Journal of Psychiatric Research 37 (2003) 325–333

www.elsevier.com/locate/jpsychires

Clinician recognition of anxiety disorders in depressed outpatients

Mark Zimmerman*, Iwona Chelminski
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence, RI 02905, USA

Received 5 September 2002; received in revised form 7 January 2003; accepted 23 January 2003

Abstract
The recognition of anxiety disorders in depressed patients has potential clinical significance because their presence predicts
poorer outcome and may influence treatment selection. In routine clinical settings, an unstructured diagnostic interview is
typically used to assess patients at the initiation of treatment. Unstructured interviews, however, may result in missed diag-
noses, with potential negative clinical consequences. The goals of the present study were to examine whether anxiety disorders
are less frequently identified using a routine unstructured clinical evaluation than a semi-structured diagnostic interview in
patients with a principal diagnosis of major depressive disorder (MDD), and to determine patients’ desire for treatment for
comorbid anxiety disorders. Psychiatric outpatients with MDD were evaluated with either a semi-structured or an unstructured
diagnostic interview. Current DSM-IV anxiety disorder diagnoses were compared in the two, nonoverlapping, groups of depressed
psychiatric outpatients seen in the same practice setting. Patients with comorbid anxiety disorders who were interviewed with
the semi-structured interview were asked if they wanted treatment to address their anxiety symptoms. Individuals interviewed
with the semi-structured interview were diagnosed with significantly more current anxiety disorders than individuals who were
assessed with an unstructured interview. There was variability in patients’ desire for treatment of the different anxiety dis-
orders, though for each disorder the majority of patients wanted treatment to address the anxiety symptoms. In psychiatric
outpatients with a principal diagnosis of MDD psychiatrists underrecognize anxiety disorder comorbidity for which patients want
treatment.
# 2003 Elsevier Science Ltd. All rights reserved.
Keywords: Anxiety disorders; Depression; Comorbidity; Semi-structured interview; Desire for treatment

1. Introduction Methods to Improve Diagnostic Assessment and Ser-

Anxiety is frequent in depressed patients, though
most studies of this relationship have been of symptoms
of anxiety rather than diagnosable anxiety disorders
(Clayton et al., 1991; Joffe et al., 1993; Van Valkenburg
et al., 1984). Five studies of the full range of DSM-
defined anxiety disorders in depressed psychiatric out-
patients each found that when diagnoses are based on
semi-structured diagnostic interviews more than 40% of
the patients had a comorbid anxiety disorder (Fava et
al., 2000; Melartin et al., 2002; Pini et al., 1997; San-
derson et al., 1990; Zimmerman et al., 2000).
During the last 2 years three reports have questioned
the adequacy of the unstructured clinical diagnostic
interview. In an earlier report from the Rhode Island
* Corresponding author. Tel.: +1-401-277-0724; fax: +1-401-277-
0726.
E-mail address: mzimmerman@lifespan.org (M. Zimmerman).
0022-3956/03/$ - see front matter # 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0022-3956(03)00020-7
vices (MIDAS) project, we found much lower comor-
bidity rates in psychiatric outpatients diagnosed
according to unstructured clinical interviews than a
standardized research interview (Zimmerman and Mat-
tia, 1999). Shear and colleagues in Pittsburgh (Shear et
al., 2000) and Basco and colleagues in Texas (Basco et
al., 2000) reported similar results.
Previously we examined diagnostic underdetection in
a broad cross-section of psychiatric outpatients by
comparing diagnostic frequencies in two separate
cohorts of patients, one evaluated with an unstructured
clinical interview and the other evaluated with a semi-
structured research diagnostic interview (Zimmerman
and Mattia, 1999). In the present report we narrow our
focus to the detection of anxiety disorders in depressed
patients because of the high frequency of this comor-
bidity, and the potential impact this comorbidity might
have on treatment planning. As an indicator of the
potential importance of anxiety disorder comorbidity
326 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
on treatment planning with depressed patients we asked
patients whether they were interested in having treat-
ment directed towards the comorbid anxiety disorder.
Thus, in the present report from the Rhode Island
MIDAS project we examined the following three ques-
tions: (1) In psychiatric outpatients diagnosed with
major depressive disorder (MDD), how well do psy-
chiatrists do in detecting the presence of comorbid
anxiety disorders? (2) Are there differences between the
anxiety disorders regarding patients’ desire for treat-
ment? (3) Do psychiatrists underrecognize anxiety dis-
order comorbidity for which patients want treatment?
2. Methods
More than two thousand patients were evaluated
upon presentation for outpatient treatment to the
Rhode Island Hospital Department of Psychiatry out-
patient practice. This private practice group pre-
dominantly treats individuals with medical insurance
(including Medicare but not Medicaid) on a fee-for-ser-
vice basis, and it is distinct from the hospital’s out-
patient residency training clinic that predominantly
serves lower income, uninsured, and medical assistance
patients.
We examined psychiatric diagnoses made during the
initial intake evaluation in two nonoverlapping cohorts
of patients—in one group patients were interviewed by
attending psychiatrists with an unstructured clinical
interview (n=1352), and in the other group patients
interviewed with the Structured Clinical Interview for
DSM-IV (n=800). The diagnostic procedures employed
in each group are described further below. Not all
patients were interviewed with the SCID because of the
lack of availability of diagnostic raters and patients’
preference for the briefer unstructured evaluation. It
should be noted that in our earlier report comparing the
diagnostic practices of clinicians and researchers the
samples were ascertained sequentially (Zimmerman and
Mattia, 1999). That is, 500 patients were evaluated by
clinicians, and subsequent to this 500 patients were
interviewed with the SCID. That was not the case in the
present study in which the two groups of patients were
ascertained during the same time period, though group
assignment was not based on random assignment. The
patients in our prior report are not included in the pre-
sent analyses.
Before the initial evaluation all patients completed the
Psychiatric Diagnostic Screening Questionnaire (PDSQ,
Zimmerman and Mattia, 2001a,b) as part of their initial
paperwork. The PDSQ is a broad-based screening
questionnaire assessing the symptoms of DSM-IV
mood, eating, anxiety, substance use, and somatoform
disorders. Because the validity of the PDSQ was under
investigation, the clinicians were kept blind to the
patients’ responses on the questionnaire. The institu-
tional review board reviewed and approved the eval-
uation protocol, and all participants provided written
informed consent.
All patients were presenting for their initial diagnostic
evaluation in a community based, hospital affiliated,
outpatient psychiatric practice. For convenience, we
refer to the patients interviewed with the SCID (which
was followed by an unstructured interview by their
treating psychiatrist) as the SCID sample, and the
patients interviewed only with the psychiatrist’s
unstructured clinical interview as the nonSCID sample.
In the non SCID sample, unstructured diagnostic eval-
uations were conducted by board certified or board eli-
gible attending psychiatrists. Diagnoses were based on
DSM-IV criteria. Clinicians completed a standardized
intake form modeled on the Intake Evaluation Form of
Mezzich and colleagues (1981). The intake form inclu-
ded space for a narrative description of the chief com-
plaint, history of present illness, and past psychiatric
history. In addition, there was a checklist to record the
presence or absence of substance use problems, a his-
tory of sexual or physical abuse, psychotic symptoms,
panic attacks, phobias, obsessions, compulsive beha-
vior, and all of the symptoms of major depression. On
the last page of the five-page form clinicians recorded
patients’ DSM-IV multiaxial diagnoses. Research assis-
tants recorded the results of the clinician’s diagnostic
evaluation written on the last page of the intake form,
and collected demographic information from the narra-
tive. When estimating disorder prevalence rates for
clinical diagnoses, we included as cases patients whom
the clinicians diagnosed with a ‘‘ruleout’’ disorder.
When patients called to schedule their initial
appointment they were offered the opportunity to
receive a more comprehensive evaluation than the usual
unstructured clinical evaluation. The patients were told
that they would be interviewed by two people—first by
a diagnostic rater who would conduct a comprehensive
evaluation, and then by a psychiatrist. After the SCID,
the rater presented the case to a psychiatrist who
reviewed the findings of the evaluation with the patient.
If the psychiatrist obtained additional information to
modify the diagnosis this was discussed with the SCID
rater. Although not systematically recorded, it was rare
for a diagnosis to be added after the psychiatrist’s
review of the case.
The core of the diagnostic evaluation was the January
1995 DSM-IV patient version of the SCID (First et al.,
1995). During the course of the study, joint-interview
diagnostic reliability information has been collected on
47 patients. For mood and anxiety disorders the Kappa
coefficients were: MDD (k=0.91), dysthymic disorder
(k=0.88), bipolar disorder (k=0.85), panic disorder
(k=1.0), social phobia (k=0.84), obsessive-compulsive
disorder (OCD; k=1.0), specific phobia (k=0.91), gen-
 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
eralized anxiety disorder (GAD; k=0.93), and post-
traumatic stress disorder (PTSD; k=0.91). Details
regarding interviewer training and supervision are avail-
able in other reports from the MIDAS project (Zimmer-
man and Mattia, 1999, 2001a,b; Zimmerman et al., 2000).
Two questions about reasons for seeking treatment
were asked: ‘‘Was (symptoms of disorder) one of the
main reasons you decided to seek treatment now?’’ If
the patient responded ‘‘no’’ to this question, they were
asked: ‘‘Now that we’ve talked about (symptoms of
disorder), would you like your treatment here to address
these symptoms?’’ When asking these questions the
interviewer reviewed the features of the disorder that
had just been described so the patient understood to
what the question referred.
In our analyses, first we compared the frequency of
current DSM-IV anxiety disorders in the SCID and
nonSCID samples. Then, we determined the percentage
of patients in the SCID sample who indicated that they
wanted treatment for each of the comorbid diagnoses.
Finally, we recomputed the prevalence of anxiety dis-
orders in the SCID sample by requiring both disorder
presence and desire for treatment, and compared this to
the prevalence rate in the nonSCID sample. This
addresses the question of whether psychiatrists under-
recognize anxiety disorder comorbidity for which
patients want treatment. t-Tests were used to compare
the samples on continuously distributed variables.
Categorical variables were compared by the chi-square
statistic, or by Fisher’s Exact test if the expected value
in any cell of a 22 table was less than 5. The degree of
inequality between the rates of diagnoses in the two
samples was tested using odds ratios (OR) calculated
with 95% confidence intervals (CI).
3. Results
3.1. Comparability of the samples
A principal diagnosis of current nonbipolar MDD
was given to 610 patients in the nonSCID sample and
300 patients in the SCID sample. Patients diagnosed
with bipolar depression are not included in this report.
The depressed patients in the nonSCID sample were
significantly older than the depressed patients in the
SCID sample (Table 1). In addition, patients in the
nonSCID sample were significantly less likely to have
attended some college and to be white. There was no
difference in gender or marital status.
Patients in the clinical and SCID samples were com-
pared on the PDSQ self-report symptom scale, control-
ling for age. There were no significant differences
between the groups on each of the 13 PDSQ subscale
scores. Thus, despite significant, albeit modest, differ-
ences in demographic characteristics, the SCID and
327
clinical patient samples were clinically similar as asses-
sed by a self-report measure of DSM-IV symptoms.
3.2. Anxiety disorder comorbidity rates in depressed
outpatients diagnosed clinically or by a semistructured
diagnostic interview
More current anxiety disorders were diagnosed in the
SCID than the nonSCID sample (1.0  1.1 vs. 0.3  0.6,
t=10.4, P < 0.001). The data in Table 2 shows that each
anxiety disorder except PTSD was significantly more
frequently diagnosed in the SCID sample. Social phobia
and specific phobia were more than 15 times more fre-
quently diagnosed in the SCID sample.
To determine whether the difference in diagnostic
frequencies between the SCID and clinical interview was
a general phenomenon or specific to anxiety disorders
we compared the two groups on the second most fre-
quently diagnosed class of disorders—substance use
disorders. There was no difference between SCID and
clinically diagnosed patients in rates of current alcohol
abuse/dependence [6.0% vs. 4.9%, w2=0.5, n.s.;
OR=1.2 (95% C.I. 0.7–2.2)] or drug abuse/dependence
[4.7% vs. 3.4%, w2=0.8, n.s.; OR=1.4 (95% C.I. 0.7–
2.7)].
The effect of demographic factors on anxiety disorder
comorbidity detection was determined by examining the
study group by demographic variable interaction term
in an analysis of variance model that included sex, edu-
cation, marital status, age, and assessment method as
variables. None of the interaction terms was significant.
The mean number of anxiety disorder diagnoses was
higher in the SCID than the nonSCID samples for
women (1.1  1.1 vs. 0.3  0.5, t=9.36, P < 0.001) and
men (0.9  1.1 vs. 0.3  0.6, t=4.79, P < 0.001), currently
married (0.9  1.1 vs. 0.3  0.6, t=5.59, P < 0.001) and
not married patients (1.1  1.1 vs. 0.3  0.6, t=8.75,
P < 0.001), patients above and below the median age of
39 years (age 539: 0.9 1.1 vs. 0.3 0.5, t=6.55,
P< 0.001; age 438: 1.1 1.2 vs. 0.3 0.6, t=8.14,
P< 0.001), and patients who did or did not go beyond a
high school education (some college: 0.9 1.1 vs. 0.3 0.5,
t=8.48, P< 0.001; high school graduate or less: 1.2 1.1
vs. 0.3 0.6, t=6.60, P< 0.001).
3.3. Patients desire for treatment of their comorbid
anxiety disorders
Table 3 shows that the depressed patients evaluated
with the SCID most often wanted treatment of their
symptoms of GAD, panic disorder, and PTSD. One-
half to two-thirds of patients wanted treatment of social
phobia, OCD, and specific phobia. Overall, 86% of the
depressed patients with at least one anxiety disorder
wanted their treatment to address a comorbid anxiety
disorder.
328 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333

Table 1
Demographic characteristics of patients with a principal diagnosis of DSM-IV major depressive disorder in clinical and SCID samples

Clinical (n=610) SCID (n=300) w2 P

N % N %

Female gender 424 69.6 203 67.7 0.4 n.s.

Caucasian 484 79.3 264 88.0 10.3 <0.01

Education 10.9 <0.05

Less than 12th grade 84 14.0 27 9.0
HS graduation or equivalency 170 28.2 74 24.7
Some college 190 31.6 125 41.6
Four year college or more 158 26.2 74 24.7

Marital status 10.7 n.s.

Married 254 42.8 122 40.7
Living together 35 5.9 17 5.7
Widowed 24 4.0 4 1.3
Separated 48 8.1 20 6.7
Divorced 108 18.2 51 17.0
Never married 124 20.9 86 28.7

Mean S.D. Mean S.D. t P

Age 40.8 14.3 38.8 11.8 2.3 P<0.05

Table 2
Frequency of current DSM-IV anxiety disorders in patients with a principal diagnosis of major depressive disorder in clinical and SCID samples

Anxiety disorders Clinical (n=610) SCID (n=300) OR 95% CI w2 P

N % N %

Panic disorder 49 8.1 47 15.7 2.1 1.4–3.2 12.4 <0.001

Specific phobia 5 0.8 37 12.3 17.0 6.6–43.8 60.6 <0.001
Social phobia 13 2.1 98 32.7 22.3 12.2–40.6 175.0 <0.001
Obsessive compulsive disorder 20 3.3 26 8.7 2.8 1.5–5.1 12.2 <0.001
Posttraumatic stress disorder 47 7.7 34 11.3 1.5 1.0–2.4 3.3 0.07
Generalized anxiety disorder 41 6.7 60 20.0 3.5 2.3–5.3 35.9 <0.001
Any anxiety disorder 144 23.6 172 57.3 4.3 3.2–5.8 100.9 <0.001

Table 3
Desire for treatment for current DSM-IV comorbid anxiety disorders in SCID patients with a principal diagnosis of major depressive disorder

Anxiety disorders Frequency of the disorder Desire for treatment

N N %

Panic disorder 47 46 97.9

Specific phobia 37 21 56.8
Social phobia 98 72 73.5
Obsessive compulsive disorder 26 21 80.8
Posttraumatic stress disorder 34 30 88.2
Generalized anxiety disorder 60 55 91.7
Any anxiety disorder 172 149 86.6

We re-computed the prevalence of anxiety disorders order. The data in Table 4 shows that the rate of each
in the SCID sample by raising the diagnostic thresh- anxiety disorder (except PTSD) remained significantly
old by requiring both the presence of the disorder as higher in the SCID sample than in the nonSCID
well as the patients’ desire for treatment of the dis- sample.
 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
Table 4
Frequency of current DSM-IV anxiety disorders in patients with a principal diagnosis of major depressive disorder in clinical and SCID samples
Anxiety disorders Clinical (n=610)
N %
Panic disorder 49 8.1
Specific phobia 5 0.8
Social phobia 13 2.1
Obsessive compulsive disorder 20 3.3
Posttraumatic stress disorder 47 7.7
Generalized anxiety disorder 41 6.7
Any anxiety disorder 144 23.6
a
Indicates patients with the disorder who wanted treatment for it.
4. Discussion
Our results suggest that in psychiatric outpatients
with a principal diagnosis of MDD psychiatrists under-
recognize anxiety disorder comorbidity, and when an
anxiety disorder is present patients usually want their
treatment to address the comorbid anxiety disorders.
There are several alternative explanations for the lower
rate of anxiety disorders in the nonSCID than the SCID
sample. First, it is possible that the difference in
comorbidity rates reflects true sample differences, and
the nonSCID sample was a less severely ill group. This
is, however, extremely unlikely because patients in the
two samples scored similarly on the PDSQ anxiety dis-
order subscales. This makes it less likely that the diag-
nostic differences between the samples reflect a real
inter-sample difference in level of pathology. Sig-
nificantly more patients in the nonSCID than the SCID
sample received a principal diagnosis of MDD, though
the two groups scored similarly on the PDSQ depres-
sion subscale. Because nondepressive disorders were
more frequently diagnosed when the SCID was used, it
is likely that some of the SCID patients received a
principal diagnosis of a nondepressive disorder with
comorbid MDD, and this accounts for the difference
between groups in diagnosing principal MDD.
Second, it is possible that the lower anxiety disorder
rates in the nonSCID sample are the result of clinicians’
deliberate underdocumentation of psychopathology. If
clinicians censor from their records diagnostic informa-
tion that patients are most embarrassed, ashamed, or
stigmatized by, then it would be inappropriate to con-
clude that comorbidity was not being detected. How-
ever, post hoc conversations with the clinicians in the
practice indicated that they did not deliberately omit
diagnostic information from the patients’ charts. In
addition, the drug and alcohol use disorders were diag-
nosed with equal frequency in the SCID and nonSCID
samples. This, too, is inconsistent with the censoring
hypothesis.
Third, underdiagnosis may be a local rather than a
widespread problem. Perhaps the clinicians in our prac-
329
SCID (n=300)+ desire for treatmenta w2 P
N %
46 15.3 11.5 <0.001
21 7.0 27.7 <0.001
72 24.0 113.6 <0.001
21 7.0 6.5 <0.05
30 10.0 1.4 n.s.
55 18.3 28.7 <0.001
149 49.7 62.6 <0.001
tice are poor diagnosticians who failed to detect
comorbidity. While it is not possible to rule out this
possibility, elswhere we reported that the likelihood of
detecting a comorbid disorder by the clinicians in our
practice is higher than the rates found in other reports
of comorbidity based on clinical evaluations (Zimmerman
and Mattia, 1999). Moreover, our findings are con-
sistent with those of other studies comparing unstruc-
tured clinical evaluations with the results of semi-
structured diagnostic interviews (Basco et al., 2000;
Shear et al., 2000). Thus, it does not appear that the
psychiatrists in this study were more likely than other
psychiatrists to underrecognize diagnostic comorbidity.
Fourth, perhaps the problem is not with clinician
underdiagnosis but with semi-structured research inter-
view overdiagnosis. Interviews such as the SCID are
viewed as diagnostic ‘‘gold standards,’’ but it is possible
that they are too sensitive and result in false positive
diagnoses. Or perhaps we were biased to overdiagnose
on the SCID. Inconsistent with this is the comparability
of the anxiety disorder rates in our study with those of
other studies that used research diagnostic interviews
for assessing anxiety disorders in depressed patients
(Fava et al., 2000; Melartin et al., 2002; Pini et al., 1997;
Sanderson et al., 1990). Also inconsistent with the
SCID-overdiagnosis hypothesis is that when the results
of the SCID evaluations were presented to the clin-
icians, the clinicians made more diagnoses in the
patients’ clinical charts (data available upon request).
Because clinicians confirmed the SCID diagnoses, and
recorded more diagnoses in their patients’ charts com-
pared to when they conducted unstructured clinical
evaluations, it is less likely that diagnostic bias accounts
for our findings.
4.1. Implications of anxiety disorders in depressed
patients
The recognition of comorbidity is not simply of
academic interest—it has important clinical signi-
ficance. Epidemiological studies such as the National
Comorbidity Study have demonstrated that depressed
330 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
individuals with a history of anxiety disorders are at
increased risk for hospitalization, suicide attempt, and
greater impairment from the depression (Kessler et al.,
1994, 1996). The co-occurrence of anxiety disorders in
depressed patients has been associated with a more
chronic course of depression in psychiatric patients,
primary care patients, and epidemiological samples.
Van Valkenberg et al. (1984) reported that depressed
patients with anxiety neurosis (diagnosed according to
the Washington University criteria) had poorer out-
come and greater psychosocial impairment than
depressed patients without an anxiety disorder. In the
NIMH Collaborative Depression Study, the presence of
panic attacks predicted a lower recovery during the first
2 years of the follow-up interval (Coryell et al., 1988).
Grunhaus and colleagues (Grunhaus, 1988) similarly
found poorer outcome in depressed patients with
comorbid panic disorder than depressed patients with-
out panic. In an 8-month follow-up of depressed pri-
mary care patients treated with nortriptyline or
interpersonal therapy, patients with a history of GAD
or panic disorder were less likely to have recovered from
their depressive episode (Brown et al., 2000). In the
Medical Outcomes Study, panic or phobic disorder, but
not GAD, coexisting with MDD predicted a lower
remission rate 1 year after the initial evaluation, though
2 years after the evaluation only panic disorder was
significantly associated with a lower remission rate
(Sherbourne and Wells, 1997). Gaynes and colleagues
(Gaynes et al., 1999) prospectively followed 68 primary
care patients with MDD every 3 months for 1 year after
the initial diagnostic evaluation. Half of the patients
had a coexisting anxiety disorder, the most frequent
being social phobia. Twelve months after intake the
patients with a comorbid anxiety disorder were sig-
nificantly more likely to still be in an episode of depres-
sion, and they experienced more disability days during
the course of the 12 months than the depressed patients
without an anxiety disorder.
There are few controlled treatment studies of the
prognostic or treatment implications of anxiety dis-
orders in depressed patients because many of these
studies exclude patients with clinically significant
comorbid anxiety disorders (Bennie et al., 1995; New-
house et al., 2000; Rapaport et al., 1996; Tollefson et al.,
1994a). We are not aware of any effectiveness studies, in
which exclusion criteria are minimal, that have exam-
ined the prognostic significance of comorbid anxiety
disorders. Nor are there studies of the influence of
comorbid anxiety disorders on treatment selection for
patients seen in routine clinical practice. While there are
several controlled studies of the prognostic significance
of anxious features in depressed patients (Joffe et al.,
1993; Tollefson et al., 1994b), we do not consider these
studies here because of the uncertain relationship
between the severity of anxiety features and a diagnosis
of a comorbid anxiety disorder (Fava et al., 2000).
However, at least three controlled studies of the prog-
nostic significance of anxiety disorders in depressed
patients have been conducted.
Fava and colleagues (Fava et al., 1997) treated nearly
300 depressed outpatients with fluoxetine and found
that patients with a comorbid anxiety disorder were less
likely to respond than depressed patients without a
comorbid anxiety disorder. In Brown, Schulberg and
colleagues’ (1996) primary care study of nortriptyline
and interpersonal therapy, the presence of a comorbid
anxiety disorder was associated with a nonsignificantly
higher rate of premature discontinuation from treat-
ment, and patients with a lifetime history of panic dis-
order had a lower recovery rate than patients without
panic. Levitt et al., (1993) treated 31 depressed out-
patients with seasonal affective disorder (SAD) with
light therapy and 25 patients without SAD with desi-
pramine or imipramine. The presence of a comorbid
anxiety disorder did not predict response to light ther-
apy in the patients with SAD. In the patients without
SAD who were treated with a TCA, the presence of a
comorbid anxiety disorder was associated with a sig-
nificantly lower response rate. None of these studies
included a placebo group.
The poorer outcome of anxious depressed patients
compared to nonanxious depressed patients, particu-
larly in naturalistic longitudinal studies of the course of
depression, raises the question of whether improving the
detection of anxiety disorders would result in improved
outcome. The clinical implications of underdiagnosing
anxiety disorders in depressed patients depend on two
factors—(1) whether or not anxiety disorders have an
impact on the longitudinal course of depression, and (2)
the availability of effective treatment that is specific for
anxiety disorders. As reviewed above, the literature
suggests that the presence of a comorbid anxiety dis-
order is associated with a poorer outcome. The second
question is whether or not appropriate intervention will
improve outcome. It is logical to speculate that
improved diagnostic practice, resulting in improved
detection of anxiety disorders and treatment directed to
the additional concerns related to anxiety disorders, will
result in improved treatment outcome. However, it is
also possible that the presence of a comorbid anxiety
disorder will be associated with poorer outcome even
when the diagnosis is known. In studies finding that the
presence of a comorbid anxiety disorder was associated
with a greater likelihood of depression chronicity, it is
not clear whether the health care providers were aware
of the researchers’ anxiety disorder diagnoses. It is
therefore unknown if the greater chronicity of depres-
sion in patients with high anxiety was due to the failure
of appropriate treatment or the failure to provide
appropriate treatment. There are no studies that have
examined the important question of whether the treat-
 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
ment of depressed patients with and without comorbid
anxiety disorders should differ; though clinical experi-
ence and inference from the extant literature suggests
that the presence of a comorbid anxiety disorder
impacts upon case formulation and treatment planning.
4.2. Treatment planning in depressed patients with
comorbid anxiety disorders
Experts in the treatment of depression with comorbid
anxiety disorders have described how knowledge of a
comorbid anxiety disorder might impact upon the
treatment of MDD (Nutt, 1999; Pollack and Marzol,
2000; Roy-Byrne, 1999). For example, treatment plan-
ning for depressed patients with a comorbid anxiety
disorder could include referral for CBT for the anxiety
disorder. Choice and dosing of pharmacologic agents
might also vary. Depressed patients with a comorbid
panic disorder might have a benzodiazepine prescribed
as well as an antidepressant at treatment onset in order
to achieve more rapid relief from the panic attacks. If an
SSRI is prescribed, dosage titration might be more gra-
dual (Gorman et al., 1987). The best empirically sup-
ported treatment decision is the preferential selection of
an SSRI over a TCA in the treatment of depressed
patients with comorbid OCD (Hoehn-Saric et al., 2000).
Depression comorbid with social phobia might also be
preferentially prescribed an SSRI. The addition of a
benzodiazepine might be considered in depressed
patients with comorbid GAD.
In the recently revised APA Practice Guideline for the
treatment of MDD (2000), four suggestions were made
regarding the treatment of depression comorbid with an
anxiety disorder: initiate antidepressant medication at
lower than usual dosages and slowly titrate upwards;
SSRIs and clomipramine are effective for OCD and
therefore should be considered when treating depressed
patients with comorbid obsessive features; buproprion
has not been found to be effective in the treatment of
panic disorder (and although the guidelines do not spe-
cifically state this, the inference is that this medication
should not be considered a first line treatment for
depressed patients with this comorbidity); and benzo-
diazepines may be beneficial augmenting agents in the
short term. Except for the single OCD study, none on
the treatment suggestions described above have been
subjected to empirical testing.
4.3. Future directions
The literature is consistent concerning the prevalence
and impact of anxiety disorder comorbidity in depressed
patients. Substantial rates of comorbid disorders have
been found in epidemiological and clinical populations
using structured research diagnostic interviews. How-
ever, much lower comorbidity rates have been found in
331
clinical populations using unstructured clinical inter-
views. Given that the structured interview is considered
the diagnostic gold standard, this suggests that comor-
bidity is underdiagnosed in routine clinical settings.
Structured interviews such as the SCID are too long
and unwieldy for use in routine outpatient mental
health settings. A less time consuming semi-structured
interview, such as the Mini International Neu-
ropsychiatric Interview (MINI, Sheehan et al., 1998) is
brief enough to be incorporated into clinical practice;
however, this would require a significant change in how
clinicians conduct their diagnostic evaluations. It is
likely that clinicians already in practice will resist such a
change. The difficulty of convincing clinicians to use a
brief semi-structured interview in clinical practice, even
when underrecognition of psychopathology has been
well established, was reported by Spitzer and colleagues
(1999) in their research on the PRIME-MD in primary
care settings. It is well known that changing physician
behavior is difficult, and we believe that there will be
significant obstacles to overcome in getting clinicians to
routinely use a measure such as the MINI. It is more
likely that clinicians would use an inexpensive, screening
instrument that does not intrude on the clinician’s usual
practice but provides clinically relevant diagnostic
information. Potentially, a reliable and valid self-report
screening questionnaire would enhance and not inter-
fere with usual clinical practice. Elsewhere we described
the reliability and validity of a broad-based screening
questionnaire for Axis I disorders (Zimmerman and
Mattia, 2001a,b), and in a separate report we examine the
ability of the scale to detect comorbid anxiety disorders
in patients with a principal diagnosis of MDD (sub-
mitted for publication). The completion of paperwork
before an initial evaluation is common in physicians’
offices. The advantage of the empirically developed
measures such as the PDSQ over home-grown forms is
that the psychometric and diagnostic properties of the
scientifically studied instruments have been established
thereby guiding the interpretation of the results.
Finally, our review of the treatment literature indi-
cates that there are few placebo-controlled studies that
have examined the effectiveness of treatments for
patients with comorbid depression and anxiety dis-
orders. Because of the high frequency of this comorbid-
ity, this area of treatment research warrants further
study. Also sparse are studies examining differences
between active treatment and placebo in patients with
and without an anxiety disorder. For example, Smith,
Londborg and colleagues recently found that depressed
patients treated with fluoxetine and clonazepam
responded more rapidly than patients treated with
fluoxetine plus placebo (Londborg et al., 2000; Smith et
al., 1998). Unfortunately, they did not examine whether
this difference was true of patients with and without an
anxiety disorder. Future treatment studies should
332 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
examine whether the presence or absence of a comorbid
anxiety disorder in depressed patients warrants different
treatment approaches.
Acknowledgements
This research was supported, in part, by grants
MH48732 and MH56404 from the National Institute of
Mental Health.
References
APA. Practice guideline for the treatment of patients with major
depressive disorder (revision). Washington (DC): APA; 2000.
Basco MR, Bostic JQ, Davies D, Rush AJ, Witte B, Hendrickse W, et
al. Methods to improve diagnostic accuracy in a community mental
health setting. American Journal of Psychiatry 2000;157:1599–605.
Bennie EH, Mullin JM, Martindale JJ. A double-blind multicenter
trial comparing sertraline and fluoxetine in outpatients with major
depression. Journal of Clinical Psychiatry 1995;56:229–37.
Brown C, Schulberg HC, Madonia MJ, Shear MK, Houck PR.
Treatment outcomes for primary care patients with major depres-
sion and lifetime anxiety disorders. American Journal of Psychiatry
1996;153:1293–300.
Brown C, Schulberg HC, Prigerson HG. Factors associated with
symptomatic improvement and recovery from major depression in
primary care patients. General Hospital Psychiatry 2000;22:242–50.
Clayton PJ, Grove WM, Coryell W, Keller M, Hirschfeld R, Fawcett
J. Follow-up and family study of anxious depression. American
Journal of Psychiatry 1991;148:1512–7.
Coryell W, Endicott J, Andreasen NC, Keller MB, Clayton PJ,
Hirschfield RMA, et al. Depression and panic attacks: the sig-
nificance of overlap as reflected in follow-up and family study data.
American Journal of Psychiatry 1988;145:293–300.
Fava M, Rankin MA, Wright E, Alpert JE, Nierenberg AA, Pava J, et
al. Anxiety disorders in major depression. Comprehensive Psy-
chiatry 2000;41:97–102.
Fava M, Uebelacker LA, Alpert JE, Nierenberg AA, Pava JA,
Rosenbaum JF. Major depressive subtypes and treatment response.
Biological Psychiatry 1997;42:568–76.
First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical
interview for DSM-IV Axis I Disorders—patient edition (SCID-I/P,
version 2.0). New York: Biometrics Research Department, New
York State Psychiatric Institute; 1995.
Gaynes BN, Magruder KM, Burns BJ, Wagner HR, Yarnall KSH,
Broadhead WE. Does a coexisting anxiety disorder predict persis-
tence of depressive illness in primary care patients with major
depression? General Hospital Psychiatry 1999;21:158–67.
Gorman JM, Liebowitz MR, Fyer AJ, Goetz D, Campeas D, Fyer
MR, et al. An open trial of fluoxetine in the treatment of panic
attacks. Journal of Clinical Psychopharmacology 1987;7:329–32.
Grunhaus L. Clinical and psychobiological characteristics of simulta-
neous panic disorder and major depression. American Journal of
Psychiatry 1988; 145:1214-1221.
Hoehn-Saric R, Ninan P, Black DW, Stahl S, Greist JH, Lydiard B, et
al. Multicenter double-blind comparison or sertraline and desipra-
mine for concurrent obsessive-compulsive and major depressive
disorders. Archives of General Psychiatry 2000;57:76–82.
Joffe RT, Bagby RM, Levitt A. Anxious and nonanxious depression.
American Journal of Psychiatry 1993;150:1257–8.
Kessler R, McGonagle K, Zhao S, Nelson C, Hughes M, Eshleman S,
et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric
disorders in the United States. Results from the National Comor-
bidity Survey. Archives of General Psychiatry 1994;51:8–19.
Kessler R, Nelson C, McGonagle K, Liu J, Swartz M, Blazer D.
Comorbidity of DSM-III-R major depressive disorder in the general
population: results from the US National Comorbidity Survey.
British Journal of Psychiatry Supplement 1996;30:17–30.
Levitt AJ, Joffe RT, Brecher D, MacDonald C. Anxiety disorders and
anxiety symptoms in a clinic sample of seasonal and non-seasonal
depressives. Journal of Affective Disorders 1993;28:51–6.
Londborg PD, Smith WT, Glaudin V, Painter JR. Short-term cother-
apy with clonazepam and fluoxetine: Anxiety, sleep disturbance and
core symptoms of depression. Journal of Affective Disorders 2000;
61:73–9.
Melartin TK, Rytsala HJ, Leskela US, Lestela-Mielonen PS, Sokero
TP, Isometsa ET. Current comorbidity of psychiatric disorders
among DSM-IV major depressive disorder patients in psychiatric
care in the Vantaa Depression Study. Journal of Clinical Psychiatry
2002;63:126–34.
Mezzich JE, Dow JT, Rich CL, Costello AJ, Himmelhoch JM.
Developing an efficient clinical information system for comprehen-
sive psychiatric institute, II: initial evaluation form. Behavior
Research Method Instrument 1981;13:464–78.
Newhouse PA, Krishnan KRR, Doraiswamy PM, Richter EM, Batzar
ED, Clary CM. A double-blind comparison of sertraline and fluox-
etine in depressed elderly outpatients. Journal of Clinical Psychiatry
2000;61:559–68.
Nutt DJ. Care of depressed patients with anxiety symptoms. Journal
of Clinical Psychiatry 1999;60(Suppl):23–7.
Pini S, Cassano G, Simonini E, Savino M, Russo A, Montgomery S.
Prevalence of anxiety disorders comorbidity in bipolar depression,
unipolar depression and dysthymia. Journal of Affective Disorders
1997;42:145–53.
Pollack MH, Marzol PC. Pharmacotherapeutic options in the treat-
ment of comorbid depression and anxiety. CNS Spectrums 2000;5:
23–30.
Rapaport M, Coccaro E, Sheline Y, Perse T, Holland P, Fabre L, et
al. A comparison of fluvoxamine and fluoxetine in the treatment of
major depression. Journal of Clinical Psychopharmacology 1996;16:
373–8.
Roy-Byrne PP. Anxiety in primary care depression: how does it lead to
poor outcomes and what can we do about it? General Hospital
Psychiatry 1999;21:151–3.
Sanderson WC, Beck AT, Beck J. Syndrome comorbidity in patients
with major depression or dysthymia: prevalence and temporal rela-
tionships. American Journal of Psychiatry 1990;147:1025–8.
Shear MK, Greeno C, Kang J, Ludewig D, Frank E, Swartz HA, et al.
Diagnosis of nonpsychotic patients in community clinics. American
Journal of Psychiatry 2000;157:581–7.
Sheehan DV, LeCrubier Y, Sheehan KH, Amorin P, Janavs J, Weiller
E, et al. The Mini-International Neuropsychiatric Interview
(M.I.N.I.): the development and validation of a structured diag-
nostic psychiatric interview for DSM-IV and ICD-10. Journal of
Clinical Psychiatry 1998;59(Suppl. 20):22–33.
Sherbourne CD, Wells KB. Course of depression in patients with
comorbid anxiety disorders. Journal of Affective Disorders 1997;43:
245–50.
Smith WT, Londborg PD, Glaudin V, Painter JR. Short-term aug-
mentation of fluoxetine with clonazepam in the treatment of
depression: a double-blind study. American Journal of Psychiatry
1998;155:1339–45.
Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-
report version of PRIME MD: the PHQ primary care study. Pri-
mary care evaluation of mental disorders. Patient Health Ques-
tionnaire. JAMA 1999;282:1737–44.
Tollefson GD, Greist JH, Jefferson JW, Heiligenstein JH, Sayler ME,
Tollefson SL, et al. Is baseline agitation a relative contraindication
for a selective serotonin reuptake inhibitor: a comparative trial of
 M. Zimmerman, I. Chelminski / Journal of Psychiatric Research 37 (2003) 325–333
fluoxetine versus imipramine. Journal of Clinical Psychopharma-
cology 1994a;14:385–91.
Tollefson GD, Holman SL, Sayler ME, Potvin JH. Fluoxetine, pla-
cebo, and tricyclic antidepressants in major depression with and
without anxious features. Journal of Clinical Psychiatry 1994b;55:
50–9.
Van Valkenburg C, Akiskal HS, Puzantian V, Rosenthal T. Anxious
depressions: clinical, family history, and naturalistic outcome-com-
parisons with panic and major depressive disorders. Journal of
Affective Disorders 1984;6:67–82.
Zimmerman M, Mattia JI. Psychiatric diagnosis in clinical practice: is
333
comorbidity being missed? Comprehensive Psychiatry 1999;40:182–
91.
Zimmerman M, Mattia JI. The Psychiatric Diagnostic Screening
Questionnaire: development, reliability and validity. Comprehensive
Psychiatry 2001a;42:175–89.
Zimmerman M, Mattia JI. A self-report scale to help make psychiatric
diagnoses: the Psychiatric Diagnostic Screening Questionnaire
(PDSQ). Archives of General Psychiatry 2001b;58:787–94.
Zimmerman M, McDermut W, Mattia J. The frequency of anxiety
disorders in psychiatric outpatients with major depressive disorder.
American Journal of Psychiatry 2000;157:1337–400.