with complete
response
in both
samples,
accounting
for 12%-13%
of the outcome
variance,
and was also associated
with good outcome
on depression
severity
in the total sample.
The most
consistent

predictor

findings

Am

J Psychiatry

demonstrated

148:8,

that

August

pa-

1991

SOTSKY,

1. Patient

TABLE

Variables

Studied

for Their

Effect

on Outcome

of a Trial of Psychotherapy

GLASS,

or Pharmacotherapy

SHEA,

ET AL.

in a Sample

of De-

pressed Patients

Variable

Patients Who
Completed
Therapy Trial
(N l62)

Instrument

Age (years)
Mean
SD
Sex (female)
N

Sociodemographic

form

Sociodemographic

f0

Sociodemognaphic

Single
N
0/
_-

depression

Research

Diagnostic

depressionc

Research

Diagnostic

history

of affective

disorder

Family

psychiatric

0/

of current

episode

>6 months

Research

Diagnostic

I0

of onset

(<3

months)

Schedule

for Affective

Disorders

dysfunction

scone

Dysfunctional

Attitude

58
35.8

80
33.5

64
39.5

91
38.1

43
26.7

71
29.8

40
24.8

68
28.6

Social dysfunction
Mean

score

Social

Adjustment

Social

Schedule

Attitudes

141
59.0

68
42.2

100
42.0

141.6
35.6

139.3
34.9

2.9
0.8

2.9
0.7

2.7
0.8

2.7
0.8

12.0
4.6

12.4
4.7

Scaler

SD

Work dysfunction
score
Mean
SD
Anxiety score
Mean
SD
Patient expectation
of improvement
(much or completely
better)
N

97
59.9

Scalee

SD

Adjustment

for Affective

and expectations

Disorders

and

Schizophrenia

form
115
71.0

0/
f0

alncludes
bPercents
cDefined

63
26.4

and Schizophrenia

0/

Cognitive
Mean

37
22.8

Criteria

0/

Acuteness
N

96
40.2

historyd

N
Duration
N

67
41.4

Criteria

0/

Famil;

168
70.3

Criteria

0/

Double
N

109
67.3

...

Endogenous
N

35.0
8.5

form

0/

Separa
N

35.3
8.2
form

0/

Marital
status
Married
N

Total Group
of Patients
(N=239)L

seven patients
who completed
the trial but did not have termination
evaluations.
are based on slightly varying Ns because of missing data in some instances.
as major depressive
disorder plus chronic minor depression
on intermittent
depressive

162
68.1

disorder.

Presence
of family history indicated
by confirmed
diagnosis
of depression
or mania in the patients parents, siblings, or children.
Total scale score, where a low score indicates
the absence of dysfunctional
attitudes
(range=0-280).
tMean for 1 1 items in social and leisure activities
subscale,
where a low score indicates
the absence of impairment
(range
1-5).
for applicable
items in the work outside the house, work at home, and student
subscales,
where a low score indicates
the absence
impairment
(range=
1-5).
FSum of five subscale
items including
panic and psychic and somatic
anxiety symptoms
(range=4-30).
Patients
global response
regarding
his on her expectation
of improvement
with treatment.

tients,
particularly
males,
who had a lower pretreatment level of social dysfunction,
who were separated
or divorced,
and who had higher
interpersonal
sensitivity and overall
higher
satisfaction
with social relationships
were more responsive
to interpersonal
psy-

Am

J Psychiatry

1 48:8,

August

1991

of

chotherapy.
In addition,
there was some evidence
that
patients
with more acute onset
and endogenous
depressive
episodes
but not double depression
responded
more favorably
to this psychotherapy.
Imipramine
with clinical management
(imipramine-

1001

PREDICTORS

PATIENT

TABLE

PatIent

2.

OF RESPONSE

Predictor

Main

Effects for Two Measures

of Outcome

in Depressed

Patients

Who Completed

a Trial of Psychotherapy

or

Pharmacotherapy
Outcome

Dc pression

Predictor

Variable

Patients With
Scores Below
Median or
Depression
Subtype
Absent

Patients With
Scores Above
Median or
Depression
Subtype
Present

Adjusted
Mean

SE

Adjusted
Mean

SE

8.5

0.8

10.7

0.8

11.4

1.1

8.8

10.5
8.6
9.8
8.7

0.8
0.7
0.9
0.9

8.1
11.5
9.6
10.3

Cognitive
dysfunction
Patient expectation
of
improvement
Endogenous
depression
Double depression
Social dysfunction
Age
adfl,

Severity

(N

0/,o

3.6

0.06

43/79

0.7

4.3

0.04

0.9
1.1
0.8
0.8

3.9
4#{149}9a
0.0
1.7

0.02
0.04
n.s.
n.s.

(N=156)

Log Linear
Analysis

144)

x2

(dfl)

54

25/77

32

8.0

0.005

53/111

48

15/45

33

2.6

0.11

37/94
52/115
39/76
40/76

39
45
51
53

31/62
16/40
29/80
28/80

SO
40
36
35

2.0
0.2
2.8
4.5

n.s.
n.s.
0.09
0.03

143.

or

had

a low

expectation

of

improvement

Predictors

of Response

Across

Treatments

The 13 variables
most consistently
predictive
of outcome within
treatments,
which were selected
for examination
of potential
prediction
of outcome
across all
treatments
or of differential
outcome
among
treatments,
were age, sex, marital
status, endogenous
depression,
double
depression,
family history
of affective
disorder,
duration
of current episode,
acuteness
of onset, cognitive
dysfunction,
social dysfunction,
work
dysfunction,
anxiety,
and patient
expectation
of improvement.
Table 1 shows
their distribution
in both

1002

Response
Patients With
Scores Above
Median or
Depression
Subtype
Present

F
(df=1,

with treatment
responded
more poorly.
Placebo
with
clinical
management
(placebo-CM).
Among
the more
consistent
predictors,
patients
of
younger
age and with higher
expectation
of improvement appeared
to respond
more favorably
to placeboCM. Patients
with higher levels of initial anxiety
and
depression
severity
responded
less favorably,
as did
patients
with double
depression,
who had a lower likelihood
of complete
response.
Low cognitive
dysfunction and dramatic
personality
disorder
were associated
with worse outcome
on depression
severity in the total
sample
only, suggesting
a possible
relation
to attrition
in this condition.
Main

Complete
Patients With
Scores Below
Median on
Depression
Subtype
Absent

ANCOVA

CM). Higher
work
dysfunction
was the most robust
predictor
of good outcome
with imipramine-CM
in the
completer
sample
for both complete
response
and depression
severity.
The most consistent
predictor
findings indicated
that, overall,
the patients
who showed
the most work dysfunction
responded
best to the effects of imipramine-CM,
as did those with highest
depression
severity
and endogenous
or primary
depression,
but those
with
dramatic
personality
disorder
responded
poorly.
In the total sample,
patients
who
were not married,
had a high level of cognitive
dysfunction,

Measure

155)

samples,

the

instruments

with

which

they

were

as-

sessed, and notes on their content

and scoring.
Overall
predictor
effects.
Six patient
predictors
of
outcome
of the episode
of depression
across
all treatment

conditions

were

identified

from

the

main

effects

in the ANCOVAs
and log linear analyses
in the completer
sample
(table
2), and another
predictor
was
identified
in the total sample
only.
Lower
cognitive
dysfunction

and

provement
were
greater
likelihood
level of depression
main

effects

for

higher

patient

expectation

significantly
associated
of complete
response
severity
at termination.
expectation

of

im-

with both a
and a lower
Significant

of improvement

were

also

present
in the total sample
for both measures,
and a
trend effect was present
for cognitive
dysfunction
on
complete
response.
Although
not evident
in the cornpleter sample,
shorter
duration
of the current
episode
was significantly
associated
with both
complete
response
(2=2.9,
df=1,
p=O.O9)
and lower depression
severity

(F=S.43,

df=1,

228,

p=O.O2)

in

the

total

sample,
suggesting
that the influence
of length of episode on recovery
was more notable
among
patients
who discontinued
treatment,
particularly
in the placebo condition.
Endogenous
depression
was significantly
associated
with lower depression
severity,
whereas
double depression was associated
with higher depression
severity,
in
both the completer
and total samples.
However,
neither variable
predicted
complete
response,
suggesting
a
relation
to residual
depressive
symptoms
but not remission

per

se across

all conditions.

Lower

social

dys-

function
was significantly
associated
with a greater
likelihood
of complete
response
in both samples
but
was not related
to level of residual
depressive
symptoms. There was one significant
main effect of age on
complete
response
in the completer
sample
only, with
older patients
less responsive,
particularly
in the pharmacotherapy
conditions.

Am

J Psychiatry

148:8,

August

1991

SOTSKY,

FIGURE
1. Social Dysfunction
as a Predictor of Differential
Response
to Treatment
in the Total Sample of Depressed Patients

FIGURE

2. Cognitive

(N=239)

(N=239)a

GLASS,

SHEA,

ET AL.

Dysfunction as a Predictor of Differential

Rein the Total Sample of Depressed Patients

sponse to Treatment

20

20

-15
E15

c
I

a)

10

>
0)
C,)
C

C,)

10

U)

U)

a)

ci)

I.-

a0)

a.
a)

0
CBT

IPT

Ml

CBT

PLA

Low Social Dysfunctionb

aCBTcognitivebehavion

therapy;

PT

High Social

IPT=intenpersonal

apy; IMI=imipramine;
PLA=placebo.
b1p- significantly
less than PLA (t=3.6,

df=6S,

Ml

CBT

PLA

Dysfunction

psychothen-

p=O.000S).

Am J Psychiatry

148:8,

August

1991

Ml

Low Cognitive
aCBT

CBT

PtA

DySfUflCtiO&

cognitive-behavior

therapy;

less than

IPT

PLA (t=2.7,

that group
and the lowest
dysfunction
group.
Thus,
most differentiated
treatment

PT

Ml

High Cognitive

df=S9,

df=S6,

PLA

Dysfunction

interpersonal

apy; IMI=imipramine;
PLA=placebo.
bIMI significantly
less than PLA (t=3.8,
significantly

Differential
predictor
effects. In the ANCOVAs,
two
of the variables,
social dysfunction
and cognitive
dysfunction,
demonstrated
significant
differential
treatment effects on depression
severity
as outcome
in the
total sample.
Because
of considerable
heterogeneity
of
regression
with regard
to pretreatment
depression
Severity, these analyses
included
only marital
status as a
covariate.
For social dysfunction
(figure
1), as measured by the score on the social and leisure
activities
subscale
of the Social Adjustment
Scale, there was a
significant
overall
Treatment
by Predictor
interaction
(F=2.84,
df=3,
229, p=O.O4).
When the sample
was
divided
at the median
score into high and low social
dysfunction,
the significant
treatment
effect appeared
only in the group with low social dysfunction
(F=4.37,
df=3, 116, p=O.OO6),
such that interpersonal
psychotherapy
patients
had the lowest
mean depression
severity scores
at termination,
significantly
superior
to
scores in the placebo-CM
group.
Although
there were
no significant
differences
among
treatments
in the
group
with
high social
dysfunction
(F= 1.44,
df=
3, 1 1 1, n.s.), it should
be noted
that interpersonal
psychotherapy
patients
had the highest
mean severity
in

IPT

psychother-

pO.0003);

CBT

p=O.0O9).

severity
in the low social
level of social
functioning
response
among
patients

who received
interpersonal
For cognitive
dysfunction

psychotherapy.
(figure 2), as measured

by

the total
score
on the Dysfunctional
Attitude
Scale,
there
was a significant
overall
Treatment
by Predictor
interaction
(F4.27,
df3,
229, pO.OO6)
in the total
sample.
When
separate
ANCOVAs
were
performed
for the high and low cognitive
dysfunction
groups
divided
at the median,
the significant
treatment
effect
appeared
only in the low cognitive
dysfunction
group
(F=4.97,
df=3,
112,
p=O.OO3),
such
that
patients

who
ceived

received

imipramine-CM

and

cognitive-behavior

lower

depression

patients

who

imipramine-CM

severity
received

yielded

therapy

patients
had

who

re-

significantly

scores

at termination

than

placebo-CM.

Treatment

with

the

lowest

mean

depression

severity
score.
Among
the high cognitive
dysfunction
group,
there
were
no significant
differences
between
any of the active
treatments
and placebo-CM
treatment
(F= 1.56, df3,
1 iS, n.s).
It is important
to note
that neither
predictor
directly
distinguished
differential

1003

PATIENT

FIGURE

to

PREDICTORS

OF RESPONSE

3. Work Dysfunction

Treatment in the Completer

15O

as a Predictor
Sample

of Differential

of Depressed

Response

Patients

(N=

response
than
did
ratio4.6;

if they
were
treated
with
imipramine-CM
those
with
high cognitive
dysfunction
(odds
X25.8,
df=1,
p<O.OS).

There
was a further
dysfunction
(2=6.7,
the significant
treatment

mine-CM,

indicating

significant
interaction
for work
df=3,
p=O.O8)
(figure
3), and
effect
was again
for imipra-

that

patients

with

high

work

dys-

function
in the completer
sample
who were treated
with
imipramine-CM
had a significantly
greater
chance
of
complete
response
than those
with low work
dysfunction (odds
ratio=S.0;
2=3.7,
df=1,
p=O.O6).

DISCUSSION

The results
of this collaborative
clinical
treatment
trial
comparing
the efficacy
of two specific
forms
of
psychotherapy
with active
and placebo
pharmacotherapy demonstrate
the relevance
of patient
characteristics for the prediction
of outcome
from
an episode
of
major
depressive
disorder.
Several
characteristics
of
the depressive
episode
and
patient
functioning
and
cognition
were indicators
of overall
prognosis
without
regard
to the specific
treatment
received.
These
six patient predictors
of depression
severity
or complete
response
were social
dysfunction,
cognitive
dysfunction,
patient
expectation
of improvement,
endogenous
depression,
double
depression,
and duration
of current
episode.

The

results

of these

analyses

also

provide

evidence

for a limited
number
of characteristics
of patient
function that significantly
predicted
differential
response
to
psychotherapy
or pharmacotherapy
with
imipramine
compared
to placebo.
There
were
no significant
predictors
of differential
response
among
the three
active
treatments.
Among
patients
with
better
initial
social
adjustment
(e.g.,
low social
dysfunction),
those
who
received
interpersonal
psychotherapy
became
significantly
less depressed
than
those
who
received
place-

bo-CM

and

had

a higher

rate

of complete

response

than
those
with
high
social
dysfunction.
Among
patients
with
less perfectionistic
and socially
dependent
attitudes
(e.g., low cognitive
dysfunction),
those
who
received
treatment
with imipramine-CM
or cognitivebehavior
therapy
became
significantly
less depressed
than
those
who
received
placebo-CM,
and
those
treated
with imipramine-CM
also had a higher
rate of
complete
response
than those
with high cognitive
dysfunction.
Among
patients
with
more
impairment
of
function
at work,
school,
or home
(e.g.,
high
work
dysfunction),
those
who received
imipramine-CM
had

a higher rate of complete

work dysfunction.
The

response
differential

than those
predictor

with low
effects of

social
and cognitive
dysfunction
were observed
in the
total sample
only, which
may have been because
of 1)
the larger
size of the total
sample,
2) the comparison

with

all placebo-treated

patients

rather

than

placebo

completers
only, or 3) the inclusion
of the full range
of
outcomes,
including
attrition,
thereby
reflecting
differential
acceptability
of the treatments,
an important

1004

Am

J Psychiatry

148:8,

August

1991

SOTSKY,

These

patient

pre-

ET AL.

ent limitations
of the multiple
regression
analytic
approach.
Nevertheless,
where the interesting
patterns of
predictors
of response
within
individual
treatment
conditions
are consistent
with the results of the main
analyses,
we include
them, with appropriate
statistical
caution,
in the discussion.
Given the historical
difficulty of replicating
predictors
across studies,
we have
emphasized
in our interpretation
the consistent
pattern
of findings
across
samples
and measures
of outcome.
We believe that the main results may be of both theoretical and clinical
interest,
particularly
because
of the
uncommon
effort to compare
predictors
of differential
outcome
with a placebo
control.
Our finding that social dysfunction
was a significant
predictor
of differential
response
to interpersonal
psychotherapy
is consistent
with the finding
from the individual
treatment
analyses
that greater
impairment
in
social function
was associated
with poorer
response
to
interpersonal

psychotherapy

greater

and recovery

from

may also provide

of the treatments

differential

SHEA,

social support,
social satisfaction,
and the ability
to
develop
a good relationship
have been associated
with
favorable
response
to psychotherapy
(31, 34-38).
However,
this specific
relation
with pretreatment
social adjustment
was neither
observed
nor previously
reported
for patients
treated with cognitive-behavior
therapy,
the other psychotherapy
in our study. Thus,
while the study shows that low social dysfunction
predicts favorable
general
prognosis
for outcome
from
depression,
it also provides
evidence
of a specific
responsiveness
to interpersonal
psychotherapy
among
those patients.
Less impairment
in cognitive
function
as measured
by the Dysfunctional
Attitude
Scale appears
to be a
general
predictor
of good prognosis
as well as a specific predictor
of good response
to cognitive-behavior
therapy
(on depression
severity)
and imipramine-CM
(on both outcome
measures).
In the two previous
studies that examined
the relation
of dysfunctional
attitudes to treatment
response,
high cognitive
dysfunction was also associated
with poor outcome
at the
termination
of group cognitive-behavior
therapy
(16)
and poor outcome
at 1-year follow-up
after individual
cognitive-behavior
therapy (17). Although
in our study
cognitive-behavior
therapy
appeared
specifically
to improve dysfunctional
attitudes
concerning
the need for
social approval
(2), there was a less favorable
antidepressant
response
to cognitive-behavior
therapy
in patients with greater
cognitive
dysfunction.
This pattern
of findings
suggests
that there may be an important
distinction
between
the empirical
effects of cognitive
techniques
in changing
dysfunctional
attitudes
and a
theory
that links the presence
of dysfunctional
attitudes
in depression
to a preferential
response
to cognitive therapy.
To our knowledge,
the relation
of dysfunctional
attitudes
to outcome
with
other
psychotherapies
or
pharmacotherapy
has not been reported.
The finding
that in the total sample,
low cognitive
dysfunction
predicted
greater
likelihood
of complete
response
and

aspect
dictors
ificity

of effectiveness.

GLASS,

indirect
evidence
of the specby identifying
characteristics

most responsive
to those modalities.
We consider
the findings
that emerged
from both
the main analyses
across
treatments
and the preliminary
multiple
regression
analyses
within
individual
treatment
conditions
exploratory
in nature
and in
need of further
replication.
The main data analyses
(ANCOVAs
and log linear analyses)
were based on 13
independent
variables
and S2 analyses
(two dependent
variables

and

two

samples);

with

an

alpha

level

of

0.10,
would

approximately
one predictor
and five analyses
be expected
to be significant
by chance alone.
Although
eight variables
were identified
as significant
predictors
and there were 16 significant
main effects
and five interactions
among
the analyses,
some findings (i.e., for age) may have been chance
effects and
may not be replicable.
With the number
of initial patient variables
and the size of the samples
within
the
preliminary
individual
treatment
analyses,
there is a
greater

risk

of chance

interpersonal

initial

findings,

on

depression.

termination

adjustment
for

depressed

the

measures

One

psychotherapy

social

considering

(4)

reported

predicted

good

patients,

of

previous

but

inher-

severity

study
that

of

good

outcome
only

on

at
meas-

ures of social function,

not depression.
Another
psychotherapy
study (3 1) also reported
that pretreatment
social
function
predicted
social function
at termination. The finding
that favorable
response
to interpersonal psychotherapy
is associated
not only with good
social adjustment
but with previous
attainment
of a
marital

relationship,

higher

satisfaction

with

social

re-

lationships
in general,
and heightened
interpersonal
sensitivity
seems consistent
with reports
in the general
psychotherapy
literature
that various
indicators
of social competence
or achievement
are associated
with
good psychotherapy
response,
whereas
social impairment is not. Poor social skills and poor interpersonal
relationships
have been reported
to be related to poor
outcome
of psychotherapy
(32, 33), while perceived

AmJPsychiatry

148:8,

August

1991

improvement

in depression

severity

for patients

treated with imipramine-CM

than for patients
treated
with placebo-CM
was unanticipated.
The better outcome of patients
who expressed
less socially
dependent
and perfectionistic
attitudes
may be consistent
with the
early reports
that patients
with neurotic
(particularly,
histrionic
and labile) traits and with personality
disorders respond
poorly to tricyclic
antidepressants
(7, 3942). Conversely,
the differential
predictor
and individual treatment
results
suggest
that patients
with more
socially
dependent,
dysfunctional
attitudes
may be
more responsive
to placebo treatment
(3). The possible
relation of these attitudes
to drug therapy compliance,
tolerance
of side effects, and acceptance
of pharmacotherapy
remains
to be understood.
Cognitive
dysfunction
did not predict poor response
to interpersonal
psychotherapy
in this study. Indeed, it
appears that the least cognitively
impaired
patients
responded
more favorably
to cognitive
therapy,
and the
least socially
impaired
patients
responded
most favor-

100s

PATIENT

PREDICTORS

OF

RESPONSE

ably to interpersonal
psychotherapy.
One possible
explanation
for these results is that each psychotherapy
relies on specific
and different
learning
techniques
to
alleviate
depression,
and thus each may depend on an
adequate
capacity
in the corresponding
sphere of patient function
to produce
recovery
with the use of that
approach.
Therefore,
patients
with good social function may be better able to take advantage
of interpersonal strategies
to recover
from depression,
while patients
without
severe
dysfunctional
attitudes
may
better utilize cognitive
techniques
to restore
mood and
behavior.
Patients
with more impairment
in social or
cognitive
function
might be further overwhelmed
and
demoralized
by a treatment
approach
that requires reliance
on those
capacities
to achieve
improvement.
Such patients
might respond
better to an alternative
psychotherapy
or combination
treatment
or require
longer-term
psychotherapeutic
intervention.
Work dysfunction
is a major aspect of overall social
adjustment

in depression,

measuring

impaired

perfor-

mance,

subjective
distress,
and interpersonal
function.
Among
patients
who completed
treatment
with irnipramine-CM,
impairment
of work function
was a significant
differential
predictor
of recovery,
and the resuits on both outcome
measures
within
the individual
treatment
analyses were consistent.
On the contrary,
in
the few previous
studies,
social impairment,
work disability,
and poor employment
history
have been related to poor outcome
with antidepressant
medication
(39, 43). However,
in our study imipramine-CM
was
previously
reported
(1) to show consistent,
significant
superiority
over placebo-CM
on measures
of recovery
and symptomatic
improvement
among
the more severely impaired
and depressed
patients,
as defined by
the Global
Assessment
Scale. Furthermore,
we observed

(manuscript

by J.T.

Watkins

et al.,

submitted

for publication)
that imipramine-CM
had a significant
early advantage
for improvement
in global social adjustment
at 4 weeks and 12 weeks of treatment
among
the more severely
depressed
patients.
To the extent
that impaired
work function
in depression
may result
from diminished
interest,
energy,
initiative,
and concentration,
psychomotor
retardation,
and social withdrawal,
preferential
improvement
with imipramine
would be consistent
with the recognized
clinical effects
of tricyclic
antidepressants
on these symptoms.
This
pattern
of findings
suggests
that more severe depression, impairment,
and work
dysfunction
are patient
characteristics
which are especially
responsive
to pharmacotherapy
with imipramine
and which may be of
value in the selection
of patients
for this modality.
In this study endogenous
depression
was an overall
predictor
of lower depression
severity
at termination
across all conditions.
Previous
studies,
though,
have
reported
that endogenous
depression
is a negative
indicator
of response
to psychotherapy,
both
interpersonal
psychotherapy
(18) and cognitive-behavior
therapy
(13).
However,
Kovacs
et al. (14) found
endogenous
depression
to be a positive
predictor
of
outcome
for patients
who completed
treatment
with

1006

either a tricyclic
antidepressant
or cognitive-behavior
therapy,
while Blackburn
et al. (44) found no effect of
endogenous
features
on response
to either treatment.
In our individual
treatment
analyses
for interpersonal
psychotherapy,
endogenous
depression
predicted
reduction
of depression
severity.
This relationship
was
not observed
for cognitive-behavior
therapy.
In the individual
treatment
analyses
for irnipramine-CM,
our
finding
that endogenous
depression
was associated
with complete
response
and depression
severity
corroborates
the many previous
reports
that the endogenous subtype
of depression
is a major indicator
of response
to tricyclic
antidepressants
(7, 14, 18, 19, 45).
The lack of differential
predictive
effect for endogenous depression
may be a result of measuring
outcome
after 4 months,
since the differential
effect of imipramine-CM
on endogenous
symptoms
was most manifest at 8 and 12 weeks of treatment
(manuscript
by J.T.
Watkins
et a!., submitted
for publication).
The reports
of situational
depression
as a predictor
of negative
outcome for tricyclics
and positive
outcome
for psychotherapy were not replicated,
however.
The presence
of double depression
and the duration
of the depressive
episode
are important
aspects
of the
course
of illness that appear
to influence
response
to
treatment.
In a large naturalistic
study uncontrolled
for treatment,
double depression
was associated
with
favorable
outcome
from the major depressive
episode
only, but with poor outcome
if outcome
was defined as
full recovery
from the underlying
chronic
minor
depression
as well (46-48).
In our controlled
treatment
trial, double
depression
was predictive
of higher
depression
severity
at termination
but not of complete
response,
suggesting
a relation
to degree
of improvement but not remission
per se across all treatment
conditions.
Within
the individual
treatment
analyses,
double depression
predicted
lack of complete
response
from the episode
among
patients
treated
with placebo-CM
but not among those who received
one of the
three active treatments.
This may suggest
that with
active treatment,
recovery
from the major depressive
episode
is achieved
as readily
by patients
with double
depression
as by those without
chronic
illness, but that
more
residual
depressive
symptoms
persist
among
those with double
depression.
However,
patients
with
double
depression
treated
only by placebo-CM
do not
recover as readily. Results at follow-up
should be most
interesting,
since previous
studies have noted the greatest impact
of double
depression
on subsequent
course
after recovery
from the initial episode
(38, 48).
Longer
duration
of the current
episode
predicted
higher depression
severity
and a lower rate of complete
response
in the total sample
but not the completer
sample,
suggesting
that the influence
of chronicity
on
recovery was greater among patients who did not complete treatment,
most notably
in the placebo-CM
condition.
This finding
is consistent
with many previous
studies
that have reported
a negative
relation
between
duration
of illness and clinical
outcome
of psychotherapy
(49-52),
imipramine
and other tricyclic
anti-

Am

J Psychiatry

148:8,

August

1991

SOTSKY,

depressants
(34, 39, 53-55),
and placebo
(34, 56). Previous
reports
have
indicated
that
acute
onset
of
depression
is a positive
indicator
of response
to both
tricyclic
antidepressant
treatment
(7, 9, 45) and psychotherapy
(33). In our study acute onset was associated

with

complete

response

among

patients

tions.

Acute

dictor

onset

did

of differential

analyses.

We

not

emerge

treatment

therefore

consider

as a significant

outcome
this

to be only

evidence
supporting
earlier findings.
Last, patients
with higher
expectation
ment had a higher
likelihood
of recovery
level of depression
in both samples.

severity
across
Within
individual

in the

treatment
treatment

pre-

The National
Institute of Mental Health Treatment
of Depression
Collaborative
Research
Program
is a multisite
program
initiated
and
sponsored
by the Psychosocial
Treatments
Research
Branch,
Division of Extramural
Research
Programs
(now part of the Mood,
Anxiety
and Personality
Disorders
Research
Branch,
Division
of
Clinical Research),
NIMH.
The program
was funded by cooperative
agreements
with six participating
sites (George Washington
University, grant MH-33762;
University
of Pittsburgh,
MH-33753;
University
of Oklahoma,
MH-33760;
Yale University,
MH-33827;
Clarke Institute of Psychiatry,
MH-3823
I ; and Rush PresbyterianSt. Lukes Medical
Center,
MH-35017).
The principal
NIMH
collaborators
were Irene Elkin, Ph.D., Coordinator;
Tracie Shea, Ph.D.,
Associate
Coordinator;
John P. Docherty,
M.D.; and Morris B. Parloff, Ph.D. The principal
investigators
and project
coordinators
at
the three participating
research sites were George Washington
University:
Stuart M. Sotsky,
M.D., and David R. Glass, Ph.D.; University
of Pittsburgh:
Stanley D. Imber, Ph.D., and Paul A. Pilkonis,
Ph.D.;
and University
of Oklahoma:
John T. Watkins,
Ph.D., and
William
Leber, Ph.D. The principal
investigators
and project coondinators
at the three sites responsible
for training
therapists
were
Yale University:
Myrna Weissman,
Ph.D., Eve Chevron,
M.S., and
Bruce J. Rounsaville,
M.D.; Clarke Institute
of Psychiatry:
Brian F.
Shaw, Ph.D., and T. Michael Vallis, Ph.D.; and Rush Presbyterian-

148:8,

August

4.

S.

6.

7.

8.

9.
10.

1 1.

12.

13.

ACKNOWLEDGMENTS

J Psychiatry

2.

3.

the negative
influence
of lower expectation
of improvement appeared
to occur among
patients
who received
only placebo-CM
or an incomplete
course
of imipramine (in the total sample
only, not among
completers
of imipramine
treatment).
Low expectation
of response
to pharmacotherapy
has been previously
reported
to predict
attrition
but not clinical
outcome
(57). In the psychotherapy
literature,
the relation
of
patient
expectations
to outcome
has been generally
positive
(5, 6), consistent
with these results.
Other
components
of patient
expectations
and attitudes
regarding
treatment
and depression
remain
to be explored.
Since the pattern
of findings
for several patient
predictors
suggested
a relation
to outcome
among
patients who did not complete
treatment,
analyses
of predictors
of attrition
are planned.
Furthermore,
the identification
of potential
patient
predictors
of long-term
prognosis
after initial
treatment
response
will be of
considerable
clinical
interest.

Am

1. Elkin

limited

conditions
analyses,

1991

ET AL.

REFERENCES

main

of improveand lower

SHEA,

St. Lukes Medical

Center:
Jan A. Fawcett,
M.D., and Phillip Epstein, M.D. Collaborators
in the data management
and data analysis
aspects of the program
were C. James Klett, Ph.D., Joseph F. Collins,
Sc.D., and Rodenic Gillis of the Veterans
Administration
Cooperative Studies Program,
Perry Point, Md.

who

completed
imipramine
treatment,
and it predicted
reduction
in depression
severity
among
patients
treated
with interpersonal
psychotherapy,
but only in the preliminary
analyses
within
individual
treatment
condi-

GLASS,

14.

Is.

16.
17.

18.

19.

20.

I, Shea MT, Watkins

JT, et al: National
Institute
of Mental Health
Treatment
of Depression
Collaborative
Research
Program:
general effectiveness
of treatments.
Arch Gen Psychiatry 1989; 46:971-983
Imben SD, Pilkonis
PA, Sotsky SM, et al: Mode-specific
effects
among three treatments
for depression.
J Consult Clin Psychol
1990; 58:352-359
Frank JD: Therapeutic
components
of psychotherapy:
a 25-year
progress
report of research.
J Nerv Ment Dis 1974; 159:325342
Rounsaville
BJ, Weissman
MM, Pnusoff BA: Psychotherapy
with depressed
outpatients:
patient
and progress
variables
as
predictors
of outcome.
Br J Psychiatry
1981; 138:67-74
Lubonsky
L, Auenbach
AH, Chandler
M, et al: Factors
influencing the outcome
of psychotherapy:
a review of quantitative
research.
Psychol Bull 1971; 75:145-185
Garfield
SL: Research
on client variables
in psychotherapy,
in
Handbook
of Psychotherapy
and Behavior
Change:
An Empirical Analysis,
2nd ed. Edited by Garfield
SL, Bengin AE. New
York, John Wiley & Sons, 1978
Bielski RJ, Fniedel RO: Depressive
subtypes
defined by response
to phanmacotherapy.
Psychiatn
Clin North
Am 1979; 2:483497
Klein DF, Davis JM: Review of mood-stabilizing
drug literatune,
in Diagnosis
and Drug Treatment
of Psychiatric
Disorders.
Edited by Klein DF, Davis JM. Baltimore,
Williams
& Wilkins,
1969
Joyce PR, Paykel ES: Predictors
of drug response
in depression.
Arch Gen Psychiatry
1989; 46:89-99
Elkin I, Parloff MB, Hadley
SW, et al: NIMH
Treatment
of
Depression
Collaborative
Research
Program:
background
and
research
plan. Arch Gen Psychiatry
1985; 42:305-316
Simons AD, Lustman
PJ, Wetzel RD, et al: Predicting
responses
to cognitive
therapy
of depression:
the role of learned resourcefulness. Cognitive
Therapy
and Research
1985; 9:79-89
Woody
GE, McLellan
AT, Luborsky
L, et al: Severity of psychiatnic symptoms
as a predictor
of benefits
from psychotherapy: the Veterans
Administration-Penn
study. Am J Psychiatry
1984; 141:1172-1177
Gallagher
DE, Thompson
LW: Effectiveness
of psychotherapy
for both endogenous
and nonendogenous
depression
in older
adult outpatients.
J Genontol 1983; 38:707-712
Kovacs M, Rush AJ, Beck AT, et al: Depressed
outpatients
treated with cognitive
therapy
on pharmacothenapy:
a one-year
follow-up.
Arch Gen Psychiatry
1981; 38:33-39
Murphy
GE, Simons AD, Wetzel RD, et al: Cognitive
therapy
and phanmacotherapy:
singly and together
in the treatment
of
depression.
Arch Gen Psychiatry
1984; 41:33-41
Keller KE: Dysfunctional
attitudes
and cognitive
therapy for
depression.
Cognitive
Therapy
and Research
1983; 7:437-444
Simons AD, Murphy
GE, Levine JL, et al: Cognitive
therapy
and pharmacothenapy
for depression:
sustained
improvement
over one year. Arch Gen Psychiatry
1986; 43:43-48
Prusoff BA, Weissman
MM, Klerman
GL, et al: Research
Diagnostic
Criteria subtypes
of depression:
their role as predictors
of differential
response
to psychotherapy
and drug treatment.
Arch Gen Psychiatry
1980; 37:796-803
Klenman
GL, Weissman
MM, Prusoff
BA: RDC
endogenous
depression
as a predictor
of response
to antidepressant
drugs
and psychotherapy.
Adv Biochem
Psychopharmacol
1982; 32:
165-174
Endicott
J, Spitzer RL: A diagnostic
interview:
the Schedule
for
Affective
Disorders
and Schizophrenia.
Arch Gen Psychiatry
1978; 38:837-844

1007

PATIENT

21.
22.

23.
24.

25.

PREDICTORS

Hamilton
MA:
surg Psychiatry

OF

A rating
1960;

RESPONSE

scale

for depression.

J Neurol

Neuro-

40.

Waskow

IE: Specification
of the technique
variable
in the
NIMH
Treatment
of Depression
Collaborative
Research
Program, in Psychotherapy
Research:
Where Are We and Where
Should We Go? Edited by Williams
JBW, Spitzer RL New
York, Guilford
Press, 1984
Rounsaville
BJ, Chevron
ES, Weissman
MM: Specification
of
techniques
in interpersonal
psychotherapy.
Ibid
Shaw BB: Specification
of the training and evaluation
of cognitive therapists for outcome studies. Ibid
Klerman
GL, Weissman
MM, Rounsaville
BJ, et al (eds): Interpersonal
Psychotherapy
of Depression.
New York, Basic Books,
1984

26.

27.

28.
29.

30.
31.

32.

33.

34.

35.

36.

Beck AT, Rush AJ, Shaw BF, et al (eds): Cognitive

Therapy of
Depression.
New York, Guilford Press, 1979
Fawcett
J, Epstein P, Fiester SJ, et al: Clinical managementimipramine/placebo
administration
manual: NIMH
Treatment
of Depression Collaborative
Research
Program.
Psychopharmacol Bull 1987; 23:309-324
Beck AT, Ward CH, Mendelsohn
M, et al: An inventory
for
measuring
depression.
Arch Gen Psychiatry
1961;
4:561-571
Franc J: All possible
subsets
regression,
in BMDP Statistical
Software.
Edited by Dixon WJ. Los Angeles, University
of California Press, 1985
Neter J, Wasserman
W, Kutner
MM (eds): Applied
Linear Statistical Models, 2nd ed. Homewood,
Ill, Irwin, 1985
Billings AG, Moos RH: Life stressors
and social resources
affect
posttreatment
outcomes
among depressed
patients.
J Abnorm
Psychol
1985; 94:140-153
Luborsky
L: The patients
personality
and psychotherapeutic
change, in Research in Psychotherapy,
vol 2. Edited by Strupp
H, Luborsky
L. Washington,
DC, American
Psychological
As-

sociation,

1962

Auerbach

AH,

37.

38.

39.

1008

42.
43.
44.

45.
46.

47.

48.

49.

so.

Luborsky

outcome

in a group

intervention

for depression.

S2.

53.

54.

Consult Clin Psychol 1983; 51:1-7

McLean
PD, Hakstian
AR: Clinical
depression:
comparative
efficacy of outpatient
treatments.
J Consult Clin Psychol 1978;
47:818-836
Gonzales
LR, Lewinsohn
PM, Clarke
GN: Longitudinal
follow-up of unipolar
depressives:
an investigation
of predictors
of
relapse. J Consult Clin Psychol 1985; 53:461-469
Banki CM: Some clinical and biochemical
predictors
of outcome in depression.
Adv Biochem
Psychopharmacol
1984; 39:
147-151

41.

Si.

L, Johnson
M: Clinicians
predictions
of outcome of psychotherapy:
a trial of a prognostic
index. Am
J Psychiatry
1972; 128:830-835
Rosenbaum
M, Friedlander
J, Kaplan S: Evaluation of results of
psychotherapy.
Psychosom
Med 1956; 8:113-132
Billings
AG,
Moos
RH: Psychosocial
processes
of remission
in unipolar
depression:
comparing
depressed
patients
with
matched community
controls.
J Consult Clin Psychol 1985; S3:
314-325
Steinmetz
JL, Lewinsohn
PM, Antonuccio
DO: Prediction
of
individual

Klein

DF: Diagnosis
and pattern
of reaction
to drug treatment:
derived
formulations,
in The Role and Methodology
of Classification
in Psychiatry
and Psychopathology:
Public
Health Service Publication
1584. Edited by Katz MM, Cole JO,
Barton
WE. Washington,
DC,
National
Institute
of Mental
Health, 1968
Nelson
JC, Charney
DS, Quinlan
DM: Characteristics
of autonomous
depression.
J Nerv Ment Dis 1980; 163:637-643
Charney
DS, Nelson
JC, Quinlan
DM: Personality
traits and
disorder in depression.
Am J Psychiatry
1981; 138:1601-1604
Covi L, Lipman RS, Alarcon RD, et al: Drug and psychotherapy
interactions
in depression.
Am J Psychiatry
1976; 133:502-508
Blackburn
IM, Bishop S, Glen AIM, et al: The efficacy of cognitive therapy in depression:
a treatment
trial using cognitive
therapy
and pharmacotherapy,
each alone and in combination.
BrJ Psychiatry 1981; 139:181-189
Downing
RW, Rickels K: Predictors of amitriptyline
response in
outpatient
depressives.
J Nerv Ment Dis 1972; 154:248-263
Keller MB, Shapiro RW: Double
depression:
superimposition
of acute depressive
episodes
on chronic
depressive
disorders.
Am J Psychiatry
1982; 139:438-442
Keller MB, Shapiro
RW, Lavori
PE, et al: Relapse
in major
depressive
disorder:
analysis with the life table. Arch Gen Psychiatry
1982; 39:911-915
Keller MB, Lavori PW, Endicott J, et al: Double
depression:
two-year
follow-up.
Am J Psychiatry
1983; 140:689-694
Pilkonis
P, Imber 5, Lewis P, et al: A comparative
outcome
study of individual,
group, and conjoint
psychotherapy.
Arch
Gen Psychiatry
1984; 41:431-437
Shapiro AK, Struening
E, Shapiro E, et al: Prognostic
correlates
of psychotherapy
in psychiatric
outpatients.
Am J Psychiatry
1976; 133:802-808
Fairweather
GW, Simon R, Gebhard ME, et al: Relative Effectiveness of Psychotherapeutic
Programs:
A Multicritenia
Comparison
of Four Programs
for Three Different
Patient Groups.
Psychol Monographs
1960; 74(5, Whole Number
492)
Fulkerson
SC, Barry JR: Methodology
and research
on the
prognostic
use of psychological
tests- Psychol
Bull 1961; 58:
177-204
Raskin A, Boothe H, Reatig N, et al: Initial response to drugs in
depressive
illness and psychiatric
and community
adjustment
a
year later. Psychol Med 1978; 8:71-79
Kiloh LG, Ball JRB, Garside LW: Prognostic
factors in treatment of depressive
states with imipramine.
Br Med J 1962;
1: 1225-1227
Finnerty RJ, Goldberg
HL: Specific response to imipramine
and
doxepin in psychoneurotic
depressed
patients with sleep disturbance. J Clin Psychiatry
1981; 42:275-279
Raskin A, Boothe H, SchulterbrandtJG,
et al: A model for drug
use with depressed
patients.
J Nerv Ment Dis 1973; 1S6:130142
Rickels K, Raab E, DeSilvenio
R, et al: Drug treatment
in depression:
antidepressant
or tranquilizer?
JAMA 1967; 201:675681

clinically

23:56-62

55.

56.

57.

Am

J Psychiatry

1 48:8,

August

1991