Two-year longitudinal study of post-stroke mood disorders: dynamic changes in correlates of depression at one and two years

As part of a prospective study of 103 stroke patients, we have analyzed the relation between depression and associated variables at 3 months, 6 months, 1 year, and 2 years after stroke. At all intervals up to and including 1 year poststroke, patients with left hemisphere strokes showed a strong relation between severity of depression and distance of the lesion on computed tomography scan from the frontal pole. At 2 years poststroke, this relation was no longer significant. The correlation between depression and impairment in activities of daily living peaked at 6 months and thereafter fell but remained significant at 1 and 2 years poststroke. The correlation between depression and cognitive impairment and between depression and social functioning fluctuated--with most correlations at 1 and 2 years follow-up nonsignificant. Although the conclusions that can be drawn from this study are limited by the fact that less than half of the original patients were followed up at each time, these declining correlations between depression and associated variables at 1 and 2 years follow-up may reflect the natural course of major depression which spontaneously remits between 1 and 2 years after stroke. The persisting significant association of impairment in activities of daily living with depression may reflect the effect of severe depression in sustaining and possibly retarding recovery from physical impairment.     

A two-year longitudinal study of poststroke mood disorders. In-hospital prognostic factors associated with six-month outcome

In a prospective study of mood disorders in stroke patients, variables obtained during the acute hospitalization were examined for their relationship to outcome at either 3- or 6-month follow-up. Distance of the lesion on computerized axial tomography scan from the frontal pole in patients with left anterior infarcts was significantly associated with severity of depression at 3 and 6 months poststroke. In addition, intellectual and functional physical impairment in-hospital were significantly correlated with severity of depression and social functioning scores at 3 and 6 months poststroke. Thus, patients who develop depression during the first 6 months poststroke may be responding to the severity of their impairment whereas the patients who develop depressions during the acute poststroke period may have a neuroanatomical and neurophysiological basis for their depression. Although other explanations might be proposed, the dynamic nature of the relationship between depression and associated variables during the first 6 months poststroke indicates that etiology of poststroke depression may be different depending upon the time of onset of the depression after brain injury.     

The impact of poststroke depression on recovery in activities of daily living over a 2-year follow-up

The impact of clinically diagnosed depression on recovery in activities of daily living over a 2-year follow-up was examined in a prospective study of 63 stroke patients. Although impairment in activities of daily living, neurologic diagnoses and findings, lesion location and volume as measured on computed tomographic scan, demographic variables, cognitive impairment, and social functioning were comparable between depressed (n = 25) and nondepressed (n = 38) patients during their acute hospitalization, the two groups had different patterns of recovery in activities of daily living. At 2 years after suffering a stroke, patients with an in-hospital diagnosis of depression (either major or minor depression) were significantly more impaired in both physical activities and language functioning than were non-depressed patients. Among patients with major depression, this disparity in the recovery profile was present even after the depression had remitted. This study emphasizes the need for early recognition and treatment of poststroke depression.     

Prevention of poststroke depression: 1 year randomised placebo controlled double blind trial of mianserin with 6 month follow up after therapy

OBJECTIVES: (1) To test whether early prophylactic antidepressive treatment by mianserin is able to prevent poststroke depression, and (2) to discover whether mianserin as an antidepressant has any beneficial influence on the outcome of ischaemic stroke. METHODS: A randomised, double blind, placebo controlled study involved 100 consecutive patients under 71 years old admitted to hospital for an acute ischaemic stroke; they were enrolled to receive 60 mg/day mianserin or placebo for 1 year. They were examined on admission, and at 2, 6, 12, and 18 months with depression, stroke, and functional outcome scales. RESULTS: According to DSM-III-R, the prevalence of major depression was 6% at the initial stage, 11% at 1 year, and 16% at 18 months. At no time point did prevalences differ between the treatment groups, nor were differences found in depression scales, although at 2 months a greater improvement from initial assessment on the Hamilton depression scale was evident in patients on mianserin (p=0.05). Some beneficial changes on the Hamilton depression scale and Beck depression inventory were found in patients older than 56 (median age) and in men treated with mianserin, but not in other subgroups. Mianserin treatment did not affect stroke outcome as measured by neurological status, nor did it have any influence on functional outcome as measured by Rankin scale or Barthel index. CONCLUSION: It was not possible to show that early initiation of antidepressant therapy can prevent poststroke depression, because the prevalence of poststroke depression remained low even in patients on placebo. In this stroke population with a low rate of depressive patients, antidepressive medical treatment failed to affect stroke outcome.     

Does cognitive recovery after treatment of poststroke depression last? A 2-year follow-up of cognitive function associated with poststroke depression

OBJECTIVE: Cognitive impairment is common after stroke and may be caused by poststroke depression. Remission of poststroke major depression after treatment has been associated with improvement in cognitive function. The current study was designed to examine how long that cognitive improvement lasts and to compare depressed patients' cognitive status with that of nondepressed patients with comparable lesions. METHOD: Seventeen patients with poststroke depression and cognitive impairment who had early and sustained remission of their depression during a double-blind treatment study were compared with 42 nondepressed stroke patients who remained nondepressed throughout the follow-up. Mood and cognitive function were followed-up over 2 years with the Hamilton Depression Rating Scale and Mini-Mental State Examination (MMSE). RESULTS: In the patients with early and sustained remission of depression, there was rapid improvement of cognitive function, which was maintained over 2 years. Their initial MMSE score of 23.3 (SD=4.2) improved to 26.6 (SD=3.5) at 3 months and was 26.1 (SD=3.6) at 2 years. The nondepressed patients showed essentially no change in cognitive function over 2 years (initial MMSE score: mean=26.3, SD=3.1; score at 2-year follow-up: mean=25.7, SD=4.1). CONCLUSIONS: Cognitive function, once improved after remission of poststroke depression, is likely to remain stable over the next 2 years in the absence of subsequent reinjury to the central nervous system. Cognitive impairment due to poststroke depression is reversible and can be quantified separately from cognitive impairment on the basis of the location and extent of ischemic brain damage.     

The effect of early versus late antidepressant treatment on physical impairment associated with poststroke depression: is there a time-related therapeutic window?

Impairments in activities of daily living (ADL) are common after stroke and may be related to poststroke depression. We have demonstrated that remission of poststroke major depression was associated with improvement in ADL. The administration of antidepressants within the first 3 months after stroke has been shown to prevent poststroke depression, early administration might also improve recovery of ADL among patients with stroke. This study examines the effect of early versus late treatment with antidepressants on recovery in ADL. Among 62 patients after stroke, the therapeutic effect of a 3-month course of antidepressants begun during the first month after stroke was compared with the effect of treatment begun after 1 month. The severity of impairment was measured using the Functional Independence Measure (FIM) and post-treatment outcome was assessed over the following 21 months. Although both the early and late treatment groups showed improvements in FIM scores during the 3 months of treatment, the early treatment group improved significantly more than the late treatment group. After the treatment, the early treatment group maintained this improvement over 2 years while the late treatment group deteriorated over time. There were no significant differences in the 2 groups that would explain the findings. Recovery in ADL impairment after stroke appeared to be enhanced by the use of antidepressant medication if treatment was started within the first month after stroke. These findings are consistent with the hypothesis that there may be a time-related therapeutic window in the treatment of physical impairment associated with poststroke depression.     

A two-year longitudinal study of post-stroke mood disorders: dynamic changes in associated variables over the first six months of follow-up

We are prospectively studying a group of 103 stroke patients over the first 2 years after infarction to determine the variables which are associated with the development of depression. At both 3 and 6 months post-stroke, patients with left hemisphere infarcts showed a strong relationship between severity of depression and distance of the lesion on CT scan from the frontal pole. The strength of this association was unchanged from the immediate post-infarction period. In contrast, the correlation between degree of functional physical impairment and severity of depression steadily increased over the 6 month follow-up. The correlation between severity of depression and Mini-Mental score or between depression and social functioning score dropped between in-hospital and 3 months but then increased significantly between 3 and 6 months post-stroke. Age did not correlate with depression beyond the acute post-stroke period. Whether the increasing strength of the relationships between impairment and depression over the first 6 months post-stroke indicates that continued depression led to delayed recovery or whether continued severe impairments led to depression is not known, however, this issue will be addressed in further data evaluation from this prospective study.     

Two-year longitudinal study of poststroke mood disorders: diagnosis and outcome at one and two years

As part of a prospective study of mood disorders in stroke patients, interviews were obtained from 37 patients at 1 year and 48 patients at 2 years follow-up. In-hospital evaluations for these 65 follow-up patients found that 9 patients (14%) had symptom clusters of major depression, 12 patients (18%) had symptom clusters of dysthymic or minor depression, and 44 patients (68%) did not meet the DSM III diagnostic criteria for depression. Although overall prevalence of depression did not change significantly over time, the prognosis for individual patients, depending on diagnostic group, was different. All of the follow-up patients with major depression in-hospital were improved by 2 years, with a significant reduction in their mean depression scores and improvement in their activities of daily living, whereas only 30% of follow-up patients with dysthymic depression improved by this time. There was no significant improvement in their mean depression scores or mean activities of daily living score. Of the patients followed up who were not depressed in-hospital, 34% had developed major or minor depression by 2 years, and their mean depression scores were significantly increased. These data suggest that the prevalence of depression among the follow-up patients remains high (between 30 and 40%) for the first 2 years after stroke, but that untreated poststroke major depression has a natural course of about 1-2 years, with associated improvement in activity of daily living scores, whereas the prognosis for poststroke dysthymic depression is frequently unfavorable and often persists for greater than 2 years.     

The Effect of Poststroke Depression on Recovery from Stroke

Background : Stroke is a major health problem and poststroke depression is known to be one of the frequent and severe psychiatric complications following stroke.
Methods : Based on the results of structured psychiatric mental state exams and DSM diagnostic criteria, the prevalence of poststroke depression has been examined in numerous study populations throughout the world. Longitudinal examinations have documented the effect of poststroke depression on recovery from stroke.
Results : The mean prevalence of poststroke major depression was 21.1 % and minor depression was 17.1% among hospitalized or outpatient samples. Community samples showed a slightly lower rate of 14.1% and 9.1%, respectively. Furthermore, the existence of poststroke depression leads to poorer physical recovery, greater cognitive impairment, and worse recovery in activities of daily living compared with non-depressed patients. Several studies have also found that poststroke depression is associated with increased mortality compared with non-depressed patients who had comparable strokes and similar premorbid risk factors. Finally, several studies have found that successful treatment of poststroke depression improves both cognitive and physical recovery and decreases mortality.
Conclusion : The current review documents the beneficial effect of identifying and treating poststroke depression on both recovery and survival following stroke.     

The sensitivity and specificity of the Center for Epidemiologic Studies Depression Scale in screening for post-stroke depression

The present study examines the sensitivity and specificity of the Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument for post-stroke depression. Eighty stroke patients were evaluated by a research nurse over a two-year period using the CES-D and also by a trained psychiatrist using a standardized interview for affective, cognitive, physical and social functioning. CES-D scores correlated significantly with DSM-III diagnoses of depression in-hospital and at three months, six months, and one year follow-up but not at two years follow-up, reflecting the natural course of these depressions, as well as the predictive validity of the CES-D. Furthermore, at a cut-off point of 16, the CES-D was found to have a specificity of 90 percent, a sensitivity of 86 percent and a positive predictive value of 80 percent and thus may be a potentially useful screening instrument for post-stroke depression.     

Comparison of patients with and without poststroke major depression matched for size and location of lesion

Patients who developed major depression within two years following stroke (n = 13) were compared with patients who did not become depressed in the same period (n = 13) but who did have a similar size and location of lesion as in the depressed group. Although the depressed patients were not significantly different from the nondepressed patients in background characteristics, history of depressive disorder, neurological impairment, or social functioning, the depressed group had greater cognitive impairment as measured by Mini-Mental State score. In addition, the depressed group had significantly larger lateral and third ventricular to brain ratios than nondepressed patients on computed tomographic scan analysis. The results suggest that poststroke depression itself may produce an intellectual impairment; subcortical atrophy, which likely preceded the stroke lesion, may produce a vulnerability for depression following stroke.     

Risk factors for and correlates of poststroke depression following discontinuation of antidepressants

The authors randomly assigned nondepressed patients at least 3 months poststroke to receive nortriptyline, fluoxetine, or placebo for 3 months using double-blind methodology. Patients were followed at 3, 6, 9, and 21 months for new onset of depression. In patients treated with antidepressants, lesion volume and degree of social impairment were associated with subsequent late-onset of poststroke depression at 6 and 9 months. In the placebo group, severity of impairment in activities of daily living, at 3 and 9 months, was associated with late onset poststroke depression. Differences in the clinical/pathological correlates may reflect subtle differences in the pathophysiology of poststroke depression following prophylactic antidepressants.     

Poststroke depression: prevalence, diagnosis, treatment, and disease progression.

In recent years, poststroke depression has attracted worldwide interest. This review focuses on the major research themes that have emerged. Pooled data from studies conducted throughout the world have found prevalence rates for major depression of 19.3% among hospitalized patients and 23.3% among outpatient samples. The diagnosis of poststroke depression is most appropriately based on a structured mental state exam and DSM-IV criteria for depression due to stroke with major depressive-like episode or depressive features. Rarely, poststroke patients may also develop bipolar mood disorder. The treatment of poststroke depression has been examined in several placebo-controlled randomized clinical trials with both nortriptyline and citalopram showing efficacy. The progression of recovery following stroke can be altered by treating depression, which has been shown to improve recovery in activities of daily living and cognitive impairment and to decrease mortality. In addition, two studies have demonstrated that poststroke depression can be prevented using antidepressant medication, which also decreases the frequency of associated physical illness. Furthermore, two studies have shown that premorbid depression can significantly increase the risk of stroke over the subsequent 10-15 years. The mechanisms underlying the association of cerebrovascular diseases and mood disorder are important areas for future investigation.     

Course and Predictors of Subjective Cognitive Complaints During the First 12 Months after Stroke

Background: Subjective Cognitive Complaints (SCC) are common after stroke. This study documents the prevalence and course of SCC in the first year after stroke and determines which patient characteristics in the first 3 months predict subsequent SCC at 1-year follow-up. Methods: Using a longitudinal design, 155 patients (mean age 64.0 ± 11.9 years; 69.7% men) were assessed at 3 and 12 months after stroke. SCC were assessed using the Checklist for Cognitive and Emotional consequences following stroke (CLCE) inventory (content component [CLCE-c] and worry component [CLCE-w]). Potential predictors of 12 months SCC included demographics, stroke severity, objective cognitive impairment, psychological factors (depression, anxiety, perceived stress, fatigue, personality traits, coping style), and activities of daily life functioning assessed at 3 months poststroke. Multiple hierarchical linear regression analyses were used to determine predictors of SCC at 12 months poststroke. Results: SCC remained stable from 3 to 12 months over time (CLCE-c from 3.3 ± 2.4 to 3.3 ± 2.6; CLCE-w: from 1.9 ± 2.2 to 2.1 2.5). Independent predictors of SCC at 12 months were baseline CLCE-c (β = 0.54) and perceived stress (β = 0.23) for content, and baseline CLCE-w (β = 0.57) and depressive symptoms (β = 0.23) for worry. Conclusions: Patients who report SCC at 3 months after stroke are likely to continue having these complaints at 1 year follow-up. Perceived stress and depressive symptoms additionally increase the likelihood of having SCC at 12 months, independent of SCC at 3 months poststroke. Rehabilitation programs that target reduction of stress and depression in the first months after stroke might reduce sustained SCC and improve well-being.     

Psychosocial risk factors in poststroke depression: a systematic review.

OBJECTIVE: To review systematically the psychosocial risk factors for poststroke depression. METHODS: Medline was searched using the key words "poststroke depression" (PSD) for the period January 1, 1966, to June 30, 2000; using the key words "cerebrovascular disease" and "depression" it was searched from June 1, 1996, to June 30, 2000. Corollary articles were obtained from the bibliographies. Inclusion criteria were as follows: original research in French or English; prospective, case-control or cross-sectional study design; assessment of PSD in the first 6 months following the stroke; an acceptable definition of depression; an acceptable definition of stroke; and at least one psychosocial risk factor. Interrater reliability was tested for the selection and quality of the articles. A qualitative risk factor analysis was conducted. RESULTS: The risk factors most consistently associated with PSD are a past history of depression, past personal psychiatric history, dysphasia, functional impairments, living alone, and poststroke social isolation. Risk factors not associated with PSD are dementia and cognitive impairment. Controversial risk factors are age, socioeconomic status (SES), prior social distress, dependency in regard to activities of daily living (ADL), and sex. CONCLUSIONS: Over approximately 30 years, some 25 qualitative studies have addressed psychosocial risk factors for PSD. Further studies should aim for quantitative analysis. The results suggest that identifying psychiatric history and preventing social deterioration and impairment should be part of multidisciplinary efforts to care for poststroke patients.     

A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction

BACKGROUND: The high incidence of post-stroke depression has been claimed to reflect a specific, stroke related pathogenesis in which lesion location plays an important role. To substantiate this claim, post-stroke depression should occur more often than depression after another acute, life threatening, disabling disease that does not involve cerebrovascular damage. OBJECTIVES: To compare the cumulative one year incidence of depression after stroke and after myocardial infarction, taking into consideration differences in age, sex, and the level of handicap. METHODS: In a longitudinal design, 190 first ever stroke patients and 200 first ever myocardial infarction patients were followed up for one year. Depression self rating scales were used as a screening instrument to detect patients with depressive symptoms. Major and minor depression was assessed at one, three, six, nine, and 12 months after stroke or myocardial infarction according to DSM-IV criteria, using the structured clinical interview from DSM-IV. The severity of depressive symptoms was measured with the Hamilton depression rating scale. Level of disability and handicap was rated with the Rankin handicap scale. RESULTS: The cumulative one year incidence of major and minor depression was 37.8% in stroke patients and 25% in patients with myocardial infarction (hazard ratio 1.6; p = 0.06). This difference disappeared after controlling for sex, age, and level of handicap. In addition, no differences were found in the severity of depressive symptoms or in the time of onset of the depressive episode after stroke or myocardial infarction. CONCLUSIONS: Depression occurs equally often during the first year after stroke and after myocardial infarction when non-specific factors such as sex, age, and level of handicap are taken into account. Thus the relatively high incidence of post-stroke depression seems not to reflect a specific pathogenic mechanism. Further research is needed to investigate whether vascular factors play a common role in the development of depression after stroke and myocardial infarction.     

Functional and neuroanatomic correlations in poststroke depression: the Sunnybrook Stroke Study

BACKGROUND AND PURPOSE: The purpose of our study was to determine the functional and neuroanatomic correlates of poststroke depressive symptoms. METHODS: Patients with consecutive admissions to a regional stroke center for new-onset unilateral hemispheric stroke who met World Health Organization and National Institute of Neurological and Communicative Disorders and Stroke criteria were eligible for inclusion in a longitudinal study. Acutely, patients underwent CT scanning, and at 3 months and 1 year after stroke, depressive symptoms were assessed by using both the Montgomery-Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale. The Functional Independence Measure (FIM) served as an indication of functional outcome and was obtained at 1 month, 3 months, and 1 year after stroke, along with other demographic information. The Talairach and Tournoux stereotactic atlas was used for the primary determination of CT lesion localization. Lesion proximity to the anterior frontal pole was also measured. RESULTS: Eighty-one patients participated in the longitudinal study. Stepwise linear regression analyses generated a highly significant model (F(3,76)=9.8, R(2)=28%, P<0.0005), with lower 1-month total FIM scores, living at home, and damage to the inferior frontal region predicting higher depression scores at 3 months. Similarly, lower 3-month total FIM scores correlated with higher 3-month depression scores, and lower 1-year total FIM scores correlated with higher 1-year depression scores. CONCLUSIONS: Functional measures correlated with poststroke depression across time and, together with neuroanatomic measures, predicted depressive symptoms longitudinally. Although inferior frontal lesion location, irrespective of side, appeared to play a role as a risk factor in this study, the degree of functional dependence after stroke imparted the greatest risk.     

Phenomenological characteristics of poststroke depression: early- versus late-onset.

OBJECTIVE: Authors compared poststroke major (n=17) or minor (n=28) depression diagnosed 3 to 6 months poststroke with major (n=16) or minor (n=22) depression diagnosed at 12 to 24 months to identify changes in the phenomenological characteristics of poststroke depression over time. METHODS: Depressive symptoms were divided into vegetative, psychological symptoms, and melancholic features elicited by the Present State Exam (PSE). Patients were also examined for severity of depression, social impairment, and neurological findings. RESULTS: Early-onset poststroke major depression was associated with a higher frequency of vegetative symptoms and larger lesion volume than late-onset major depression. Similarly, early-onset minor depression was associated with poorer social functioning and a higher frequency of melancholic, vegetative, and psychological symptoms than late-onset minor depression. CONCLUSION: These findings suggest that the phenomenological characteristics of both major and minor poststroke depression change over time and that both early-onset major and minor poststroke depression may result from similar etiological mechanisms provoked by brain injury.     

Treatment of cognitive impairment after poststroke depression : a double-blind treatment trial

BACKGROUND AND PURPOSE: Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion. Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy. We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial. METHODS: Patients with major (n=33) or minor (n=14) depression participated in a double-blind treatment study with nortriptyline or placebo. They were examined for change in depressive mood, measured by the Hamilton Rating Scale for Depression (HAM-D), and change in cognitive impairment, assessed by the Mini-Mental State Examination (MMSE), after treatment with nortriptyline or placebo. Cognitive treatment response, as measured by the MMSE, was compared between patients whose depression did and did not respond to treatment. RESULTS: Patients whose poststroke depression remitted (predominantly associated with nortriptyline treatment) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit (predominantly associated with placebo treatment). CONCLUSIONS: Our findings support the contention that poststroke major depression leads to a "dementia of depression." Prior studies failed to show an effect of treatment because the effect size was too small. Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke.     

Mortality and poststroke depression: a placebo-controlled trial of antidepressants

OBJECTIVE: Poststroke depression has been shown to increase mortality for more than 5 years after the stroke. The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up. METHOD: A total of 104 patients were randomly assigned to receive a 12-week double-blind course of nortriptyline, fluoxetine, or placebo early in the recovery period after a stroke. Mortality data were obtained for all 104 patients 9 years after initiation of the study. Demographic and clinical measurements were collected at 3, 6, 9, 12, 18, and 24 months after the stroke. Survival data were analyzed by using the Kaplan-Meier method. RESULTS: Of the 104 patients, 50 (48.1%) had died by the time of the 9-year follow-up. Of 53 patients who were given full-dose antidepressants, 36 (67.9%) were alive at follow-up, compared with only 10 (35.7%) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment, after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled. There were no intergroup differences in severity of stroke, impairment in cognitive functioning and activities of daily living impairment, and other medications received. CONCLUSIONS: Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.