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Prevalence and comorbidity of dysthymic disorder among psychiatric outpatients
Journal of Aflectiue Disorders, 24 (1992) 63-71 0 1992 Elsevier Science Publishers J3.V. All rights reserved 01650327/92/$05.00
63
JAD 00864
John C.
arkowitz,
my E. Moran, Jmes
H. Kocsis and Allen J. Frances a
Dep&,rtmentof Psychiatry, Cornel! Unirersiry Medical College and a Department of Pwchiatry, Calm&a of Physicians and Surgeons, New York, NY, USA
UniLtersityCollege
(Received 12 August 1991) (Revision received 17 October 1991) (Accepted 30 October 1991)
We investigated prevalence and comorbidity of DSM-III dysthymic disorder in a psychiatric outpatient clinic. Seventy-five consecutive outpatients received structured interviews. Prevalence of dysthymic disorder was 36% in the consecutive sample. Thirty-four dysthymic and 56 non-dysthymic patients were compared for comorbidity. Dysthymic subjects were more likely to meet criteria for major depression, social phobia, and avoidant, self-defeating, dependent, and borderline personality disorders. Dysthymic disorder was usually of early onset f predating comorbid disorders, and had often not received adequate antidepressant treatment. These results help define dysthymic disorder as prevalent, usually predating axis I comorbidity, and associated with particular axis II diagnoses.
Key words: Dysthymic disorder; Prevalence; Comorbidity
Dysthymic disorder (DD) is a major public health problem: affecting more than 3% of com-
Address for correspondence: Dr. J.C. Markowitz, 525 East 68th Street, New York, NY 10021, USA. * This material was presented in part at the 142nd annual meeting of the American Psychiatric Association, San Fran~2x0, May 6- 12, 1989.
munity samples (Weissman et al., 1988) and 2636% of patients in psychiatric clinics (Keller and Shapiro, 1982; Keller et al., 1983; Rounsaville et al., I O80; Mezzich et al., 1990). Pesearch has suggested that dysthytnic disorder frequently coexists with other psychiatric and medical diagnoses (Weissman et al., 1988; Kocsis et al., 1990). This comorbidity raises important questions about the primacy and causality of the diagnosis of DD. Dysthymic disorder might occur as a secondary complication of other pre-existing disorders, as
an epiphenomenon of those disorders, ar as a primary entity that predisposes to the development of additional morbidity. Criticism of the DSM-III criteria for DD (KOCsis and Frances, 1987) led to major revisions in DSM-IIIR Dysthymia (American Psychiatric Association, 1987). Difficulties had included failure to account for heterogeneity of chronic depressions, similarity of thresholds for severity criteria separating DD from major depression (MDD), and lack of delineation of course of illness. Changes in DSM-IIIR permitted psychiatrists to refine distinctions in the diagnosis of chronically depressed patients by differentiating primary from secondary dysthymias, early (before age 21) from late age of onset; and by distinguishing major depression, either chronic or in partial remission, from dysthymia itself, which was defined as having a less severe, more insidious onset. These distinctions have permitted subtyping of chronic depression, the value and utility of which requires further research. This study had four goals. We sought to investigate the prevalence of DD amongst general psychiatric outpatients, in contrast to most previous studies, which have examined prevalence of DD in samples selected for major depression (Keller and Shapiro. 1982; Keller et al., 1983; Rounsaville et al., 1980). Comorbidity data exist for a large community sample (Weissman et al., 1988), but these are based on the Diagnostic tcrview Schedule, an instrument with debatable reliability for DD (Eaton and Kessler, B985). There :>re no reports in the literature assessing DD among psychiatric outpatients using the Structured Clinical Interview for DEM-III (Spitzer and Williams, 1985). A second goal was to compare patterns of psychiatric and medical comorbidity in patients who either met or did not meet DSM-III criteria for DD. It is important to compare comorbidlty of DD with non-dysthymics from the same clinic population, as population base rates can influence lates of comorbid diagnoses. A third question was to determine tePmporal relationships of ages of onset between DD and concurrent psychiatric or medical diagnoses. Finally, we were interested in relationships between research and clinical determination of DD diagnoses, and in the influence of clinical diagno-
sis on the type and appropriateness of treatment received (Weissman and KIerman, 1977). We hypothesized that DD w _S:dbe clinicaliy underdiagnosed, and that a majority of patients receiving the research diagnosis of DD would not have received adequate somatic antidepressant treatment. Methods To study the prevalence of DD, we approached a consecutive sample of individuals presenting for outpatient evaluation at the Payne Whitney Clinic, an urban university psychiatric center treating a mix of tertiary care and com&nity patients. Informed written consent was obtained for interview with the Structured Clinical Interview for DSM-III Patient Version (SCID-P) (Spitzer and Williams, 1985) and for Personality Disorders (SCID-II) (Spitzer et al., 1986), and an instrument to assess axis III diagnoses and axes IV and V scores. Based on this interview, we determined whether subjects met criteria for DSM-III dysthymic disorder, Akiskal’s dysthymic subtypes (1983), and for DSM-IIIR dysthymia (American Psychiatric Association, 1987). One hundred and twenty-four patients were tipproached. Three did not speak English, one was mentally retarded; of the remaining 120, 75 (62.5%) agreed to and completed the SCID-P. This constitutes the sample for the DD prevalence study. For the studies of comorbidity and clinical diagnosis and treatment, the sample included the above 75 cases plus 15 cases interviewed during a pilot phase, not based on consecutive applicants for treatment. Thus the sample for these analyses totaled 90 subjects. One subject completed the SCID-P only. Subjects were interviewed by two of the authors (J.C.M. and M.E.M.), who achieved a mean interrater reliability of K = 0.88 (n = 14) for all diagnoses on the SCID and a mean K = 0.93 on the SCID-II (n = 12). This included complete concordance on the diagnoses of DD and MDD (Cohen, ‘1960).Wh en raters disagreed, diagnoses were then reviewed and decided by consensus. Axis III diagnoses were assessed through obtaining a medical history and review of systems. We recorded the presence of severe chronic or life-threatening medical illness. Evaluation of
65
treatment history included anamnesis, and chart review of prior hospitalizations, electroconvulsive therapy (ECT), pharmacotherapy, and psychotherapy The thr .hold for including antidepressant trials as minimally adequate was a dosage of 2 150 mg of imipramine or the equivalent for other tricyclic antidepressants for at least 3 weeks. Benzodiazepine treatment was counted if it involved standing doses of at least 5 mg diazepam equivalents for more than 2 months. A psychotnerapy trial was defined as a minimum of 6 months of at least weekly therapy. Prior to data analysis, group values on dimensional variables were checked for normality of distribution. Parametric or nonparametric tests, particularly t tests and the Wilcoxon rank sum test (WRST), were then used for group comparisons. esults Peel ulertce arrd mbtypes of DD
Twenty-seven of 75 consecutive new evaluations, or 36%, fulfilled DSM-III criteria for DD by SCID. Using DSM-IIIR criteria, 21 (28%) qualified for primary dysthymia, five (6%) secondary dysthymia, and one (1%) chronic major depression. Of DSM-IIIR primary dysthymics, 14 had early onset, seven late; all five secondary
dysthymics had late onset. Classification according to Akiskal’s (1983) subtypes yielded three primary depressions with residual chronicity, three chronic secondary dysphorias, and the remainder of insidious onset (‘characterologic’). Pilot data on the first 42 patients have been previously reported (Kocsis et al., 1990). Comparative comorbidity of outpatients with and without DSM-III DD
For pooled (non-consecutive) samples, dysthymic subjects (n = 34) were predominantly female (79%), single @2%), Caucasian (62%), and averaged 38.2 + 10.9 years of age (Table 1). They reported depressive symptoms for an average of 15.3 + 13.8 years (range: 2-45). Mean age of onset was 20.7 + 12.1 years (range: < 5-50). Dysthymics did not differ significantly from non-dysthymics (H = 56) or from protocol refusers (n = 46) in age, sex, marital status, or race. Comparing the interviewed dysthymic and non-dysthymic subjects revealed differences in frequency of comorbid diagnoses (Tables 2 and 3). Not counting DD, dysthymic subjects had a mean 2.1 comorbid axis I diagnoses versus a mean total of 1.7 diagnoses for non-DD subjects. Dysthymics were more likely to meet criteria for MDD (P < 0.01) and social phobia (P < 0.02, by
TABLE I CHARACTERISTIC’S
BY DSM-IIIR SUBTYPE OF CHRONIC DEPRESSION Secondary
Primary Early
Late
N Age
17 36.5
7 38.3
7 38.4
SD Age of DD onset
10.7 12.3
10.5 32.3 X.6 100
10.6 25.6 1 I.6 ‘71
SD
C’rFemale % Having axis I I diagnosis Order of onset
DD before MDD DD after MDD DD before AD DD after AD
4.9
65
Chronic major depression 3
46.7 154 34.7 13.6 IO0
XK
86
86
12 0
3 1
3 1 1
_* 3” 2
3
1
7”” 9 **
1 ** -J **
DD, dysthymic disorder; MDD, major deprtissive disorder: AD, any DSM-III simultaneous onset.
67
anxiety disorder.
* By definition.
** C~X Case of
66
WRST). No other axis I disorder differed signifi-
cantly between dysthymic and non-dysthymic subjects. Dysthymic subjects suffered from significantly more axis II diagnoses (1.7 vs. 1.0, P < 0.004 by WRST;. Dysthymics were more likely to have self-defeating (P = O.i)OOl),avoidant (P = 0.0002), borderline (P < 0.02), and dependent personality disorders (P < 0.03, all by WRST). Numbers of axis III diagnoses and ratings on axes IV and V did not differ significantly. Comorbidity did not differ among dysthymics by DSM-IIIR subtype. The five dysthymics with significant axis III diagnoses had. respectively: mild cerebral palsy, Stein-Leventhal syndrome, multiple chronic med-
ical illnesses, recent HIV infection, and (treated) hypothyroidism. Llysthymic versus major depressive subjects
To assess whether increased comorbidity might generally reflect the presence of any affective disorder, we compared the dysthymic group to the subsample of non-dysthymic subjects having a history of MDD (n = 21). The groups still differed in comorbidity: dysthymic subjects had a greater mean number of axis II diagnoses (1.7 vs. 1.0, P < 0.03, WRSTJ, greater likelihood of selfdefeating (P < 0.003) and avoidant (P < 0.02) personality disorders, and trends toward greater likelihood of social phobia (P < 0.07) and border-
TABLE 2 AXIS I DIAGNOSES: LIFETIME BY SCID-P Dysthymia (n = 34)
Other (n = 56)
PI
%
11
%
34 23 0 1 0 I
(100) (68) (01 (31 (O! (3)
0 21 6 4 2 3
(0) (38) (11) (7) (4) (51
Obsessive compulsive disorder I-Iypochondriasis Somatization disorder Bulimia Panic disorder Agoraphobia Simple phobia Social phobia Post-traumatic stress disorder Generalized anxiety disorder Substance abuse Schizophrenia Dementia Organic mood disorder Other
4 1 1 4 9 1 4 5 4 4 8 0 0 0 2
(121 (31 (3) (121 (261 (31 (121 (151 021 (121 (241 (01 (01 (01 (61
3 0 2 2 11 3
5 2
(5) (0) (4) (4) (20) (4) (41 (2) (91 (91 (21) (9) (2) (91 (41
None *
0
3
(5)
Mean number of axis I diagnoses/subject (excluding dysthymic disorder)
2.1
Dysthymic disorder Major depression Bipolar disorder Cyclothymic disorder Schizo-affective disorder Adjustment disorder
CO)
2 1 5 5 12 5
1.7
* By definition, all dysthymic subjects met criteria for one axis I disorder. Two (6%) dysthymic subjects did not meet criteria for a comorbid axis I disorder.
67 TABLE 3 AXIS II DIAGNOSES BY SCID-II Dysthymia (n = 341
Other (n = 55)
n
n
%
Cluster A Paranoid Schizoid Schizotypal
1 0 4
Cluster B Borderline Histrionic Narcissistic Antisocial
8 4 2 0
Cluster C Avoidant Dependent Obsessive compulsive Passive aggressive
(31 (0) (12) (24) (12)
(61 (0)
% 6 0 2
(111 (0) (4)
3 11 6 1
(6) (20)
(32) (21) (61 (0)
1 3 6 2
(2) (5) (11) (4)
6
(181
14
(261
12
(351
1
(21
No axis II diagnosis
5
(15)
15
(271
Mean number of axis II diagnoses/subject
1.7
Self-deteating
Two 32%
One 32% Fig. 2. Dysthymic disorder: number of axis II comorbid diagnoses (n = 34).
(111 (21
11 7 2 0
Not otherwise specified
None 12%
1.0
additional four (12%) by age 25, and six more (18%) by age 32. DD more frequently preceded (II = 18) than followed (n = 5) MDD, and more often than not antedated anxiety disorders (n = II DD first, n = 8 anxiety disorders first, n = 2 simultaneous onset). Fourteen (41%) of the subjects with DD met criteria for current MDD at time of interview; 23 (68%) had a lifetime history of MDD, and hence of ‘double depression’ (i.e., superimposed MDD and DD (Keller and Shapiro, 1982)). Comorbid patterns of dysthymic subjects
line personality disorder (P < 0.07, all WRST). Non-dysthymic subjects with MDD had significantly higher mean axis V ratings (58.6) than dysthymic (41.9) and all other subjects (41.1) (Kruskal-Wallis one-way ANOVA, corrected x * = 6.76, P = 0.03). Chronology of comorbidity
Temporal trends emerged from the cross-sectional comorbidity data. Nineteen (56%) of the dysthymics had developed DD before age 21, an 7 comorbid
Figs. 1 and 2 demonstrate the overlap among SCID axis I and axis II diagnoses, respectively, in dysthymic subjects. For example, five (22%) of 23 dysthymics meeting criteria for MDD also met criteria for panic disorder. Frequent overlap was also found across axis I and axis II. Ten (91%) of 11 who met criteria for avoidant personality disorder also met criteria for at least one axis I anxiety disorder. Half of dysthymic subjects meeting criteria for self-defeating, 71% qualifying for avoidant, and 75% with borderline personality disorders met criteria for MDD as well.
dlaanoses
Clinical diagnosis and prior ma tmen t 3% 4 COmOrbid diagnoses 5 comorbld diagnoses 3% 2 comorbld
diagnoses
35% 1 comorbld
diagnosis
24%
Fig.
1. Dysthymic
disorder: axis I comorbid (n = 34).
diagnoses
Charts were available for 30 of the 34 dysthymic subjects. Review disclosed that clinical diagnosis of DD had been considered in only 13 (43%) cases, and as a ‘rule out’ in five of those. Of the 54 subjects found not to have DD by SCID, clinicians considered the diagnosis in three (5%) cases. Chart data obtainable on 39 of 46 new evaluations who refused or were excluded
from research participation uncovered clinical consideration of dysthymia in eight (21%). Assessing prior treatment of the 34 dysthymics revealed that three (9%) had received none, and another only homeopathic doses of amitriptyline/perphenazine and lithium. Twenty (59%) had histories of tricyclic antidepressant (TCA) treatment, in at least one case with good prior response, although only 14 (41%) treatments met our defined threshold of adequacy. Ten dysthymics (29%) had been hospitalized at least once; three (9%) had been treated with ECT. Seventeen (50%) had received benzodiazepine trials (two had received mly benzodiazepines), and six (18%) neuroleptics (one orzl~ neuroieptics), generally in small doses but sometimes for years. Twenty-three (68%) had undergone psychotherapy, sometimes for decades, without reported symptom resolution; for five (lS%)), psychothcrapy had been the sole treatment. Discussion
Examining a general psychiatric outpatient sample, we found a high point prevaiencc of DSM-III dysthymic disorder based on structured clinical interview. The prevalence rate of 36% was similar to the 26% and 36% rates of intermittent depression noted by Keller and Shapiro ounsaville et al. (1980), respectively, in studies of patients selected for the diagnosis of major depression, using Research Diagnostic Criteria. The prevalence of DD in the current study was greater than the 20% prevalence of DSM-III DD reported by Mezzich and colleagues ( 1990) in a larger sample of consecutive outpatient evaluations diagnosed using the Initial Evaluation Form. Thus at least as a diagnosis based on research methods, DD appears to be highly prevalent in general outpatient psychiatric settings such as OUI own. Qne study of DD in a community sample considered chronic depression a non-specific accompaniment to a spectrum of psychiatric and medical disorders, questioning whether DD represents a discrete psychiatric disorder (Weissman et al., 1988). Our findings challenge that concern. Most of our subjects reported that symptoms of DD
began at an early age, and that DD antedated other psychiatric diagnoses. Major depression (in 68%) and social phobia (in 15%) were th e only axis I diagnoses more frequent among the DD group than the non-dysthymic comparison group. The meaning of this coincidence of DD and MDD. sometimes called ‘double depression’ (Keller and Shapiro, 19821, remains controversial. Overlap in symptom criteria may make qualification for MDD artificially high among dysthymics (Kocsis and Frances, 1987). Only one or two additional symptoms are necessary to meet the severity threshold for MDD. If anything, the surprise lay in finding so many dysthymic patients who did not qualify for lifetime history of MDD. Compared to the 31 double depressed subjects of Klein et al. (1988!, this dysthymic sample had less likelihood of substance abuse (24% vs. 45%) but relatively similar frequencies of anxiety disorders (68% vs. 71%) and eating disorders ( 12% vs. 23%). In comparison to dysthymics in the general population (Weissman et al., 1988), our DD outpatients had roughly comparable rates of substance abuse (24% vs. 30%), but higher rates of MDD (68% vs. 39%), panic disorder (26% vs. 11W, and any anxiety disorder (68% vs. 46%). Patterns of comorbidity may help differentiate community from clinical dysthymia. The axis II findings revive the question of whether DD should, as in the past, be considered a personality disorder (Kocsis and Frances, 1988; Frances, 1980; Phillips et al., 1990). Eighty-five percent of dysthymics had at least one axis II diagnosis, a higher percentage than in previous studies. Although this could reflect an oversensitivity of the SCID-II to personality disorder, the non-DD sample acts as a control: significantly more axis II diagnoses appeared among the dysthymic group. Of note, the personality disorders found most strongly associated with DD share definitional overlap with ‘chronic depressive’ symptoms: avoidance, withdrawal, dependence, and self-destructive behavior. Although DSM-III removed chronic depression from the personality disorder section, these data suggest that patients with DD may still be diagnosed on axis II under the guises of self-defeating, avoidant and p~ihaps borderline and dependent personality disorders.
69
One third of DD subjects were diagnosed self-defeating and roughly another third avoidant; MDD subjects by and large lacked these diagnoses. In similar fashion, the overlap of axis I and axis II diagnoses may reflect the effects of symptomatic chronicity rather than artifacts of the SCID interviews: over time, anxiety symptoms may be experienced by a dysthymic individual as character, and merge imperceptibly into avoidant personality disorder. The axis II results resemble earlier studies of DD in percentage of dependent and borderline personality disorders (Koenigsberg et al., 1985; Kocsis et al., 1986). The prevalence of self-defeating personality disorder among the DD subjects suggests that this diagnosis may have accounted for the high percentage of ‘atypical-mixed’ personality disorders in studies which did not include this diagnosis iiiocsis et al., 1986, 1988). The associations between DD and self-defeating personality disorder, and between DD and avoidant personality disorder, are intriguing and clinically plausible. Not all dysthymic patients develop these personality disorders, but their presence in association with an affective disorder may be a clinical indication of dysthymia, as opposed to major depression. The temporal sequence of onset of DD and comorbid diagnoses has received little study (Friedman c:t a,:. H&3; Kovacs et al., 1984; Cloninger et al., I990). DD in this sample most often preceded other psychiatric diagnoses. Where it did not, in several cases subjects initially suffered from an anxiety disorder (see Table 1). While an association between affective and anxiety disorders is unsurprising (Barlow et al., 1986), this finding suggests alternative hypotheses. Early onset anxiety disorders might predispose patients to the later development of dysthymia, or might represent early symptomatic manifestations of the disorder that follows. Five (15%) subjects with primary dysthymia (two early and three late onset) described chronic depression prcccdcd by a phobia or other anxiety disorder. Such anxiety disorders might represent proobfomad dysthymia. Temporal sequence of diagnoses and potential interaction of DD with anxiety disorders are interesting arcas for future research. Cbur data contradict the assertion of Cloninger tilid tither:;
(1990) that dysthymia typically postdates anxiety disorders. Although cross-sectional, retrospective data make conclusions about temporal associations tentative, our findings suggest that chronic depression followed four temporal patterns. Primary dysthymia (71% of this sample) had insidious onset at an early age and became complicated by subsequent axis I diagnoses, particularly MDD. Secondary dysthymia (21%) followed in the wake of other axis I, II, or III disorders. Chronic major depression (9%) represented the persistence of MDD, which was characterized by more acute onset at an older age and greater symptomatic severity. These findings provide some validation of the early/late onset and primary/secondary criteria introduced in the DSMIIIR definition of dysthymia. We speculate that prodromal dysthymia might represent a fourth pattern, wherein anxiety disorders herald later onset of dysthymia. In summary, we found chronic depression and affective disorder generally - to have high prevalence among psychiatric outpatients. Pure dysthymic disorder was less common (lo/75 = 13%) than DD associated with MDD (double depression; 16/75 = 21%) or MDD alone (21/75 = 28%). Validity of these findings may be affected by the limited sample size and by selection bias, although most patients approached participated in the protocoi. The validity of retrospective diagnoses elicited from patients must be viewed with caution: memories of depressed patients may be subject to retrospective falsification. Yet one study fouud that patients recall chronic depression with good reliability upon 4year follow-up (Prusoff et al., 1988). Until more results emerge from prospective study of children and adolescents, our retrospective data remain valuable. Distinguishing relative validity of research and clinical diagnoses is complex. Although commonly used, the SCID and SCID-II have yet to demonstrate diagnostic validity. Yet there has long been a suspicion that chronic depression is ‘underrecognized and poorly treated’ in the community (Weissman and Klerman, 1977; Weissman et al., 1988). Only 43% of our dysthymic subjects identified by rese2lch pr~?tocoi as reporting early
onset and chronicity had DD recorded as a clinical diagno.;is - this despite clinicians’ awareness of our ongcing dysthymic research during patient evaluations. The majority had received bcnzodiazepines but not adequate trials of antidepressant medication. Only 41% of DD subjects eventually received adequate antidepressant medication; many received only psychotherapy or other medication for extended periods. This suggests underrecognition and mistreatment of DD (Weissman and Klerman, 19771, and the need for education of psychiatrists to recognize it. Given the high prevalence of DD found among outpatients and the historical likelihood of misdiagnosis or mistreatment, we recommend that psychiatrists carefully evaluate all outpatients for dysthymia. The multiplicity of diagnoses our subjects carried offers an explanation for misdiagnosis: comorbid diagnoses may mask chronic depression, or cause it to be dismissed as secondary. Based on recent research conducted on outpatient dysthymics (Kocsis et al., 1988; Akiskal et al., 1980), pharmacotherapy trials may be indicated tar such patients, particularly if the clinical history suggests primacy of dysthymia and initial psychotherapy has failed. The current results should be understood as an initial study whose generalizability may bc limited. Yet chart review of research non-participants suggested clinical consideration of dysthymia in more than 20% of those cases as well. Given the tendency of clinicians to underdiagnose DD, this implies our interviewed sample was not overly skewed to DD patients. Dysthymic disorder appears to be a heterogeneous syndrome whose symptoms trespass on other axis I and axis II diagnostic boundaries. Thus multiple comorbidity associated with DD may be most revealing for what it signifies about the single disorder, or dysthymic subtype, a patient suffers from. Further, prospective research in dysthymia is necessary to replicate our findings and to more clearly delineate early traumata, family history, biological markers, and distinct dysthymic subtypes. Future pharmacotherapy research trials should address comorbidity and its effect on response to medication. Such trials may help determine whether comorbid psychiatric diagnoses represent aspects and symptoms of
chronic depression, noses.
or are truly separate
drag-
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Phillips. K.A., Gunderson, J.G., Hirschfeld, R.M.A. and Smith, L..E. (1990) A review of the depressive personality. Am. J. Psychiatry 147, 830-837. Prusoff, B.A., Merikangas, K.R. and Weissman, M.M. (1988) Lifetime prevalence and age of onset of psychiatric disorders: recall 4 years later. J. Psychiat. Res. 22, 107-l 17. Rounsaville, B.J.. Sholomkas, D. and Prusoff, B.A. (1980) Chronic mood disorders in depressed outpatients. J. Affect. Disord. 2, 73-88. Spitzer, R.L. and Williams, J.B.W. (1985) Structured clinical interview for DSM-III-patient version (SCID-P, 3/ l/85). Biometrics Research Department, New York State Psychiatric Institute, New York, NY. Spitzer, R.L., Williams, J.B.W. and Gibbon, M. (19&h) Structured clinical interview for DSM-III-R personality disorders (SCID-II, 10/15/86). Biometrics Research Department, New York State Psychiatric Institute, New York, NY. Weissman. M.M. and Klerman, G.L. (1977) The chronic depressive in the community: underrecognized and poorly treated. Compr. Psychiatry 18, 523-531. Weissman, M.M., Leaf, P.J., Bruce, M.L. and Florio, L. (1988) The epidemiology of dysthymia in five communities: rates, risks, comorbidity, and treatment. Am. J. Psychiatry 145, 815-819.
63
JAD 00864
John C.
arkowitz,
my E. Moran, Jmes
H. Kocsis and Allen J. Frances a
Dep&,rtmentof Psychiatry, Cornel! Unirersiry Medical College and a Department of Pwchiatry, Calm&a of Physicians and Surgeons, New York, NY, USA
UniLtersityCollege
(Received 12 August 1991) (Revision received 17 October 1991) (Accepted 30 October 1991)
We investigated prevalence and comorbidity of DSM-III dysthymic disorder in a psychiatric outpatient clinic. Seventy-five consecutive outpatients received structured interviews. Prevalence of dysthymic disorder was 36% in the consecutive sample. Thirty-four dysthymic and 56 non-dysthymic patients were compared for comorbidity. Dysthymic subjects were more likely to meet criteria for major depression, social phobia, and avoidant, self-defeating, dependent, and borderline personality disorders. Dysthymic disorder was usually of early onset f predating comorbid disorders, and had often not received adequate antidepressant treatment. These results help define dysthymic disorder as prevalent, usually predating axis I comorbidity, and associated with particular axis II diagnoses.
Key words: Dysthymic disorder; Prevalence; Comorbidity
Dysthymic disorder (DD) is a major public health problem: affecting more than 3% of com-
Address for correspondence: Dr. J.C. Markowitz, 525 East 68th Street, New York, NY 10021, USA. * This material was presented in part at the 142nd annual meeting of the American Psychiatric Association, San Fran~2x0, May 6- 12, 1989.
munity samples (Weissman et al., 1988) and 2636% of patients in psychiatric clinics (Keller and Shapiro, 1982; Keller et al., 1983; Rounsaville et al., I O80; Mezzich et al., 1990). Pesearch has suggested that dysthytnic disorder frequently coexists with other psychiatric and medical diagnoses (Weissman et al., 1988; Kocsis et al., 1990). This comorbidity raises important questions about the primacy and causality of the diagnosis of DD. Dysthymic disorder might occur as a secondary complication of other pre-existing disorders, as
an epiphenomenon of those disorders, ar as a primary entity that predisposes to the development of additional morbidity. Criticism of the DSM-III criteria for DD (KOCsis and Frances, 1987) led to major revisions in DSM-IIIR Dysthymia (American Psychiatric Association, 1987). Difficulties had included failure to account for heterogeneity of chronic depressions, similarity of thresholds for severity criteria separating DD from major depression (MDD), and lack of delineation of course of illness. Changes in DSM-IIIR permitted psychiatrists to refine distinctions in the diagnosis of chronically depressed patients by differentiating primary from secondary dysthymias, early (before age 21) from late age of onset; and by distinguishing major depression, either chronic or in partial remission, from dysthymia itself, which was defined as having a less severe, more insidious onset. These distinctions have permitted subtyping of chronic depression, the value and utility of which requires further research. This study had four goals. We sought to investigate the prevalence of DD amongst general psychiatric outpatients, in contrast to most previous studies, which have examined prevalence of DD in samples selected for major depression (Keller and Shapiro. 1982; Keller et al., 1983; Rounsaville et al., 1980). Comorbidity data exist for a large community sample (Weissman et al., 1988), but these are based on the Diagnostic tcrview Schedule, an instrument with debatable reliability for DD (Eaton and Kessler, B985). There :>re no reports in the literature assessing DD among psychiatric outpatients using the Structured Clinical Interview for DEM-III (Spitzer and Williams, 1985). A second goal was to compare patterns of psychiatric and medical comorbidity in patients who either met or did not meet DSM-III criteria for DD. It is important to compare comorbidlty of DD with non-dysthymics from the same clinic population, as population base rates can influence lates of comorbid diagnoses. A third question was to determine tePmporal relationships of ages of onset between DD and concurrent psychiatric or medical diagnoses. Finally, we were interested in relationships between research and clinical determination of DD diagnoses, and in the influence of clinical diagno-
sis on the type and appropriateness of treatment received (Weissman and KIerman, 1977). We hypothesized that DD w _S:dbe clinicaliy underdiagnosed, and that a majority of patients receiving the research diagnosis of DD would not have received adequate somatic antidepressant treatment. Methods To study the prevalence of DD, we approached a consecutive sample of individuals presenting for outpatient evaluation at the Payne Whitney Clinic, an urban university psychiatric center treating a mix of tertiary care and com&nity patients. Informed written consent was obtained for interview with the Structured Clinical Interview for DSM-III Patient Version (SCID-P) (Spitzer and Williams, 1985) and for Personality Disorders (SCID-II) (Spitzer et al., 1986), and an instrument to assess axis III diagnoses and axes IV and V scores. Based on this interview, we determined whether subjects met criteria for DSM-III dysthymic disorder, Akiskal’s dysthymic subtypes (1983), and for DSM-IIIR dysthymia (American Psychiatric Association, 1987). One hundred and twenty-four patients were tipproached. Three did not speak English, one was mentally retarded; of the remaining 120, 75 (62.5%) agreed to and completed the SCID-P. This constitutes the sample for the DD prevalence study. For the studies of comorbidity and clinical diagnosis and treatment, the sample included the above 75 cases plus 15 cases interviewed during a pilot phase, not based on consecutive applicants for treatment. Thus the sample for these analyses totaled 90 subjects. One subject completed the SCID-P only. Subjects were interviewed by two of the authors (J.C.M. and M.E.M.), who achieved a mean interrater reliability of K = 0.88 (n = 14) for all diagnoses on the SCID and a mean K = 0.93 on the SCID-II (n = 12). This included complete concordance on the diagnoses of DD and MDD (Cohen, ‘1960).Wh en raters disagreed, diagnoses were then reviewed and decided by consensus. Axis III diagnoses were assessed through obtaining a medical history and review of systems. We recorded the presence of severe chronic or life-threatening medical illness. Evaluation of
65
treatment history included anamnesis, and chart review of prior hospitalizations, electroconvulsive therapy (ECT), pharmacotherapy, and psychotherapy The thr .hold for including antidepressant trials as minimally adequate was a dosage of 2 150 mg of imipramine or the equivalent for other tricyclic antidepressants for at least 3 weeks. Benzodiazepine treatment was counted if it involved standing doses of at least 5 mg diazepam equivalents for more than 2 months. A psychotnerapy trial was defined as a minimum of 6 months of at least weekly therapy. Prior to data analysis, group values on dimensional variables were checked for normality of distribution. Parametric or nonparametric tests, particularly t tests and the Wilcoxon rank sum test (WRST), were then used for group comparisons. esults Peel ulertce arrd mbtypes of DD
Twenty-seven of 75 consecutive new evaluations, or 36%, fulfilled DSM-III criteria for DD by SCID. Using DSM-IIIR criteria, 21 (28%) qualified for primary dysthymia, five (6%) secondary dysthymia, and one (1%) chronic major depression. Of DSM-IIIR primary dysthymics, 14 had early onset, seven late; all five secondary
dysthymics had late onset. Classification according to Akiskal’s (1983) subtypes yielded three primary depressions with residual chronicity, three chronic secondary dysphorias, and the remainder of insidious onset (‘characterologic’). Pilot data on the first 42 patients have been previously reported (Kocsis et al., 1990). Comparative comorbidity of outpatients with and without DSM-III DD
For pooled (non-consecutive) samples, dysthymic subjects (n = 34) were predominantly female (79%), single @2%), Caucasian (62%), and averaged 38.2 + 10.9 years of age (Table 1). They reported depressive symptoms for an average of 15.3 + 13.8 years (range: 2-45). Mean age of onset was 20.7 + 12.1 years (range: < 5-50). Dysthymics did not differ significantly from non-dysthymics (H = 56) or from protocol refusers (n = 46) in age, sex, marital status, or race. Comparing the interviewed dysthymic and non-dysthymic subjects revealed differences in frequency of comorbid diagnoses (Tables 2 and 3). Not counting DD, dysthymic subjects had a mean 2.1 comorbid axis I diagnoses versus a mean total of 1.7 diagnoses for non-DD subjects. Dysthymics were more likely to meet criteria for MDD (P < 0.01) and social phobia (P < 0.02, by
TABLE I CHARACTERISTIC’S
BY DSM-IIIR SUBTYPE OF CHRONIC DEPRESSION Secondary
Primary Early
Late
N Age
17 36.5
7 38.3
7 38.4
SD Age of DD onset
10.7 12.3
10.5 32.3 X.6 100
10.6 25.6 1 I.6 ‘71
SD
C’rFemale % Having axis I I diagnosis Order of onset
DD before MDD DD after MDD DD before AD DD after AD
4.9
65
Chronic major depression 3
46.7 154 34.7 13.6 IO0
XK
86
86
12 0
3 1
3 1 1
_* 3” 2
3
1
7”” 9 **
1 ** -J **
DD, dysthymic disorder; MDD, major deprtissive disorder: AD, any DSM-III simultaneous onset.
67
anxiety disorder.
* By definition.
** C~X Case of
66
WRST). No other axis I disorder differed signifi-
cantly between dysthymic and non-dysthymic subjects. Dysthymic subjects suffered from significantly more axis II diagnoses (1.7 vs. 1.0, P < 0.004 by WRST;. Dysthymics were more likely to have self-defeating (P = O.i)OOl),avoidant (P = 0.0002), borderline (P < 0.02), and dependent personality disorders (P < 0.03, all by WRST). Numbers of axis III diagnoses and ratings on axes IV and V did not differ significantly. Comorbidity did not differ among dysthymics by DSM-IIIR subtype. The five dysthymics with significant axis III diagnoses had. respectively: mild cerebral palsy, Stein-Leventhal syndrome, multiple chronic med-
ical illnesses, recent HIV infection, and (treated) hypothyroidism. Llysthymic versus major depressive subjects
To assess whether increased comorbidity might generally reflect the presence of any affective disorder, we compared the dysthymic group to the subsample of non-dysthymic subjects having a history of MDD (n = 21). The groups still differed in comorbidity: dysthymic subjects had a greater mean number of axis II diagnoses (1.7 vs. 1.0, P < 0.03, WRSTJ, greater likelihood of selfdefeating (P < 0.003) and avoidant (P < 0.02) personality disorders, and trends toward greater likelihood of social phobia (P < 0.07) and border-
TABLE 2 AXIS I DIAGNOSES: LIFETIME BY SCID-P Dysthymia (n = 34)
Other (n = 56)
PI
%
11
%
34 23 0 1 0 I
(100) (68) (01 (31 (O! (3)
0 21 6 4 2 3
(0) (38) (11) (7) (4) (51
Obsessive compulsive disorder I-Iypochondriasis Somatization disorder Bulimia Panic disorder Agoraphobia Simple phobia Social phobia Post-traumatic stress disorder Generalized anxiety disorder Substance abuse Schizophrenia Dementia Organic mood disorder Other
4 1 1 4 9 1 4 5 4 4 8 0 0 0 2
(121 (31 (3) (121 (261 (31 (121 (151 021 (121 (241 (01 (01 (01 (61
3 0 2 2 11 3
5 2
(5) (0) (4) (4) (20) (4) (41 (2) (91 (91 (21) (9) (2) (91 (41
None *
0
3
(5)
Mean number of axis I diagnoses/subject (excluding dysthymic disorder)
2.1
Dysthymic disorder Major depression Bipolar disorder Cyclothymic disorder Schizo-affective disorder Adjustment disorder
CO)
2 1 5 5 12 5
1.7
* By definition, all dysthymic subjects met criteria for one axis I disorder. Two (6%) dysthymic subjects did not meet criteria for a comorbid axis I disorder.
67 TABLE 3 AXIS II DIAGNOSES BY SCID-II Dysthymia (n = 341
Other (n = 55)
n
n
%
Cluster A Paranoid Schizoid Schizotypal
1 0 4
Cluster B Borderline Histrionic Narcissistic Antisocial
8 4 2 0
Cluster C Avoidant Dependent Obsessive compulsive Passive aggressive
(31 (0) (12) (24) (12)
(61 (0)
% 6 0 2
(111 (0) (4)
3 11 6 1
(6) (20)
(32) (21) (61 (0)
1 3 6 2
(2) (5) (11) (4)
6
(181
14
(261
12
(351
1
(21
No axis II diagnosis
5
(15)
15
(271
Mean number of axis II diagnoses/subject
1.7
Self-deteating
Two 32%
One 32% Fig. 2. Dysthymic disorder: number of axis II comorbid diagnoses (n = 34).
(111 (21
11 7 2 0
Not otherwise specified
None 12%
1.0
additional four (12%) by age 25, and six more (18%) by age 32. DD more frequently preceded (II = 18) than followed (n = 5) MDD, and more often than not antedated anxiety disorders (n = II DD first, n = 8 anxiety disorders first, n = 2 simultaneous onset). Fourteen (41%) of the subjects with DD met criteria for current MDD at time of interview; 23 (68%) had a lifetime history of MDD, and hence of ‘double depression’ (i.e., superimposed MDD and DD (Keller and Shapiro, 1982)). Comorbid patterns of dysthymic subjects
line personality disorder (P < 0.07, all WRST). Non-dysthymic subjects with MDD had significantly higher mean axis V ratings (58.6) than dysthymic (41.9) and all other subjects (41.1) (Kruskal-Wallis one-way ANOVA, corrected x * = 6.76, P = 0.03). Chronology of comorbidity
Temporal trends emerged from the cross-sectional comorbidity data. Nineteen (56%) of the dysthymics had developed DD before age 21, an 7 comorbid
Figs. 1 and 2 demonstrate the overlap among SCID axis I and axis II diagnoses, respectively, in dysthymic subjects. For example, five (22%) of 23 dysthymics meeting criteria for MDD also met criteria for panic disorder. Frequent overlap was also found across axis I and axis II. Ten (91%) of 11 who met criteria for avoidant personality disorder also met criteria for at least one axis I anxiety disorder. Half of dysthymic subjects meeting criteria for self-defeating, 71% qualifying for avoidant, and 75% with borderline personality disorders met criteria for MDD as well.
dlaanoses
Clinical diagnosis and prior ma tmen t 3% 4 COmOrbid diagnoses 5 comorbld diagnoses 3% 2 comorbld
diagnoses
35% 1 comorbld
diagnosis
24%
Fig.
1. Dysthymic
disorder: axis I comorbid (n = 34).
diagnoses
Charts were available for 30 of the 34 dysthymic subjects. Review disclosed that clinical diagnosis of DD had been considered in only 13 (43%) cases, and as a ‘rule out’ in five of those. Of the 54 subjects found not to have DD by SCID, clinicians considered the diagnosis in three (5%) cases. Chart data obtainable on 39 of 46 new evaluations who refused or were excluded
from research participation uncovered clinical consideration of dysthymia in eight (21%). Assessing prior treatment of the 34 dysthymics revealed that three (9%) had received none, and another only homeopathic doses of amitriptyline/perphenazine and lithium. Twenty (59%) had histories of tricyclic antidepressant (TCA) treatment, in at least one case with good prior response, although only 14 (41%) treatments met our defined threshold of adequacy. Ten dysthymics (29%) had been hospitalized at least once; three (9%) had been treated with ECT. Seventeen (50%) had received benzodiazepine trials (two had received mly benzodiazepines), and six (18%) neuroleptics (one orzl~ neuroieptics), generally in small doses but sometimes for years. Twenty-three (68%) had undergone psychotherapy, sometimes for decades, without reported symptom resolution; for five (lS%)), psychothcrapy had been the sole treatment. Discussion
Examining a general psychiatric outpatient sample, we found a high point prevaiencc of DSM-III dysthymic disorder based on structured clinical interview. The prevalence rate of 36% was similar to the 26% and 36% rates of intermittent depression noted by Keller and Shapiro ounsaville et al. (1980), respectively, in studies of patients selected for the diagnosis of major depression, using Research Diagnostic Criteria. The prevalence of DD in the current study was greater than the 20% prevalence of DSM-III DD reported by Mezzich and colleagues ( 1990) in a larger sample of consecutive outpatient evaluations diagnosed using the Initial Evaluation Form. Thus at least as a diagnosis based on research methods, DD appears to be highly prevalent in general outpatient psychiatric settings such as OUI own. Qne study of DD in a community sample considered chronic depression a non-specific accompaniment to a spectrum of psychiatric and medical disorders, questioning whether DD represents a discrete psychiatric disorder (Weissman et al., 1988). Our findings challenge that concern. Most of our subjects reported that symptoms of DD
began at an early age, and that DD antedated other psychiatric diagnoses. Major depression (in 68%) and social phobia (in 15%) were th e only axis I diagnoses more frequent among the DD group than the non-dysthymic comparison group. The meaning of this coincidence of DD and MDD. sometimes called ‘double depression’ (Keller and Shapiro, 19821, remains controversial. Overlap in symptom criteria may make qualification for MDD artificially high among dysthymics (Kocsis and Frances, 1987). Only one or two additional symptoms are necessary to meet the severity threshold for MDD. If anything, the surprise lay in finding so many dysthymic patients who did not qualify for lifetime history of MDD. Compared to the 31 double depressed subjects of Klein et al. (1988!, this dysthymic sample had less likelihood of substance abuse (24% vs. 45%) but relatively similar frequencies of anxiety disorders (68% vs. 71%) and eating disorders ( 12% vs. 23%). In comparison to dysthymics in the general population (Weissman et al., 1988), our DD outpatients had roughly comparable rates of substance abuse (24% vs. 30%), but higher rates of MDD (68% vs. 39%), panic disorder (26% vs. 11W, and any anxiety disorder (68% vs. 46%). Patterns of comorbidity may help differentiate community from clinical dysthymia. The axis II findings revive the question of whether DD should, as in the past, be considered a personality disorder (Kocsis and Frances, 1988; Frances, 1980; Phillips et al., 1990). Eighty-five percent of dysthymics had at least one axis II diagnosis, a higher percentage than in previous studies. Although this could reflect an oversensitivity of the SCID-II to personality disorder, the non-DD sample acts as a control: significantly more axis II diagnoses appeared among the dysthymic group. Of note, the personality disorders found most strongly associated with DD share definitional overlap with ‘chronic depressive’ symptoms: avoidance, withdrawal, dependence, and self-destructive behavior. Although DSM-III removed chronic depression from the personality disorder section, these data suggest that patients with DD may still be diagnosed on axis II under the guises of self-defeating, avoidant and p~ihaps borderline and dependent personality disorders.
69
One third of DD subjects were diagnosed self-defeating and roughly another third avoidant; MDD subjects by and large lacked these diagnoses. In similar fashion, the overlap of axis I and axis II diagnoses may reflect the effects of symptomatic chronicity rather than artifacts of the SCID interviews: over time, anxiety symptoms may be experienced by a dysthymic individual as character, and merge imperceptibly into avoidant personality disorder. The axis II results resemble earlier studies of DD in percentage of dependent and borderline personality disorders (Koenigsberg et al., 1985; Kocsis et al., 1986). The prevalence of self-defeating personality disorder among the DD subjects suggests that this diagnosis may have accounted for the high percentage of ‘atypical-mixed’ personality disorders in studies which did not include this diagnosis iiiocsis et al., 1986, 1988). The associations between DD and self-defeating personality disorder, and between DD and avoidant personality disorder, are intriguing and clinically plausible. Not all dysthymic patients develop these personality disorders, but their presence in association with an affective disorder may be a clinical indication of dysthymia, as opposed to major depression. The temporal sequence of onset of DD and comorbid diagnoses has received little study (Friedman c:t a,:. H&3; Kovacs et al., 1984; Cloninger et al., I990). DD in this sample most often preceded other psychiatric diagnoses. Where it did not, in several cases subjects initially suffered from an anxiety disorder (see Table 1). While an association between affective and anxiety disorders is unsurprising (Barlow et al., 1986), this finding suggests alternative hypotheses. Early onset anxiety disorders might predispose patients to the later development of dysthymia, or might represent early symptomatic manifestations of the disorder that follows. Five (15%) subjects with primary dysthymia (two early and three late onset) described chronic depression prcccdcd by a phobia or other anxiety disorder. Such anxiety disorders might represent proobfomad dysthymia. Temporal sequence of diagnoses and potential interaction of DD with anxiety disorders are interesting arcas for future research. Cbur data contradict the assertion of Cloninger tilid tither:;
(1990) that dysthymia typically postdates anxiety disorders. Although cross-sectional, retrospective data make conclusions about temporal associations tentative, our findings suggest that chronic depression followed four temporal patterns. Primary dysthymia (71% of this sample) had insidious onset at an early age and became complicated by subsequent axis I diagnoses, particularly MDD. Secondary dysthymia (21%) followed in the wake of other axis I, II, or III disorders. Chronic major depression (9%) represented the persistence of MDD, which was characterized by more acute onset at an older age and greater symptomatic severity. These findings provide some validation of the early/late onset and primary/secondary criteria introduced in the DSMIIIR definition of dysthymia. We speculate that prodromal dysthymia might represent a fourth pattern, wherein anxiety disorders herald later onset of dysthymia. In summary, we found chronic depression and affective disorder generally - to have high prevalence among psychiatric outpatients. Pure dysthymic disorder was less common (lo/75 = 13%) than DD associated with MDD (double depression; 16/75 = 21%) or MDD alone (21/75 = 28%). Validity of these findings may be affected by the limited sample size and by selection bias, although most patients approached participated in the protocoi. The validity of retrospective diagnoses elicited from patients must be viewed with caution: memories of depressed patients may be subject to retrospective falsification. Yet one study fouud that patients recall chronic depression with good reliability upon 4year follow-up (Prusoff et al., 1988). Until more results emerge from prospective study of children and adolescents, our retrospective data remain valuable. Distinguishing relative validity of research and clinical diagnoses is complex. Although commonly used, the SCID and SCID-II have yet to demonstrate diagnostic validity. Yet there has long been a suspicion that chronic depression is ‘underrecognized and poorly treated’ in the community (Weissman and Klerman, 1977; Weissman et al., 1988). Only 43% of our dysthymic subjects identified by rese2lch pr~?tocoi as reporting early
onset and chronicity had DD recorded as a clinical diagno.;is - this despite clinicians’ awareness of our ongcing dysthymic research during patient evaluations. The majority had received bcnzodiazepines but not adequate trials of antidepressant medication. Only 41% of DD subjects eventually received adequate antidepressant medication; many received only psychotherapy or other medication for extended periods. This suggests underrecognition and mistreatment of DD (Weissman and Klerman, 19771, and the need for education of psychiatrists to recognize it. Given the high prevalence of DD found among outpatients and the historical likelihood of misdiagnosis or mistreatment, we recommend that psychiatrists carefully evaluate all outpatients for dysthymia. The multiplicity of diagnoses our subjects carried offers an explanation for misdiagnosis: comorbid diagnoses may mask chronic depression, or cause it to be dismissed as secondary. Based on recent research conducted on outpatient dysthymics (Kocsis et al., 1988; Akiskal et al., 1980), pharmacotherapy trials may be indicated tar such patients, particularly if the clinical history suggests primacy of dysthymia and initial psychotherapy has failed. The current results should be understood as an initial study whose generalizability may bc limited. Yet chart review of research non-participants suggested clinical consideration of dysthymia in more than 20% of those cases as well. Given the tendency of clinicians to underdiagnose DD, this implies our interviewed sample was not overly skewed to DD patients. Dysthymic disorder appears to be a heterogeneous syndrome whose symptoms trespass on other axis I and axis II diagnostic boundaries. Thus multiple comorbidity associated with DD may be most revealing for what it signifies about the single disorder, or dysthymic subtype, a patient suffers from. Further, prospective research in dysthymia is necessary to replicate our findings and to more clearly delineate early traumata, family history, biological markers, and distinct dysthymic subtypes. Future pharmacotherapy research trials should address comorbidity and its effect on response to medication. Such trials may help determine whether comorbid psychiatric diagnoses represent aspects and symptoms of
chronic depression, noses.
or are truly separate
drag-
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