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ScienceDirect Comprehensive Psychiatry 55 (2014) 463 – 467 www.elsevier.com/locate/comppsych

Predictors of remission from chronic depression: A prospective study in a nationally representative sample Vito Agosti New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA

Abstract Purpose: The aims of this study were to identify predictors of remission from chronic depression in a prospective longitudinal general population survey; second, to determine the relative level functioning and well-being of those in remission. Methods: The sample included respondents who met the criteria for major depressive disorder from Wave 1 (2001–2002) and through Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Results: Panic Disorder, Generalized Anxiety Disorder, Cluster B personality disorders and a history of Physical Abuse were correlated with reduced likelihood of chronic depression remission. The functioning and well-being of the remitted group was below the norm. Conclusions: These prognostic factors are similar to those found in clinical samples. Despite remission from chronic depression, a significant proportion have impairments in functioning. © 2014 Elsevier Inc. All rights reserved.

1. Introduction Several studies of large clinical populations found that a considerable proportion of patients had persistent forms of major depression disorder (MDD). The National Institutes of Mental Health (NIMH) Collaborative Program on the Psychobiology of Depression study observed that 7% of subjects with major depression did not remit during the first 5 years of follow-up [1]. Twenty-five percent of patients in Sequential Treatment Alternatives to Relieve Depression trial had a current episode of MDD lasting N2 years [2]. General population studies have also observed that the prevalence of chronic depression to be considerable. Three cross-sectional, retrospective, studies have been conducted. The Canadian Community Health Study observed that 26.8% of subjects with a lifetime MDD had an episode which endured ≥2 years [3]. Three prospective follow-up of general populations have noted substantial rates of persistent depression. The Zurich Cohort Study observed that 23% had a chronic course of depression over a 20 year follow-up period. [4]. A similar rate, 20%, over 2 years, was found in The Netherlands Mental Health Survey and Incidence Study (NEMESIS), [5]. The Baltimore Epidemiologic Catchment Area (ECA) E-mail address: [email protected]. 0010-440X/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.comppsych.2013.09.016

reported that 15% cases with MDD dot not have a 1 year period of remission over the course of 23 years [6]. Few prospective studies of clinical samples have examined predictors of chronic depression. Two large prospective longitudinal studies of clinical populations with mood disorders were found in the literature. A 10-year prospective study of a relatively large cohort of patients with Dysthymic Disorder (DD), with or without superimposed MDD, found that older age, less education, concurrent anxiety disorder, greater familial aggregation for chronic depression, a history of childhood sexual abuse, and personality disorders predicted more impaired functioning and depression severity [7]. The NIMH Collaborative Program observed that among the subgroup who recovered from MDD, mild chronic depression increased the risk of relapse to MDD [8]; and a longer episode of MDD was associated with longer time to remission [9]. The only prospective study which examined predictors of remission from chronic depression was derived from a clinical sample [7]. Since clinical samples typically represent more severe forms of psychopathology, it is unclear if Klein et al. [7] findings are applicable to the general population. Hence, this study sought to identify predictors of remission in a prospective longitudinal study. A secondary aim was to determine the relative functioning and wellbeing of those in remission.

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V. Agosti / Comprehensive Psychiatry 55 (2014) 463–467

2. Methods 2.1. Sample This study used data from both waves of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). The nationally representative 2001 to 2002 Wave 1 sample contained 43,093 U.S. adults 18 and older living in households and noninstitutional group quarters (response rate = 81.0%). The 2004 to 2005 Wave 2 followup sample contained 34,653 of the original respondents, 86.7% of those eligible for reinterview, for a cumulative response rate of 70.2%. Detailed information on the sample design and weighting is available where [10,11] instruments have exhibited a good level of reliability, κ = 0.74 [12]. This report is based on a subsample of Wave 1 NESARC respondents classified with chronic depression who were reinterviewed at Wave 2 (N = 411). All potential respondents were informed in writing about the nature of the survey, uses of the survey data, voluntary nature of their participation, and legally mandated confidentiality of identifiable survey information. The research protocol received full ethical review and approval from the U.S. Census Bureau and the U.S. Office of Management and Budget. 2.2. Measures Chronic Depression was defined as a current episode of MDD of N2 years’ duration and/or dysthymic disorder at Wave 1. The Alcohol Use Disorders and Associated Disability Interview Schedule–DSM-IV Version (AUDADISIV) [12] was used to assess psychiatric disorders. All personality disorders were assessed by algorithms requiring the specific numbers of diagnostic criteria, as well as evidence of long-term maladaptive patterns of thinking, functioning and emotion [13–17]. Personality disorders, except for antisocial, were assessed with an introduction and repeated reminders asking respondents to answer about how they felt or acted “most of the time, throughout your life regardless of the situation or whom you were with.” Subjects were asked not to include symptoms occurring only when depressed, manic, anxious, drinking heavily, using drugs, recovering from the effects of alcohol or drugs, or physically ill. Avoidant, dependent, histrionic, obsessive-compulsive, paranoid, and schizoid personality disorders were assessed at Wave 1; borderline, narcissistic, and schizotypal were assessed at Wave 2. Lifetime antisocial personality disorder was assessed at Wave 1, with adult symptoms re-assessed at Wave 2. This study measured functioning with the RAND MOS36 Item Short Form Health Survey (MOS-36). The MOS-36 [18] consists of 36 items that measure domains of physical health, emotional health, social functioning and general quality of life. The scale comprised measures assessing eight different components of health including: physical disability

(e.g. does your health limit you in completing moderately physical activities such as vacuuming?), physical role functioning (e.g., have you had any problems with your work or other regular daily activities as a result of your physical health?), emotional role functioning (e.g., have you had any problems with your work or other regular daily activities as a result of your emotional health?), perceptions of general health (e.g., rating of overall general health), mental health (e.g., have you been calm ? Have you been depressed?), vitality (e.g., did you feel full of pep?), bodily pain (e.g., how much did pain interfere with you normal work?), and social functioning (e.g., how much of the time has your physical or emotional problems interfered with social activities? [19] Lower MOS scores indicate impaired functioning; higher scores indicate better functioning. 2.3. Statistical analyses Weighted frequencies, and their respective 95% confidence intervals were computed to derive sociodemographic correlates and clinical features of chronic depression at Wave 1. Univariate statistics were used to test for significant demographic and clinical differences between remitters and non-remitters. Variables which manifested significant between group differences (p b .10) were then entered into a logistic regression model [20]. The SPSS complex analysis module was used to adjust for the complex survey design and population sampling weights using the computer package SPSS Complex Samples Statistics (Version 14.0) [21]. Differences between MOS scores at follow-up between the remitted group and the general population were examined with pairwise t-tests. Given sufficiently large samples, any difference will eventually achieve statistical significance even if its clinical significance remains negligible. Because effect sizes are independent of sample size, effect size (ES) was calculated for each comparison. Cohen [22] offered the following approximate guidelines for interpreting ES scores: 0.20 (small), 50 (medium) and 0.80 (large). 3. Results The majority of respondents with chronic depression were female and white; nearly half had attended some college; 82% earned less than $35,000; and 60% were not working full-time at Wave 1 (Table 1). The majority of the sample, 62%, had dysthymic disorder with superimposed major depression. The most prevalent past year comorbid Axis I disorder in the sample was generalized anxiety disorder; approximately one-third had a Cluster A, B, or C personality disorder; high rates of childhood abuse were reported (Table 2). Sixty-seven percent of the cases no longer met criteria for Dysthymic Disorder or Major Depression at Wave 2. Multivariate logic regression results revealed that older age, separated or divorced marital status, cluster PDs A and B panic disorder, generalized anxiety disorder, and a history

V. Agosti / Comprehensive Psychiatry 55 (2014) 463–467 Table 1 Demographic characteristics of subjects with chronic depression at Wave 1. N = 747 % Gender Male Female Age 18–30 31–44 N44 Race White Non-White U.S. born Yes No Education bHigh school High school ≥College Individual income $0–$19,990 $20,000–$34,999 $35,000–$69,999 ≥$70,000 Marital status Married Cohabiting Widowed Divorced Separated Never married Employed full-time Yes No

SE

Table 2 Clinical characteristics of respondents with chronic depression at Wave 1 and rates of remission at Wave 2. %

95% CI

30.2 69.8

.9 .9

28,32 68,72

19.9 32.0 48.4

.9 .9 1.0

18,22 30,34 47,50

85.3 14.7

.5 .5

84,86 17,16

89 11

.4 .4

89,90 10,11

29.9 23.4 46.7

.8 .9 .8

28,32 22,25 45,48

62.5 20.7 12.0 4.8

1.0 .8 .4 .4

61,65 19,22 11,13 4,6

44 3.2 7.5 21.9 3.7 20.1

1.0 .2 .3 1.1 .4 .7

42,46 3,4 7,8 19,24 3,5 19,22

39.6 60.4

1.0 1.0

38,42 58.63

of physical abuse or sexual abuse were correlated with reduced likelihood of remission between Wave 1 and Wave 2. Unexpectedly, Emotional Neglect was found to increase the probability of remission (Table 3). The functioning of respondents in remission was significantly below the norm; effect size difference were moderate to large. Disability related to Emotional Role Functioning and Mental Health Functioning manifested the largest between group differences (Table 4).

4. Discussion The results of this prospective general population study are in line with findings from a large clinical sample of outpatients with chronic depression, who were systematically assessed every 30 months for a period of 10 years [7]. That study observed a significant association between anxiety and personality disorders, child abuse, and a reduced likelihood of remission. These findings also parallel data derived from another NESARC study, which reported that personality disorder increased the likelihood of chronic course among subject

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Wave 1 past year axis I disorders Major depression Dysthymic disorder Panic disorder Social anxiety disorder Specific phobia Generalized anxiety disorder Substance use Disorders⁎ Personality disorders Any cluster A disorder Any cluster B disorder Any cluster C disorder Dependent Avoidant Obsessive Histrionic Paranoid Schizoid Schizotypal Narcissistic Borderline Antisocial Childhood adversity Emotional neglect Physical abuse Emotional abuse Sexual abuse Physical neglect Remission

SE

95% CI

.9 .9 .2 .7 .6 .8 .7

.36,.39 60,64 3.,4 12,15 15,17 22,25 13,16

30.9 29.3 30.4 3.6 13.8 21.3 5.0 19.4 14.0 12.8 10.4 22.0 10.2

.9 .9 1.0 .3 .8 .7 .4 .7 .6 .5 .7 .9 .5

29,33 27,31 29,32 3,4 12,16 20,23 4,6 18,21 13,15 12,14 9,12 20,24 9,11

19.5 32.1 87.4 27.4 45.1 65

.9 1.1 .7 1.0 1.0

18,21 30,34 86,88 26,29 43,47

N = 747 37.9 62.1 3.5 13.3 16.0 23.6 14.5

⁎ Alcohol or illicit drug use disorders.

with MDD [23] and decreased the odds of remission among respondents with early-onset chronic depression [24]. Unexpectedly, females were found to have decreased likelihood of abatement from persistent depression. Given the lack of other studies demonstrating a link between gender and remission from chronic depression, this finding should be viewed with caution, and clearly warrants replication. Three clinical variables were discovered to lower the odds of remission: childhood physical abuse, anxiety disorder

Table 3 Logistic regression model predicting remission from chronic depression at Wave 2.

Demographics White Female Personality disorders Cluster B Axis I disorders Panic disorder Simple phobia Generalized anxiety disorder Childhood adversity Physical abuse

OR

95% CI

1.4 .41

.93,2.2 .28,.62

.56

.35,.73

.31 .61 .50

.12,.88 .34,.89 .41,.89

.49

.44,.97

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Table 4 Comparison of Short-Form health scores of normative sample with remitted chronic depression respondents.

Physical disability Mental disability scale Physical functioning Physical role functioning Bodily pain General health Vitality Social functioning Emotional role functioning Mental health

Community

Remitted

Sample N = 19,575

Group N = 747

Mean

SD

Mean

SD

50.3 53.2 50.9 50.5 51.7 50.0 53.6 52.7 50.4 53.9

10.9 9.1 10.9 10.5 10.5 12.0 11.0 9.5 10.6 9.8

44.6 45.6 44.9 44.6 44.4 43.6 46.0 46.1 43.7 41.6

13.6 11.2 13.7 12.7 14.4 13.8 11.9 13.4 .66 .56

Effect Size

.47 .75 .48 .43 .64 .46 .70 .61 1.2 .79

and Cluster B personality disorders. We offer possible mechanisms through which these factors affected the course of illness. The severe stress associated with physical abuse during childhood may disrupt the development of trust in others and healthy self-esteem. These deficits hinder the establishment and maintenance of positive social feedback [25], which has been found to enhance the odds or remission in dysthymia [26] and various subtypes of major depression [27–31]. Studies have noted that a subgroup of individuals have genetically based neurobiological dysfunction, which, when combined with childhood abuse, increases the risk for a broad range of psychiatric disorders [32–38]. Accordingly, we conjecture that this environment x gene diathesis is manifested by impulsivity, a characteristic of Cluster B Personality Disorders, and high levels of anxiety, a feature of Anxiety Disorders. These sequelae possibly hinder the development of the internal and external resources needed to recover from chronic depression. A dearth of studies have examined social functioning of chronically depressed patients in remission. Several researcher teams have noted that depression remission may not connote healthy functioning and wellbeing [39,40]. The few follow-up studies that examined functioning outcomes of chronically depressed patients who responded to acute treatment have yielded inconclusive results. One investigation found that social functioning was clinical indistinguishable from a normal control group [41], while another study found it to be below normal [42]. Hence this study provides needed data to fill a gap in our knowledge. This investigation noted that remitted chronically depressed respondents were considerably more physically disabled, had greater pain and lethargy, lower self-rated general health and lower levels of psychological wellbeing than the community norm. The later outcome manifested the largest clinically significant difference, suggesting that they had considerable levels of residual dysphoria. Subsyndromal depression has been found to be associated with below

impaired functioning in a large primary care setting and outpatient settings [43–45]. The World Health Organization defined mental health “as a state of well-being in which every individual realizes his or her own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community” [46]. There has been an increased discussion in the literature about what constitutes remission from depression. Some investigators have questioned whether the absence of a DSM disorder connotes a state of health [40,47–50]. This study has several limitations. The NESARC survey was based on the assumption made by Diagnostic and Statistical Manual for Mental Disorders, 4th Edition (DSMIV) [51] that personality disorders are trait characteristics which are stable over time. Therefore cases who had remitted personality disorders could not be detected. It is possible that in a subgroup of individuals, remissions from personality disorders precedes remission from chronic depression. Second, the depression remission status may have biased the recollection of personality disorder symptoms. Third, subthreshold depression was not assessed. References [1] Mueller TI, Keller MB, Leon AC, Solomon DA, Shea MT, Coryell W, et al. Recovery after 5 years of unremitting major depressive disorder. Arch Gen Psychiatry 1996;53:794-9. [2] Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006;163:28-40. [3] Satyanarayana S, Enns MW, Cox BJ, Sareen J. Prevalence and correlates of chronic depression in the canadian community health survey: mental health and well-being. Can J Psychiatry 2009;54:389-98. [4] Angst J, Gamma A, Rossler W, Ajdacic V, Klein DN. Long-term depression versus episodic major depression: results from the prospective Zurich study of a community sample. J Affect Disord 2009;115:112-21. [5] Spijker J, de Graaf R, Bijl RV, Beekman AT, Ormel J, Nolen WA. Duration of major depressive episodes in the general population: results from The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Br J Psychiatry 2002;181:208-13. [6] Eaton WW, Shao H, Nestadt G, Lee HB, Bienvenu OJ, Zandi P. Population-based study of first onset and chronicity in major depressive disorder. Arch Gen Psychiatry 2008;65:513-20. [7] Klein DN, Shankman SA, Rose S. Dysthymic disorder and double depression: prediction of 10-year course trajectories and outcomes. J Psychiatr Res 2008;42:408-15. [8] Keller MB, Lavori PW, Endicott J, Coryell W, Klerman GL. “Double depression”: two-year follow-up. Am J Psychiatry 1983;140:689-94. [9] Keller MB, Lavori PW, Mueller TI, Endicott J, Coryell W, Hirschfeld RM, et al. Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry 1992;49:809-16. [10] Grant BF, Goldstein RB, Chou SP, Huang B, Stinson FS, Dawson DA, et al. Sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance use, mood and anxiety disorders: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Mol Psychiatry 2009;14:1051-66. [11] Grant BF, Kaplan K. Source and Accuracy Statement for the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions

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Predictors of remission from chronic depression: a prospective study in a nationally representative sample.

The aims of this study were to identify predictors of remission from chronic depression in a prospective longitudinal general population survey; secon...
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