phenomenology and severity of major depression and comorbid lifetime anxiety disorders in primary...

A ~ ~ ~ W 2 : 2 1 & 2 1 8 (1996)

PHENOMENOLOGY AND SEVERITY OF MAJOR DEPRESSION AND COMORBID LIFETIME ANXIETY DISORDERS IN PRIMARY MEDICAL CARE PRACTICE

Charlotte Brown, Herbert C. Schulberg, and M. Katherine Shear

The psychiatn’c history and presenting clinical characteristics of 2 76 depressed primary care patients with and without a lifetime comorbid anxiety disorder were studied in a randomized control trial of treatments for major depression. Our findings indicate that distinctive patterns of depressive symptoms and severity, Jicnctional impairment, comorbidity of other DSM-In-R Axis I and Axis 11 disorders, and treatment participation are associated with lifetime histories of panic and generalized anxiety disorder. The most consistent difler- ences are evident between patients with major depression alone and those with major depression and a lifetime panic disorder. The latter presented with greater depressive severity, greater impairment in physical and psychosocial Jicnctioning, and were more likely to have a history of alcohol dependence, somatization disorder, and avoidant personality disorder. Discriminant Jicnc- tion analysis indicated that 66% of depressed patients with lifetime panic disorder could be correctly distinguished f r o m those without such comorbidity on the basis of the severity of somatic and aflective symptoms but not cognitive symptoms of depression. Further, depressed patients with lifetime panic disorder were more likely to prematurely terminate both pharmacotherapy and psychotherapy during each treatment’s acme phase. Implications for the diagnosis and treatment of major depression with comorbid anxiety disorder in primary care patients are discussed. Anxiety 2:210-218 (1996). @ 1996 Wiky-~iss, Inc.

Key Words: major depression, comorbid anxiety disorder, primary care practice

INTRODUCTION I he common co-occurrence of mood and anxiety

disorders has frequently been reported in studies of community (Regier et al., 1990) and psychiatric popula- tions (Clayton, 1990; Sanderson et al., 1990; DiNardo and Barlow, 1990). Even higher rates for this pattern of psychopathology were found in community samples with chronic medical illnesses (Wells et al., 1988). Depression’s comorbidity with anxiety disorders has also been investigated in the primary medical sector where its point prevalence has been estimated as 67% when assessed with symptom rating scales (Zung et al., 1990) and as ranging from 32% to 62% when evaluated with structured diagnostic interviews (Ormel et al., 1991; Schulberg et al., 1995). There also is grow- ing awareness that 10% to 20% of primary care patients experience mixed anxiety depression, i.e., distressing symptoms of depression and anxiety which fail to meet

0 1996 WILEY-LISS, INC.

DSM-111-R criteria for either of these diagnoses (Zinbarg et al., 1994; Stein et al., 1995).

As to whether depression and anxiety are most val- idly classified as singular or distinct forms of psychopathology within the DSM system given their high comorbidity, Liebowitz et al. (1990) suggest that some subtypes of the disorders possibly lie on a continuum and blend with each other (e.g., dysthymia and generalized anxiety disorder), whereas other subtypes appear

University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Received for publication April 21, 1996; accepted May 15, 1996.

Address reprint requests to Charlotte Brown, Ph.D., Western Psychiatric Institute and Clinic, 381 1 O’Hara Street, Pittsburgh, PA 1521 3.

Comorbid Depression and Anxiety 211

distinct (e.g., major depression and panic disorder). They note, however, that co-occurrence of even the presum- ably distinct forms of depression and anxiety is associated with greater symptomatic severity, decreased treatment responsiveness, and increased familial rates for either or both of these disorders. While other studies have concluded that the two disorders are distinct, since depression does not necessarily lead to an autonomous anxiety disorder (Thompson et al., 1989; Coryell et al., 1992), nevertheless there is agreement that this complex clinical pattern requires further study.

Such research is particularly needed and timely in the primary medical care sector where the development of casefinding instruments such as the PRIME- MD (Spitzer et al., 1994) is leading to the identification of numerous patients meeting DSM-IV criteria for both a mood and anxiety disorder. Internists and family physicians caring for such patients are faced with the diagnostic dilemma of how to distinguish the symptom patterns associated with each of these comorbid disorders, and to judge their prognostic and treatment implications. The diagnostic and therapeutic com- plexities associated with comorbid psychopathology have been investigated among psychiatric patients (Bronisch and Hecht, 1990; Clark et al., 1994), but have to date received little attention with regard to primary care patients who experience comorbid depression and anxiety as well as general medical illnesses (Shear and Schulberg, 1995). Accepting Kupfer and Carpenter’s (1990) cautionary note that a patient’s picture of symptom comorbidity possibly is specific to the health care setting in which it is presented, we have investigated the nature of current major depression comorbid with a lifetime anxiety disorder in an ambulatory medical population. This report compares the phenomenology and severity of these and other DSM disorders reported by patients who are comorbid for major depression and generalized anxiety or panic disorder with patients experiencing major depression alone.

PATIENTS AND METHODS The psychiatric history and presenting clinical char-

acteristics of depressed primary care patients with and without a lifetime comorbid anxiety disorder were studied in a sample of 276 patients recruited for a randomized control trial of treatments for major depression in two internal medicine clinics and two family health centers in Pittsburgh, Pennsylvania (Schulberg et al., 1993). Potential participants were patients ages 18-65 presenting in the waiting rooms of the four study sites. Each patient was informed by a Research Associate that the University of Pittsburgh School of Medicine was conducting an IRB-approved study of treatments for major depression among ambulatory medical patients and informed consent was sought for a three-phase assessment of eligibility for the clinical trial.

Initial screening for depression involved administration of the Center for Epidemiologic Studies-Depression

Scale (CES-D: Radloff, 1977). Participants scoring 22 or higher and not receiving depression-specific treatment were then asked to continue with a second assessment in which the research associate administered the Diag- nostic Interview Schedule’s (DIS) Depression section (Robins et al., 1981) which was modified to provide a current diagnosis of depression (Von Korff and An- thony, 1982). As previously reported (Schulberg et al., 1995), individuals meeting DSM-111-R criteria for a current major depression were then asked to meet with a consultation-liaison psychiatrist a t the health center for a further assessment to establish psychiatric and medical eligibility. Patients were excluded if they: (1) exhibited psychotic symptoms; (2) were positive for suicidality in terms of ideation, plans, and prior at- tempts; (3) had a history of bipolar illness; (4) had an organic mood syndrome, including those associated with medical illness or drugs; (5) had an unstable general medical condition as indicated by clinical history, physical examination, or laboratory findings; (6) abused alcohol or drugs within the past two months; or (7) had any medical contraindication to the nortriptyline be- ing prescribed in the treatment trial.

Two-hundred seventy-six patients met protocol criteria and provided informed consent for a randomized assignment to one of the following three treatment conditions: (1) interpersonal psychotherapy (IPT) provided within treatment manual therapy standards as described by Herman et al. (1984); (2) nortriptyline (NT) provided within manualized pharmacotherapy standards as described by Fawcett et al. (1987); and (3) usual care, i.e., any intervention deemed appropriate by the treating physician, including no depression- specific treatment, antidepressant medication, coun- selling, referral for psychotherapy, etc.

Following randomization, study patients were administered additional sections of the DIS and the Structured Clinical Interview for DSM-11-R Personal- ity Disorders (Spitzer et al., 1990) by clinical evaluators unaware of patients’ treatment assignments to determine the presence of other lifetime psychiatric (Axis I) and any personality (Axis 11) disorders. A hier- archical rule was used to classify comorbid anxiety diagnoses. Depressed patients with generalized anxiety disorder alone were assigned to the MDD+GAD group (n=62); those with comorbid panic disorder alone (n=19) or panic disorder and generalized anxiety disorder (n=84) were assigned to the MDD+Panic group. This report is based on the sample of 233 patients who completed protocol assessments and were diagnosed with either a current major depression alone (MDD), a current major depression with lifetime generalized anxiety disorder (MDD+GAD), or current major depression with lifetime panic disorder (MDD+Panic).

Additional baseline assessments included those of depressive severity with the Beck Depression Inven- tory (BDI: Beck, 1978) and the 17-item Hamilton Rating Scale-Depression (HRS-D: Hamilton, 1986); medical severity with the Duke Severity of Illness

212 Brown et al.

Scale (DUSOI: Parkerson et al., 1989); patient’s self- report of number of prior depressive episodes and prior inpatient and outpatient treatment; functional impairment with the Global Assessment Scale (GAS: Endicott et al., 1976), and patient’s perception of psychosocial and physical functioning with the Medical Outcomes Study (MOS) Short-Form 36 (Ware and Sherbourne, 1992); health beliefs with the Health Lo- cus of Control Scale (HLC: Wallston et al., 1976); and stressful life events with the Psychiatric Epidemiology Research Interview (PEN: Dohrenwend et al., 1978). The HRS-D was administered by clinical evaluators unaware of a patient’s treatment assignment and whose interrater reliability exceeded 0.90.

STATISTICAL ANALYSES One-way analyses of variance were used for ordinal

data and chi-square tests for categorical data to evalu- ate differences between diagnostic groups in demographic and baseline clinical characteristics and in symptom patterns.

In addition to assessing overall depressive severity with BDI and HRS-D total scores, patterns of symptom severity were also evaluated for each diagnostic group on the BDI and HRS-D factors identified by Brown et al. (1995). Patients’ scores on each factor were computed and one-way analyses of variance were performed to compare intergroup differences. In order to determine whether specific symptom patterns could distinguish depressed patients with and without lifetime panic disorder, a discriminant function analysis was performed using diagnostic group (MDD+Panic, MDD with or without GAD) as the dependent variable and BDI and HRS-D factor scores as independent variables.

Baseline psychosocial and physical health-related functioning were assessed with the MOS Short Form- 36. Using procedures developed by Ware et al. (1995), the eight MOS scales were aggregated into the Physi- cal Component Scale (PCS) and the Mental Compo- nent Scale (MCS). The algorithms for scoring the PCS and MCS utilized standardized scores (based upon a U.S. general population sample) which were transformed to have a mean of SO and a standard de- viation of 10. In addition, results are presented for individual MOS scales.

Finally, chi-square analyses were performed to compare diagnosis-specific differences in the proportions of patients participating in the acute and continuation phases of the randomized clinical trial. Clinical outcomes for both standardized treatments are detailed in a separate report (Brown et al., in press).

RESULTS DEMOGRAPHIC AND CLINICAL CHARACTERISTICS

Depressed patients with a comorbid panic or generalized anxiety disorder were significantly older than those with major depression alone (F=S.O, df=2, 230, p=.008), but the three groups did not differ on the other measured demographic variables (see Table 1).

Table 2 indicates that patients with a lifetime comorbid panic disorder exhibited significantly greater depressive severity than patients with major depression alone or with comorbid generalized anxiety on the self-report CES-D (F=6.3, df=2, 227, p=.002) and BDI (F=13.3, df=2, 224, p=.OOOl), and the clinician-rated HRS-D (F=5.2, df=2, 230, p=.006). Furthermore, a significantly greater proportion of panic-disordered patients were se- verely depressed (HRS-D 225) at baseline compared to patients with major depression alone or major depression with comorbid GAD k2=7.5, df=2, p=.02). More of the former group also had a history of inpatient psychiatric hospitalization k2=S.S, df=2, p=.Ol). However, the three diagnostic groups did not differ with regard to history of prior outpatient treatment, number of prior depressive episodes, or severity of medical illness.

PSYCHOSOCIAL AND PHYSICAL FUNCTIONING

Psychosocial and physical functioning was more im- paired among depressed patients with comorbid panic disorder than among patients with major depression alone. The former group reported greater impairment on the MOS in social functioning (F=4.5, df=2, 225, p=.Ol) and physical functioning (F=5.6, df=2, 225, p=.004) as well as poorer general health (F=8.4, df=2, 226, p=.0003; see Table 3). Depressed patients with comorbid panic disorder and generalized anxiety disorder did not differ on these measures. However, a

TABLE 1. Demographic characteristics

MDD MDD+GAD MDD+Panic X 5. D. n X S. D. n X S. D. n

AgeaXb 34.8 11.3 68 40.8 12.2 62 3 9.6 11.7 103 Gender: female 84% 68 77% 62 87% 103 ZHS education 81% 68 84% 62 83 % 103 Employed F/FT 46% 66 48% 62 36% I03 Married 32% 68 34% 62 27% 103 % White 63 % 68 58% 62 49% 103

‘MDD+Panic signifirantly different fiom MDD (pc .OF). bMDD~GAD significantly differentfiom MDD (pc .OS).

Comorbid Depression and Anxiety 213

TABLE 2. Baseline clinical characteristics

MDD MDD+GAD MDD+Panic X S. D. n X S. D. n X S. D. n

CES-D",~ 35.8 8.8 67 35.5 8.3 62 39.7 8.5 101 BDI",' 21.0 8.9 67 26.3 10.4 59 28.9 9.7 101 HRS-D"~ 22.4 4.5 68 22.0 5 .O 62 24.3 5.3 103 % HRS-D 225* 30.9 68 35.5 62 50.5 103 DUSOI

Comorbidity index 33.0 17.5 68 34.8 15.4 62 34.9 15.2 103 No. depressive

episodes 2.4 .9 54 2.5 .8 40 2.6 .7 71 % Prior outpatient

treatment 39.3% 61 44.2 % 52 50.6% 83 % Prior inpatient

treatment** 14.1% 50 18.2% 44 35.1% 74

'MDD+Panic significantly differentfiom MDD (p< .OF). bMDD+Panic sign2ficantly different fiom MDD+GAD (pc .OF). 'MDD+GAD significantly different fiom MDD (p< .OF). r 2 X = 75, df=2, p = .02. **X2=8.F, df=2, p = .01.

history of either of these anxiety disorders was associated with poorer self-reported mental health than for major depression alone (F=11.0, df=2, 222, p=.OOOl).

disorder were judged as functioning more poorly than patients with major depression alone (F=36.0, df=2, 230, p=.OOOl; see Table 3).

HEALTH LOCUS OF CONTROL, SOCIAL Wken piychosocial functioning was assessedA with the clinician-rated GAS, depressed patients with panic disorder were iudaed more imDaired than those with AND comorbid GA6 a ld major depiession alone, while depressed patients with comorbid generalized anxiety

Patients with comorbid panic disorder perceived themselves as having less control over their health sta-

TABLE 3. Patients' perception of psychosocial and physical functioninga

MDD MDD+GAD MDD+Panic X S. D. n X S. D. n X S. D. n

MOS component scales MOS MCS 29.3 9.4 65 26.7 10.0 58 26.0 8.8 98 MOS PCSb 44.5 11.0 65 43.7 10.9 58 40.4 10.7 98

Individual MOS scales Energy/fatigue 28.0 16.5 66 25.6 18.1 60 21.9 15.7 99 General healthb 55.1 24.1 67 47.8 20.7 60 40.8 21.6 102 Pain 54.9 27.1 67 55.1 24.2 60 48.1 25.6 101 Physical

functioningb 72.6 27.3 67 66.4 26.1 60 58.4 27.7 101 Role physical 31.5 35.4 67 36.0 39.0 60 25.5 33.2 102 Mental healthbld 42.7 16.4 66 35.4 17.9 60 30.3 16.0 99 Role mental 20.2 34.6 66 21.6 31.8 60 18.0 30.9 101 Social

functioningb 49.1 24.6 67 39.6 19.9 60 38.6 24.3 101

locus of controlb 22.4 5.2 67 23.1 4.9 59 25.2 6.3 99

54.6 7.1 68 50.9 6.7 62 46.5 5.2 103 GASb,c,d Health

P E N Major life eventsd 12.1 8.6 65 17.6 14.4 58 14.8 11.9 98

ISEL total score 68.2 21.8 67 60.8 19.5 59 61.3 21.4 101

"Medical Outcomes Study N O S ) scales bMDD+Panic significantly different fiom MDD (pc .OF). 'MDD+Panic significantly differentfiom MDD+GAD (pc .OF). dMDD+GAD significantly dzfferentfiom MDD (pc .OF).

214 Brown et al.

tus than the other two diagnostic groups (F=5.4, df=2, 222, p.005). While the three groups perceived similar degrees of social support and number of stressful life events in the preceding six months, patients with comorbid generalized anxiety disorder reported significantly more distress associated with these events than patients with depression alone (F=3.4, df=2, 2 18, p . 0 3 ; see Table 3 ) .

OTHER AXIS I AND AXIS I1 PSYCHIATRIC DISORDERS

Nine percent of patients with major depression alone met DSM-111-R criteria for lifetime alcohol dependence compared to 21% and 28% of comorbid anxiety-disordered patients (x2=8.8, df=2, p=.Ol; see Table 4). The diagnosis of comorbid panic disorder was also strongly associated with lifetime somatization disorder, whether diagnosed by stringent DSM-111-R criteria (x2=9.3, df=2, p=.009) or the Escobar (Escobar et al., 1987) criteria k2=26.3, df=2, p=.OOOl). Panic- disordered patients were also significantly more likely to have a DSM-111-R Axis I1 diagnosis (x2=15.0, df=2, p=.0006) compared to patients with major depression alone or comorbid generalized anxiety disorder (82 % vs. 52% and 64%, respectively). This difference was largely due to the greater proportion of panic-disordered patients meeting criteria for avoidant personality disorder (Cluster C).

DEPRESSIVE SYMPTOM PATTERNS Depressive symptom patterns associated with co-

morbid anxiety disorders were assessed with BDI and HRS-D factor scores (Brown et al., 1995). Table 5 indicates that patients with a lifetime panic or general-

TABLE 4. Comorbid DSM-111-R Axis I and Axis I1 disorders

ized anxiety disorder reported greater impairment on the BDI Negative Self-Focus Factor (sense of failure, sense of punishment, self-hate, self-blame, hopeless- ness, suicidal thoughts, and guilt) than did patients with major depression alone (F=10.3, df=2, 225, p=.OOOl). Furthermore, when compared to patients with major depression alone, those with comorbid panic disorder experienced significantly more severe distress on the following symptom factors: HRS-D Anxiety (agitation, somatic and psychological anxiety), F=8.8, df=2, 230, p=.0002; HRS-D Depression Typical (depressed mood, guilt and suicidal ideation), F=4.4, df=2, 229, p=.Ol; HRS-D Health Concerns (insight and hypochondriasis), F=3.2, df=2, 230, p=.04; BDI Sleep/Hypochondriasis (hypochondriasis and sleep), F=10.6, df=2, 225, p=.OOOl; and BDI Anhedonia and Functional Impairment (anhedonia, fatigue, irritabil- ity, indecision, work inhibition and dissatisfaction), F=10.4, df=2, 225, p=.OOOl. Thus, compared to patients with major depression alone, those with a lifetime panic disorder exhibited greater severity on cognitive, affective, and somatic symptoms. Patients with comorbid GAD differed from the former group only on the cognitive and affective features of depression.

W e therefore assessed whether panic-disordered patients could be distinguished from depressed patients with and without generalized anxiety disorder using discriminant function analysis. Patients were classified as having major depression and lifetime panic disorder (n=lOO), or major depression with and without generalized anxiety disorder (n=124). BDI and HRS-D factor scores were used as independent variables. W e found that 66% of patients with a lifetime panic disorder and 70% of depressed patients without

MDD MDD+GAD MDD+Panic n % n % n %

Axis I Alcohol dependencea 68 8.8 62 21.1 102 27.5 Any drug use

(excluding ETOH) 68 7.4 62 12.9 102 19.6 Somatizationb 68 0 61 0 100 7.0

Somatization' 68 17.6 62 14.5 102 47.1 (DSM-111-R)

(Escobar) Axis I1

Cluster A 58 19.0 52 28.8 85 36.5

Cluster cd 58 31.0 52 40.4 85 69.4

disorder' 58 51.7 52 63.5 87 81.6

Cluster B 58 20.7 52 28.8 85 35.3

Any Axis I1

'X2=8.8, df=2, p=.O1. 'X2=9,3, df=2, p=.009. E 2 X =26.3, df=2, p=.OOOl.

dX2=23. 1, df=2, p=. 00001. eX2=1 Y.0, df=2, p=.OOO6.

Comorbid Depression and Anxiety 21F

TABLE 5. Hamilton Depression Rating Scale and Beck Depression Inventory Factor Scores by diagnosis

MDD+GAD MDD+Panic MDD X S. D. n X S. D. n X S. D. n

BDI Factors Negative self focusafc 5.9 4.2 67 8.5 4.8 60 9.0 4.4 101 Anhedonia/energy” 7.3 2.8 67 8.4 3.0 60 9.5 3.4 101 Sleep/hypochondriasisa 2 .o 1.2 66 2.5 1.5 61 3.1 1.6 101 Weight 1 .2 1.3 67 1.1 1.4 61 1.2 1.3 100 Libido 1.2 1 .o 67 1.5 I .O 61 1.4 l .I 102

HRS-D Factors Anxiety’,’ 4.6 1.8 68 4.9 1.7 62 5.6 1.6 103 Weight 1.3 1.4 68 I .o 1 .2 62 1.2 1.3 103 Depression typicalaib 5.1 1.6 68 5.1 1.7 61 5.7 1.6 103 Health concernsa 1 .5 1.2 68 1.1 1 .O 62 1.6 1.1 103 Sleep/libido 3 . 3 1.7 68 3.3 I .6 60 3.6 1.7 103 Anhedonia/energy 4.1 .9 68 4.2 .9 62 4.0 1.2 103

“MDD+Panic significantly dzfermtfiom MDD (p< .OF). bMDD+Panic significantly drfferentfjom MDD+GAD (p< .OF), ‘MDDcGAD significantly dtfferentfi-om MDD (p< .OF).

panic disorder could be correctly classified (Wilks lambda=.83, x2=41.2, df=4, p=.OOOl) by their scores on BDI and HRS-D factors assessing sleep disturbance and health preoccupation (BDI Sleep/Hypochondria- sis Factor); agitation, psychological, and somatic anxiety (HRS-D Anxiety Factor), anhedonia, fatigue, irritation, work inhibition, and dissatisfaction (BDI Anhedonia and Functional Impairment Factor); and guilt, suicidal ideation and depressed mood (HRS-D Depression Typical Factor). Thus, depressed patients with a history of panic disorder could be distinguished from depressed patients with or without generalized anxiety disorder by the predominance of somatic symptoms, functional impairment, suicidality and mood disturbance, but not on cognitive symptoms of depression.

IMPACT OF ANXIETY DISORDERS ON TREATMENT PARTICIPATION

Table 6 details treatment participation patterns for patients randomized to psychotherapy and pharmacotherapy during each treatment’s acute and continuation phase. Statistical analyses did not yield significant

diagnostic group differences for IPT even though only 38% of depressed patients with lifetime panic disorder completed its two phases, compared to 55% of depressed patients with or without generalized anxiety disorder. Depressed patients receiving NT had similar overall completion rates, regardless of whether or not they had lifetime histories of comorbid panic or generalized anxiety disorder.

DISCUSSION This study found distinctive depressive symptom

and severity patterns, levels of functional impairment, comorbidity of other DSM-111-R Axis I and Axis I1 personality disorders, and treatment adherence associated with lifetime panic and generalized anxiety disorder among depressed primary care patients. Before addressing these findings, several of the study’s meth- odologic features warrant consideration. The Diag- nostic Interview Schedule (DIS) as administered by the investigators assessed lifetime GAD or panic disorder, but it did not determine which patients met DSM-111-R criteria for a current diagnosis. It is there-

TABLE 6. Attrition rates for patients randomized to psychotherapy (IPT) and pharmacotherapy (NT)

IPT NT MDD MDD+GAD MDD+Panic MDD MDD+GAD MDD+Panic (n=29) (n=20) (n=32) (n=2 1) (n=2 8) (n=27)

Acute phase Dropout 9 (31%) 8 (40%) 17 (53%) 6 (29%) 9 (32%) 13 (48%) Treatment completed 20 (69%) 12 (60%) 1s (47%) 15 (71%) 19 (68%) 14 (52%)

Dropout 4 (20%) 1(8%) 3 (20%) 6 (40%) 9 (47%) 4 (29%) Treatment completed 16 (80%) 11 (92%) 12 (80%) 9 (60%) 10 (53%) 10 (71%)

Continuation phase

Overall completion rate (%) 5s 55 38 43 36 37

216 Brown et al.

fore unknown what proportion of patients were experiencing clinically significant levels of panic or generalized anxiety disorder upon entering the trial, or whether the major depressive disorder was primary or secondary to the anxiety disorder. Further, since 82% of patients diagnosed with a lifetime panic disorder also met criteria for lifetime GAD, it cannot be determined whether the increased depressive severity of panic-disordered patients is due to the presence of panic disorder or whether it is due to the effect of multiple comorbid anxiety disorders. Finally, we found that a greater proportion of patients with lifetime panic disorder also met criteria for somatization disorder (see Table 4). However, clinicians conceivably encountered difficulty distinguishing symptoms of somatization disorder in patients experiencing symptoms of panic and, therefore, “overdiagnosed” somatization disorder in this sample.

In keeping with past studies (Coryell et al., 1992; Grunhaus et al., 1994; Liebowitz et al., 1990), we found that depressed patients with lifetime panic disorder consistently exhibited greater symptomatic severity and functional impairment than patients with major depression alone. However, patients with generalized anxiety disorder presented a more mixed picture as has been reported previously (Clark et al., 1994). Given the pattern of multiple comorbidity among patients with panic disorder, it cannot be determined whether their more severe clinical presentation is due to the “burden” associated with multiple diagnoses or to the presence of lifetime panic disorder alone. Nev- ertheless, our data concur with those of Sherbourne et al. (1996) who found that the majority of currently depressed primary care patients had one or more anxiety disorders, particularly GAD or panic disorder. Thus, as primary care physicians increasingly diagnose and treat major depression, they should expect that many of their depressed patients will present with this more clinically severe and diagnostically complex picture.

Given that increased depressive psychopathology appears strongly associated with lifetime panic disorder, are there other diagnostic features and/or symptom patterns associated with such comorbidity? Consistent with other reports (Noyes, 1990), increased lifetime alcohol dependence appears associated with both panic and generalized anxiety disorder. The presence of somatization disorder and avoidant personality disorder in depressed patients with lifetime panic disorder is another distinctive diagnostic feature among these patients.

Our analysis of predominant symptom patterns among the study’s three diagnostic groups indicated that patients with generalized anxiety disorder differed from those with major depression alone in the severity of cognitive and affective symptoms. However, the symptom pattern associated with lifetime panic disorder seems to reflect increased overall severity on a broader spectrum of depressive psychopathology. Nevertheless, the discriminant function analysis indicates that a distinguishing feature of depression co-

morbid with lifetime panic is the presence of more severe somatic and affective but not cognitive symptoms of the mood disorder.

Taken together, these findings suggest that depressed patients with lifetime generalized anxiety disorder are more diagnostically similar to those with major depression alone, while the severity of current somatic symptoms and associated functional impairment are distinguishing features of panic disorder. These findings replicate prior reports indicating that panic disordered patients score higher on a variety of self-report indices of somatic symptoms (Hoehn- Saric, 1981; Barlow et al., 1984) and psychophysi- ologic measures (Barlow et al., 1984) than generalized anxiety disorder patients. Our results are also consistent with genetic findings about major depression’s similarities with generalized anxiety disorder (Kendler et al., 1992) and dissimilarities with panic disorder (Weissman et al., 1993).

Our findings have important implications for the diagnosis and treatment of depression in primary care settings. The presence of comorbid anxiety with clinically significant somatic symptoms may impede the accurate diagnosis of depression among primary care patients (Kirmayer et al., 1993; Schulberg et al., in press). Since panic disorder is consistently associated with more severe pathology (symptomatic distress, functional impairment, and multiple comorbidities), primary care physicians should be prepared to assess patients for symptoms of this disorder as well as depression. This is particularly crucial since depressed patients experiencing comorbid panic disorder are at high risk for suicidal behavior (Warshaw et al., 1995).

Comorbid anxiety disorders may also affect treatment adherence. Our analyses of attrition patterns (Table 6) possibly may have lacked statistical power to detect diagnosis-specific differences. However, our finding that 5 1 % of panic-disordered patients discon- tinued treatment in the acute phase of either pharmacotherapy or psychotherapy suggests that the presence of a lifetime panic disorder adversely affects treatment adherence. Thus, primary care physicians should carefully consider choice of treatment for depressed primary care patients presenting with a history of panic disorder. For example, when pharmacologic treatments are preferred, antidepressants with more favor- able side effect profiles such as the SSRIs may be preferable so as not to arouse somatic-like sensations of panic. For patients preferring nonpharmacologic treatment, cognitive behavioral treatment rather than psychodynamic psychotherapy may be a more appropriate intervention. Finally, the importance of addressing patient preference when choosing the treatment, discuss- ing possible medication side effects and carefully moni- toring them during the initial phase of treatment cannot be overemphasized.

Acknowledgments. This research was supported by National Institute of Mental Health grants MH01328, MHS3817 (C.B.) and MH4581S (H.C.S.).

Cornorbid Depression and Anxiety 217

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