Keywords

depression, depressive disorders, integrative review, predictors, risk factors, stroke

 

Authors

  1. Babkair, Lisa A.

Abstract

ABSTRACT: Background: Poststroke depression (PSD) is the most common stroke-related emotional disorder and affecting one-third of stroke survivors at any time up to 5 years after stroke. Poststroke depression affects rehabilitation after stroke and may delay recovery. The purpose of this integrative review is to analyze the state of the science in regard to risk factors for PSD. Methods: The electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo were searched. Inclusion criteria included (1) peer-reviewed primary observational Western studies, (2) PSD as the primary outcome, (3) included adult stroke survivors, and (4) and published after 2004. The integrative review guidelines were used for analysis. Results: From an original of 406 articles identified, 18 met the inclusion criteria and were reviewed: 3 cross-sectional, 14 prospective cohort, and 1 case control. The most common risk factors associated with PSD are stroke severity, cognitive impairment, physical disability, and functional dependency. Others factors including demographic and social factors and medical history were not consistent across studies. Conclusions: Overall, quality of the research was limited by small sample sizes, selection bias, number of selected variables, and lack of multivariate analyses. Nurses should identify patients at risk for PSD through early depression screening and provide interventions to enhance rehabilitation and improve recovery.

 

Article Content

The emotional health of stroke survivors is as important as their physical health and cognitive functions. Annually, approximately 15 million people who have stroke globally are at risk of developing poststroke depression (PSD).1 Poststroke depression is classified as the most common stroke-related emotional disorder. It affects one-third of stroke survivors at any time up to 5 years after stroke.1 Poststroke depression affects rehabilitation after stroke and may delay recovery if left untreated.2 Most stroke survivors who experience PSD experience increased dependency in activities of daily living, worse cognitive recovery, a delayed return to social activities, decreased quality of life, and increased mortality compared with their peers who did not develop PSD.3,4 Although most of the literature is consistent in reporting the negative consequences and poor outcomes associated with PSD, its prevalence, screening, diagnosis, and risk factors are still subject to debate.5

 

Awareness of biopsychosocial risk factors for PSD may help in facilitating clinical identification and providing early interventions that enhance stroke outcomes and rehabilitation. Nurses can intervene early during poststroke acute phase if they can identify patients at risk.6 Therefore, identifying the risk factors for PSD is extremely important in the management of stroke survivors. The purpose of this integrative review is to analyze the state of the science in regard to risk factors for PSD.

 

Methods

An integrative review guideline was used because it allows for the narrative integration of findings from qualitative and quantitative research related to the phenomenon of concern.7 Integrative reviews use a systematic method for searching, evaluating the literature, analyzing, and synthesizing data to arrive at a comprehensive understanding of the selected topic.7

 

The electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo were searched using the following terms: "risk factors," "predictors," "stroke," "poststroke," "transient ischemic attack," "depression," "depressive disorder," "depression symptoms," and "PSD." All articles for consideration included PSD as the primary outcome. Other inclusion criteria were peer-reviewed primary observational Western studies, written in English, and published after 2004. The integrative review focused on studies conducted on Western countries because the standard of care for stroke varies based on resource availability and clinical practice. Furthermore, the search was limited to all studies published after 2004 because of the advancements in stroke research and treatment in the last decade. Other types of studies excluded were experimental studies, secondary data analyses, studies that examined only 1 or 2 risk factors, and general literature reviews.

 

The initial electronic search identified 400 studies, and 18 articles fulfilled the inclusion criteria, including 6 studies obtained via reference lists. Of the 18 articles ultimately included in this review, 14 were prospective cohort studies, along with 1 case-control and 3 cross-sectional studies.

 

The final sample was critically appraised for methodological rigor and subsequently analyzed for PSD risk factors.7 The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was selected for use in this review for its validity in assessing health science research and quality of reporting on observational studies.8 The quality of the studies was limited by small sample size, selection bias, number of selected variables, and lack of multivariate analyses. However, caution was applied when drawing conclusions based on their findings.

 

Results

Overview

The literature reviews uncovered three major risk factor categories: demographic and social factors, medical and psychiatric history, and stroke characteristics and outcomes. Four risk factors were also identified that did not fit into the aforementioned categories: baseline depression symptoms, melancholy index, crying, and nonacceptance of disability. Poststroke depression was the primary outcome in all 18 studies, measured by 9 different measurement tools. Eight studies used the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria to diagnose PSD, whereas the others used 1 or 2 different screening tools to measure depression (Tables 1, 2).

  
Table 1 - Click to enlarge in new windowTABLE 1 Summary of Studies
 
Table 2 - Click to enlarge in new windowTABLE 2 List of the Risk Factors and Their Association With PSD Across the Studies

The number of risk factors examined in each study ranged from 4 to 20, with a mean of 10 predictors per study. Most of the risk factors were subjective and required observer reports or self-reports (ie, stroke severity, physical impairment, or cognitive impairment). Few studies contained objective measures such as blood pressure, homocysteine,9 leptin levels,10 or body mass index.11

 

The composite number of subjects enrolled in the studies was 4097, with a mean age between 56.3 and 80 years. The percentage of women ranged from 32% to 55%, and the percentage of men ranged from 44.7% to 68%, across the studies. All of the studies that reported their enrollment methods (n = 14) used consecutive enrollment except for 4 studies that did not specify their enrollment methods.12-15 Fifteen studies enrolled subjects after a stroke from hospitals, 2 studies enrolled subjects from rehabilitations centers,16,17 and 1 study enrolled subjects from the community.9 Data collection at baseline ranged from 2 days to 9 months after the stroke,16,18 with a follow-up period ranging from 1 month to 10 years.10,19 Four studies collected data at only 1 time point, including 3 cross-sectional studies and 1 case-control study.9,11,20,21

 

Demographic and Social Factors

Age and sex were the most frequently examined risk factors, and they yielded controversial results. Age was not associated with PSD in 7 studies, whereas 3 studies reported an association. Carota et al12 found that a younger age (<68 years) was a significant predictor for PSD within the first year after stroke (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.30-4.13; P = .004), whereas 2 studies revealed that older age groups > 68 years10 or > 75 years20 were associated with depression (see Table 2).

 

Fourteen studies examined the association of sex with PSD. Nine of the studies reported that a person's sex did not have an effect on someone's risk for PSD. However, 4 studies identified female sex as a risk factor for PSD,10,16,22,23 and 1 study found that men who experience depressive symptoms 6 months after stroke had a higher risk of chronic PSD.17

 

Nine studies examined other sociodemographic factors and found conflicting results. Whereas Chatterjee et al9 and Schepers et al17 found no association between level of education and PSD, Nys et al23 and Sienkiewicz-Jarosz et al24 reported that participants who developed depression had significantly lower levels of education. Social support from family members or friends was also examined in 6 studies. Three studies found no association between marital status and PSD,9,17,20 whereas 3 studies found that having social support, staying with a partner or a friend after discharge from the hospital, and being married lowered the risk for PSD.15,18,22 Moreover, De Ryck et al13 reported that patients with relationship problems had 3 times greater risk of becoming depressed 18 months after stroke (OR, 3.09; 95% CI, 1.31-7.26).

 

Employment status was considered in 4 studies. Three reported no association between PSD and employment status,9,17,24 and 1 study found that early return to work after stroke increased the level of depression at 3 months, as well as participating in sports and exercise.15 However, being involved in leisure activities such as listening to music lowered the risk of depression.15

 

Medical and Psychiatric History

A history of stroke or transient ischemic attack was examined across studies. Two studies found that the risk of depression was not associated with a previous incidence of stroke.11,14 However, 4 studies found that stroke survivors with a history of stroke had a higher risk of developing PSD during the period ranging from 6 months to 4 years after their ensuing stroke.9,16,19,23 Five studies excluded participants with a history of stroke to better control for confounding.9,10,15,17,25 Furthermore, 1 study reported that prestroke brain atrophy was not associated with PSD,21 and another study found that prestroke dementia was associated with PSD.19

 

Prestroke cardiovascular risk factors including ischemic heart disease, atrial fibrillation, hypertension, peripheral vascular disease, diabetes mellitus (DM), and dyslipidemia were also commonly investigated. Four studies found no association between ischemic heart disease and atrial fibrillation with PSD,9,11,19,20 and 4 studies yielded the same results for hypertension and peripheral vascular disease.14,19,20,23 In contrast, Chatterjee et al9 and Tennen et al11 found that hypertension was an independent predictor for PSD at 4 and 9 months after stroke. Furthermore, 2 studies found conflicting results when examining the association between the number of vascular risk factors and the risk for PSD. Allan et al19 reported that the number of vascular risk factors was significantly associated with PSD at 1 year, whereas Tennen et al11 found no association. Six studies also examined DM as another comorbidity, but only Nys et al23 found DM to be a significant predictor for depressive symptoms 6 months after stroke (OR, 10.0; 95% CI, 1.5-6.7). Four studies examined dyslipidemia and hypercholesterolemia as risk factors, but they failed to find an association with PSD.9,11,14,19

 

Biological markers as risk factors were assessed in 2 studies. Homocysteine and serum folate levels were associated with PSD. Chatterjee et al9 reported that higher serum homocysteine and lower folate levels increased the risk of PSD at 9 months (OR, 14.2; 95% CI, 13.1-15.4; P = .046). Moreover, Jimenez et al10 reported that leptin levels higher than 20.7 ng/mL at day 7 +/- 2 predicted the development of depression at 1 month.

 

Lifestyle was only addressed in 5 studies. All 5 studies showed that PSD was not associated with one's history as a smoker,9,11,14,19,23 and two of the studies failed to show an association between alcohol consumption and PSD.9,23 Only 1 study examined obesity as a risk factor, and no association was found.11

 

Approximately 50% of the studies examined patient and family history of depression as a predictor for PSD. Four studies reported that prestroke depression or a family history of depression had no association with the risk of PSD,11,12,14,21 whereas 3 studies found that a positive patient and family history increased the risk of PSD.9,16,25 Chatterjee et al9 reported the risk of PSD as 2 times higher at 9 months for patients with a history of depression (OR, 2.6; 95% CI, 1.0-6.4; P = .03).

 

Stroke Characteristics and Outcomes

Stroke type varied among the studies. Eleven studies included patients with both ischemic and hemorrhagic stroke, whereas 7 studies limited their samples to patients with ischemic stroke (see Table 1). Only Schepers et al,17 examined the association of stroke subtypes with the risk for PSD, and they reported no association at 1 and 3 years after stroke. Furthermore, the association between stroke lesion location and PSD drew great attention across studies; however, none of the studies verified a positive correlation.

 

The studies found several risk factors that were consistently related to stroke outcomes. Stroke severity was examined in 11 studies and yielded inconsistent findings. Most of the studies defined stroke severity as a patient's prognosis using standardized clinical measures (ie, National Institutions of Health Stroke Scale and Canadian Neurological Scale). Six studies reported no association between stroke severity and the risk of PSD,10,14,15,18,20,23 whereas 5 studies reported that stroke severity was a significant predictor for PSD within the 1- to 4-month period after stroke.11,13,18,21,24 Not all studies examining stroke severity evaluated poststroke disability. Only 7 studies examined disability as a risk for PSD, and only one of the studies showed no association,14 whereas 6 studies reported that the risk of PSD was higher with moderate to severe disability.10,13,16,18,21,25

 

Cognitive impairment was another risk factor well recognized across 9 studies. However, there was a disagreement in the measurement scales for cognitive impairment. Four studies failed to show an association between cognitive impairment after stroke and the risk for PSD.11,18,20,25 Five studies found a significant association between PSD and cognitive impairment, but they differed in their follow-up periods and statistical analyses. Three studies reported a significant association based on bivariate analysis,13,19,21 whereas 2 studies conducted a multivariate analysis, controlling for other confounders.9,23

 

Unilateral neglect, in which the patient is unaware of 1 side of his/her body, was one of the risk factors investigated in 2 studies. Schepers et al17 reported no association between unilateral neglect at 6 months after stroke in predicting PSD at 1 and 3 years, whereas Nys et al23 reported that patients with unilateral neglect within 3 weeks after stroke had a higher risk for PSD at 6 months (OR, 9.5; 95% CI, 1.9-48.5). Moreover, aphasia was considered by 3 studies, all of which found a significant association between aphasia and PSD using bivariate analysis.12,13,16

 

Functional independency and activities of daily living are crucial outcomes for stroke survivors. The associations of these factors with PSD were assessed by 12 studies. Eleven studies used the Barthel Index measure and showed that the risk for PSD was greater with higher functional dependency. Only 1 study found no association of functional dependency with the risk of PSD.23

 

Other Risk Factors

Three studies examined the association of depression at baseline, first-time assessment, and prediction of PSD at the time of follow-up. Although the studies used 5 different tools to diagnose or assess depression after stroke and administered them at different times, all identified that depressive symptoms at baseline were significant predictors of PSD.19,21,23 In addition, Fuentes et al14 examined the melancholy index, a subscale of the Hamilton Depression Rating Scale, as a predictor for PSD. They reported that the melancholy index showed a higher OR of PSD at 3 months. Only 1 study examined fatigue as a predictor for PSD and found no association.17

 

One study examined personal behaviors, such as crying, overt sadness, and apathy, as markers for PSD. Carota et al12 reported that crying behaviors during the first few days after stroke onset was a significant marker for PSD at 3 and 12 months (OR, 2.66; 95% CI, 1.35-5.27; P = .005). In addition, Townend et al26 reported that the patients' non-acceptance of their disability at 1 month independently predicted depression at 9 months (OR, 1.19; 95% CI, 1.05-1.35).

 

Discussion

This integrative review identified that the most common risk factors associated with PSD are stroke severity, cognitive impairment, physical disability, and functional dependency. Using a multivariate statistical analysis and controlling for confounders strengthened the results of these studies. These findings support the results of the systematic reviews of observational studies.3,4

 

Prestroke depression was found to be associated with PSD3,4; however, only 3 studies in the integrative review found that the history of depression was associated with PSD.9,16,25 The controversial findings are due to the restrictions in the inclusion and exclusion criteria across studies. Some studies excluded participants with previous depression, severe aphasia, or history of stroke, all of which may be risk factors for PSD. Hackett and Pickles1 included studies that examined patients with prestroke depression or poststroke aphasia in their systematic reviews, both of which are considered important subgroups. However, most of the studies included in this integrative review excluded aphasic patients, which masked the association of aphasia with PSD.

 

Others factors, including demographic and social factors and medical history, were not consistent across studies. The methodological variations among the studies reviewed provide a great explanation for the controversial findings. Variations included sample sizes, settings, time of the assessment, inclusion and exclusion criteria, PSD assessment tools, numbers of variables, and statistical analyses. De Ryck et al5 highlighted the need for more targeted longitudinal studies with adequate numbers of patients using simple repeatable methods and a wise selection of variables to minimize the large controversy.

 

Poststroke depression is common among survivors up to 5 years after stroke. Nurses are often the first to notice PSD, perform initial assessments, and request consultations. This review found that PSD was defined and assessed differently across studies. Several depression screening tools with different cutoff points were used without adequate justification for why each particular tool was used. Lack of standardized screening methods might hinder early depression assessment and delay recovery. The American Heart Association recommends using the 9-item Patient Health Questionnaire because of its brevity and strong psychometric properties over other depression measures among the population with stroke.6

 

Nurses play an important role in the patient education process within different settings. The American Heart Association recommends that nurses should raise patients' awareness about depression risk factors and encourage them to report the signs and symptoms of depression in their early stages.6 The presence of depression might affect stroke survivors' participation in physical rehabilitation and adherence to medication to achieve maximal recovery after stroke. Therefore, nurses are encouraged to use multiple assessment methods including observation, interviewing, and screening tools to identify patients at risk for PSD earlier.

 

This review was limited to the Western studies and lacked cultural variation, race, and ethnicity as risk factors. This review focused only on observational studies, and no qualitative studies were included. Most of the reviewed studies used a convenience sample without conducting a power analysis. Nevertheless, this integrative review adds to the existing literature by examining biopsychosocial factors.

 

Future research should be directed at effective interventions for physical disability and functional dependency. Qualitative studies are recommended to understand stroke survivors' experience with PSD, factors that worsen or ameliorate PSD, and preferred treatment.

 

Conclusions

Poststroke depression is the most common emotional disorder and affects one-third of stroke survivors. It affects rehabilitation and delays recovery, increases mortality, and decreases quality of life. Stroke severity, physical disability, and functional dependency are the most common risk factors for PSD. Nurses should identify patients at risk for PSD through early depression screening and provide interventions to enhance rehabilitation and improve recovery.

 

Acknowledgments

The author thanks Deborah A. Chyun, PhD, RN, FAHA, FAAN; Madeline A. Naegle, PhD, PMHCNS-BC, FAAN; Allison Squires, PhD, RN, FAAN; Susan Kaplan Jacobs, MLS, MA Health Sciences Librarian; and Neesha Ramchandani, PNP, CDE.

 

References

 

Hackett ML, Pickles K. Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. Int J Stroke. 2014;9(8):1017-1025. [Context Link]

 

Robinson RG, Jorge RE. Post-stroke depression: a review. Am J Psychiatry. 2016;173(3):221-231. [Context Link]

 

Ayerbe L, Ayis S, Wolfe CD, et al. Natural history, predictors and outcomes of depression after stroke: systematic review and meta-analysis. Br J Psychiatry. 2013;202(1):14-21. [Context Link]

 

Kutlubaev MA, Hackett ML. Part II: predictors of depression after stroke and impact of depression on stroke outcome: an updated systematic review of observational studies. Int J Stroke. 2014;9(8):1026-1036. [Context Link]

 

De Ryck A, Brouns R, Geurden M, et al. Risk factors for poststroke depression: identification of inconsistencies based on a systematic review. J Geriatr Psychiatry Neurol. 2014;27(3):147-158. [Context Link]

 

Miller EL, Murray L, Richards L, et al. Comprehensive overview of nursing and interdisciplinary rehabilitation care of the stroke patient: a scientific statement from the American Heart Association. Stroke. 2010;41(10):2402-2448. [Context Link]

 

Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546-553. [Context Link]

 

von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573-577. http://www.ncbi.nlm.nih.gov/pubmed/17938396. Accessed May 5, 2015. [Context Link]

 

Chatterjee K, Fall S, Barer D. Mood after stroke: a case control study of biochemical, neuro-imaging and socio-economic risk factors for major depression in stroke survivors. BMC Neurol. 2010;10:125. [Context Link]

 

Jimenez I, Sobrino T, Rodriguez-Yanez M, et al. High serum levels of leptin are associated with post-stroke depression. Psychol Med. 2009;39(7):1201-1209. [Context Link]

 

Tennen G, Herrmann N, Black SE, et al. Are vascular risk factors associated with post-stroke depressive symptoms? J Geriatr Psychiatry Neurol. 2011;24(4):215-221. [Context Link]

 

Carota A, Berney A, Aybek S, et al. A prospective study of predictors of poststroke depression. Neurology. 2005;64(3):428-433. [Context Link]

 

De Ryck A, Fransen E, Brouns R, et al. Poststroke depression and its multifactorial nature: results from a prospective longitudinal study. J Neurol Sci. 2014;347(1-2):159-166. [Context Link]

 

Fuentes B, Ortiz X, Sanjose B, et al. Post-stroke depression: can we predict its development from the acute stroke phase? Acta Neurol Scand. 2009;120(3):150-156. [Context Link]

 

Jean FA, Swendsen JD, Sibon I, et al. Daily life behaviors and depression risk following stroke: a preliminary study using ecological momentary assessment. J Geriatr Psychiatry Neurol. 2013;26(3):138-143. [Context Link]

 

Paolucci S, Gandolfo C, Provinciali L, et al. Quantification of the risk of post stroke depression: the Italian multicenter observational study DESTRO. Acta Psychiatr Scand. 2005;112(4):272-278. [Context Link]

 

Schepers V, Post M, Visser-Meily A, et al. Prediction of depressive symptoms up to three years post-stroke. J Rehabil Med. 2009;41(11):930-935. [Context Link]

 

Townend BS, Whyte S, Desborough T, et al. Longitudinal prevalence and determinants of early mood disorder post-stroke. J Clin Neurosci. 2007;14(5):429-434. [Context Link]

 

Allan LM, Rowan EN, Thomas AJ, et al. Long-term incidence of depression and predictors of depressive symptoms in older stroke survivors. Br J Psychiatry. 2013;203(6):453-460. [Context Link]

 

Fure B, Wyller TB, Engedal K, et al. Emotional symptoms in acute ischemic stroke. Int J Geriatr Psychiatry. 2006;21(4):382-387. [Context Link]

 

Snaphaan L, van der Werf S, Kanselaar K, et al. Post-stroke depressive symptoms are associated with post-stroke characteristics. Cerebrovasc Dis. 2009;28(6):551-557. [Context Link]

 

Brown C, Hasson H, Thyselius V, et al. Post-stroke depression and functional independence: a conundrum. Acta Neurol Scand. 2012;126(1):45-51. [Context Link]

 

Nys GM, van Zandvoort MJ, van der Worp HB, et al. Early cognitive impairment predicts long-term depressive symptoms and quality of life after stroke. J Neurol Sci. 2006;247(2):149-156. [Context Link]

 

Sienkiewicz-Jarosz H, Milewska D, Bochynska A, et al. Predictors of depressive symptoms in patients with stroke-a three-month follow-up. Neurol Neurochir Pol. 2010;44(1):13-20. http://www.ncbi.nlm.nih.gov/pubmed/20358481. Accessed June 16, 2016. [Context Link]

 

Leentjens AF, Aben I, Lodder J, et al. General and disease-specific risk factors for depression after ischemic stroke: a two-step Cox regression analysis. Int Psychogeriatr. 2006;18(4):739-748. [Context Link]

 

Townend E, Tinson D, Kwan J, et al. "Feeling sad and useless": an investigation into personal acceptance of disability and its association with depression following stroke. Clin Rehabil. 2010;24(6):555-564. [Context Link]