Testing a model of Depression and Functional Status in Stroke Survivors.

Abstract: Depression negatively affects functional status and recovery potential for patients with many chronic diseases and for elderly patients. The purpose of this research was to determine what could be said with confidence regarding the relationships between post-stroke depression,

functional

status, and the mediating strategies of physical rehabilitation and pharmacologic treatment. To accomplish this purpose, a model of depression and functional status in stroke survivors was proposed and tested using meta-analytic techniques. Using a derived conceptual model derived f, it was proposed that depression and functional status were related and could be mediated when they operated through the health care system. An extensive review of the stroke research completed after 1989 resulted in the identification of 31 subject-studies that examined depression and functional status in the post-stroke survivors. Twenty-six the studies were non-experimental and 5 were randomized clinical trials. Meta-analytic methods were used to synthesize the results of the subject-studies. A small to moderate population Effect Size (ES) r of .25 (P = .000, k = 21, N = 2310) with a Binomial Effect Size Display (BESD) of .37 - .63 was found for a homogenous grouping of non-experimental studies examining the relationship between depression and functional status in the post-stroke population. A moderate to large ESr of .43 (P = .000, k = 5, N = 182), with a BESD of .29 - .71, was found for a homogeneous grouping of experimental studies examining the relationship between depression and functional status in the post-stroke population when mediated by physical rehabilitation and pharmacologic treatment for depression. Analysis of the derived model, Depression and Functional Status in Stroke Survivors, supports the existence of a statistically and clinically significant relationship between depression and functional status, and pharmacologic treatment and physical rehabilitation mediate that relationship. The reciprocal interaction between depression and functional status can best be approached through appropriate and timely treatment of both post-stroke manifestations, depression and functional deficit.

Key words: Model of Depression, Functional Status in Stroke Survivors

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Stroke, the third leading cause of death, is the most common disabling disease. Approximately 731,000 persons suffer a stroke yearly in the United States (Gorelick, Sacco, Smith, Alberts, Mustone-Alexander, Rader et al., 1999). Over 4 million American stroke survivors are alive today. Approximately 2/3 of the individuals who suffer a stroke survive and require some level of rehabilitation (National Institute of Neurological Disorders [NINDS], 2002).

Depression, a common complication of stroke, leads to increased mortality and morbidity, impedes the process of rehabilitation, is associated with poor outcomes, and increased hospital stays ((Turner-Stokes & Hassan, 2002a, 2002b). Depression is a common disabling condition observed by primary care providers (Ostir, Markides, Peek & Goodwin, 2001). In a community based study, D Epiro (1999) found that 10% of the population had symptoms meeting the criteria for major depression and an additional 20% of the population had symptoms of depression that did not meet the criteria for major depressions. Depressed patients from this population with gastrointestinal disease, diabetes, heart disease, stroke, and cancer responded slower and less favorably to medical intervention, had lower survival rates, and a decreased quality of life.

BACKGROUND AND SIGNIFICANCE

Post-stroke depression is associated with cognitive, functional and social deficits which limits rehabilitation outcomes (Tulane-Stokes, 2002a, 200b). Researchers have examined the prevalence of post-stroke depression alone and in combination with functional status, the relevance of location of the stroke lesion to the occurrence and severity of depression and effect on functional status, and the influence of various medications and treatments in mediating depression and functional status. Gordon and Hibbard (1997) reviewed 10 years of research related to post-stroke depression. Despite recognition of depression as the most common untreated disability secondary to stroke, there is a lack of consensus regarding the cause of the depression, appropriate treatment for depression, and long-term consequences of treatment or failure to treat. Nurses work with stroke patients at the acute, rehabilitation, and chronic stages of stroke. Access to accurate definitive information regarding the relationship between post-stroke depression and functional status will enable nurses to provide more holistic nursing intervention at all stages of stroke recovery.

Post-Stroke Depression

Suggested explanations of causation for post-stroke depression include: depression is a direct result of brain damage (Astrom, 1996; Hermann, Bartels, Schumacher, & Wallesch, 1995; Robinson & Price, 1982), depression is an emotional reaction to the stroke disability (Birkett, 1998), depression is a response to situational stress and loss (Swartzman, Gibson, & Armstrong, 1998) or a combination of those factors. As recently as 1991, Bruckbauer noted that acceptance of depression as an inevitable grief reaction possibly explained the lack of attention to post-stroke depression as part of the post-stroke treatment plan. Swartzman and others (1998) reported that 40% of the acute stroke patients suffered from depression, from 40% to 60% of the stroke rehabilitation patients suffered from depression, and 16% to 23% of the population based, chronic stroke patients, suffered from depression.

Functional Status

Unlike depression, the etiology of post-stroke functional deficits is known to be caused by damage to the brain. Functional status disabilities include problems with mobility, basic activities of daily living, instrumental activities of daily living, and communication (U. S. Department of Health and Human Services, 1995). The combination of deficits and degree of functional disability is related to the location of the stroke lesion (Hayn & Fisher, 1997). Functional disabilities are highest in the immediate aftermath of the stroke, 1 to 3 weeks. Wade and Hewer (1987) reported that only 27% of the patients they studied could walk independently 1-week post stroke, but 85% were able to walk independently after 6 months. Improving functional status is the primary goal of post-stroke rehabilitation.

Relationship between Post-Stroke Depression and Functional Status

Despite frequent consideration of both depression and functional status in the post-stroke population, findings relevant to any relationship between the two variables remains unclear. Schubert, Taylor, Lee, Mentari, and Tamaklo (1992) did an extensive review of research studies examining the relationship between depression and functional status. Of the 11 studies supporting a relationship between depression and functional status, five focused on post-stroke patients. Six studies reviewed by Schubert and others (1992) did not support and relationship between functional status and depression, four of these studies focused on the post-stroke patient. Studies by Chemerinski, Robinson, Arndt, and Kosier (2001), Pohjasvaara, Vataja, Leppavuori, & Erkinjuntti (2001), and Sharpe, Hawton, Seagroatt, Bamford, House, Molyneux, Sandercock, & Warlow (1994) all identified strong associations between depression and functional status in a variety of post-stroke populations. The purpose of this research is to determine what can be said with confidence regarding the relationships between post-stroke depression, functional status, and the mediating strategies of physical rehabilitation and pharmacologic treatment. To accomplish this purpose, a model of depression and functional status in stroke survivors is proposed and tested using meta-analytic techniques.

CONCEPTUAL FRAMEWORK

Two conceptual frameworks were considered for instrumental guidance of this research project. Each contributed uniquely to understanding the relationship between post-stroke depression, functional status, and treatment modalities but lacked the integration of concepts in a manner sufficient to guide this research.

Huber and Oermann's Model of Outcome Initiative

From the context of quality management in nursing, Huber and Oermann (1999) discussed the relationship between quality and outcomes. Four categories of outcomes are identified: patient/family outcomes, provider outcomes, organizational outcomes, and social/community outcomes. These authors stress the importance of examining outcomes from a balanced and comprehensive approach, recognizing that examining quality from a patient's perspective alone, might fail to address the organizational or community perspective. Acknowledging that all of the variables that affect outcomes cannot be examined simultaneously, two conceptualizations for outcome management were elaborated.

The first conceptualization represents a narrow focus on selected outcomes. A simple linear path moving from a selected patient characteristic through a nursing intervention to an outcome was proposed as a method to observe the influence of nursing intervention on the outcome of the selected patient characteristic. The contextual view presented by Huber and Oermann recognizes the multifaceted, complex, and often-competing domains present in outcome initiatives.

Engel's Biopsychosocial Model

Effective treatment for post-stroke patients requires a model integrating physiologic, behavioral, environmental, and social factors that influence stroke outcomes. The biopsychosocial model (Engel, 1977), a multifactoral approach, is applicable to the rehabilitation needs of post-stroke patients (Swartzman, et al., 1998). Health and illness are balanced by the interplay of organismic, behavioral, and environmental factors (Engel). Engel argued that the biomedical model alone could not account for all aspects of an illness. The biomedical model fails to account for the social, psychological, and behavioral dimensions of the illness. Although Engel did not specifically define all the concepts of the biopsychosocial model or map the constructs, he did propose that the biopsychosocial model be adopted as a framework for teaching and treatment in the real world of health care.

Derived Model

Drawing from the multifactoral approach of the biopsychosocial model proposed by Engel (1977) and the approach to outcome management by Huber and Oermann (1999), a new derivation specific to the relationship between post-stroke depression, functional status, and mediating strategies is proposed. The derived model, Depression and Functional Status in Stroke Survivors, is presented in Figure 1. The model begins with two factors of the biopsychosocial model, depression, representing a psychological factor and functional status, representing a biological factor. Two mediating strategies are introduced, pharmacologic treatment for depression and physical rehabilitation for improving functional status. Treatment outcomes are represented by level of improvement in depression and functional status operating through the mediating strategy(s). Construction of the model, from individual characteristics through the health care system represented as mediating strategies to the outcomes, follows the paths outlined by Huber and Oermann (1999).

[FIGURE 1 OMITTED]

HYPOTHESIZED ASSUMPTIONS

Three hypotheses representing the proposed assumptions of the model were tested.

1. Depression and diminished functional status coexist in post-stroke patients.

2. Mediating strategies targeting one of the biopsychosocial factors positively influences the outcome of both factors.

3. Mediating strategies targeting the biopsychosocial factors positively influence the outcome of both factors beyond the level attained when only one factor is targeted.

SETTING AND POPULATION

The setting was the domain of research addressing consequences commonly attributed to stroke. The population was comprised of all completed research measuring depression and functional status for post-stroke patients. Eligible studies were identified through computer-aided search mechanisms, review of published study reference lists, and letters to primary author's requesting their assistance locating non-published or missed but applicable studies. Sample selection was limited to studies completed after 1989. The sample was further limited to studies reporting an association between depression and functional status that allowed calculation of an effect size (ESr).

METHODOLOGY

The meta-analytic approach allowed the researcher to synthesize findings from studies asking common research questions but relying on disparate operational definitions, research methods, and/or sampling techniques. Glass, McGaw, and Smith (1981) provided the theoretical direction for this quantitative synthesis while Hunter and Schmidt (1990), Rosenthal, Rosnow, and Rubin (2000), and Wolf (1986) provided the technical direction for application of the statistical procedures. META Version 5.3 (Schwarzer, 1989) is a computer program for meta-analysis (MA) that is distributed under the User Supported Concept that allows use, copy, and distribution of the software as long as it is done for free. The META program was used to transform subject-study summary statistics to ESr and to calculate the statistics for the MA.

Additionally, tests for homogeneity of effect size allowed the researcher to conclude whether or not a subject-study(s) was influencing the effect size. Heterogeneity of effect size is indicative of a study(s) that might need to be excluded from the MA. Exclusions of such subject-study(s) increased the validity of the overall MA. The META 5.3 calculated the three indicators of homogeneity recommended by Hunter and Schmidt (1990):

1. Residual standard deviation, which should be less than 1/4 of the population effect size.

2. The percentage of observed variance that can be accounted for by sampling error, which should be at least 75%.

3. A chi-square test of homogeneity, which should not be significant.

The final MA was limited to logically derived homogenous aggregates of the data.

The population effect size for all subject-studies and the specified data aggregates indicated by the hypothesized assumptions were compared for determination of significance. Following Hunter and Schmidt's (1990) recommendation, a population ES is considered significant if its 95% CI does not include 0 or if the p value associated with the Z statistics is < .05.

Rosenthal, Rosnow, and Rubin (2000), recommended that the Binomial Effect Size Display (BESD) be used to estimate clinical significance rather than the more commonly referenced r2, explained variance. The BESD is based on a point-biserial r represented as a 2 x 2 contingency table with rows corresponding to a dichotomized independent variable (e.g., treatment vs. placebo) and columns that correspond to a dichotomized outcome variable (e.g., improved vs. not improved). Clinical significance can be estimated by comparing the success rate of subjects who improved with treatment to the success rate of subjects who improved without treatment.

SAMPLE

Forty-five studies examining functional status and depression in the post-stroke patient that were completed after 1989 were identified. Of those 45 studies, 26 studies reported some measure of association between functional status and depression that allowed calculation of an ESr and are identified as non-experimental studies. Five of the 45 studies were randomized clinical trials (RCT) that examined the relationship between functional status and depression when mediated by physical rehabilitation and pharmacologic treatment of post-stroke depression. A total of 31 subject-studies were included in the meta-analyses (MAs).

RESULTS

The non-experimental subject-studies were heterogeneous by all three tests of interstudy ES variance (Table 1, line 1). Two tools, cluster analysis and stem-and-leaf-display, were used to examine the non-experimental studies for potential mediating effects. Five outliers were identified in the assessment of subject-studies. The removal of the 5 outliers resulted in a homogeneous subset of non-experimental studies (Table 1, line 2). The MA for the RCTs was homogenous (Table 1, line 3). Only homogeneous aggregates of the data were used for testing hypothesized assumptions.

The first hypothesized assumption states that depression and diminished functional status coexist in post-stroke patients. It is supported by the MA of both the homogenous subset of non-experimental studies represented on line 2 of Table 1 (k = 21, N = 2320) and the RCTs represented on line 3 of Table 1 (k = 5, N = 182). The weighted ESr = .25 (CI, .18 - .33) for the homogenous subset of non-experimental studies reflects a small to moderate effect size that is significant (p = .000) with a fail-safe N of 85, critical r of .05. The weighted ESr = .43 (CI, .43 - .43) for the RCTs reflects a moderate to large effect size that is significant (p = .000) with a fail-safe N of 38, critical r of .05.

The second hypothesized assumption states that mediating strategies targeting one of the biopsychosocial factors positively influences the outcome of both factors. The BESD (.37 - .63) from the subset of non-experimental studies provides an estimate of expected improvement in one of the conditions, either depression or functional status (Table 1, line 2). The nature of the non-experimental research precludes identification of the specific variable or the mediating technique represented by the BESD; however, most of the patients included in the non-experimental studies were involved in physical rehabilitation at some point during the post-stroke time trajectory and only a few of the depressed patients were treated with anti-depressant therapy (Pohjasvaara, et al., 1998, Parikh, et al., 1990, Angeleri, et al., 1993, and Schubert et al., 1992).

The third hypothesized assumption suggests that mediating strategies targeting both of the biopsychosocial factors positively influence the outcome of both factors beyond the level attained when only one factor is targeted. The assumption is supported by the BESD (.29 - .71) of RCTs (line 3, Table 1). Patients included in RCTs were all provided rehabilitation for functional deficits and were either treated for depression or given a placebo. The purposeful treatment of both conditions results in the opportunity for improvement from a success rate of .29 without treatment for depression to a success rate of .71 with treatment for depression.

DISCUSSION AND CONCLUSIONS

Depression and Functional Status in Stroke Survivors, Figure 2, reflects the relationship between functional status and depression in post-stroke patients and the influence of the mediating strategies on depression and functional status as indicated by the MAs. The ESrs for the relationship between depression and functional status is indicated under the Biopsychosocial Factors. The BESD at the first outcome level reflects the proportion of the post-stroke population whose functional status or depression would improve as a result of one mediating strategy, most likely physical rehabilitation. The BESD at the second outcome level reflects the proportion of the post-stroke population whose functional status and depression would improve as a result of both mediating strategies.

[FIGURE 2 OMITTED]

Two primary conclusions can be drawn from the MA. First that there is a significant relationship between high depression and low functional status in the post-stroke population. Second, physical rehabilitation and pharmacologic treatment of depression significantly mediates that negative relationship.

Relationship Between Depression and Functional Status

Past research regarding the relationship between depression and functional status has produced various although not necessarily spurious or contradictory results. The mere nature of research with human beings presents the opportunity for such diverse approaches that consistent findings are an enigma. Meta-analytic research is a respected method for unifying the disparate results of such research. The MA of non-experimental subject-studies supported the assumption that a negative relationship exists between depression and functional status in the post-stroke patient.

An impressive finding from the Sunnybrook Stroke Study (Herrmann, Black, Lawrence, Szekely, & Szalai, 1998) was the significance of the negative relationship between depression and activities of daily living. The relationships were measured at 3-months and 1-year, the negative correlations ranged from .26 to .41. Kauhanen, Korpelainen, Hiltunen, Brusin, Mononen, Maatta and others (1999) reported similar results at 3-months and 1-year. In another longitudinal study of 85 patients assessed at the acute stage and 6-months post-stroke, van de Weg, Kuik, and Lankhorst (1999) reported similar findings, depressed patients had significantly lower functioning at both assessments than the non-depressed patients.

Contrary findings were reported by Zalewski, Keller, Bowers, Miske, and Gradman (1994). Pre and post rehabilitation scores on the Functional Independence Measure were higher for depressed patients than for non-depressed patients. The authors offered several plausible explanations for this difference. First there was the potential for omitting the cognitively impaired from the study because of the difficulty assessing depression. Second there was the potential to exclude patients with the most severely impaired functioning from rehabilitation. In a study of 52 post-stroke patients residing in long term care facilities, van Rooijen, Gingher, Gordon, and Mann (1990), found no relationship between depression and functional status regardless of time elapse from stroke.

This brief examination of diverse findings indicates the extreme importance and timeliness of MA to synthesize and draw conclusions regarding the true nature of depression and functional status in the post-stroke patient. One can readily see the relationship between depression and functional status using the Pearson correlation ESr = .25, depression explains 6% of the variance seen in functional status for the non-experimental studies and the ESr = .43, depression explains 18% of the variance seen in functional status for the RCTs. However, how that impacts clinical practice is somewhat more difficult to envision. The BESD is the best method for translating the ES into information that is meaningful to clinical practice. The MA suggests that treatment of depression and physical rehabilitation could increase the proportion of post-stroke patients with higher levels of functioning from 29% to 71%.

Mediating Effects of Pharmacologic Treatment and Rehabilitation

No attempts were made to isolate the influence of any particular psychotropic drug or category of drug used in the treatment of post-stroke depression. Drugs used by researchers contributing to the MA were from all categories of antidepressants and methylphenidate a central nervous system (CNS) stimulant. Considered together, all drugs used to treat depression in the post-stroke patient positively influenced both depression and functional status. Chermerinski et al., (2001) noted that remittance of depression both with or without treatment, improved functional status.

Dam, Tonin, DeBoni, Pizzolato, Casson, Ermani and others (1996), found that patients treated with fluoxetine as an adjunct to physical therapy yielded a significantly larger number of patients with good functional recovery compared to maprotoline or placebo treated patients. Both the fluoxetine and maprotoline significantly decreased patients' level of depression. In a similar study, Miyai and Reding (1998) found functional improvements higher in the groups treated with fluoxetine and trazodone than in the group treated with desipramine. However, depression improved significantly regardless of drug choice.

Methylphenidate, a CNS stimulant was studied by Grade, Redford, Chrostowski, Toussaint, and Blackwell (1998). The findings indicated significant improvement in both depression and functioning for post-stroke patients treated with methylphenidate. Grade and colleagues attributed the effectiveness of methylphenidate to the overlapping CNS mechanisms of recovery for depression and motor functioning.

Despite the recent increase in clinical trials examining the efficacy of pharmacologic treatment of post-stroke depression, drug therapy is limited in the post-stroke population. Perhaps the frequently encountered side effects associated with psychotropic drug use in healthy adults have prevented use of psychotropic drugs in this more fragile population. However, the response of patients treated in the clinical trials was so remarkable that it is clearly an option for the depressed post-stroke patient that should not be ignored.

Almost without exception, every subject-study included in the MA made the recommendation that clinicians not discount the prevalence or impact of depression on the overall recovery of the post-stroke survivor. From the Sunnybrook Stroke Study, Herrmann and colleagues concluded that diagnosis and treatment of depression are essential elements of optimal recovery. Clark and Smith (1998) concluded that early recognition and treatment of depression is essential to optimal social and functional recovery in the post-stroke survivor. Other authors identified the under-reporting of post-stroke depression and the importance of investigating treatment options (Kauhanen et al., 1999; Paollucci, Antonucci, Pratesi, Trabellesi, Grasso, & Lubich, 1999; Pohjasvaara, Leppavuori, Siira, Vataja, Kaste, & Erkinjuntti, 1998; van de Weg, Kuik, & Lankhorst, 1999).

The mind and body cannot be separated. In a criticism of medicine for attempting to separate the bioloagical or physical side of illness from the psychosocial issues that innuence it, Engel (1977) called medicine to embrace a biopsychosocial approach. For explanation, Engel considered diabetes a somatic disease and schizophrenia a mental disease. The biochemical nature of diabetes does not sufficiently explain why some diabetics assume the sick role and others adapt and function as though healthy. Likewise, psychosocial parameters do not adequately explain the manifestation of schizophrenia. For many healthcare providers a stroke is a biologic event and the treatment has been purely targeted at the physical attributes of the stroke.

A holistic approach targeting all biopsychosocial factors is required to affect positive outcomes in the post-stroke survivor. Holistic approaches to health and illness care are not new to nursing. Knowledge related to the prevalence and severity of post-stroke depression and its relationship to functional status will enable the nurse n provide timely theory based interventions that will significantly affect outcomes.

Table 1. Summary of Meta-Analyses

Study Groupings                 k      N      Weighted    Weighted
                                               P & Z      ESr & CI

1. Non-experimental             26    3326    p .000,      r = .20,
                                              Z 11.474    .05 - .45
                                                          .40 - .60

2. Non-experimental,
outliers removed                21    2310    p .000,      r = .25,
                                              Z 12.36     .18 - .33
                                                          .37 - .63

3. RCT function & depression     5     182    p .000,      r = .43,
                                               Z 6.06     .43 - .43
                                                          .29 - .71

Study Groupings                   Tests of       Fail-Safe
                                 Homogeneity      N @ .05

1. Non-experimental             Heterogeneous       76
                                 RSD = .13,
                                %OV = 30.41,
                                  x2 = 85.5
                                  p = .000

2. Non-experimental,
outliers removed                 Homogeneous        85

3. RCT function & depression     Homogeneous        38

RSD = Residual Standard Deviation, %OV = Percent Observed Variance

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Note. References marked with an asterisk indicate studies included in the meta-analysis.

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