General Hospital Psychiatry 37 (2015) 245–250
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The association between the severity of poststroke depression and clinical outcomes after first-onset stroke in Korean patients☆,☆☆ Geun-Young Park, M.D., Ph.D. a, Sun Im, M.D., Ph.D. a, Chang Hoon Oh, M.D. a, Soo-Jung Lee, M.D., Ph.D. b, Chi-Un Pae, M.D., Ph.D. b,c,⁎ a b c
Department of Rehabilitation Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA
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Article history: Received 16 September 2014 Revised 26 February 2015 Accepted 27 February 2015 Keywords: Post-stroke depression Stroke Severity Clinical outcomes Rehabilitation
a b s t r a c t Objective: The purpose of the present study is to evaluate the association between poststroke depression (PSD) and clinical outcomes in first-onset stroke patients who are undergoing a rehabilitation program. Methods: The present study included 180 inpatients that were recruited consecutively and followed up over a 6month observational period. Poststroke depression was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Symptoms of depression and clinical outcomes were assessed using the Beck Depression Inventory, the modified Barthel Index (MBI) and the Mini Mental State Examination (MMSE). All patients were assessed at baseline and at the end of the 6-month observational period. Results: Of the 180 patients, 127 (70.6%) were diagnosed with minimal-to-mild depression (MMD), and 53 (29.4%) were diagnosed with moderate-to-severe depression (MSD). The mean change in MBI scores from baseline to 6 months was significantly higher (P=.029) in the MMD group (23.8) than in the MSD group (8.6). The odds ratio for an unfavorable outcome (MBI score b60) in patients with MSD was approximately 3.5 in relation to patients with MMD. The mean change in MMSE score (4.4 versus 7.4) was not significantly different between the MMD and MSD groups. Conclusion: The present findings suggest that the severity of PSD may be associated with clinical outcomes in Korean patients 6 months after a first-onset stroke. Our data agree with previous findings, which indicate that clinicians should carefully evaluate symptoms of depression in stroke patients during routine clinical practice. The methodological shortcomings of the present study may require further studies with adequate power and improved design to clarify the association between PSD and clinical outcomes following stroke. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Major depressive disorder (MDD) is a common mental illness that includes emotional, cognitive and somatic symptoms [1]. Among the elderly population, the incidence of depression increases substantially with the number of somatic symptoms [2,3] even in the absence of other comorbid conditions. Poststroke depression (PSD) is commonly observed in patients following a stroke. In a recent meta-analysis of 61 studies with 25,488 patients, the pooled frequency of PSD was approximately 31% [4]. There is significant variation in the reported prevalence of PSD, which ranges from 5% to 65% [5]. This variation can be attributed to a number of factors including ethnicity, use of different diagnostic criteria, sample size, time interval between the stroke event and assessment, and ☆ The English in this document has been revised by Elsevier Language Editing Plus Service. ☆☆ Disclosure: The authors have no conflicts of interest to disclose. ⁎ Corresponding author at: Department of Psychiatry, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Sosa-Ro 327, Wonmi-gu, Bucheon-si, Gyeonggi-do, Republic of Korea. Tel.: +82 32 340 7067; fax: +82 32 340 2544. E-mail address: [email protected] (C.-U. Pae). http://dx.doi.org/10.1016/j.genhosppsych.2015.02.009 0163-8343/© 2015 Elsevier Inc. All rights reserved.
methodological differences in case selection and use of screening tools. The estimated prevalence of PSD in Korea is approximately 15% [6]. Overall psychiatric issues such as indifference, depression, anxiety, anger and bipolar symptoms are observed in approximately 20%–40% of stroke patients [7]. Poststroke depression has been found to be negatively associated with clinical and functional outcomes in stroke patients. For example, it can lead to a reduced quality of life (QoL), impair activities of daily living (ADL), decrease functional independence, reduce social interactions and reduce the success of rehabilitation. Moreover, PSD increases the burden on health care resources and is associated with a higher mortality rate [8–12]. It has also been linked to cognitive impairments, such as attention deficit, decreased learning ability and executive functions, and slow physical recovery. It is of note that the negative relationship with PSD remains even after remission of depression and is associated with functional deterioration over time [13,14]. It is difficult to determine the precise nature of the relationship between PSD and stroke and the manner in which they are associated with each other in clinical practice. Indeed, the association between neurological complications (e.g., impairments of gait balance) and psychiatric symptoms (e.g., depression) in the aftermath of a stroke has yet
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to be fully characterized. The neurological complications underlying the cognitive, physical and functional impairments associated with stroke have been investigated at length, yet the psychiatric symptoms observed after stroke have received relatively little attention in both research and clinical practice. The most likely reason for the lack of data is that psychiatric symptoms are considered to be additional and secondary manifestations resulting from stroke even though they are frequently observed in patients with stroke. Clinicians need a better understanding of the relationship between psychiatric symptoms and stroke because of the high prevalence of these symptoms in patients with stroke and the consequent and significant delay in clinical recovery and increased risk of mortality. Additionally, it is reasonable to assume that the proper and timely detection of psychiatric symptoms and initiation of rehabilitation will enhance the response to treatment and improve outcomes for patients with stroke. Few studies have investigated the association between PSD and long-term clinical outcomes after a first stroke, particularly in an Asian population. Therefore, the aim of the present study was to investigate the association between baseline severity of PSD symptoms and clinical outcomes of Korean patients with first-onset stroke after 6 months of rehabilitation treatment in a naturalistic setting. We hypothesized that PSD [minimal-to-mild depression (MMD) versus moderate-to-severe depression (MSD)] may be differentially associated with functional outcomes in stroke patients who have undergone a rehabilitation program. 2. Methods 2.1. Patients This study included patients who were admitted to a rehabilitation program within 2–4 weeks of hospital admission for a first-onset ischemic stroke. All patients were consecutively enrolled from the Department of Rehabilitation Medicine at Bucheon St. Mary’s Hospital, Korea, between 2009 and 2011. A diagnosis of PSD was made by board-certified psychiatrists using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients with additional Axis I psychiatric disorders other than depression were excluded to avoid any potential biases from comorbid psychiatric disorders. The presence of comorbid conditions was determined following an assessment of patient medication and/or clinical history by the treating physicians. The study complied with the Declaration of Helsinki and other ethical principles regarding human experimentation. The study protocol was approved by the Institutional Review Board (IRB) of Bucheon St. Mary’s Hospital in Bucheon, Kyeonggi-Do, Korea (IRB approval number: HC13RISI0015). 2.2. Study procedure The present investigation was a 6-month observational study that included collection of sociodemographic data at baseline during person-to-person interviews based on case report forms and the use of self- and clinician-rated scales. Typically, stroke patients were transferred from the Center for Cerebrovascular Attacks to the Department of Rehabilitation Medicine for rehabilitation after completion of acute phase treatment lasting 2–4 weeks. Therefore, the baseline assessment of PSD and stroke symptoms was performed approximately 2–4 weeks after the stroke event, and follow-up visits varied according to the clinical status of each patient during routine clinical practice; the principal visit interval was 1 month. The post-acute-phase 4-week rehabilitation program was conducted in the Department of Rehabilitation Medicine during the hospitalization period. It consisted of a complex program of universal activities that were performed five times per week. Group and individual exercises included in the program are as follows: neurodevelopmental treatment for 30 min; gait or mattress training (for coordination and balance) for 30 min, which focused on the disabled lower limb and
amelioration of gait patterns; functional ADL training for 30 min; occupational therapy for 30 min and modality applications such as heat therapy, electrotherapy and functional electrical stimulation. Additionally, all patients participated in group therapy, music therapy and a 30-min period of manipulation exercises intended to train the hand and improve upper limb function. After discharge, all patients underwent a similar or modified rehabilitation program in an outpatient clinic based on clinical status. 2.3. Symptom assessment The study used the measures below to assess depressive and strokerelated symptoms in patients. Assessments were performed at baseline and at the end of the 6-month observational period. The Korean version of the Beck Depression Inventory (BDI) was used to assess the severity of depression at baseline [15]. The reliability and validity of the BDI are 0.86 and 0.89, respectively. It has a mean correlation of 0.72 with the Hamilton Depression Rating Scale. On this scale, higher total scores indicate more severe depressive symptoms; a score between 0 and 9 indicates minimal depression, a score between 10 and 16 indicates mild depression, a score between 17 and 29 indicates moderate depression, and a score between 30 and 63 indicates severe depression. To evaluate the association between baseline severity of PSD and clinical outcomes a priori defined, all subjects were classified as having either MMD (BDI score of 0–16) or MSD (BDI score ≥17) at baseline. The modified Barthel Index (MBI) [16] was used to evaluate the severity of impairments in ADL. It assesses self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers and stair climbing). The reliability of the MBI is 0.89, and it has a correlation of 0.91 with the Barthel score. The Mini-Mental State Examination (MMSE) [17] was used to quantitatively assess the cognitive status of patients. Since its development in 1975, the MMSE has been validated and extensively used in both clinical practice and research. The reliability of the MMSE is 0.89, and it has a correlation of 0.78 with the Blessed Orientation Memory-Information score. 2.4. Clinical outcomes The primary end point of the study was the mean change in the MBI score from baseline to 6 months. The secondary end points were the mean change in the MMSE score from baseline to 6 months and the proportion of patients who had an unfavorable outcome versus a favorable outcome based on the MBI score at 6 months. The nature of an unfavorable outcome was defined using an MBI score b 60, as suggested by Sulter et al. [18], rather than by attempting to define a favorable outcome (no consensus has been agreed for the definition of a favorable outcome). Sulter et al. [18] proposed that patient outcomes should be determined using multiple measures and should be defined as poor (unfavorable) based on multiple factors (i.e., death, institutionalization due to stroke or an MBI score b60). According to a systematic review of stroke studies [18], the MBI was used in 13 clinical trials and served as a primary outcome measure in 7 clinical trials; 2 of these trials compared mean scores, and 2 trials used median scores. The present study defined an unfavorable outcome as an MBI score b 60 at 6 months because the MBI is the most commonly used rating scale for the assessment of ADL in stroke patients. 2.5. Statistical analyses For all descriptive statistics, continuous variables were presented as means with standard deviations (S.D.), and categorical variables were presented as frequencies. To examine group differences in sociodemographic characteristics at baseline, an analysis of variance (ANOVA) or an analysis of covariance (ANCOVA) was used for continuous variables where appropriate, and a χ 2 or Fisher’s Exact Test was used for categorical
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variables. The correlation coefficients for baseline BDI score, change of MBI score and the MBI score at final follow-up were also calculated. The scores of the MMD and MSD groups were compared using ANOVA for symptoms and other clinical parameters that were reported as continuous variables. The mean changes in the MBI and MMSE scores between baseline and 6 months were compared between the MMD and MSD groups using ANCOVA and age, number of comorbid conditions and baseline scores as covariates. Logistic regression analysis was performed to determine the association between baseline severity of PSD and the risk of an unfavorable outcome. Age, sex, education level, work status, family history of stroke, past history of depression, income level, alcohol use, tobacco use, marital status, number of comorbidities and baseline scores of BDI, MMSE and MBI were included as covariates in the regression model. In the regression model, the dependent variable was unfavorable outcome and the independent variable was the severity of PSD (MMD vs. MSD). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the severity of PSD were also calculated for an unfavorable outcome. The odds ratio (OR) and 95% confidential intervals (CIs) were calculated. It was determined that, using these statistical parameters and taking into account adjustment for covariates, the study would have a power of 80.0% to detect a medium effect of 0.4824. This corresponded to a value of 15.2 for the mean difference in the changes in MBI score from baseline to 6 months between the MMD and MSD groups. All statistical analyses were conducted using the NCSS 2007 and PASS 2008 software packages (NCSS LLC, Kaysville, UT, USA). Statistical significance was two-tailed and set at Pb.05. 3. Results
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higher; 65% of patients were classified as middle class; 61% of patients had a job prior to the stroke event; and 37% of patients had a comorbid condition (Table 1). The mean BDI, MMSE and MBI scores at baseline were 12.9, 20.1 and 41.7, respectively (Table 1). 3.1.2. Group comparisons (MMD versus MSD) Out of a total of 180 patients, 127 (70.6%) were diagnosed with MMD and 53 (29.4%) were diagnosed with MSD. As expected, the mean BDI score for the MMD group (7.5) was significantly lower than that of the MSD group (27.8) (Table 1). There were no significant differences in terms of sociodemographic variables between the groups at baseline in terms of age, sex, education level, work status, family history of stroke and psychiatric disorders, past history of depression, socioeconomic status, use of alcohol and tobacco, and the number of comorbid conditions (Table 1). The proportion of comorbid conditions more than one was significantly higher in the MSD group than the MMD group. There were no difference in the mean baseline MBI score between the MSD and MMD groups; however, the mean baseline MMSE score was significantly higher in the MMD group compared with the MSD group (Table 1). 3.2. Clinical outcomes 3.2.1. Primary end points The mean change in the MBI score across all patients was 19.9, which represented an increase of 47.7% between baseline and 6 months. The mean change in the MBI score between baseline and 6 months was significantly greater (F=4.910, P=.029) in the MMD group (23.8, 55.9%) than in the MSD group (8.6, 21.9%); the magnitude of the group difference was 15.2 (Fig. 2).
3.1. Baseline characteristics 3.2.2. Secondary end points 3.1.1. Total subjects The patient disposition is summarized in Fig. 1. The study included 180 patients with an average age of 61.0 (13.3) years. Approximately 84% of patients were married and 16% were widowed, unmarried or separated; 64% of the patients were educated to middle school level or
3.2.2.1. Mean changes in the MMSE. The mean change in the MMSE score across all patients was 5.2, which represented an increase of 25.9% between baseline and 6 months (Fig. 2). There was no significant difference between the MMD and MSD groups in terms of the mean change
Fig. 1. The patients’ disposition in the present study.
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Table 1 Clinical variables by the baseline depression severity between MMD and MSD groups Remark Age Sex Education Work status Family history of stroke Past history of depression Socioeconomic status Use of alcohol Use of tobacco Marital status Comorbidity proportion Comorbidity number BDI⁎ MMSE⁎ MBI⁎
Female ≥ Middle school Employed Yes ≥ Middle income Yes Yes Married ≥1
MMD (n=127)
MSD (n=53)
Total (N=180)
F or χ2/P values
60.4 (14.0) 59 (46.5) 89 (70.0) 85 (66.9) 19 (15.0) 11 (8.7) 82 (64.6) 55 (43.3) 63 (49.6) 105 (82.7) 41 (32.3) 0.9(0.9) 7.5(4.7) 20.9(6.9) 42.6(30.3)
62.6 (11.2) 33 (62.3) 36 (67.9) 35 (66.0) 13 (24.5) 9 (17.0) 38 (71.7) 23 (27.7) 27 (50.9) 47 (88.7) 26 (49.1) 1.1(0.8) 27.8(9.9) 17.9(8.2) 39.2(29.6)
61.0 (13.3) 92(51.1) 115(63.9) 110(61.1) 32(17.8) 23(12.8) 120(66.7) 78(43.3) 90(50.0) 152(84.4) 67(37.2) 1.0(0.9) 12.9(11.1) 20.1(7.4) 41.7(30.1)
NS NS NS NS NS NS NS NS NS NS 4.502/.042 NS 300.235/b.0001 4.917/.028 NS
Data represent number (S.D.) or number (percent). NS, not significant. Statistical comparisons with ANOVA or Fisher’s Exact Test. ⁎ Baseline scores.
in MMSE score (4.4 versus 7.4, respectively; F= 0.564, P= .456) from baseline to 6 months. 3.2.2.2. Unfavorable versus favorable outcomes. Patient outcomes at 6 months was defined a priori as favorable or unfavorable based on an MBI score b60. Approximately one half of the study participants exhibited an unfavorable outcome. The OR for an unfavorable outcome in the MSD group was approximately 3.5 relative to the MMD group (Table 2). Further analysis of these groups using different criteria for an unfavorable outcome (MBI score b 75 and b 85) showed that patients with MSD retained a substantially higher risk of an unfavorable outcome compared with patients with MMD (Table 2). Logistic regression analyses outlined the association between baseline severity of PSD (MSD) and unfavorable outcome (Table 3). The sensitivity of using the severity of PSD to predict an unfavorable clinical outcome in the MSD group was 0.714, the specificity was 0.585, the positive predictive value was 0.370, the negative predictive value was 0.857, the positive likelihood ratio was 1.723, and the negative likelihood ratio was 0.488. The baseline BDI score had a weak correlation with the change (r=−0.185, P=.064) in MBI score and a negative correlation with the final MBI score (r=−0.196, P=.044). The change in MBI score was positively correlated with the final MBI score (r=0.541, Pb.001). 4. Discussion The present study demonstrated that symptoms of depression are significantly associated with long-term clinical outcomes as measured by MBI score at 6-month follow up. These results agree with findings
from previous studies, which report that depression has a significant association with treatment response to rehabilitation in stroke patients [8–14,19–23]. Similar to previous findings [8–12], the baseline BDI score study was 12.9 in the present study, and 29.5% of patients exhibited symptoms consistent with at least moderate depression, which is consistent with a clinical diagnosis of MDD. Therefore, the study results show that PSD is a common mental condition in stroke patients; they also support previous findings that the prevalence of depression in stroke patients in Western and East Asian populations is between 30% and 50% [12,24]. The present findings are also consistent with a recent European multicenter study of 1064 patients [25] which found that, of the 383 patients diagnosed with PSD (36%), approximately 80% of these patients were found to have mild depression with dysthymia rather than MDD. The severity of PSD had a consistent and significant effect on the clinical outcomes of stroke patients. The mean change in MBI score was 2.8fold higher in the MMD group than in the MSD group. The percentage improvement in MBI score was also higher in the MMD group than in the MSD group, with a difference in magnitude of 34%. Further analysis of these groups using different criteria for an unfavorable outcome (MBI score b75 and b85) showed that patients with MSD had a substantially higher risk of an unfavorable outcome than patients with MMD. When the NPV was used as a predictor of an unfavorable clinical outcome in the MSD group, patients with MMD had a probability of 85.7% for a favorable clinical outcome. These findings suggest that the absence of severe depression, (e.g., MSD) in stroke patients may predict a more favorable clinical outcome. The baseline BDI score had a weak negative correlation with the change in MBI score, and a significant and negative correlation with the final MBI score. These findings also indicate the
Table 2 Proportion of favorable versus unfavorable outcome as priori defined at 6 months between MMD and MSD groups*.
Clinical outcome Favorable Unfavorable† Additional clinical outcome results Favorable Unfavorable‡ Favorable Unfavorable§
Fig. 2. The percentage improvement in MMSE (P=.456) and MBI (P=.029) scores from baseline to the end of follow-up (6 months) between MMD and MSD.
MMD (n=82)
MSD (n=28)
Total (N=110)
48 (58.5) 34 (41.5)
8 (28.6) 20 (71.4)
56 (50.9) 54 (49.1)
37 (45.1) 45 (54.9) 27 (32.9) 55 (67.1)
4 (14.3) 24 (85.7) 4 (14.3) 24 (85.7)
41 (37.2) 69 (63.8) 31 (31.8) 79 (68.2)
Data represent number (percent); definition of unfavorable clinical outcome, †b60, ‡b75, § b85 in MBI score at 6 months; *Fisher’s Exact Test; †P=.008, OR for unfavorable outcome in MSD=3.529, 95% CIs, 1.280–9.973; ‡P= .003, OR=4.933, 95% CIs, 1.442–18.528; § P=.087, OR=2.945, 95% CIs, 0.849–11.180.
G.-Y. Park et al. / General Hospital Psychiatry 37 (2015) 245–250 Table 3 The regression model for the association between severity of PSD and unfavorable outcome
Baseline severity of PSD
B
S.E.
Wald
OR (95% CIs)
P value
1.168
0.521
5.039
3.217 (1.160–8.924)
.025
potential association between baseline severity of PSD and long-term outcomes relating to ADL. The mean changes in MMSE scores from baseline to 6 months did not differ significantly between the MMD and MSD groups. This suggests that the severity of PSD in stroke patients is less likely to be associated with improvement of cognitive function than ADL. Alternatively, it is possible that the MMSE score is not sensitive enough to detect differences in treatment responses between patients with MMD and those with MSD. This clinical issue requires further research using a robust study design. The present study has several strengths compared with previous studies. It is the first study to adopt the proposed criteria for unfavorable outcomes, as defined by MBI score, and used additional criteria in the form of different threshold scores for treatment response. The results also help to address the lack of long-term studies investigating the association of baseline severity of PSD with clinical outcomes in stroke patients, particularly in an Asian population. We believe that the findings from this study contribute substantially to current understanding of the relationship between the severity of PSD and the clinical outcomes of stroke patients. The present study has several methodological limitations. The power of the present sample appeared to be sufficient (80%) to detect an effect size of 0.5, which corresponds to the magnitude of difference in MBI scores from baseline to 6 months between the MMD and MSD groups. However, a larger sample size would provide greater sensitivity for the detection of smaller differences between the MMD and MSD groups. A larger sample size would enable post hoc analyses to address pertinent clinical issues relating to the nature of stroke and baseline demographic factors. Moreover, the duration of the follow-up period (6 months) may have been insufficient to detect the long-term effects of baseline depression [26]. For example, the South London Stroke Register study [27], which followed up patients for up to 10 years, demonstrated that depression is independently associated with poor health outcomes. Inherent methodological shortcomings, such as the timing of the assessment of PSD, the clinical heterogeneity of PSD and various clinical differences in stroke, should also be considered limitations of the study, as described previously [12]. This study did not evaluate other psychological factors that might affect clinical outcomes in stroke patients, such as personality and anxiety. A neurotic personality is associated with a lower QoL in stroke patients [28], and anxiety is also strongly related with QoL as a negative predictor than depression [29]. As the present study employed a naturalistic observational approach, which does not provide details of the clinical course for each patient, the number of follow-up visits between baseline and the end of observation at 6 months was insufficient. The disadvantages of cohort study also include potential large sample size requirements, long follow-up periods, possible misclassification of diagnosis (i.e., selection bias) and disease outcomes (i.e., development of advanced diagnosis techniques and treatments during follow-up), potential loss of significant portion of cohort (i.e., bias in results) and a need to perform reassessment on a frequent basis (i.e., natural course of disease), eventually leading to impediments in data acquisition and results as well as huge expenses and resources [30]. Finally, it should be clearly taken into mind that a cohort study cannot determine any causal relationship between certain clinical factors (i.e., depression) and disease outcomes (i.e., stroke outcome) since the study methodology itself may be affected by known confounders such as stroke severity as well as hidden unknown confounders leading to possible faulty conclusion. Therefore, we have
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found only that potential association between PSD and stroke outcomes may exist in the present study. 5. Conclusion The present findings demonstrated a negative association between baseline severity of PSD and functional recovery after 6 months of rehabilitation treatment in Korean patients after a first-onset stroke. Early detection and management of the symptoms of depression in patients with a first stroke should be taken into account during routine clinical practice. This consideration will facilitate tailored therapy for individual patients and will be helpful in supporting clinicians during the clinical decision-making process with respect to functional improvement in patients. Acknowledgement This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0003). References [1] Kroenke K. Patients presenting with somatic complaints: epidemiology, psychiatric comorbidity and management. Int J Methods Psychiatr Res 2003;12:34–43. [2] Greden JF. Physical symptoms of depression: unmet needs. J Clin Psychiatry 2003; 64(Suppl. 7):5–11. [3] Kroenke K, Spitzer RL, Williams JB, Linzer M, Hahn SR, deGruy III FV, et al. Physical symptoms in primary care. Predictors of psychiatric disorders and functional impairment. Arch Fam Med 1994;3:774–9. [4] 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: 1017–25. [5] Johnson JL, Minarik PA, Nystrom KV, Bautista C, Gorman MJ. Poststroke depression incidence and risk factors: an integrative literature review. J Neurosci Nurs 2006; 38:316–27. [6] Choi-Kwon S, Han K, Choi S, Suh M, Kim YJ, Song H, et al. Poststroke depression and emotional incontinence: factors related to acute and subacute stages. Neurology 2012;78:1130–7. [7] Fedoroff JP, Starkstein SE, Parikh RM, Price TR, Robinson RG. Are depressive symptoms nonspecific in patients with acute stroke? Am J Psychiatry 1991;148:1172–6. [8] Williams LS, Ghose SS, Swindle RW. Depression and other mental health diagnoses increase mortality risk after ischemic stroke. Am J Psychiatry 2004;161:1090–5. [9] Haghgoo HA, Pazuki ES, Hosseini AS, Rassafiani M. Depression, activities of daily living and quality of life in patients with stroke. J Neurol Sci 2013;328:87–91. [10] Mutai H, Furukawa T, Araki K, Misawa K, Hanihara T. Long-term outcome in stroke survivors after discharge from a convalescent rehabilitation ward. Psychiatry Clin Neurosci 2013;67:434–40. [11] Farner L, Wagle J, Engedal K, Flekkoy KM, Wyller TB, Fure B. Depressive symptoms in stroke patients: a 13 month follow-up study of patients referred to a rehabilitation unit. J Affect Disord 2010;127:211–8. [12] Dafer RM, Rao M, Shareef A, Sharma A. Poststroke depression. Top Stroke Rehabil 2008;15:13–21. [13] Sinyor D, Amato P, Kaloupek DG, Becker R, Goldenberg M, Coopersmith H. Poststroke depression: relationships to functional impairment, coping strategies, and rehabilitation outcome. Stroke 1986;17:1102–7. [14] Parikh RM, Robinson RG, Lipsey JR, Starkstein SE, Fedoroff JP, Price TR. The impact of poststroke depression on recovery in activities of daily living over a 2-year followup. Arch Neurol 1990;47:785–9. [15] Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71. [16] Granger CV, Dewis LS, Peters NC, Sherwood CC, Barrett JE. Stroke rehabilitation: analysis of repeated Barthel index measures. Arch Phys Med Rehabil 1979;60:14–7. [17] Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12: 189–98. [18] Sulter G, Steen C, De Keyser J. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke 1999;30:1538–41. [19] Pohjasvaara T, Vataja R, Leppavuori A, Kaste M, Erkinjuntti T. Depression is an independent predictor of poor long-term functional outcome post-stroke. Eur J Neurol 2001;8:315–9. [20] Kotila M, Numminen H, Waltimo O, Kaste M. Post-stroke depression and functional recovery in a population-based stroke register. The Finnstroke study. Eur J Neurol 1999;6:309–12. [21] Saxena SK, Ng TP, Koh G, Yong D, Fong NP. Is improvement in impaired cognition and depressive symptoms in post-stroke patients associated with recovery in activities of daily living? Acta Neurol Scand 2007;115:339–46. [22] Chemerinski E, Robinson RG, Kosier JT. Improved recovery in activities of daily living associated with remission of poststroke depression. Stroke 2001;32:113–7.
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The association between the severity of poststroke depression and clinical outcomes after first-onset stroke in Korean patients☆,☆☆ Geun-Young Park, M.D., Ph.D. a, Sun Im, M.D., Ph.D. a, Chang Hoon Oh, M.D. a, Soo-Jung Lee, M.D., Ph.D. b, Chi-Un Pae, M.D., Ph.D. b,c,⁎ a b c
Department of Rehabilitation Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA
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Article history: Received 16 September 2014 Revised 26 February 2015 Accepted 27 February 2015 Keywords: Post-stroke depression Stroke Severity Clinical outcomes Rehabilitation
a b s t r a c t Objective: The purpose of the present study is to evaluate the association between poststroke depression (PSD) and clinical outcomes in first-onset stroke patients who are undergoing a rehabilitation program. Methods: The present study included 180 inpatients that were recruited consecutively and followed up over a 6month observational period. Poststroke depression was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Symptoms of depression and clinical outcomes were assessed using the Beck Depression Inventory, the modified Barthel Index (MBI) and the Mini Mental State Examination (MMSE). All patients were assessed at baseline and at the end of the 6-month observational period. Results: Of the 180 patients, 127 (70.6%) were diagnosed with minimal-to-mild depression (MMD), and 53 (29.4%) were diagnosed with moderate-to-severe depression (MSD). The mean change in MBI scores from baseline to 6 months was significantly higher (P=.029) in the MMD group (23.8) than in the MSD group (8.6). The odds ratio for an unfavorable outcome (MBI score b60) in patients with MSD was approximately 3.5 in relation to patients with MMD. The mean change in MMSE score (4.4 versus 7.4) was not significantly different between the MMD and MSD groups. Conclusion: The present findings suggest that the severity of PSD may be associated with clinical outcomes in Korean patients 6 months after a first-onset stroke. Our data agree with previous findings, which indicate that clinicians should carefully evaluate symptoms of depression in stroke patients during routine clinical practice. The methodological shortcomings of the present study may require further studies with adequate power and improved design to clarify the association between PSD and clinical outcomes following stroke. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Major depressive disorder (MDD) is a common mental illness that includes emotional, cognitive and somatic symptoms [1]. Among the elderly population, the incidence of depression increases substantially with the number of somatic symptoms [2,3] even in the absence of other comorbid conditions. Poststroke depression (PSD) is commonly observed in patients following a stroke. In a recent meta-analysis of 61 studies with 25,488 patients, the pooled frequency of PSD was approximately 31% [4]. There is significant variation in the reported prevalence of PSD, which ranges from 5% to 65% [5]. This variation can be attributed to a number of factors including ethnicity, use of different diagnostic criteria, sample size, time interval between the stroke event and assessment, and ☆ The English in this document has been revised by Elsevier Language Editing Plus Service. ☆☆ Disclosure: The authors have no conflicts of interest to disclose. ⁎ Corresponding author at: Department of Psychiatry, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Sosa-Ro 327, Wonmi-gu, Bucheon-si, Gyeonggi-do, Republic of Korea. Tel.: +82 32 340 7067; fax: +82 32 340 2544. E-mail address: [email protected] (C.-U. Pae). http://dx.doi.org/10.1016/j.genhosppsych.2015.02.009 0163-8343/© 2015 Elsevier Inc. All rights reserved.
methodological differences in case selection and use of screening tools. The estimated prevalence of PSD in Korea is approximately 15% [6]. Overall psychiatric issues such as indifference, depression, anxiety, anger and bipolar symptoms are observed in approximately 20%–40% of stroke patients [7]. Poststroke depression has been found to be negatively associated with clinical and functional outcomes in stroke patients. For example, it can lead to a reduced quality of life (QoL), impair activities of daily living (ADL), decrease functional independence, reduce social interactions and reduce the success of rehabilitation. Moreover, PSD increases the burden on health care resources and is associated with a higher mortality rate [8–12]. It has also been linked to cognitive impairments, such as attention deficit, decreased learning ability and executive functions, and slow physical recovery. It is of note that the negative relationship with PSD remains even after remission of depression and is associated with functional deterioration over time [13,14]. It is difficult to determine the precise nature of the relationship between PSD and stroke and the manner in which they are associated with each other in clinical practice. Indeed, the association between neurological complications (e.g., impairments of gait balance) and psychiatric symptoms (e.g., depression) in the aftermath of a stroke has yet
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to be fully characterized. The neurological complications underlying the cognitive, physical and functional impairments associated with stroke have been investigated at length, yet the psychiatric symptoms observed after stroke have received relatively little attention in both research and clinical practice. The most likely reason for the lack of data is that psychiatric symptoms are considered to be additional and secondary manifestations resulting from stroke even though they are frequently observed in patients with stroke. Clinicians need a better understanding of the relationship between psychiatric symptoms and stroke because of the high prevalence of these symptoms in patients with stroke and the consequent and significant delay in clinical recovery and increased risk of mortality. Additionally, it is reasonable to assume that the proper and timely detection of psychiatric symptoms and initiation of rehabilitation will enhance the response to treatment and improve outcomes for patients with stroke. Few studies have investigated the association between PSD and long-term clinical outcomes after a first stroke, particularly in an Asian population. Therefore, the aim of the present study was to investigate the association between baseline severity of PSD symptoms and clinical outcomes of Korean patients with first-onset stroke after 6 months of rehabilitation treatment in a naturalistic setting. We hypothesized that PSD [minimal-to-mild depression (MMD) versus moderate-to-severe depression (MSD)] may be differentially associated with functional outcomes in stroke patients who have undergone a rehabilitation program. 2. Methods 2.1. Patients This study included patients who were admitted to a rehabilitation program within 2–4 weeks of hospital admission for a first-onset ischemic stroke. All patients were consecutively enrolled from the Department of Rehabilitation Medicine at Bucheon St. Mary’s Hospital, Korea, between 2009 and 2011. A diagnosis of PSD was made by board-certified psychiatrists using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients with additional Axis I psychiatric disorders other than depression were excluded to avoid any potential biases from comorbid psychiatric disorders. The presence of comorbid conditions was determined following an assessment of patient medication and/or clinical history by the treating physicians. The study complied with the Declaration of Helsinki and other ethical principles regarding human experimentation. The study protocol was approved by the Institutional Review Board (IRB) of Bucheon St. Mary’s Hospital in Bucheon, Kyeonggi-Do, Korea (IRB approval number: HC13RISI0015). 2.2. Study procedure The present investigation was a 6-month observational study that included collection of sociodemographic data at baseline during person-to-person interviews based on case report forms and the use of self- and clinician-rated scales. Typically, stroke patients were transferred from the Center for Cerebrovascular Attacks to the Department of Rehabilitation Medicine for rehabilitation after completion of acute phase treatment lasting 2–4 weeks. Therefore, the baseline assessment of PSD and stroke symptoms was performed approximately 2–4 weeks after the stroke event, and follow-up visits varied according to the clinical status of each patient during routine clinical practice; the principal visit interval was 1 month. The post-acute-phase 4-week rehabilitation program was conducted in the Department of Rehabilitation Medicine during the hospitalization period. It consisted of a complex program of universal activities that were performed five times per week. Group and individual exercises included in the program are as follows: neurodevelopmental treatment for 30 min; gait or mattress training (for coordination and balance) for 30 min, which focused on the disabled lower limb and
amelioration of gait patterns; functional ADL training for 30 min; occupational therapy for 30 min and modality applications such as heat therapy, electrotherapy and functional electrical stimulation. Additionally, all patients participated in group therapy, music therapy and a 30-min period of manipulation exercises intended to train the hand and improve upper limb function. After discharge, all patients underwent a similar or modified rehabilitation program in an outpatient clinic based on clinical status. 2.3. Symptom assessment The study used the measures below to assess depressive and strokerelated symptoms in patients. Assessments were performed at baseline and at the end of the 6-month observational period. The Korean version of the Beck Depression Inventory (BDI) was used to assess the severity of depression at baseline [15]. The reliability and validity of the BDI are 0.86 and 0.89, respectively. It has a mean correlation of 0.72 with the Hamilton Depression Rating Scale. On this scale, higher total scores indicate more severe depressive symptoms; a score between 0 and 9 indicates minimal depression, a score between 10 and 16 indicates mild depression, a score between 17 and 29 indicates moderate depression, and a score between 30 and 63 indicates severe depression. To evaluate the association between baseline severity of PSD and clinical outcomes a priori defined, all subjects were classified as having either MMD (BDI score of 0–16) or MSD (BDI score ≥17) at baseline. The modified Barthel Index (MBI) [16] was used to evaluate the severity of impairments in ADL. It assesses self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers and stair climbing). The reliability of the MBI is 0.89, and it has a correlation of 0.91 with the Barthel score. The Mini-Mental State Examination (MMSE) [17] was used to quantitatively assess the cognitive status of patients. Since its development in 1975, the MMSE has been validated and extensively used in both clinical practice and research. The reliability of the MMSE is 0.89, and it has a correlation of 0.78 with the Blessed Orientation Memory-Information score. 2.4. Clinical outcomes The primary end point of the study was the mean change in the MBI score from baseline to 6 months. The secondary end points were the mean change in the MMSE score from baseline to 6 months and the proportion of patients who had an unfavorable outcome versus a favorable outcome based on the MBI score at 6 months. The nature of an unfavorable outcome was defined using an MBI score b 60, as suggested by Sulter et al. [18], rather than by attempting to define a favorable outcome (no consensus has been agreed for the definition of a favorable outcome). Sulter et al. [18] proposed that patient outcomes should be determined using multiple measures and should be defined as poor (unfavorable) based on multiple factors (i.e., death, institutionalization due to stroke or an MBI score b60). According to a systematic review of stroke studies [18], the MBI was used in 13 clinical trials and served as a primary outcome measure in 7 clinical trials; 2 of these trials compared mean scores, and 2 trials used median scores. The present study defined an unfavorable outcome as an MBI score b 60 at 6 months because the MBI is the most commonly used rating scale for the assessment of ADL in stroke patients. 2.5. Statistical analyses For all descriptive statistics, continuous variables were presented as means with standard deviations (S.D.), and categorical variables were presented as frequencies. To examine group differences in sociodemographic characteristics at baseline, an analysis of variance (ANOVA) or an analysis of covariance (ANCOVA) was used for continuous variables where appropriate, and a χ 2 or Fisher’s Exact Test was used for categorical
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variables. The correlation coefficients for baseline BDI score, change of MBI score and the MBI score at final follow-up were also calculated. The scores of the MMD and MSD groups were compared using ANOVA for symptoms and other clinical parameters that were reported as continuous variables. The mean changes in the MBI and MMSE scores between baseline and 6 months were compared between the MMD and MSD groups using ANCOVA and age, number of comorbid conditions and baseline scores as covariates. Logistic regression analysis was performed to determine the association between baseline severity of PSD and the risk of an unfavorable outcome. Age, sex, education level, work status, family history of stroke, past history of depression, income level, alcohol use, tobacco use, marital status, number of comorbidities and baseline scores of BDI, MMSE and MBI were included as covariates in the regression model. In the regression model, the dependent variable was unfavorable outcome and the independent variable was the severity of PSD (MMD vs. MSD). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the severity of PSD were also calculated for an unfavorable outcome. The odds ratio (OR) and 95% confidential intervals (CIs) were calculated. It was determined that, using these statistical parameters and taking into account adjustment for covariates, the study would have a power of 80.0% to detect a medium effect of 0.4824. This corresponded to a value of 15.2 for the mean difference in the changes in MBI score from baseline to 6 months between the MMD and MSD groups. All statistical analyses were conducted using the NCSS 2007 and PASS 2008 software packages (NCSS LLC, Kaysville, UT, USA). Statistical significance was two-tailed and set at Pb.05. 3. Results
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higher; 65% of patients were classified as middle class; 61% of patients had a job prior to the stroke event; and 37% of patients had a comorbid condition (Table 1). The mean BDI, MMSE and MBI scores at baseline were 12.9, 20.1 and 41.7, respectively (Table 1). 3.1.2. Group comparisons (MMD versus MSD) Out of a total of 180 patients, 127 (70.6%) were diagnosed with MMD and 53 (29.4%) were diagnosed with MSD. As expected, the mean BDI score for the MMD group (7.5) was significantly lower than that of the MSD group (27.8) (Table 1). There were no significant differences in terms of sociodemographic variables between the groups at baseline in terms of age, sex, education level, work status, family history of stroke and psychiatric disorders, past history of depression, socioeconomic status, use of alcohol and tobacco, and the number of comorbid conditions (Table 1). The proportion of comorbid conditions more than one was significantly higher in the MSD group than the MMD group. There were no difference in the mean baseline MBI score between the MSD and MMD groups; however, the mean baseline MMSE score was significantly higher in the MMD group compared with the MSD group (Table 1). 3.2. Clinical outcomes 3.2.1. Primary end points The mean change in the MBI score across all patients was 19.9, which represented an increase of 47.7% between baseline and 6 months. The mean change in the MBI score between baseline and 6 months was significantly greater (F=4.910, P=.029) in the MMD group (23.8, 55.9%) than in the MSD group (8.6, 21.9%); the magnitude of the group difference was 15.2 (Fig. 2).
3.1. Baseline characteristics 3.2.2. Secondary end points 3.1.1. Total subjects The patient disposition is summarized in Fig. 1. The study included 180 patients with an average age of 61.0 (13.3) years. Approximately 84% of patients were married and 16% were widowed, unmarried or separated; 64% of the patients were educated to middle school level or
3.2.2.1. Mean changes in the MMSE. The mean change in the MMSE score across all patients was 5.2, which represented an increase of 25.9% between baseline and 6 months (Fig. 2). There was no significant difference between the MMD and MSD groups in terms of the mean change
Fig. 1. The patients’ disposition in the present study.
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Table 1 Clinical variables by the baseline depression severity between MMD and MSD groups Remark Age Sex Education Work status Family history of stroke Past history of depression Socioeconomic status Use of alcohol Use of tobacco Marital status Comorbidity proportion Comorbidity number BDI⁎ MMSE⁎ MBI⁎
Female ≥ Middle school Employed Yes ≥ Middle income Yes Yes Married ≥1
MMD (n=127)
MSD (n=53)
Total (N=180)
F or χ2/P values
60.4 (14.0) 59 (46.5) 89 (70.0) 85 (66.9) 19 (15.0) 11 (8.7) 82 (64.6) 55 (43.3) 63 (49.6) 105 (82.7) 41 (32.3) 0.9(0.9) 7.5(4.7) 20.9(6.9) 42.6(30.3)
62.6 (11.2) 33 (62.3) 36 (67.9) 35 (66.0) 13 (24.5) 9 (17.0) 38 (71.7) 23 (27.7) 27 (50.9) 47 (88.7) 26 (49.1) 1.1(0.8) 27.8(9.9) 17.9(8.2) 39.2(29.6)
61.0 (13.3) 92(51.1) 115(63.9) 110(61.1) 32(17.8) 23(12.8) 120(66.7) 78(43.3) 90(50.0) 152(84.4) 67(37.2) 1.0(0.9) 12.9(11.1) 20.1(7.4) 41.7(30.1)
NS NS NS NS NS NS NS NS NS NS 4.502/.042 NS 300.235/b.0001 4.917/.028 NS
Data represent number (S.D.) or number (percent). NS, not significant. Statistical comparisons with ANOVA or Fisher’s Exact Test. ⁎ Baseline scores.
in MMSE score (4.4 versus 7.4, respectively; F= 0.564, P= .456) from baseline to 6 months. 3.2.2.2. Unfavorable versus favorable outcomes. Patient outcomes at 6 months was defined a priori as favorable or unfavorable based on an MBI score b60. Approximately one half of the study participants exhibited an unfavorable outcome. The OR for an unfavorable outcome in the MSD group was approximately 3.5 relative to the MMD group (Table 2). Further analysis of these groups using different criteria for an unfavorable outcome (MBI score b 75 and b 85) showed that patients with MSD retained a substantially higher risk of an unfavorable outcome compared with patients with MMD (Table 2). Logistic regression analyses outlined the association between baseline severity of PSD (MSD) and unfavorable outcome (Table 3). The sensitivity of using the severity of PSD to predict an unfavorable clinical outcome in the MSD group was 0.714, the specificity was 0.585, the positive predictive value was 0.370, the negative predictive value was 0.857, the positive likelihood ratio was 1.723, and the negative likelihood ratio was 0.488. The baseline BDI score had a weak correlation with the change (r=−0.185, P=.064) in MBI score and a negative correlation with the final MBI score (r=−0.196, P=.044). The change in MBI score was positively correlated with the final MBI score (r=0.541, Pb.001). 4. Discussion The present study demonstrated that symptoms of depression are significantly associated with long-term clinical outcomes as measured by MBI score at 6-month follow up. These results agree with findings
from previous studies, which report that depression has a significant association with treatment response to rehabilitation in stroke patients [8–14,19–23]. Similar to previous findings [8–12], the baseline BDI score study was 12.9 in the present study, and 29.5% of patients exhibited symptoms consistent with at least moderate depression, which is consistent with a clinical diagnosis of MDD. Therefore, the study results show that PSD is a common mental condition in stroke patients; they also support previous findings that the prevalence of depression in stroke patients in Western and East Asian populations is between 30% and 50% [12,24]. The present findings are also consistent with a recent European multicenter study of 1064 patients [25] which found that, of the 383 patients diagnosed with PSD (36%), approximately 80% of these patients were found to have mild depression with dysthymia rather than MDD. The severity of PSD had a consistent and significant effect on the clinical outcomes of stroke patients. The mean change in MBI score was 2.8fold higher in the MMD group than in the MSD group. The percentage improvement in MBI score was also higher in the MMD group than in the MSD group, with a difference in magnitude of 34%. Further analysis of these groups using different criteria for an unfavorable outcome (MBI score b75 and b85) showed that patients with MSD had a substantially higher risk of an unfavorable outcome than patients with MMD. When the NPV was used as a predictor of an unfavorable clinical outcome in the MSD group, patients with MMD had a probability of 85.7% for a favorable clinical outcome. These findings suggest that the absence of severe depression, (e.g., MSD) in stroke patients may predict a more favorable clinical outcome. The baseline BDI score had a weak negative correlation with the change in MBI score, and a significant and negative correlation with the final MBI score. These findings also indicate the
Table 2 Proportion of favorable versus unfavorable outcome as priori defined at 6 months between MMD and MSD groups*.
Clinical outcome Favorable Unfavorable† Additional clinical outcome results Favorable Unfavorable‡ Favorable Unfavorable§
Fig. 2. The percentage improvement in MMSE (P=.456) and MBI (P=.029) scores from baseline to the end of follow-up (6 months) between MMD and MSD.
MMD (n=82)
MSD (n=28)
Total (N=110)
48 (58.5) 34 (41.5)
8 (28.6) 20 (71.4)
56 (50.9) 54 (49.1)
37 (45.1) 45 (54.9) 27 (32.9) 55 (67.1)
4 (14.3) 24 (85.7) 4 (14.3) 24 (85.7)
41 (37.2) 69 (63.8) 31 (31.8) 79 (68.2)
Data represent number (percent); definition of unfavorable clinical outcome, †b60, ‡b75, § b85 in MBI score at 6 months; *Fisher’s Exact Test; †P=.008, OR for unfavorable outcome in MSD=3.529, 95% CIs, 1.280–9.973; ‡P= .003, OR=4.933, 95% CIs, 1.442–18.528; § P=.087, OR=2.945, 95% CIs, 0.849–11.180.
G.-Y. Park et al. / General Hospital Psychiatry 37 (2015) 245–250 Table 3 The regression model for the association between severity of PSD and unfavorable outcome
Baseline severity of PSD
B
S.E.
Wald
OR (95% CIs)
P value
1.168
0.521
5.039
3.217 (1.160–8.924)
.025
potential association between baseline severity of PSD and long-term outcomes relating to ADL. The mean changes in MMSE scores from baseline to 6 months did not differ significantly between the MMD and MSD groups. This suggests that the severity of PSD in stroke patients is less likely to be associated with improvement of cognitive function than ADL. Alternatively, it is possible that the MMSE score is not sensitive enough to detect differences in treatment responses between patients with MMD and those with MSD. This clinical issue requires further research using a robust study design. The present study has several strengths compared with previous studies. It is the first study to adopt the proposed criteria for unfavorable outcomes, as defined by MBI score, and used additional criteria in the form of different threshold scores for treatment response. The results also help to address the lack of long-term studies investigating the association of baseline severity of PSD with clinical outcomes in stroke patients, particularly in an Asian population. We believe that the findings from this study contribute substantially to current understanding of the relationship between the severity of PSD and the clinical outcomes of stroke patients. The present study has several methodological limitations. The power of the present sample appeared to be sufficient (80%) to detect an effect size of 0.5, which corresponds to the magnitude of difference in MBI scores from baseline to 6 months between the MMD and MSD groups. However, a larger sample size would provide greater sensitivity for the detection of smaller differences between the MMD and MSD groups. A larger sample size would enable post hoc analyses to address pertinent clinical issues relating to the nature of stroke and baseline demographic factors. Moreover, the duration of the follow-up period (6 months) may have been insufficient to detect the long-term effects of baseline depression [26]. For example, the South London Stroke Register study [27], which followed up patients for up to 10 years, demonstrated that depression is independently associated with poor health outcomes. Inherent methodological shortcomings, such as the timing of the assessment of PSD, the clinical heterogeneity of PSD and various clinical differences in stroke, should also be considered limitations of the study, as described previously [12]. This study did not evaluate other psychological factors that might affect clinical outcomes in stroke patients, such as personality and anxiety. A neurotic personality is associated with a lower QoL in stroke patients [28], and anxiety is also strongly related with QoL as a negative predictor than depression [29]. As the present study employed a naturalistic observational approach, which does not provide details of the clinical course for each patient, the number of follow-up visits between baseline and the end of observation at 6 months was insufficient. The disadvantages of cohort study also include potential large sample size requirements, long follow-up periods, possible misclassification of diagnosis (i.e., selection bias) and disease outcomes (i.e., development of advanced diagnosis techniques and treatments during follow-up), potential loss of significant portion of cohort (i.e., bias in results) and a need to perform reassessment on a frequent basis (i.e., natural course of disease), eventually leading to impediments in data acquisition and results as well as huge expenses and resources [30]. Finally, it should be clearly taken into mind that a cohort study cannot determine any causal relationship between certain clinical factors (i.e., depression) and disease outcomes (i.e., stroke outcome) since the study methodology itself may be affected by known confounders such as stroke severity as well as hidden unknown confounders leading to possible faulty conclusion. Therefore, we have
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found only that potential association between PSD and stroke outcomes may exist in the present study. 5. Conclusion The present findings demonstrated a negative association between baseline severity of PSD and functional recovery after 6 months of rehabilitation treatment in Korean patients after a first-onset stroke. Early detection and management of the symptoms of depression in patients with a first stroke should be taken into account during routine clinical practice. This consideration will facilitate tailored therapy for individual patients and will be helpful in supporting clinicians during the clinical decision-making process with respect to functional improvement in patients. Acknowledgement This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0003). References [1] Kroenke K. Patients presenting with somatic complaints: epidemiology, psychiatric comorbidity and management. Int J Methods Psychiatr Res 2003;12:34–43. [2] Greden JF. Physical symptoms of depression: unmet needs. J Clin Psychiatry 2003; 64(Suppl. 7):5–11. [3] Kroenke K, Spitzer RL, Williams JB, Linzer M, Hahn SR, deGruy III FV, et al. Physical symptoms in primary care. Predictors of psychiatric disorders and functional impairment. Arch Fam Med 1994;3:774–9. [4] 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: 1017–25. [5] Johnson JL, Minarik PA, Nystrom KV, Bautista C, Gorman MJ. Poststroke depression incidence and risk factors: an integrative literature review. J Neurosci Nurs 2006; 38:316–27. [6] Choi-Kwon S, Han K, Choi S, Suh M, Kim YJ, Song H, et al. Poststroke depression and emotional incontinence: factors related to acute and subacute stages. Neurology 2012;78:1130–7. [7] Fedoroff JP, Starkstein SE, Parikh RM, Price TR, Robinson RG. Are depressive symptoms nonspecific in patients with acute stroke? Am J Psychiatry 1991;148:1172–6. [8] Williams LS, Ghose SS, Swindle RW. Depression and other mental health diagnoses increase mortality risk after ischemic stroke. Am J Psychiatry 2004;161:1090–5. [9] Haghgoo HA, Pazuki ES, Hosseini AS, Rassafiani M. Depression, activities of daily living and quality of life in patients with stroke. J Neurol Sci 2013;328:87–91. [10] Mutai H, Furukawa T, Araki K, Misawa K, Hanihara T. Long-term outcome in stroke survivors after discharge from a convalescent rehabilitation ward. Psychiatry Clin Neurosci 2013;67:434–40. [11] Farner L, Wagle J, Engedal K, Flekkoy KM, Wyller TB, Fure B. Depressive symptoms in stroke patients: a 13 month follow-up study of patients referred to a rehabilitation unit. J Affect Disord 2010;127:211–8. [12] Dafer RM, Rao M, Shareef A, Sharma A. Poststroke depression. Top Stroke Rehabil 2008;15:13–21. [13] Sinyor D, Amato P, Kaloupek DG, Becker R, Goldenberg M, Coopersmith H. Poststroke depression: relationships to functional impairment, coping strategies, and rehabilitation outcome. Stroke 1986;17:1102–7. [14] Parikh RM, Robinson RG, Lipsey JR, Starkstein SE, Fedoroff JP, Price TR. The impact of poststroke depression on recovery in activities of daily living over a 2-year followup. Arch Neurol 1990;47:785–9. [15] Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71. [16] Granger CV, Dewis LS, Peters NC, Sherwood CC, Barrett JE. Stroke rehabilitation: analysis of repeated Barthel index measures. Arch Phys Med Rehabil 1979;60:14–7. [17] Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12: 189–98. [18] Sulter G, Steen C, De Keyser J. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke 1999;30:1538–41. [19] Pohjasvaara T, Vataja R, Leppavuori A, Kaste M, Erkinjuntti T. Depression is an independent predictor of poor long-term functional outcome post-stroke. Eur J Neurol 2001;8:315–9. [20] Kotila M, Numminen H, Waltimo O, Kaste M. Post-stroke depression and functional recovery in a population-based stroke register. The Finnstroke study. Eur J Neurol 1999;6:309–12. [21] Saxena SK, Ng TP, Koh G, Yong D, Fong NP. Is improvement in impaired cognition and depressive symptoms in post-stroke patients associated with recovery in activities of daily living? Acta Neurol Scand 2007;115:339–46. [22] Chemerinski E, Robinson RG, Kosier JT. Improved recovery in activities of daily living associated with remission of poststroke depression. Stroke 2001;32:113–7.
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