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Beyond Symptomatic Improvement: Assessing Real-World Outcomes in Patients With Major Depressive Disorder

Alan M. Langlieb and Christine J. Guico-Pabia

Published: April 15, 2010


Beyond Symptomatic Improvement: Assessing Real-World Outcomes in Patients With Major Depressive Disorder

Objective: To quantify the negative impact that major depressive disorder (MDD) has on quality of life, disability, and work, family, and overall psychosocial functioning. Available scales that assess these areas of impairment as they relate to patients with MDD are described.

Data Sources: PubMed searches were conducted using the following terms: (MDD OR major depressive disorder) AND (absenteeism OR absente*); AND (quality of life OR QOL); AND (psychosocial function*); AND (presente* OR presenteeism); AND (health care cost* OR [health care] cost*); AND (health outcome*); AND (functional outcome*); AND (family life); AND (disabil* OR disability); AND (work function*); AND (unemployment OR unemploy*). The literature search was conducted in July 2008 and was restricted to English language articles. There were no limits set on the dates of the search.

Study Selection: Two hundred twenty potential articles were identified. Among these studies, 48 presented primary data directly demonstrating the effect of MDD on quality of life, disability, and work, family, and overall psychosocial functioning.

Data Extraction: Primary data were compiled from these studies and are summarily described. Available scales that assess quality of life, disability, and work, family, and overall psychosocial functioning are also described.

Data Synthesis: MDD was found to be associated with significant disability and declines in functioning and quality of life. The Sheehan Disability Scale, the 36-item Short-Form Health Survey, and the Work Limitations Questionnaire were the most commonly used scales according to this review of the literature, but the majority of studies used direct and indirect disability measures, such as health care and other disability-related costs.

Conclusions: In addition to assessing symptomatic outcomes, physicians should routinely assess their depressed patients on “real-world” outcomes. The development of a concise functional outcome measure specific to MDD is necessary for busy clinical practices.

Prim Care Companion J Clin Psychiatry 2010;12(2):e1-e14

Submitted: April 14, 2009; accepted August 4, 2009.

Published online: April 15, 2010 (doi:10.4088/PCC.09r00826blu).

Corresponding author: Alan M. Langlieb, MD, The Johns Hopkins Bloomberg School of Public Health, 624 N Broadway, Baltimore, MD 21205 (

According to the National Comorbidity Survey (NCS), major depressive disorder (MDD) has an estimated lifetime prevalence of 16%. NCS data also reveal that the majority of participants that met MDD criteria were currently employed and during the past year experienced some form of role impairment in work, family, or social functioning. The degree of impairment was commensurate with the severity of depressive symptomatology.1 Furthermore, the World Health Organization has estimated that, among the 10 most disabling diseases (eg, diabetes, tuberculosis, hepatitis, sexually transmitted diseases), MDD is responsible for 5% of the total global disease burden associated with these disorders2 and is ranked fourth among the leading causes of disease burden.3

Clinical Points

  • Major depressive disorder is associated with significant declines in functioning and quality of life.
  • In addition to measuring the severity of depressive symptoms, clinicians and researchers should assess depressed patients’ level of functioning and quality of life.
  • A number of scales are currently available that are valid and reliable measures of functioning and quality of life.

Despite the overwhelming evidence demonstrating that MDD exerts a significantly negative effect on functioning and quality of life (Table 1), when depressed patients are assessed, either in a clinical or research setting, the focus primarily remains on the severity of depressive symptoms, with significantly less attention being paid to the impact that MDD has on these “real-world” outcomes. Other areas of medicine (eg, cardiovascular medicine,4,5 diabetes6) have begun to expand the assessment of treatment outcomes from simply measuring symptomatic improvement to include a broader range of outcomes, thereby providing a useful example of how assessing these outcomes can help in the decision-making process of the various health care stakeholders (ie, physicians, employers, and payors/managed care plans) involved in the treatment of depressed patients.

The objective of this systematic review was to quantify the negative impact that MDD has on quality of life, disability, and work, family, and overall psychosocial functioning. Available scales that assess these areas of impairment as they relate to patients with MDD are also described.

Table 1a

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Table 1b

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Table 1c

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Table 1d

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Table 1e

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Table 1f

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PubMed searches were conducted using the following terms: (MDD OR major depressive disorder) AND (absenteeism OR absente*); AND (quality of life OR QOL); AND (psychosocial function*); AND (presente* OR presenteeism); AND (health care cost* OR [health care] cost*); AND (health outcome*); AND (functional outcome*); AND (family life); AND (disabil* OR disability); AND (work function*); AND (unemployment OR unemploy*). The literature search was conducted in July 2008 and was restricted to English language articles. There were no limits set on the dates of the search.

Two hundred twenty potential articles were identified. Among these studies, 48 presented primary data directly demonstrating the effect of MDD on these outcomes. Primary data were compiled from these studies and are summarily described. Available scales that assess these outcomes are also described.

Costs Associated With MDD

The substantial direct and indirect health care costs associated with depression alone7-9 and comorbid with other conditions10-13 have been quantified by a number of large-scale evaluations. Correspondingly, depression also has been shown to negatively impact an individual’s overall health and can lead to increased costs for treating any co-occurring disorders. For instance, in 2 studies that assessed diabetic patients with and without comorbid depression, significantly higher health care costs14 and worse clinical outcomes, including higher mortality rates,15 were observed in those with a co-occurring depressive disorder.

In a large-scale assessment of employees of a major corporation,10 the per-capita health and disability costs (including direct health care expenditures and sick/disability days) associated with depression were $5,415 annually, equivalent to diabetes ($5,472), heart disease ($5,523), and back problems ($4,388), but significantly greater than hypertension ($3,372; P=.002) and a category containing “all other” reasons for filing a health claim ($1,292; P<.001). In addition, when MDD co-occurred with one of these general medical conditions, the associated health care costs increased nearly 2-fold compared to patients with the medical disorder alone. The resulting cost to the corporation was $2.2 million.10,11 In addition, other studies have demonstrated a significant association between MDD, cardiac death,16,17 and total mortality.16 Beyond medical comorbidities, MDD is also commonly comorbid with other psychiatric disorders. In particular, MDD commonly co-occurs with generalized anxiety disorder, which results in significant disability.18

Impaired Functioning and Quality of Life Associated With MDD

The terms functioning and quality of life are often used interchangeably; however, the disability associated with each and the means in which they are assessed are multidimensional and can differ significantly. Assessments of functioning generally include performance-based metrics, such as one’s ability to engage in expected or usual responsibilities at work or home, and can be assessed using objective measures, such as days of work missed, or subjectively, using patient-rated assessments. However, functioning does not distinctly involve work performance; functioning in other areas, such as in familial, societal, and marital roles, also can be adversely affected by MDD. Quality-of-life measures, on the other hand, generally describe the subjective quality of an individual’s day-to-day experiences, which involve enjoyment and satisfaction with one’s life, but also can be related to the patient’s performance in his or her expected role.

Work Functioning

A number of studies have empirically demonstrated that MDD not only negatively impacts those who are currently employed19-22 but also is associated with an increased risk for job loss.23 One large-scale analysis of NCS data suggested that those in the middle of their careers are more likely than their younger counterparts to lose their jobs as the result of a major depressive episode.24 The most obvious way that MDD impacts work performance is the elevated rates of absenteeism among depressed employees.9,10 However, the negative effect that MDD has on work performance extends beyond whether an employee is present to perform his or her job.

Presenteeism describes the impaired functioning that employees experience when they attend work but suboptimally perform their daily activities, in this case, due to their depressive symptoms. Depressed employees have been shown to be particularly prone to detriments in mental-interpersonal and time management tasks, as well as overall job performance, compared to nondepressed employees.25-28 In 1 study conducted in a large company, the lost productive time associated with MDD was reported to be nearly 6 hours per week, at a cost of $44 billion annually.28 In addition, less severe forms of depression (ie, subthreshold depressive symptoms,29,30 minor depression,31-33 and dysthymia34) also have been shown to negatively impact work functioning.

In 1 large-scale work performance study, NCS participants currently experiencing a depressive episode were compared to those with episodes that resolved >1 to 6 months ago, >6 to 12 months ago, and >12 months ago. These patients had responded to treatment but continued to experience significant residual symptoms that were more pronounced than the level seen in the euthymic controls. Patients who were currently experiencing a depressive episode were significantly more likely to experience lost days than healthy controls and those with residual symptoms; however, compared to healthy controls, depressed patients and even those with residual symptoms were significantly more likely to experience difficult days and cutback days (in which the depressed patient did not get as much done as usual) than healthy controls.29,30

A growing body of data has demonstrated that depressive symptoms include impairments in cognitive functioning that can result in declining work performance. A recently published study that assessed untreated MDD patients using work performance measures following an error or receipt of negative feedback demonstrates that dysfunctional information processing associated with depression can lead to declines in productivity.19 This study and a number of other neuroimaging studies have suggested that these maladaptive cognitive processes involve areas of the brain that are thought to be associated with the symptoms of MDD (eg, the prefrontal cortex, anterior cingulate cortex, hippocampus).19-22

Psychosocial Functioning

The components of psychosocial functioning vary between scales and sometimes overlap with assessments of work performance but are mainly differentiated by the assessment of other areas of functioning beyond the workplace. Several studies have been conducted that support the claim that MDD has a negative impact on overall social functioning.35,36 Results from an analysis of patients experiencing different levels of depressive symptomatology (ie, subthreshold depressive symptoms, minor depression/dysthymia, and MDD) have suggested that psychosocial disability increases correspondingly with the severity of depressive symptoms.37 In a more recently conducted study, which assessed patients with MDD and bipolar I and II disorder, those experiencing MDD were found to experience significant psychosocial impairment during the majority of follow-up visits.38

Quality of Life

Quality of life is difficult to concisely define due to its subjective nature and the overlap between assessing functional outcomes; therefore, measuring quality of life is more complex than the other outcomes described. For example, assessing the quality of a person’s life without examining how the individual functions in his or her expected roles, in either family life or work performance, is difficult.

The impact of a major depressive episode on health-related quality of life in individuals with39-48 or without39-43 a general medical condition has been well established in the literature, and treating MDD to a full remission of symptoms can improve quality of life to a greater extent than when significant residual symptoms are present.49,50

Treatment of the Functional Disability Associated With MDD

A number of empirically supported treatment options have demonstrated effectiveness in alleviating the disability caused by MDD,30,51-56 as well as in lowering health care costs,49,57-65 improving quality of life,50,66,67 and decreasing absenteeism in depressed patients,49,68 particularly in those who receive early and adequate treatment.69,70 For example, the Sequenced Treatment Alternatives to Relieve Depression trial, a large-scale assessment of an MDD treatment algorithm conducted in a real-world clinical setting, demonstrated that following sequential treatment alternatives for patients not reaching remission with first-line treatment can lead to significant improvements in functioning and quality of life.53,71

Despite increased usage of the multiple antidepressant medications available to patients and improvements in empirically supported treatment guidelines and algorithms, data are available that demonstrate that a disproportionately large number of patients continue to receive inadequate treatment for their depressive episodes. In a cross-sectional analysis of medical records from 2 cohorts of depressed patients (ie, 1993 to 1994 and 2003 to 2004), an increase in the use of adequate antidepressant doses was observed; however, the use of sequential antidepressant treatment options and psychotherapy remained low.72

An effective way of lowering the costs associated with MDD is to encourage physicians to use guideline-derived forms of treatment and utilize enhanced treatment options, such as incorporating care managers for monitoring the patient’s symptoms, adverse events, and adherence.73 In addition, 1 study demonstrated that by taking steps to improve employee access to effective depression treatment—for example, by lowering copayments and using a selective contracting network and a mental health destigmatization program—the likelihood of initiating treatment and having more mental health visits increased.74

The relationship between MDD, functional disability, and impaired quality of life has been suggested to be bidirectional. In addition to MDD negatively impacting functioning and quality of life, the presence of these impairments at baseline has been linked to poor antidepressant treatment response.53,75,76 It also has been suggested that functional impairment and a lower quality of life are associated with an elevated risk for the recurrence of a major depressive episode.77-79

Assessing Declines in Functioning and Quality of Life Associated With MDD

Table 2 describes some commonly used functional outcome measures and assessments of quality of life. The 36-item Short-Form Health Survey (SF-36)80 was the most widely used scale in the studies identified during our systematic review of the literature. Its length and complexity have been impediments to its regular use in clinical settings; however, a shortened 12-item version (SF-12) is also available that may be better suited for use in busy practice settings.81 In addition, the Sheehan Disability Scale (SDS)82 and the Work Limitations Questionnaire (WLQ)83 were commonly used. The SDS is widely used in research settings because it has been shown to be sensitive to treatment effects, and its concise means of assessing the overall level of functioning make it desirable for use in clinical settings as well.

Table 2

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The World Health Organization 5-item Well-Being Index,84 Social Adjustment Scale-Self-Report (SAS-SR),85 and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)86 are commonly used to assess psychosocial functioning and quality of life, whereas the Endicott Work Productivity Scale,87 Work Productivity and Activity Impairment Questionnaire,88 and WLQ83 are commonly used assessments of work dysfunction.

Perhaps the most familiar means of assessing the functional declines associated with psychiatric disorders is Axis V of the multiaxial diagnostic methodology used in the fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders.89 The Global Assessment of Functioning (GAF) asks the clinician to rate the level of functioning in relation to symptom severity. This combination of 2 distinct outcomes on 1 axis has been the primary criticism of the GAF, as a separation between these outcomes is important to obtaining an accurate level of functional disability independent of symptom severity. In addition, the Global Assessment of Relational Functioning (GARF) and Social and Occupational Functioning Assessment Scale (SOFAS) were designed as supplemental assessments of functioning to be used in conjunction with the GAF.89 The GARF was specifically designed to assess familial and other long-term relationships, whereas the SOFAS was designed to assess social and occupational functioning independent of symptom severity.89

Issues Associated With Using “Real-World” Outcome Measures

Despite the benefits of assessing functioning and quality of life to the various stakeholders involved with the treatment of MDD, the potential issues associated with using such scales must be noted. Some of the commonly used assessment tools described above have some unmet needs. Namely, they can be cumbersome for use in the clinical setting because they are generally too lengthy to administer in the ever-lessening duration of clinical visits. As was previously mentioned, a number of these scales, such as the SF-36, WLQ, SAS-SR, and Q-LES-Q, are thought to be too lengthy for use during clinical visits. In addition, there is some ambiguity as to what these scales actually measure, mainly due to the lack of consistency in the items they use and the lack of a clear gold standard. On the other hand, some scales are too specific. The assessments of work functioning, for example, focus too narrowly on the area of work dysfunction to be used alone in a clinical setting wherein a level of overall functional status is desired.

When performing follow-up assessments using these scales, it is important to note that a lag time in improvements in functional impairment has been observed in relation to improvements in depressive symptomatology. When assessing functioning, >8 weeks may be required before improvements are observed, whereas improvements in depressive symptoms generally occur sooner.90,91 A secondary analysis of data from a randomized trial investigating selective serotonin reuptake inhibitor treatment,92 which calls for a broader definition of depression remission that expands beyond symptom severity, demonstrated that depressive symptoms improve in synchrony and are correlated with work functioning, even though depressive symptoms improved to a greater degree. It is also important to note that the majority of the scales described above are not designed to diagnose MDD and are meant only to be used for screening and to assess and monitor changes in disability. If the results are suggestive of a depressive disorder, then a validated diagnostic assessment tool should be used to make a proper diagnosis.


The development of an assessment tool that can address the issues described above would be a benefit to the various parties involved with the treatment of MDD (eg, researchers, patients, health care plans). The SDS has many positive attributes but has not yet been widely accepted as the gold standard in assessing disability in patients with MDD. The limitations of the SDS include its assessment of patients on only 3 domains of functioning and the lack of a depression-specific focus. The SF-12, a shortened version of the SF-36, is another valuable assessment tool due to its more detailed assessment of disability yet compact enough length for use in clinical practice. Perhaps creating a “hybrid” scale adopting the best of various options that can become a standard measure for assessing the disability associated with MDD will become necessary. Along with assessing the impact on the emotional and physical symptoms of MDD, assessing functional disability and declines in quality of life should continue to become a routine part of clinical care and outcome measures in clinical trials that assess the efficacy of antidepressant treatment.43,78,93,94 As calls for the measurement-based care of MDD continue, particularly for primary care physicians, a thorough assessment of the impact that MDD has on a patient’s life will become a necessity.

Author affiliations: The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Dr Langlieb) and Pfizer Inc, formerly Wyeth Research, Collegeville, Pennsylvania (Dr Guico-Pabia).

Author contributions: Drs Langlieb and Guico-Pabia equally contributed to the study by analyzing and interpreting data, drafting and revising the manuscript, and obtaining funding.

Potential conflicts of interest: Dr Langlieb serves on the advisory boards for Eli Lilly and Pfizer Inc. Dr Guico-Pabia is an employee of Pfizer Inc, formerly Wyeth Research.

Funding/support: This analysis was supported by Wyeth Research, Collegeville, Pennsylvania, which was acquired by Pfizer Inc in October 2009.

Acknowledgment: Medical writing/editing support was funded by Wyeth Research. Dennis A. Stancavish, MA, provided writing support and editing support was provided by Jennifer B. Karpinski, BA, both of Embryon, LLC, A Division of Advanced Health Media, LLC (formerly Medesta Publications Group, A Business of Advogent).


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