- Email: [email protected]
Remission in depressed outpatients: More than just symptom resolution?
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JOURNAL OF PSYCHIATRIC RESEARCH
Journal of Psychiatric Research 42 (2008) 797–801
www.elsevier.com/locate/jpsychires
Remission in depressed outpatients: More than just symptom resolution? Mark Zimmerman *, Joseph B. McGlinchey, Michael A. Posternak, Michael Friedman, Daniela Boerescu, Naureen Attiullah Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Bayside Medical Center, 235 Plain Street, Providence, RI 02905, United States Received 22 December 2006; accepted 26 September 2007
Abstract Objective: In treatment studies of depression remission is defined according to scores on symptom severity scales. Normalization of functioning has often been mentioned as an important component of the definition of remission, though it is not used to identify remitted patients in studies of treatment efficacy. Conceptually, the return of normal functioning should be as fundamental to the concept of remission as is symptom resolution because the presence of both symptoms and impaired functioning are core constructs in the diagnosis of mental disorders. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined the independent and additive association between level of severity of depressive symptoms and functional impairment in predicting depressed patients’ subjective evaluation of their remission status. Methods: Five hundred and fourteen depressed psychiatric outpatients filled out a questionnaire on which they rated the severity of the symptoms of depression, the level of impairment due to depression, and their quality of life. Results: Symptom severity, functional impairment from depression, and quality of life were significantly and highly intercorrelated, and each was significantly associated with remission status. The results of a logistic regression analysis indicated that each of the three variables was a significant, independent, predictor of remission status. Discussion: In treatment studies of depression remission is narrowly defined in terms of symptom resolution. Our results support broadening the concept of remission beyond symptom levels to include assessments of functioning and quality of life. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Depression; Remission; Symptoms; Psychosocial functioning
1. Introduction Increasingly, experts in the treatment of depression have suggested that achieving remission should be viewed as the primary goal of treatment (Ballenger, 1999; Ferrier, 1999; Nierenberg and Wright, 1999; Rush et al., 1998; Rush and Trivedi, 1995; Stahl, 1999; Thase, 2003). These recommendations are based on studies that have consistently demonstrated that depressed patients who have responded
*
Corresponding author. E-mail address: [email protected] (M. Zimmerman).
0022-3956/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2007.09.004
to treatment but failed to achieve symptomatic remission continue to experience more psychosocial impairment and have a higher likelihood of recurrence of a full depressive syndrome (Faravelli et al., 1986; Judd et al., 2000; Judd et al., 1998; Paykel et al., 1995; Simons et al., 1986; Thase et al., 1992). In order to establish remission as the goal of treatment it is necessary to have a cogent conceptualization of the construct. As Keller (2003) recently noted, ideally remission would be defined biologically, based on the normalization of underlying pathophysiology. However, there are no valid biological state markers of major depressive disorder that can be used to monitor the progress of the disease. In
798
M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801
the absence of such biological tests, we are left with phenomenological definitions of remission. In treatment studies, remission is defined according to scores falling below a threshold on symptom severity scales such as the Hamilton rating scale for depression (1960) and the Montgomery–Asberg depression rating scale (Montgomery and Asberg, 1979). Normalization of functioning is often mentioned as an important component of the definition of remission, though it is not used to identify remitted patients in studies of treatment efficacy. Instead, psychosocial functioning is compared in patients who have and have not achieved symptomatic remission (Judd et al., 2000; Miller et al., 1998). Conceptually, the return of normal functioning should be as fundamental to the definition of remission as is symptom resolution because the presence of both symptoms and impaired functioning are core constructs in the diagnosis of mental disorders (American Psychiatric Association, 1994). It seems logical that each of the defining features of a disorder should be absent in order to declare that the disorder is in remission. As part of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we recently conducted a survey of the factors depressed patients considered important in defining remission from depression (Zimmerman et al., 2006a; Zimmerman et al., 2006b). We found that patients considered both symptom resolution and functional improvement important in determining remission. In fact, normalization of function was more often judged to be the most important factor in determining whether a depressive episode has remitted. In the present report from the MIDAS project, we examined the independent and additive association between level of severity of depressive symptoms and functional impairment in predicting depressed patients’ subjective evaluation of their remission status. We also examined a third variable, subjectively rated quality of life, as it has also been emphasized as an important factor in determining the adequacy of treatment response of medical disorders (Kennedy et al., 2001; Thunedborg et al., 1995). 2. Methods The study was conducted from August 2003 until July 2004. Participants were 535 psychiatric outpatients who were being treated for a DSM-IV major depressive episode in the Rhode Island Hospital, Department of Psychiatry outpatient practice. This private practice group predominantly treats individuals with medical insurance on a fee-for-service basis, and it is distinct from the hospital’s outpatient residency training clinic that predominantly serves lower income, uninsured, and medical assistance patients. The sample included 182 (34.0%) men and 353 (66.0%) women who ranged in age from 21 to 80 years (M = 44.2, SD = 11.5). The Rhode Island Hospital institutional review committee approved the research protocol, and all patients provided informed, written consent.
Patients completed two questionnaires. One of the questionnaires was a symptom measure of depression that included a question regarding functional impairment due to depression (‘‘Overall, how much have symptoms of depression interfered with or caused difficulties in your life during the past week? 0 = not at all; 1 = a little bit; 2 = a moderate amount; 3 = quite a bit; 4 = extremely’’) and quality of life (‘‘How would you rate your overall quality of life? 0 = very good, my life could hardly be better; 1 = pretty good, most things are going well; 2 = the good and bad parts are about equal; 3 = pretty bad, most things are going poorly; 4 = very bad, my life could hardly be worse.’’) (Zimmerman et al., 2004a). The questions were taken from the Diagnostic Inventory for Depression, a reliable and valid measure of depressive symptoms, psychosocial impairment due to depression, and quality of life (Zimmerman et al., 2004b). The second questionnaire assessed patients’ opinion regarding the importance of different factors in determining remission from depression. On the front side of the two-sided questionnaire the instructions read as follows: During the past decade, researchers who study the treatment of depression have discussed the best method of evaluating response to treatment. One area of controversy is what are the most important factors in determining who has responded well to treatment. Some experts say that the most important thing to look at are the symptoms of depression – a person should be considered in remission when the symptoms of depression (such as depressed mood, sleep and appetite changes, fatigue, problems concentrating, etc.) have gone away. Other experts say that the most important thing to look at is how a person is functioning, regardless of whether they are still experiencing some symptoms of depression. Other aspects of remission have also been proposed. The purpose of this brief questionnaire is to learn what patients believe are the most important factors in determining whether someone is in remission from their depression. Please rate how important you think each of the following factors are in determining whether someone is in remission from depression. After rating the importance of each item, circle the number of the item that you think is the most important factor. Before completing the questionnaire, please provide the following background information: The background information requested included gender, age, education, current level of severity of depression as rated on 5-point rating scale (0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe), and current remission status from depression (0 = no, 1 = yes). Thus, the three dependent variables (symptom severity, impairment in function, and quality of life) were rated on 5-point scales of severity. The reliability and validity of these single-item assessments of these constructs is described elsewhere (Zimmerman et al., 2006b). We computed Spearman correlation coefficients among the symptom, functioning, and quality of life ratings, and
M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801
point-biserial correlations between remission status and each of these three variables. After the univariate analyses we conducted a multivariate logistic regression analysis to determine which of the predictor variables were independently associated with remission status.
Twenty-one (3.9%) of the 535 patients did not answer the question about current remission status leaving a final sample of 514 patients. There were no demographic differences between the patients who did and did not answer this question. Half of the 514 patients (n = 260; 50.6%) considered themselves to be in remission at the time of the evaluation. The mean score on the symptom severity rating was 1.9 (SD = 1.2), indicating a mild level of severity. Correspondingly, the mean score on the psychosocial impairment item was 1.3 (SD = 1.2), indicating, on average, mild levels of impairment, and the mean on the quality of life item was 1.6 (SD = 0.9). As expected, symptom severity, functional impairment from depression, and quality of life were significantly and highly intercorrelated, and each was significantly associated with remission status (Table 1). Compared to patients who were not in remission, patients who indicated that they were in remission reported significantly lower symptom severity (1.2 ± 0.9 vs. 2.7 ± 0.9, t = 18.3, p < .001), less psychosocial impairment from depression (0.6 ± 0.8 vs. 2.0 ± 1.1, t = 16.0, p < .001), and greater life satisfaction (1.1 ± 0.6 vs. 2.1 ± 0.8, t = 15.4, p < .001). Table 2 shows the results of the logistic regression analysis. The overall model was significant, and each of the three variables was a significant, independent, predictor of remission status. The amount of variance accounted for in predicting remission status increased from 39% based on symptom severity alone to 56% based on all three variables. 4. Discussion The diagnosis of depression is based on the presence of symptoms along with functional impairment. Consequently, the definition of remission of depressive disorder
Table 1 Intercorrelation between measures of symptom severity, psychosocial impairment, quality of life and remission status in 514 depressed outpatients in ongoing treatment Depression severity Remissiona Symptom Severity Psychosocial Impairment
Table 2 Logistic regression evaluating remission status predicted by symptom severity, impairment and quality of life in 514 depressed outpatients Predictor Symptom severity Psychosocial impairment Quality of life
3. Results
.63
Psychosocial impairment .58 .77
Quality of life .57 .73 .79
a 0 = not in remission; 1 = in remission. For the other scales lower scores indicate less pathological responses (i.e. lower symptom severity, less psychosocial impairment, greater life satisfaction).
799
* ** ***
Parameter estimate
Odds ratio
95% Confidence interval
1.09*** 0.42*
.34 .66
.24–.47 .46–.94
0.62**
.54
.34–.85
Significant at p < .05. Significant at p < .01. Significant at p < .001.
should be based on the resolution of both symptoms and functional impairments. This, however, is not how the field has defined remission. Rather, in treatment studies of depression, remission has been defined in symptom terms only. Specifically, antidepressant efficacy trials have defined remission according to scores falling below a cutoff on symptom severity scales such as the Hamilton rating scale for depression and the Montgomery–Asberg depression rating scale. Thus, a depressed patient whose symptoms have nearly resolved but who has not yet returned to work because of lack of confidence would be considered to be in remission. On a common sense basis this seems inappropriate. We are unaware of any previous studies that have examined whether a multifactorial approach towards defining remission is more valid than the traditional unidimensional approach based solely on symptom severity. That is, while several studies have found that symptom-based definitions of remission predict future relapse, no studies have examined the prognostic validity of remission definitions based on both symptom status and functioning. It is conceivable that a multifactorial definition, even though more conceptually appealing than an exclusively symptom-based definition, would not be more valid than symptom-based remission definitions because symptom improvement accounts for such a large portion of the variance in determining remission status that the assessment of the other domains does not improve validity. In the present study, we examined the association between symptom severity, psychosocial impairment, and quality of life and depressed patients’ self-rated evaluation of remission status. We found that symptom severity had the highest correlation with remission status, though the correlations between remission status and psychosocial impairment and quality of life were nearly as high. Most importantly, the results of the regression analysis indicated that each of the three factors was independently associated with remission status. This is the first study to provide empirical evidence for broadening the concept of remission beyond symptom status. It will be important to extend the findings of the present study to a study of relapse. One of the principle goals of a definition of remission is to predict future morbidity, and a valid definition of remission from depression should
800
M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801
subdivide treatment responders into groups who are at higher and lower risk of relapse. This is analogous to how treatment goals for hypertension and hypercholesterolemia were derived (i.e. the prediction of future adverse health events) (Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults, 2001; Joint National Committee on Prevention Detection Evaluation and Treatment of High Blood Pressure, 1997). Current symptom-based definitions of remission, such as those based on the Hamilton rating scale for depression and Montgomery–Asberg depression rating scale, already accomplish this goal (Paykel et al., 1995; Thase et al., 1992; Van London et al., 1998). It is possible that a multifactorial definition of remission will be no better in predicting future relapse than symptom-based remission definitions because symptom status accounts for such a large portion of the variance in determining relapse that the assessment of the other variables does not improve prognostic ability. This remains an empirical question. Some limitations of the present study should be noted. The study was conducted in a single outpatient practice in which the majority of the patients was white, female, and had health insurance. The generalizability of the results to samples with different demographic characteristics needs to be demonstrated. The assessment of remission status was based on a single yes–no question on a paper-and-pencil questionnaire. It is possible that some patients did not understand the meaning of the term remission, though the term was defined in the instructions of the questionnaire. Moreover, expected differences in symptom severity, psychosocial functioning, and quality of life were found between patients who did and did not indicate that they were in remission. The assessments of symptom severity, functioning, and quality of life were also based on a single question. Elsewhere we demonstrated the reliability and validity of these single-item assessments (Zimmerman et al., 2006b). Nonetheless, perhaps the results would be different if based on more extensive assessments of these constructs. For example, it is possible that a more detailed assessment of symptom severity would be incrementally more valid than the single-item assessment, thereby accounting for more of the variance in remission status and eliminating an independent association between remission status and psychosocial functioning and quality of life. Future studies of this issue should include more comprehensive assessments of these constructs. Conflict of interest None. Contributors Author Zimmerman designed the study and wrote the manuscript. Author McGlinchey managed and conducted the statistical analyses. Authors Zimmerman, Posternak,
Friedman, Boerescu, and Attiullah collected the data. All authors contributed to and have approved the final manuscript. Role of the funding source There was no funding source for this research. References American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994. Ballenger J. Clinical guidelines for establishing remission in patients with depression and anxiety. Journal of Clinical Psychiatry 1999;60(suppl. 22):29–34. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Journal of the American Medical Association 2001;285:2486–2497. Faravelli C, Ambonetti A, Pallanti S, Pazzagli A. Depressive relapses and incomplete recovery from index episode. American Journal of Psychiatry 1986;143:888–91. Ferrier I. Treatment of major depression: is improvement enough? Journal of Clinical Psychiatry 1999;60(suppl. 6):10–4. Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 1960;23:56–62. Joint National Committee on Prevention Detection Evaluation and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Archives of Internal Medicine 1997;157:2413–2446. Judd LL, Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, et al. Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. Journal of Affective Disorders 1998;50:97–108. Judd L, Akiskal H, Zeller P, Paulus M, Leon A, Maser J, et al. Psychosocial disability during the long-term course of unipolar major depressive disorder. Archives of General Psychiatry 2000;57:375–80. Keller M. Past, present, and future directions for defining optimal treatment outcome in depression. Journal of the American Medical Association 2003;289:3152–60. Kennedy S, Eisfeld B, Cooke R. Quality of life: an important dimension in assessing the treatment of depression? Journal of Psychiatry & Neuroscience 2001;26 suppl.:S23–8. Miller I, Keitner G, Schatzberg A, Klein D, Thase M, Rush A, et al. The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine. Journal of Clinical Psychiatry 1998;59:608–19. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry 1979;134:382–9. Nierenberg A, Wright E. Evolution of remission as the new standard in treatment of depression. Journal of Clinical Psychiatry 1999;60:7–11. Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychological Medicine 1995;25:1171–80. Rush A, Trivedi M. Treating depression to remission. Psychiatric Annals 1995;25:704–9. Rush A, Crismon M, Toprac M, Trivedi M, Rago W, Shon S, et al. Consensus guidelines in the treatment of major depressive disorder. Journal of Clinical Psychiatry 1998;59(suppl 20):73–84. Simons A, Murphy G, Levine J, Wetzel R. Cognitive therapy and pharmacotherapy for depression. Archives of General Psychiatry 1986;43:43–8.
M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801 Stahl S. Why settle for sliver, when you can go for gold? Response vs. recovery as the goal of antidepressant therapy. Journal of Clinical Psychiatry 1999;60:213–4. Thase M. Evaluating antidepressant therapies: remission as the optimal outcome. Journal of Clinical Psychiatry 2003;64(suppl. 13):18–25. Thase ME, Simons AD, McGeary J, Cahalane JF, Hughes C, Harden T, et al. Relapse after cognitive behavior therapy of depression: potential implications for longer courses of treatment. American Journal of Psychiatry 1992;149:1046–52. Thunedborg K, Black C, Bech P. Beyond the Hamilton depression scores in long-term treatment of manic-melancholic patients: prediction of recurrence of depression by quality of life measurements. Psychotherapy and Psychosomatics 1995;64:131–40. Van London L, Molenaar RP, Goekoop JG, Zwinderman AH, Rooijmans HGM. Three- to 5-year prospective follow-up of outcome in major depression. Psychological Medicine 1998;28:731–5.
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Zimmerman M, Posternak M, Chelminski I. Using a self-report depression scale to identify remission in depressed outpatients. American Journal of Psychiatry 2004a;161:1911–3. Zimmerman M, Sheeran T, Young D. The diagnostic inventory for depression: a self-report scale to diagnose DSM-IV for major depressive disorder. Journal of Clinical Psychology 2004b;60:87–110. Zimmerman M, McGlinchey J, Posternak M, Friedman M, Attiullah N, Boerescu D. How should remission from depression be defined? The depressed patient’s perspective. American Journal of Psychiatry 2006a;163:148–50. Zimmerman M, Ruggero C, Chelminski I, Young D, Posternak M, Friedman M, et al. Developing brief measures for use in clinical practice: the reliability and validity of single-item self-report measures of depression symptom severity, psychosocial impairment due to depression and quality of life. Journal of Clinical Psychiatry 2006b;67:1536–41.
JOURNAL OF PSYCHIATRIC RESEARCH
Journal of Psychiatric Research 42 (2008) 797–801
www.elsevier.com/locate/jpsychires
Remission in depressed outpatients: More than just symptom resolution? Mark Zimmerman *, Joseph B. McGlinchey, Michael A. Posternak, Michael Friedman, Daniela Boerescu, Naureen Attiullah Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Bayside Medical Center, 235 Plain Street, Providence, RI 02905, United States Received 22 December 2006; accepted 26 September 2007
Abstract Objective: In treatment studies of depression remission is defined according to scores on symptom severity scales. Normalization of functioning has often been mentioned as an important component of the definition of remission, though it is not used to identify remitted patients in studies of treatment efficacy. Conceptually, the return of normal functioning should be as fundamental to the concept of remission as is symptom resolution because the presence of both symptoms and impaired functioning are core constructs in the diagnosis of mental disorders. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined the independent and additive association between level of severity of depressive symptoms and functional impairment in predicting depressed patients’ subjective evaluation of their remission status. Methods: Five hundred and fourteen depressed psychiatric outpatients filled out a questionnaire on which they rated the severity of the symptoms of depression, the level of impairment due to depression, and their quality of life. Results: Symptom severity, functional impairment from depression, and quality of life were significantly and highly intercorrelated, and each was significantly associated with remission status. The results of a logistic regression analysis indicated that each of the three variables was a significant, independent, predictor of remission status. Discussion: In treatment studies of depression remission is narrowly defined in terms of symptom resolution. Our results support broadening the concept of remission beyond symptom levels to include assessments of functioning and quality of life. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Depression; Remission; Symptoms; Psychosocial functioning
1. Introduction Increasingly, experts in the treatment of depression have suggested that achieving remission should be viewed as the primary goal of treatment (Ballenger, 1999; Ferrier, 1999; Nierenberg and Wright, 1999; Rush et al., 1998; Rush and Trivedi, 1995; Stahl, 1999; Thase, 2003). These recommendations are based on studies that have consistently demonstrated that depressed patients who have responded
*
Corresponding author. E-mail address: [email protected] (M. Zimmerman).
0022-3956/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2007.09.004
to treatment but failed to achieve symptomatic remission continue to experience more psychosocial impairment and have a higher likelihood of recurrence of a full depressive syndrome (Faravelli et al., 1986; Judd et al., 2000; Judd et al., 1998; Paykel et al., 1995; Simons et al., 1986; Thase et al., 1992). In order to establish remission as the goal of treatment it is necessary to have a cogent conceptualization of the construct. As Keller (2003) recently noted, ideally remission would be defined biologically, based on the normalization of underlying pathophysiology. However, there are no valid biological state markers of major depressive disorder that can be used to monitor the progress of the disease. In
798
M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801
the absence of such biological tests, we are left with phenomenological definitions of remission. In treatment studies, remission is defined according to scores falling below a threshold on symptom severity scales such as the Hamilton rating scale for depression (1960) and the Montgomery–Asberg depression rating scale (Montgomery and Asberg, 1979). Normalization of functioning is often mentioned as an important component of the definition of remission, though it is not used to identify remitted patients in studies of treatment efficacy. Instead, psychosocial functioning is compared in patients who have and have not achieved symptomatic remission (Judd et al., 2000; Miller et al., 1998). Conceptually, the return of normal functioning should be as fundamental to the definition of remission as is symptom resolution because the presence of both symptoms and impaired functioning are core constructs in the diagnosis of mental disorders (American Psychiatric Association, 1994). It seems logical that each of the defining features of a disorder should be absent in order to declare that the disorder is in remission. As part of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we recently conducted a survey of the factors depressed patients considered important in defining remission from depression (Zimmerman et al., 2006a; Zimmerman et al., 2006b). We found that patients considered both symptom resolution and functional improvement important in determining remission. In fact, normalization of function was more often judged to be the most important factor in determining whether a depressive episode has remitted. In the present report from the MIDAS project, we examined the independent and additive association between level of severity of depressive symptoms and functional impairment in predicting depressed patients’ subjective evaluation of their remission status. We also examined a third variable, subjectively rated quality of life, as it has also been emphasized as an important factor in determining the adequacy of treatment response of medical disorders (Kennedy et al., 2001; Thunedborg et al., 1995). 2. Methods The study was conducted from August 2003 until July 2004. Participants were 535 psychiatric outpatients who were being treated for a DSM-IV major depressive episode in the Rhode Island Hospital, Department of Psychiatry outpatient practice. This private practice group predominantly treats individuals with medical insurance on a fee-for-service basis, and it is distinct from the hospital’s outpatient residency training clinic that predominantly serves lower income, uninsured, and medical assistance patients. The sample included 182 (34.0%) men and 353 (66.0%) women who ranged in age from 21 to 80 years (M = 44.2, SD = 11.5). The Rhode Island Hospital institutional review committee approved the research protocol, and all patients provided informed, written consent.
Patients completed two questionnaires. One of the questionnaires was a symptom measure of depression that included a question regarding functional impairment due to depression (‘‘Overall, how much have symptoms of depression interfered with or caused difficulties in your life during the past week? 0 = not at all; 1 = a little bit; 2 = a moderate amount; 3 = quite a bit; 4 = extremely’’) and quality of life (‘‘How would you rate your overall quality of life? 0 = very good, my life could hardly be better; 1 = pretty good, most things are going well; 2 = the good and bad parts are about equal; 3 = pretty bad, most things are going poorly; 4 = very bad, my life could hardly be worse.’’) (Zimmerman et al., 2004a). The questions were taken from the Diagnostic Inventory for Depression, a reliable and valid measure of depressive symptoms, psychosocial impairment due to depression, and quality of life (Zimmerman et al., 2004b). The second questionnaire assessed patients’ opinion regarding the importance of different factors in determining remission from depression. On the front side of the two-sided questionnaire the instructions read as follows: During the past decade, researchers who study the treatment of depression have discussed the best method of evaluating response to treatment. One area of controversy is what are the most important factors in determining who has responded well to treatment. Some experts say that the most important thing to look at are the symptoms of depression – a person should be considered in remission when the symptoms of depression (such as depressed mood, sleep and appetite changes, fatigue, problems concentrating, etc.) have gone away. Other experts say that the most important thing to look at is how a person is functioning, regardless of whether they are still experiencing some symptoms of depression. Other aspects of remission have also been proposed. The purpose of this brief questionnaire is to learn what patients believe are the most important factors in determining whether someone is in remission from their depression. Please rate how important you think each of the following factors are in determining whether someone is in remission from depression. After rating the importance of each item, circle the number of the item that you think is the most important factor. Before completing the questionnaire, please provide the following background information: The background information requested included gender, age, education, current level of severity of depression as rated on 5-point rating scale (0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe), and current remission status from depression (0 = no, 1 = yes). Thus, the three dependent variables (symptom severity, impairment in function, and quality of life) were rated on 5-point scales of severity. The reliability and validity of these single-item assessments of these constructs is described elsewhere (Zimmerman et al., 2006b). We computed Spearman correlation coefficients among the symptom, functioning, and quality of life ratings, and
M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801
point-biserial correlations between remission status and each of these three variables. After the univariate analyses we conducted a multivariate logistic regression analysis to determine which of the predictor variables were independently associated with remission status.
Twenty-one (3.9%) of the 535 patients did not answer the question about current remission status leaving a final sample of 514 patients. There were no demographic differences between the patients who did and did not answer this question. Half of the 514 patients (n = 260; 50.6%) considered themselves to be in remission at the time of the evaluation. The mean score on the symptom severity rating was 1.9 (SD = 1.2), indicating a mild level of severity. Correspondingly, the mean score on the psychosocial impairment item was 1.3 (SD = 1.2), indicating, on average, mild levels of impairment, and the mean on the quality of life item was 1.6 (SD = 0.9). As expected, symptom severity, functional impairment from depression, and quality of life were significantly and highly intercorrelated, and each was significantly associated with remission status (Table 1). Compared to patients who were not in remission, patients who indicated that they were in remission reported significantly lower symptom severity (1.2 ± 0.9 vs. 2.7 ± 0.9, t = 18.3, p < .001), less psychosocial impairment from depression (0.6 ± 0.8 vs. 2.0 ± 1.1, t = 16.0, p < .001), and greater life satisfaction (1.1 ± 0.6 vs. 2.1 ± 0.8, t = 15.4, p < .001). Table 2 shows the results of the logistic regression analysis. The overall model was significant, and each of the three variables was a significant, independent, predictor of remission status. The amount of variance accounted for in predicting remission status increased from 39% based on symptom severity alone to 56% based on all three variables. 4. Discussion The diagnosis of depression is based on the presence of symptoms along with functional impairment. Consequently, the definition of remission of depressive disorder
Table 1 Intercorrelation between measures of symptom severity, psychosocial impairment, quality of life and remission status in 514 depressed outpatients in ongoing treatment Depression severity Remissiona Symptom Severity Psychosocial Impairment
Table 2 Logistic regression evaluating remission status predicted by symptom severity, impairment and quality of life in 514 depressed outpatients Predictor Symptom severity Psychosocial impairment Quality of life
3. Results
.63
Psychosocial impairment .58 .77
Quality of life .57 .73 .79
a 0 = not in remission; 1 = in remission. For the other scales lower scores indicate less pathological responses (i.e. lower symptom severity, less psychosocial impairment, greater life satisfaction).
799
* ** ***
Parameter estimate
Odds ratio
95% Confidence interval
1.09*** 0.42*
.34 .66
.24–.47 .46–.94
0.62**
.54
.34–.85
Significant at p < .05. Significant at p < .01. Significant at p < .001.
should be based on the resolution of both symptoms and functional impairments. This, however, is not how the field has defined remission. Rather, in treatment studies of depression, remission has been defined in symptom terms only. Specifically, antidepressant efficacy trials have defined remission according to scores falling below a cutoff on symptom severity scales such as the Hamilton rating scale for depression and the Montgomery–Asberg depression rating scale. Thus, a depressed patient whose symptoms have nearly resolved but who has not yet returned to work because of lack of confidence would be considered to be in remission. On a common sense basis this seems inappropriate. We are unaware of any previous studies that have examined whether a multifactorial approach towards defining remission is more valid than the traditional unidimensional approach based solely on symptom severity. That is, while several studies have found that symptom-based definitions of remission predict future relapse, no studies have examined the prognostic validity of remission definitions based on both symptom status and functioning. It is conceivable that a multifactorial definition, even though more conceptually appealing than an exclusively symptom-based definition, would not be more valid than symptom-based remission definitions because symptom improvement accounts for such a large portion of the variance in determining remission status that the assessment of the other domains does not improve validity. In the present study, we examined the association between symptom severity, psychosocial impairment, and quality of life and depressed patients’ self-rated evaluation of remission status. We found that symptom severity had the highest correlation with remission status, though the correlations between remission status and psychosocial impairment and quality of life were nearly as high. Most importantly, the results of the regression analysis indicated that each of the three factors was independently associated with remission status. This is the first study to provide empirical evidence for broadening the concept of remission beyond symptom status. It will be important to extend the findings of the present study to a study of relapse. One of the principle goals of a definition of remission is to predict future morbidity, and a valid definition of remission from depression should
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M. Zimmerman et al. / Journal of Psychiatric Research 42 (2008) 797–801
subdivide treatment responders into groups who are at higher and lower risk of relapse. This is analogous to how treatment goals for hypertension and hypercholesterolemia were derived (i.e. the prediction of future adverse health events) (Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults, 2001; Joint National Committee on Prevention Detection Evaluation and Treatment of High Blood Pressure, 1997). Current symptom-based definitions of remission, such as those based on the Hamilton rating scale for depression and Montgomery–Asberg depression rating scale, already accomplish this goal (Paykel et al., 1995; Thase et al., 1992; Van London et al., 1998). It is possible that a multifactorial definition of remission will be no better in predicting future relapse than symptom-based remission definitions because symptom status accounts for such a large portion of the variance in determining relapse that the assessment of the other variables does not improve prognostic ability. This remains an empirical question. Some limitations of the present study should be noted. The study was conducted in a single outpatient practice in which the majority of the patients was white, female, and had health insurance. The generalizability of the results to samples with different demographic characteristics needs to be demonstrated. The assessment of remission status was based on a single yes–no question on a paper-and-pencil questionnaire. It is possible that some patients did not understand the meaning of the term remission, though the term was defined in the instructions of the questionnaire. Moreover, expected differences in symptom severity, psychosocial functioning, and quality of life were found between patients who did and did not indicate that they were in remission. The assessments of symptom severity, functioning, and quality of life were also based on a single question. Elsewhere we demonstrated the reliability and validity of these single-item assessments (Zimmerman et al., 2006b). Nonetheless, perhaps the results would be different if based on more extensive assessments of these constructs. For example, it is possible that a more detailed assessment of symptom severity would be incrementally more valid than the single-item assessment, thereby accounting for more of the variance in remission status and eliminating an independent association between remission status and psychosocial functioning and quality of life. Future studies of this issue should include more comprehensive assessments of these constructs. Conflict of interest None. Contributors Author Zimmerman designed the study and wrote the manuscript. Author McGlinchey managed and conducted the statistical analyses. Authors Zimmerman, Posternak,
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