Prevalence and clinical features of atypical depression in depressed outpatients: a 467-case study

Psychiatry Research 86 Ž1999. 259]265

Prevalence and clinical features of atypical depression in depressed outpatients: a 467-case study Franco BenazziU Department of Psychiatry, Public Hospital ‘Morgagni’, 47100 Forlı, ` Italy Received 9 March 1998; received in revised form 12 May 1998; accepted 27 May 1998

Abstract The prevalence of DSM-IV atypical depression and differences between atypical versus non-atypical depression were investigated in 467 unipolar and bipolar depressed outpatients in private practice. Consecutive outpatients presenting for treatment of a major depressive episode were assessed with the Comprehensive Assessment of ˚ Symptoms and History following DSM-IV criteria, the Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. The prevalence of atypical depression was 38.1%. Of the variables investigated Žunipolar and bipolar diagnoses, age at onset, gender, psychosis, comorbidity, chronicity, duration of illness, recurrences, and severity., age at onset was significantly lower, and female gender, comorbidity, and bipolar II disorder were significantly more common in atypical than nonatypical depression. Comparisons between bipolar II atypical depression and unipolar atypical depression did not show significant differences, apart from age at onset. Findings suggest that there are important clinical differences between atypical and non-atypical depression in private practice outpatients. Q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Major depressive episode; Bipolar disorder; Unipolar depression; Diagnosis

1. Introduction The DSM-IV classification of mood disorders has the specifier ‘with atypical features’, applied

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Via Pozzetto 17, 48015 Castiglione di Cervia RA, Italy. Tel.: q39-0335 6191852; fax:q 39-0543-30069. E-mail address: [email protected] ŽF. Benazzi.

to major depressive episodes occurring in major depressive, bipolar IrII, and dysthymic disorders ŽAmerican Psychiatric Association, 1994.. Instead of listing atypical depression as a separate entity, the DSM-IV uses atypical depressive features as modifiers of the aforementioned mood disorders. The reported prevalence of atypical depression in depressed outpatients is between 25% and 83% ŽStewart et al., 1992; Thase et al., 1992; Asnis et

0165-1781r99r$ - see front matter Q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 1 7 8 1 Ž 9 9 . 0 0 0 3 5 - 9

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al., 1995; Sotsky, 1997.. Studies reporting lower rates used definitions of atypical depression that were underinclusive, while studies that found higher rates used definitions that were overinclusive relative to the DSM-IV criteria. Horwath et al. Ž1992., using a restrictive definition of atypical depression, found that 16% of patients with major depression had atypical depression in a nonclinical sample. Atypical depression, in comparison with nonatypical depression, has been reported to be more common in women ŽThase, 1997., both to have ŽThase et al., 1991; Horwath et al., 1992; Stewart et al., 1993a; American Psychiatric Association, 1994. and not to have ŽAsnis et al., 1995; Derecho et al., 1996. a younger age at onset, to have a more chronic course ŽStewart et al., 1993b; American Psychiatric Association, 1994., to have a higher occurrence of episodes ŽKendler et al., 1996., to have more Axis I psychiatric comorbidity ŽHorwath et al., 1992; American Psychiatric Association, 1994., to be more frequent in bipolar IrII and seasonal major depressive disorders ŽStewart et al., 1990; American Psychiatric Association, 1993, 1994; Benazzi, 1997a., to have a similar severity to that of nonatypical depression ŽAsnis et al., 1995; Derecho et al., 1996., and to have a moderate severity ŽKendler et al., 1996.. Atypical depression, compared with non-atypical depression, responds better to monoamine oxidase inhibitors than to tricyclic antidepressants ŽLiebowitz et al., 1988; Quitkin et al., 1989, 1993; Ownby and Goodnick, 1996; Stewart et al., 1997.. Biologically, atypical depression seems different from non-atypical depression Žfewer abnormalities, less impaired norepinephrine system, and hypofunction of hypothalamic CRH neurons. ŽStewart et al., 1993a; Asnis et al., 1995; Gold et al., 1995; McGinn et al., 1996.. Its family history is different from that of non-atypical depression Žfewer relatives with severe depression, more relatives with chronic depression, and high concordance in monozygotic twin pairs. ŽStewart et al., 1993a; Kendler et al., 1996.. The aim of the present study was to find the prevalence of atypical depression in unipolar and bipolar outpatients presenting for treatment of depression in a private practice. Differences

between atypical and non-atypical depression, and between atypicalrnon-atypical bipolar II and unipolar depression were studied, to determine whether atypical depression was a separate entity. Research outside academic settings, including private settings, may be more related to actual practice ŽLebowitz and Rudorfer, 1998.. A subsample of the patients were included in earlier reports ŽBenazzi, 1997a,b, 1998a,b,c..

2. Methods The study was carried out in his outpatient general psychiatry private practice by a senior psychiatrist of the Department of Psychiatry of the Public Hospital of Forlı, ` Italy. The private setting is representative of mood disorder patients who are spontaneously seeking psychiatric help in Italy, where the public setting deals mainly with the most severe patients. The inclusion criterion was the presence of a DSM-IV major depressive episode, with or without concurrent psychopharmacological treatment, occurring in major depressive, bipolar I, or bipolar II disorders Žunipolarr bipolar depression.. Concurrent treatment was included because there was no reason to think that one subgroup of patients would be more likely than another to be on treatment, apart from depression severity Žwhich did not differ significantly among the subgroups.. Furthermore, a large sample size would be expected to reduce random error. Substance abuse, severe personality disorder, and pure dysthymic disorder patients were not included, as they are rarely seen in private practice. Dysthymic disorder patients with superimposed major depressive disorder were classified under unipolar depression. Atypical depression was defined according to DSM-IV criteria. The interview was conducted by the author with the Comprehensive Assessment of Symptoms and History ŽCASH. structured interview, following DSM-IV criteria ŽAndreasen et al., 1992.. The CASH covers five Žmood reactivity, weight gain, appetite increase, hypersomnia, severe loss of energy. of the six DSM-IV atypical symptoms Žrejection sensitivity is not covered.. Its interrater reliability for the diagnosis of depres-

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sive syndrome is 0.84, and it is 1.00 for the diagnosis of manic syndrome. Three quarters of the CASH variables have an intraclass r G 0.65 for the interrater design, and half have an intraclass r G 0.65 for the test-retest design ŽAndreasen et al., 1992.. A validity study Žproband vs. informant. showed an intraclass r for agreement ) 0.7 for ˚ most items. The Montgomery and Asberg Depression Rating Scale ŽMADRS. ŽMontgomery ˚ and Asberg, 1979., and the Global Assessment of Functioning ŽGAF. Scale ŽAmerican Psychiatric Association, 1994. were used to assess the severity of depression at baseline. The problem with the MADRS is that it does not cover most DSMIV atypical symptoms, and therefore atypical depression may have a lower MADRS score Ži.e. apparently less severe. than non-atypical depression because atypical symptoms are not scored. Therefore, the GAF scale was also used to assess the severity of depression. As the GAF gives a grading of severity Žmild, moderate, serious, some reality-testing impairment, presence of delusionsrhallucinations, some danger of hurting, persistent danger of severely hurting., it obviates the need to score specific symptoms, such as the atypical ones. Furthermore, the GAF also covers functioning, which is included in the DSM-IV severity specifier of the major depressive episode Žmild, moderate, severe, with progressive impairment of functioning from mild to severe.. The GAF is considered a good technique for the assessment of overall severity of depression ŽHirschfeld, 1996.. Often, close relatives and spouses supplemented the clinical information during the interview. Axis I comorbid disorder diagnoses were made by clinical interview following DSM-IV criteria, when comorbid disorders were spontaneously reported by the patients, without systematic probing. This approach may have led to underreporting, but not to a differential misclassification related to information bias, because the sample was large and because there was no reason to think that one subgroup of patients would be more likely than another to report comorbid disorders. The prevalence of atypical depression was based on the first 467 consecutive unipolar and bipolar depressed outpatients presenting for treatment of

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depression during an 8-month period ŽJune] January.. The significance of the difference between means was assessed by t-test. The significance of the difference between proportions was tested with the x 2-test ŽYates’ corrected.. Two-way analysis of variance was used to test interaction. Simple linear regression and correlation were tested between age at baseline and age at onset. All P values were two-tailed, and the probability level was set at 0.01, as the number of comparisons increased the risk of type I error.

3. Results Prevalence of atypical depression was 38.1% Ž178r467.. Comparisons of the proportions of atypical bipolar I Ž3.9%; n s 7., bipolar II Ž60.1%; n s 107., and unipolar Ž35.9%; n s 64. patients with the proportions of nonatypical bipolar I Ž3.8%; n s 11., bipolar II Ž35.9%; n s 104., and unipolar Ž60.2%; n s 174. patients showed that bipolar II disorder was significantly more common in patients with atypical depression Ž x 2 s 25.89, d.f.s 1, Ps 0.0000., unipolar patients were significantly more common in non-atypical depression Ž x 2 s 25.93, d.f.s 1, Ps 0.0000., and the proportions of bipolar I disorders among the atypical and non-atypical groups did not differ significantly Ž x 2 s 0.00, d.f.s 1, Ps 0.9450.. Other comparisons with bipolar I patients were not done because of the small sample. The proportion of bipolar II patients with atypical features Ž50.7%; n s 107. was significantly higher than the proportion of unipolar patients with atypical features Ž28.8%; n s 64. Ž x 2 s 26.91, d.f.s 1, Ps 0.0000.. Table 1 presents comparisons between the first consecutive 254 atypical and non-atypical unipolar and bipolar II depressed patients, all of whom were extensively interviewed to collect information about many variables. As age at baseline and age at onset were highly correlated in a subsample of unipolar and bipolar II patients Ž r s 0.72, d.f.s 190, F s 207.3., only age at onset is presented to avoid duplication. Results showed that age at onset of the first major depressive episode was significantly lower, and that female gender,

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Table 1 Comparisons between atypical and non-atypical unipolarrbipolar II depression Variables

Atypical Žn s 121.

Non-atypical Žn s 133.

Age at onset of first major depressive episode wmean ŽS.D..x Žyears. Females Ž%. Unipolar Ž%. Bipolar II Ž%. Psychotic features Ž%. Axis I comorbidity Ž%. Chronic and without full interepisode recovery major depressive episode Ž) 2 years. Ž%. More than three major depressive episodes% Duration of illness from onset wmean ŽS.D..x Žyears. Baseline MADRS wmean ŽS.D..x Baseline GAF wmean ŽS.D..x

26.5 Ž12.4. 76.8 34.7 65.2 4.9 74.3 42.1

31.3 Ž14.9. 61.6 60.1 39.8 9.7 57.1 45.8

t s 2.77, d.f.s 252, Ps 0.0059 x2 s 6.84, d.f.s 1, Ps 0.0089 x2 s 16.43, d.f.s 1, P s 0.0000 x2 s 16.43, d.f.s 1, P s 0.0000 x2 s 2.12, d.f.s 1, Ps 0.1450 x2 s 8.31, d.f.s 1, Ps 0.0039 x2 s 0.35, d.f.s 1, Ps 0.5513

75.2 13.1 Ž9.8. 28.1 Ž7.8. 55.1 Ž8.1.

72.1 12.2 Ž1.0. 30.8 Ž9.7. 55.4 Ž9.5.

x2 s 0.30, d.f.s 1, Ps 0.5846 t s 1.47, d.f.s 252, Ps 0.1421 t s 2.40, d.f.s 252, Ps 0.0168 t s 0.26, d.f.s 252, Ps 0.7878

comorbidity, and bipolar II disorder were significantly more common in atypical depression. None of the other variables showed significant differences. Comorbid disorders in atypical depression were panic disorderragoraphobia Ž53.7%., obsessive-compulsive disorder Ž10.7%., bulimia nervosa Ž10.7%., generalized anxiety disorder Ž9.9%., and social phobia Ž8.2%.. Comorbid disorders in nonatypical depression were panic disorderragoraphobia Ž46.6%., obsessive-compulsive disorder Ž9.7%., generalized anxiety disorder Ž5.2%., social phobia Ž4.5%., and bulimia nervosa Ž1.5%.. More than one comorbid disorder could be present in the same patient. Table 2 presents comparisons between atypical bipolar II and atypical unipolar depression, and between atypical and non-atypical unipolar depression. The only significant difference was the lower age at onset of atypical bipolar II depression vs. atypical unipolar depression. A two-way analysis of variance of the age at onset according to the unipolarrbipolar II, and the atypicalrnonatypical distinction showed no interaction between the two factors Ž F s 1.21, d.f.s 1,250, Ps 0.2719.. The atypicalrnonatypical distinction had no significant effect on age at onset Ž F s 3.80, d.f.s 1,250, Ps 0.0525.. The bipolar IIrunipolar distinction had a significant effect on age at onset Ž F s 7.19, d.f.s 1,250, Ps 0.0078..

4. Discussion The prevalence of atypical depression in this private practice sample of unipolar and bipolar depressed outpatients was 38.1%, a rate in the lower part of the reported range ŽStewart et al., 1992; Thase et al., 1992; Asnis et al., 1995; Sotsky, 1997.. This relatively low prevalence could reflect the use in this study of the DSM-IV criteria, while previous studies used criteria that tended to be either underinclusive or overinclusive. Unipolar patients were significantly more common in nonatypical depression, while bipolar II patients were significantly more common in atypical depression, in line with previous reports ŽStewart et al., 1990; American Psychiatric Association, 1994; Benazzi, 1997a.. Age at onset was significantly lower in atypical depression, in line with some earlier studies ŽThase et al., 1991; Horwath et al., 1992; American Psychiatric Association, 1994; Thase, 1997; Stewart et al., 1993a., but not with others ŽAsnis et al., 1995; Derecho et al., 1996.. Female gender and Axis I comorbidity were significantly more common in atypical depression, in line with some reports ŽHorwath et al., 1992; American Psychiatric Association, 1994; Asnis et al., 1995., but not others ŽKendler et al., 1996.. Contrary to previous reports ŽAmerican Psychiatric Association, 1994; Kendler et al., 1996; Stewart et al., 1993b., atypical depression did not

Table 2 Comparisons among atypical bipolar II ŽAtyp Bip II., atypical unipolar ŽAtyp Unip., nonatypical bipolar II ŽNonatyp Bip II., and nonatypical unipolar ŽNonatyp Unip. depressions Variables

Atyp Unip Ž n s 42.

Nonatyp Bip II Ž n s 53.

Nonatyp Unip Ž n s 80.

Atyp Bip II vs. Atyp Unip

Nonatyp Bip II vs. Nonatyp Unip

Age at onset first major depressive episode wmean ŽS.D..x Žyears. Females Ž%.

24.2 Ž9.3. 79.7

30.9 Ž15.9. 71.4

29.6 Ž12.7. 60.3

32.4 Ž16.2. 62.5

t s 2.92, d.f.s 119, Ps 0.0042; x2 s 1.07, d.f.s 1, Ps 0.3016;

t s 0.48, d.f.s 120, Ps 0.6257 x2 s 0.97, d.f.s 1, Ps 0.3240

Duration of illness from onset wmean ŽS.D..x Žyears.

12.1 Ž9.5.

14.8 Ž10.2.

15.9 Ž10.4.

14.7 Ž13.4.

t s 1.45, d.f.s 119, Ps 0.1495

t s 0.04, d.f.s 120, Ps 0.9663

6.2

x2 s 4.52, d.f.s 1, Ps 0.0334

x2 s 0.54, d.f.s 1, Ps 0.4626

Psychotic features Ž%.

1.2

11.9

15

Axis I comorbidity Ž%.

72.1

78.5

54.7

57.5

x2 s 0.59, d.f.s 1, Ps 0.4412

x2 s 5.36, d.f.s 1, Ps 0.0206

Chronic and without full interepisode recovery major depressive episode Ž) 2 years. Ž%.

35.4

54.7

49.0

45.0

x2 s 4.20, d.f.s 1, Ps 0.0404

x2 s 1.05, d.f.s 1, Ps 0.3052

More than three major depressive episodes Ž%.

77.2

71.4

77.3

68.7

x2 s 0.49, d.f.s 1, Ps 0.4828

x2 s 0.09, d.f.s 1, Ps 0.7597

Baseline GAF wmean ŽS.D..x

55.4 Ž7.3.

54.5 Ž9.6.

54.7 Ž8.2.

56.0 Ž10.2.

t s 0.57, d.f.s 119, Ps 0.5649

t s 0.78, d.f.s 120, Ps 0.4327

Baseline MADRS wmean ŽS.D..x

28.1 Ž7.2.

28.2 Ž8.9.

30.7 Ž9.1.

30.9 Ž10.1.

t s 0.06, d.f.s 119, Ps 0.9468

t s 1.46, d.f.s 120, Ps 0.1470

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Atyp Bip II Ž n s 79.

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show more chronicity or more recurrences in this sample. The mean GAF score Žabove 50. in these atypical depression patients indicates a moderate level of severity wdepression is considered severe if the GAF score is 50 or less ŽElkin et al., 1989.x, in line with a previous report ŽKendler et al., 1996.. Mean GAF and MADRS scores did not differ significantly between atypical and nonatypical forms of depression, in line with previous reports of similar depression severity ŽAsnis et al.,1995; Derecho et al., 1996.. Discordant findings in comparison with previous reports might be related to the samples studied, different settings, and relative prevalence of bipolar patients. Private practice, outpatients are usually less severe and selected than publicruniversity inpatients and outpatients. In a general psychiatry private practice more ‘soft’ patients tend to be seen, while specialized university mood clinics Žwhere most studies were carried out. tend to see more complicated and treatment-resistant patients, who are different from the average private practice outpatient with a mild to moderate severity of depression. As the comparison in this study between atypical and nonatypical unipolar depression did not show significant differences, it seems that the bipolar II patients were the most responsible for the differences observed between atypical and non-atypical depression. However, the sample size of atypical unipolar depression was not very large, limiting the power of the analysis. The comparison between atypical bipolar II and atypical unipolar depression showed only one significant difference: a lower age at onset in bipolar II patients. The two-way analysis of variance showed no interaction of age at onset with the atypicalrnonatypical factor or the unipolarrbipolar II factor, and a significant effect on age at onset of the unipolarrbipolar II factor. The absence of an interaction between these two factors may suggest that atypical bipolar II depression and atypical unipolar depression may not be separate entities Žtogether with the absence of significant differences on the variables studied, apart from age at onset.. However, the lack of significant interaction could be a power problem, or it could also mean that the unipolarrbipolar II distinction is not relevant when distinguishing

atypical depression from non-atypical depression. The unipolarrbipolar II distinction had a significant effect on age at onset, replicating reports of a lower age at onset of bipolar II depression vs. unipolar depression ŽAmerican Psychiatric Association, 1994; Benazzi, 1997a.. In conclusion, the results of this study suggest that there may be important clinical differences Žproportion of unipolar and bipolar II disorders, percentage of female patients, age at onset, comorbidity. between atypical and non-atypical depression in private practice depressed outpatients, confirming in part previous findings in other settings. A subdivision of atypical depression into bipolar II and unipolar subtypes does not seem supported, due to the lack of clinical differences. However, the history of hypomania may support this subdivision, due to its therapeutic implications wantidepressant-induced switches, rapid cycling, mixed states, and use of mood stabilizers in bipolar disorders ŽAkiskal, 1996.x. Therefore, the identification of bipolar II atypical depression is important from a therapeutic point of view. References Akiskal, H.S., 1996. The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. Journal of Clinical Psychopharmacology 16 ŽSuppl 1., 4S]14S. American Psychiatric Association, 1993. Practice guideline for major depressive disorder in adults. American Journal of Psychiatry 150 ŽSuppl., p 14. American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association, Washington, DC, pp. 384]386. Andreasen, N.C., Flaum, M., Arndt, S., 1992. The comprehensive assessment of symptoms and history ŽCASH.. Archives of General Psychiatry 49, 615]623. Asnis, G.M., McGinn, L.K., Sanderson, W.C., 1995. Atypical depression: clinical aspects and noradrenergic function. American Journal of Psychiatry 152, 31]36. Benazzi, F., 1997a. Prevalence of bipolar II disorder in outpatient depression: a 203-case study in private practice. Journal of Affective Disorders 43, 163]166. Benazzi, F., 1997b. Antidepressant-associated hypomania in outpatient depression: a 203-case study in private practice. Journal of Affective Disorders 46, 73]77. Benazzi, F., 1998a. Chronic depression: a case series of 203 outpatients treated at a private practice. Journal of Psychiatry & Neuroscience 23, 51]55. Benazzi, F., 1998b. Late-life depression in private practice

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