depresi post stroke1

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Maree L. Hackett, Chaturangi Yapa, Varsha Parag and Craig S. AndersonStudies

Frequency of Depression After Stroke : A Systematic Review of Observational

ISSN: 1524-4628Copyright 2005 American Heart Association. All rights reserved. Print ISSN: 0039-2499. OnlineStroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514

doi: 10.1161/01.STR.0000165928.19135.352005, 36:1330-1340: originally published online May 5, 2005Stroke

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Frequency of Depression After StrokeA Systematic Review of Observational Studies

Maree L. Hackett, MA (Hons); Chaturangi Yapa, BSc; Varsha Parag, MSc (Hons);Craig S. Anderson, PhD, FRACP, FAFPHM

Background and PurposeAlthough depression is an important sequelae of stroke, there is uncertainty regarding itsfrequency and outcome.

MethodsWe undertook a systematic review of all published nonexperimental studies (to June 2004) with prospectiveconsecutive patient recruitment and quantification of depressive symptoms/illness after stroke.

ResultsData were available from 51 studies (reported in 96 publications) conducted between 1977 and 2002. Althoughfrequencies varied considerably across studies, the pooled estimate was 33% (95% confidence interval, 29% to 36%)of all stroke survivors experiencing depression. Differences in case mix and method of mood assessment could explainsome of the variation in estimates across studies. The data also suggest that depression resolves spontaneously withinseveral months of onset in the majority of stroke survivors, with few receiving any specific antidepressant therapy oractive management.

ConclusionsDepression is common among stroke patients, with the risks of occurrence being similar for the early,medium, and late stages of stroke recovery. There is a pressing need for further research to improve clinical practice inthis area of stroke care. (Stroke. 2005;36:1330-1340.)

Key Words:depression epidemiology meta-analysis stroke

Some form of depression is considered to occur in at leastone-quarter of patients in the first year after acutestroke,14 with the period of greatest risk being the first fewmonths after onset.2,5,6 However, such estimates vary consid-erably across studies because of differences in definitions,study populations and the timing of assessments, as well ascomplexities in the recognition, assessment, and diagnosis ofabnormal mood in the setting of stroke-related disability.3,4,7

The results of studies may also depend on whether subjectsare categorized on the basis of psychiatric interview usingstandard diagnostic criteria such as the Diagnostic and Sta-tistical Manual of Mental Disorders (eg, DSM-IIIR,8 DSM-IV9), or a psychiatric rating scale such as the Montgomerysberg Depression Rating Scale,10 or on the basis of aself-rating mood scale. The goal of this review was todetermine the frequency, outcome, and management of de-pression after stroke from all high-quality published studies.

Materials and MethodsThis review was restricted to published research articles, abstracts,and letters of patients with a clinical diagnosis of stroke in whom anassessment of mood was performed at a prespecified time point. Thereview included incidence studies and case series that had prospec-tive consecutive patient recruitment within clearly defined geograph-

ical and time-limited boundaries. There were no restrictions on thebasis of language, sample size, or duration of follow-up, but weexcluded studies of mixed populations (such as stroke and headinjury) unless separate results for stroke patients were identified.Studies were also excluded if they had any of the following: (1)limited to specific patient characteristics such as sex or location ofstroke lesion; (2) convenience sampling; (3) retrospective recruit-ment; or (4) there was only unstructured assessment of mood.

The primary endpoint was the proportion of patients who met thediagnostic category of depression as applied in a study, whichincluded: (1) depressive disorder, depressive symptoms, or psycho-logical distress, as defined by scores above a cut-point for abnor-mality on a standard mood scale; and (2) major depression or minordepression (or dysthymia) according to DSM-IIIR,8 DSM-IV,9 orother standard diagnostic criteria.

Studies that reported mood outcomes only as a continuousvariable, without a categorical diagnosis, were excluded.

Search Strategy and Data ExtractionData for this review were identified from the following comput-erized databases: MEDLINE, EMBASE, CINAHL, PsychINFO,Applied Science and Technology Plus, Biological Abstracts,General Science Plus, Arts and Humanities Index, Science Cita-tion Index, Social Sciences Citation Index, Sociofile, and DigitalDissertations using terms and strategy based on the CochraneStroke Group methodology (full details available on request; lastsearched June 2004). In some cases, similarities between studyreports indicated the possibility of multiple publications from the

Received November 15, 2004; final revision received January 13, 2005; accepted February 15, 2005.From the George Institute for International Health (M.L.H., C.S.A.), Neurological Diseases and Ageing Division, Royal Prince Alfred Hospital and

the University of Sydney, Australia; and the Clinical Trials Research Unit (C.Y., V.P.), Faculty of Medical and Health Sciences, the University ofAuckland, New Zealand.

Correspondence to Maree Hackett, the George Institute for International Health, PO Box M201, Missenden Road, Sydney, NSW 2050, Australia.E-mail [email protected]

2005 American Heart Association, Inc.

Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000165928.19135.35

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same cohort. In the absence of explicit cross-referencing, wejudged artic les to be from the same cohort if they met thefollowing criteria: there was evidence of overlapping recruitmentsites, study dates, and grant funding numbers; and there weresimilar or identical reported patient characteristics in the stud-ies.11 If several articles reported outcomes from the same study

population, data were taken from the first publication that referredto each follow-up period. When a variety of methods of moodassessment were undertaken, we reported results for each scale/method. Because we were unable to obtain enough information onpublications from one group of papers (the Iowa Group), wechose to present these studies separately.

TABLE 1. Frequency of Depressed Mood After Stroke: A Summary of the Population-Based Evidence

Study Country No. Assessed Time Since Stroke Depression Diagnosis/Criteria Frequency (95% CI)

Bristol Stroke Study25 UK 379 3 wk WDI (score 1936, depressed) 22 (18 to 26)

All strokes WDI (score 1518, probably depressed) 11 (8 to 14)

All strokes 377 6 mo WDI (score 1936, depressed) 20 (16 to 24)

WDI (score 1518, probably depressed) 12 (9 to 15)

All strokes 348 12 mo WDI (score 1936, depressed) 18 (14 to 22)

WDI (score 1518, probably depressed) 13 (10 to 17)

FINNSTROKE58 Finland 321 3 mo BDI (score 10) 47 (42 to 53)

BDI (score 3063 severe) 3 (1 to 5)

BDI (score 1929 moderate) 11 (8 to 14)

BDI (score 1018 mild) 28 (23 to 33)311 12 mo BDI (score 10) 47 (42 to 53)

BDI (score 3063 severe) 2 (0 to 4)

BDI (score 1929 moderate) 15 (11 to 19)

BDI (score 1018 mild) 25 (20 to 30)

rebro Stroke Study24 Sweden 231 12 mo GDS (score 5) 37 (31 to 43)

251 12 mo DSM-IV depression 27 (22 to 33)

OCSP6 UK 89 1 mo DSM-III: major depression 11 (5 to 18)

DSM-III: dysthymic disorder 1 (0 to 3)

PSE/index of definition 19 (11 to 27)

76 1 mo BDI (score 10) 32 (22 to 43)

BDI (score 13) 20 (11 to 29)

BDI (score 17) 8 (2 to 14)

119 6 mo DSM-III: major depression 9 (4 to 14)



107 6 mo BDI (score 10) 32 (23 to 41)

BDI (score 13) 15 (8 to 22)

BDI (score 17) 6 (2 to 11)

112 12 mo DSM-III: major depression 5 (1 to 9)



88 12 mo BDI (score 10) 16 (8 to 24)

BDI (score 13) 8 (2 to 14)

BDI (score 17) 1 (0 to 3)

Prevalence over 12 mo BDI (score 10) 39 (30 to 48)

ICD-9 Psychiatric disorder 22 (15 to 29)

60 35 y DSM-III-R major depression 18 (8 to 28)

PCSS2 Australia 191 4 mo DSM-III major depression 17 (12 to 22)

DSM-III minor depression 11 (7 to 15)

All strokes 294 4 mo DSM-III major depression 15 (11 to 19)

DSM-III minor depression 8 (5 to 11)

SELSS63 UK 96 5 y HADS (score10) 36 (26 to 46)

BDI indicates Beck Depression Inventory; CI, confidence interval; DSM, Diagnostic and Statistical Manual of Mental Disorders; HADS, Hospital Anxiety and

Depression Scale; OCSP, Oxford Community Stroke Study; PCSS, Perth Community Stroke Study; PSE, Present State Examination; SELSS, South East London StrokeStudy; UK, United Kingdom; WDI, Wakefield Depression Inventory.

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One reviewer (M.H.) extracted the data, and a second reviewer(C.Y.) cross-checked a selection of data extractions. Studies weregrouped into 3 categories that represented degrees of case selection.The first group, population-based studies, considered to be of thehighest (least biased) quality, consisted of studies that attempted torecruit all stroke patients, including those who were not admitted tohospital for acute care. Although not all of these studies fulfilledcertain ideal criteria for population-based stroke incidence stud-ies,12 we considered that these studies included stroke patients withthe most representative characteristics.

The other 2 categories were hospital-based studies, whichincluded all inpatients from acute care medical wards in generalhospitals, and rehabilitation-based studies, which included patientsfrom rehabilitation wards, or hospitals (including stroke units), withone study of patients recruited from an outpatient clinic13 and onestudy of patients from primary care general practices.14

Statistical AnalysisStudies were stratified by case selection, and according to the timingof mood assessment from stroke onset, defined as: acute phase(within 1 month and including date of admission to rehabilitationbeds); medium-term phase (between 1 and 6 months and including

date of discharge from rehabilitation); and long-term phase (6months or more) after stroke. Studies with follow-up assessments

that spanned 2 time points (eg, 2 to 6 weeks after stroke) wereincluded in the latter time category.

We used the depression category that included the most patients todetermine the point estimate, together with 95% confidence intervals(CIs) for each study. Pooled estimates were calculated using bothfixed and random effects. When one study contributed more than oneendpoint to the pooled estimate, sensitivity analyses were undertakenusing either the earliest or the latest assessment in that study,although data were presented herein only for the earliest assessment.Statistical heterogeneity was assessed using the standard Q statistic,with P0.05. When there was evidence of statistical heterogeneity,the random effects approach of DerSimonian and Laird15 was used topool the frequencies.

ResultsMore than 12 000 references were identified, of which 418were retrieved to assess for inclusion/exclusion criteria, and atotal of 96 reports (51 studies) were considered eligible forinclusion.

Patient Characteristics

The 6 population-based studies included 2869 patients from abase population of 1 338 981 between 1981 and 2000 (Table

TABLE 2. Frequency of Depressed Mood After Stroke: A Summary of the Hospital-Based Evidence

Author, Year Country No. Assessed Time Since Stroke Depression Diagnosis/Criteria Frequency (95% CI)

Aben, 200233 Netherlands 154 1 mo DSM-IV depression 22 (15 to 28)

Prevalence over 1 y DSM-IV major depression 23 (16 to 30)

DSM-IV minor depression 15 (9 to 21)

Andersen, 199432 Denmark 209 46 wk HDRS (score 13) 21 (15 to 26)

Bayer, 200144 Jordan 168 3 mo DSM-IV major depression 25 (19 to 32)

Berg, 200146 Finland 89 2 wk DSM-III-R major depression 6 (1 to 11)

BDI (score 10) 27 (18 to 36)

Desmond, 200327 USA 421 3 mo HDRS (score 12) 11 (8 to 14)

Ebrahim, 198764 UK 149 6 mo GHQ (score 12) 23 (16 to 30)

Eriksson, 2004*17 Sweden 13 999 3 mo Single simple question 14 (14 to 15)

Hayee, 200134 Bangladesh 161 3 mo BDI (score 10) 41 (33 to 49)

156 1 y 42 (34 to 50)

Herrmann, 199526 Germany 47 Within 2 mo DSM-III-R major depression 19 (8 to 30)

DSM-II I-R minor depression 17 (6 to 28)

Herrmann, 19985 Canada 150 3 mo MADRS (score 7) 27 (20 to 34)

ZDS (score 50) 22 (15 to 29)133 1 y MADRS (score 7) 22 (15 to 29)

ZDS (score 50) 21 (14 to 28)

Hosking, 200048 New Zealand 79 3 mo GDS (score 9) 39 (28 to 50)

Hwel, 199849 Germany 102 59 d MADRS (cut-point not stated) 55 (45 to 65)

Jaracz, 200350 Poland 72 6 mo ZDS (score 50) 46 (34 to 57)

Kotila, 198465 Finland 154 3 mo BDI (cut-point not stated) 44 (36 to 52)

1 y 29 (22 to 36)

Pohjasvaara, 199866 Finland 277 3 mo DSM-III-R major depression 26 (21 to 31)

DSM-II I-R minor depression 14 (10 to 18)

BDI (score 10) 44 (38 to 50)

276 15 mo BDI (score 10) 45 (39 to 51)Williams, 199955 USA 71 1 mo BDI (cut point not stated) 39 (28 to 50)

*Mood assessed using a single standard question.GDS indicates Geriatric Depression Scale; HDRS: Hamilton Depression Rating Scale; MADRS: Montgomery sberg Depression Rating Scale; USA: United States of

America; ZDS: Zung Depress ion Scale.

1332 Stroke June 2005



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1).1823 All these studies included patients with standardclinical criteria for stroke, although one excluded patientswith subarachnoid hemorrhage in the assessment of moodoutcomes,24 and between 38%20 and 92%19 of all strokepatients were managed in hospital. All studies excluded

patients with communication difficulties (eg, aphasia, confu-sion, dementia), so that the proportion who completed mood

assessments ranged from 61% (3-week assessment)25 to 99%(12-month assessment).24

The hospital-based studies included 16 302 patients (seeTable 2), and the rehabilitation-based studies included 6036patients (Table 3) at the initial assessment. One study17

accounted for the majority (86%) of patients in the hospital-based studies, with the remaining studies ranging in size from

TABLE 3. Frequency of Depressed Mood After Stroke: A Summary of the Rehabilitation-Based Evidence

First Author, Year,Source of Patients Country No. Assessed Time of Assessment Depression Criteria Frequency (95% CI)

strom, 199337 Sweden 76 Discharge from hospital DSM-III-R major depression 25 (15 to 35)Stroke unit 73 3 mo after stroke 31 (20 to 42)

68 1 y after stroke 16 (7 to 25)

57 2 y after stroke 19 (9 to 29)50 3 y after stroke 29 (16 to 42)

Bacher, 199038 Canada 48 Admission to hospital ZDS (score 60) 4 (0 to 10)Rehabilitation hospital ZDS (score 5059) 25 (13 to 38)

43 6 wk after admission ZDS (score 60) 9 (1 to 18)

ZDS (score 5059) 26 (13 to 39)

42 6 mo after admission ZDS (score 60) 17 (5 to 28)

ZDS (score 5059) 24 (11 to 37)

39 1 y after admission ZDS (score 60) 21 (8 to 33)

ZDS (score 5059) 31 (16 to 45)

Bendsen, 199745

Rehabilitation hospital

Denmark 128 1.5 mo after stroke DSM-III-R major depression 16 (10 to 22)

Carod-Artal, 200067

Stroke unitSpain 90 1 y after stroke HDRS (cut-point not stated) 38 (28 to 48)

Daily, 198368

Stroke unit

USA 32 Admission to unit7 d after admission

HDRS & BDI (cut-point not stated) 16 (3 to 29)25 (10 to 40)

Diamond, 199529

Geriatric rehabilitation unit

USA 14 Admission to unitDischarge from unit

GDS (score 10) 36 (11 to 61)29 (5 to 53)

Folstein, 197716


USA 20 30 d after stroke PSE ( 8 items on the 8th edition) 45 (23 to 67)

Gainotti, 199947

Neurology department &

rehabilitation center

Italy 153 2 mo after stroke24 mo after stroke4 mo after stroke

DSM-III-R major depression/HDRS (score 17

DSM-III-R major depression/HDRS (score 17)

27 (20 to 34)/32 (25 to 39)40 (32 to 48)/60 (52 to 68)

Gillen, 200169

Inpatient rehabilitation

USA 243 15 d after stroke GDS (score 15) 13 (9 to 17)

Gottlieb, 200270

Inpatient rehabilitation

Israel 65 3 mo after stroke9 mo after stroke

GDS (50% items endorsed) 63 (51 to 75)58 (46 to 70)

Jrgensen, 199971

Geriatric rehabilitation center

Germany 77 6 mo after discharge DSM-IV major depression 20 (11 to 29)

Kauhanen, 199951 Finland 101 3 mo after stroke DSM-III-R major depression 9 (3 to 15)Stroke unit 92 1 y after stroke DSM-III-R minor depression 44 (34 to 54)

DSM-III-R major depression 15 (8 to 22)

DSM-III-R minor depression 26 (17 to 35)

Kellermann, 199972

Stroke unit

Hungary 82 1 wk after admission BDI (score 10) 20 (11 to 28)

Kim, 200213

Outpatient clinic

Korea 145 312 mo after stroke DSM-IV depression (5 items), BDI (score 13) 15 (9 to 21)

King, 200239

Rehabilitation units and

general hospital

USA 53 Discharge from unit610 wk after discharge

CES-D (score 16) 30 (8 to 42)26 (14 to 38)

1 y after discharge 17 (7 to 27)2 y after discharge 23 (12 to 34)Prevalence over 2 y 51 (38 to 65)




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4726 to 42127 patients. The largest rehabilitation-based study28

contributed 50% of patients, with the remaining studiesranging in size from 1429 to 47030 patients. Only 2 separatecohorts were clearly identified from the Iowa Group, whichincluded up to 463 patients (Table 4).

Diagnosis of DepressionA variety of methods were used to diagnose depressive illnessor assess the degree of depressive symptoms, covering 10different mood scales and 4 different psychiatric interviewschedules. Mood scales were either self-completed by pa-tients (in 4 studies) or interviewer administered and scored(20 studies), and the psychiatric interviews were conductedeither alone (in 4 studies) or in combination with a self-administered or interviewer-administered mood scale (10studies). The remaining studies used either varying combina-tions of these methods, or the method was not explicitlystated in the report. Two studies used a single simple questionto diagnose depression,17,31 but these data were not included

in the pooled estimates because of the nonstandard method ofassessment.

The criteria used to define depression (or depression symp-tom burden) also varied across studies. In the main, DSMcriteria were used to define depression (in 19 studies) usinginformation from completed mood scales, and occasionallyfrom structured interviews, although the criteria for dysthy-mia were modified by excluding the requirement for symp-

toms to be present for at least 2 years. There was alsovariation in the cut-points used on the standardized moodscales, whereas there was consistency for the Montgomerysberg Depression Rating Scale (7) and the Zung Depres-sion Scale (50), these scales were used in only a minority(6) of studies, whereas multiple cut-points were used for theBeck Depression Inventory (10, 10, 13, and 17), theGeriatric Depression Scale (5, 10, 15, 50% itemspositively endorsed), and the Hamilton Depression RatingScale (8, 12, 13, 17, 18).

Frequency of Depression

Although there was considerable variation in the reportedfrequency of depression after stroke across individual studies,

TABLE 3. Continued

First Author, Year,Source of Patients Country No. Assessed Time of Assessment Depression Criteria Frequency (95% CI)

Langhorne, 2000*31

Stroke unit & hospital

Scotland 311 Duration of hospitalization Single simple question 16 (12 to 20)

Lincoln, 199814

54 GP practices

UK 84 1 mo after stroke HADS (score 10) 13 (6 to 20)

Lfgren, 199959

Geriatric stroke and

rehabilitation ward

Sweden 47 3 y after stroke DSM-IV ongoing depression 38 (24 to 52)

Malec, 199052

Rehabilitation unit

USA 20 830 d after stroke HDRS (score 8) 35 (14 to 56)

Mast, 200473


USA 195 1 wk after admission GDS (score 10) 36 (30 to 43)

Morris 199040 Australia 99 2 mo after stroke DSM-III major depression 14 (7 to 21)Hospital, geriatric unit & DSM-III minor depression 18 (10 to 26)rehabilitation hospital 56 15 mo after stroke DSM-III major depression 7 (2 to 12)

DSM-I II minor depression 5 (1 to 10)

Ng, 199557 Singapore 52 22 da after stroke DSM-III-R depressive illness 55 (42 to 69)Rehabilitation center 49 Discharge from unit 29 (16 to 42)

Paolucci, 199930

Rehabilitation unit

Italy 470 50 d after stroke HDRS (score 18) 28 (24 to 32)

Sinyor, 198653 Canada 64 59 d after stroke ZDS (score 60) 22 (12 to 32)Rehabilitation hospital ZDS (score 5059) 25 (14 to 36)

Spalletta, 200256 Italy 153 714 d after admission DSM-IV major depression 41 (33 to 49)Neuropsychiatric rehabilitation DSM-IV minor depression 17 (11 to 23)

Tang, 200274

Stroke rehabilitation unit

China 157 1 mo after stroke DSM-III-R depression 17 (11 to 24)

Van de Weg, 199954

Rehabilitation centres

Holland 85 36 wk after stroke DSM-III-R depression 35 (25 to 45)

Verdelho, 200460 France 110 6 mo after stroke MADRS (score 7) 43 (34 to 52)Acute stroke unit 96 1 y after stroke 36 (26 to 46)

71 2 y after stroke 24 (14 to 34)73 3 y after stroke 18 (9 to 27)

Weimar, 200228

Mixed

Germany 2853 1 y after stroke CES- D (score 17) 33 (31 to 35)

*Mood assessed using a single standard question.CES-D indicates Centre for Epidemiologic Studies-Depression scale; DSM, Diagnostic and Statistical Manual of Mental Disorders; GP, General Practitioner.




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TABLE 4. Selection of Publications by the Iowa Group on the Frequency of Depression After Stroke

First Author, Year Assessed/Alive Time Since Stroke Topic Depression Criteria Frequency

Cohort 1*

Robinson, 198275 103/154 Acute assessment Prevalence and severity of depression GHQ-28 5 29

GHQ-28 6 23

GHQ-28 8 17

Robinson, 198376 103 2 wk Predictors of depression DSM-III Major D 27

DSM-III Minor D 20

Robinson, 198477 40/154 3 mo Prevalence and duration of depression DSM-III Major D 22

DSM-III Minor D 27

50/154 6 mo DSM-III Major D 34

DSM-III Minor D 26

Robinson, 198778 37/154 12 mo Prevalence of depression DSM-III Major D 14

DSM-III Minor D 19

48/154 2 y DSM-III Major D 21

DSM-III Minor D 21

Parikh, 199079 63 2 y Recovery over 2 y DSM-III Major D 24

DSM-III Minor D 6

Cohort 2

Castillo, 199380 288/309 2 wk Generalized anxiety disorder and depression HDRS (no cutpoint), PSE (no cutpoint) 38

Downhill, 199481 140/309 Baseline Depression and cognitive impairment DSM-IV Major D 40

DSM-IV Minor D 35

Castillo, 199582 142/215 Baseline Correlates of early and late onset GAD Depression 51

78 3 mo DSM-III-R GAD 27

80 6 mo 27

70 12 mo 36

66 2 y 17

27

Kishi, 199683 301 Baseline Validity of observed depression DSM-IV Major D 17DSM-IV Minor D 18

Paradiso, 199784 142 Baseline Psychological symptoms associated with depression HDRS (no cut-point), PSE (no cut-point) 42

76 3 mo 38

79 6 mo 39

69 12 mo 29

66 2 y 38

Schultz, 199785 142 Baseline GAD and depression and recovery DSM-IV GAD 19

77 3 mo 22

79 6 mo 25

70 12 mo 11

66 2 y 18Shimoda, 199886 142 Baseline GAD and depression on recovery DSM-IV Major D 19

DSM-IV GAD 23

Shimoda, 199887 142 Baseline Social functioning and depression on recovery DSM-IV Major D 19

DSM-IV Minor D 25

Paradiso, 199888 301 2 wk Gender differences in depression DSM-IV Major D 17

DSM-IV Minor D 18

GAD indicates generalized anxiety disorder; GHQ, General Health Questionnaire.*Funding numbers: MH00163, NS15178, NS16332, NS18622, NS92032; recruitment period 1.5 years, or between January 1980 and July/August 1981;

populations had similar demographic characteristics.Did not report funding number NS9-2032.Funding numbers: MH00163, MH40355; populations had similar demographic characteristics.




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the pooled estimate indicates that depressive symptoms arepresent in 33% (95% CI, 29% to 36%) of all stroke survivorsat any time during follow-up (Figure). The pooled estimatefrom the population-based studies was 33% in the acute andmedium-term phases, with a slight increase to 34% in thelong-term phase of recovery after stroke. There was modestvariation in the pooled frequencies in the hospital-based(acute 36%, medium-term 32%, and long-term 34%) andrehabilitation-based studies (acute 30%, medium 36%, andlong-term 34%) over time, but the 95% CIs around all pooledfrequencies overlapped.

There was, however, more variation in the pooled frequen-cies when studies were grouped by method of mood assess-ment (data not presented). The 2 studies that used a singlesimple question to determine depression status17,31 had apooled frequency of 14% (95% CI, 14% to 15%). Thesmallest pooled frequency with standardized questionnaireswas from studies that used the Hamilton Depression RatingScale (26%; 95% CI, 11% to 42%), whereas the highestfrequency was in studies that used the Montgomery sberg

Depression Rating Scale (41%; 95% CI, 23% to 60%) or theZung Depression Scale (41%; 95% CI, 34% to 48%). The

estimates again varied when studies were grouped by type ofmood scale and timing of assessment.

The Oxfordshire Community Stroke Project,6 conductednearly 20 years ago, is the only population-based study todate that recruited controls to allow estimates of the relativerisks of depression after stroke. Using Beck DepressionInventory (scores 10) and the Present State Examinationpsychiatric interview schedule (scores 5) to determinecaseness, the study showed that the frequency of depressionin stroke survivors (20% Beck Depression Inventory; 11%Present State Examination) was twice that in controls, al-though this difference only reached statistical significance atthe 6-month follow-up assessment. In addition, 4 hospital-based studies have compared mood data in cases withcontrols, although only 1 study had controls selected from thecommunity.32 However, this latter study only assessed pa-tients with new episodes of depression within the 6 monthsafter stroke, yet still included patients with depression thathad been present for 1 year. Despite this anomaly, the 5%proportional frequency of new depression was similar in

stroke patients and controls. Another study showed no dif-ference in the cumulative 1-year incidence of depression after

Observational studies of the proportionalfrequency of depression after stroke.




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stroke compared with a randomly selected control group ofpatients with first-ever myocardial infarction (in contrast toconsecutive recruitment of stroke patients).33 Different resultswere found in 2 other studies: one study in which controlswere randomly selected from the neighboring hospital com-munity and including spouses of stroke patients27 showedmore depression in stroke survivors (11%) than controls (5%)at 3 months after stroke (odds ratio [OR], 2.52; 95% CI, 1.35to 4.80); and the other study that did not provide any detailson the selection of controls, reported that depression was alsomore common in stroke patients than controls (OR, 3.16;95% CI, 1.48 to 4.12).34

Another robust examination of the relative frequency ofdepression in stroke survivors was undertaken in The Fra-mingham Study, a prospective, observational, community-based study that enrolled middle-aged subjects who havebeen followed-up biennially since the middle of the pastcentury.35 When data from 74 of the 251 subjects whoexperienced a stroke between 1982 and 1994 were isolated

and compared with data from 74 control subjects matched forage and sex, significantly more stroke survivors (38%) weredepressed at 6 months after stroke than controls (10%). In aseparate analysis of 20-year outcomes from 148 subjectswith a stroke between 1972 and 1974,36 only 1 (11%) of 9stroke survivors met the criteria for depression comparedwith 3 (15%) of 20 nonstroke controls.

History of Depression, Antidepressants,and PsychotherapyOnly 2 population-based studies have assessed the naturalhistory of depression within individual stroke patients.6,25

Both found that only a small proportion of patients had

depressive symptoms that persisted for most of the first yearafter stroke, despite the relatively constant overall frequencyof depression among the total study population during thistime. Although some patients recovered spontaneously fromdepression within a few months, others had depressivesymptoms for the first time later after stroke. Similar resultswere found in 1 hospital-based,5 and 4 rehabilitation-basedstudies,3740 and are further confirmed by this review.

It is well-recognized that personal or family history ofdepression may place an individual at increased risk ofdepression.4143 Although no population-based studies ex-cluded patients with a history of depression from analyses, 17hospital-based and rehabilitation-based studies excluded pa-tients with recent or severe depression,13,26,30,32,38,44 55 includ-ing 6 studies in which patients using antidepressants at entrywere also excluded.30,46,48,5254

Use of antidepressants at entry or during follow-up wasassessed in less than half of the included studies, and rangedfrom 0% in the first few weeks56 to 31% at 2 years afterstroke.39 The highest proportion of adequately treatedpatients (ie, those using antidepressants who did not fulfilcriteria for depression) at the time of assessment in any onestudy was 84%.27 The highest proportion of participantsreceiving antidepressants who were inadequately treated(ie, those on antidepressants who still fulfilled criteria for

depression) was 71%,57

but this frequency ranged between17% and 36% in most studies.5,24,34,51,54,58 60 No data were

available on the proportion of stroke patients who hadreceived psychotherapy.

DiscussionWe report that one third of all people experience significantdepressive symptoms at some time after the onset of stroke.We recognize, however, that this is likely to be a conservative

estimate because of potential under-reporting (or under-recognition) of abnormal mood, and the difficulties inherentto the assessment of mood in patients with neurologicaldisability, particularly when there are communication prob-lems caused by dysphasia and/or dementia. Given the impor-tance of mood, which along with cognition, motivation, andsocial support is a key factor influencing recovery fromstroke, it is surprising that there is much misconception overthe epidemiology of stroke-associated depression, althoughthe generally poor quality of studies has obviously contrib-uted to this situation.

Whereas previous reports have acknowledged wide varia-

tion in the frequency of depression after stroke across studieslargely because of differences in patient characteristics andstudy designs, they have also suggested that the lowest andhighest frequency of depression is found among patients inpopulation-based and rehabilitation-based studies, respec-tively, potentially reflecting selection bias toward the inclu-sion of more disabled stroke survivors in the latter studies.2,5,6

Moreover, the time period of greatest risk of depression hastraditionally been considered to be the first few months ofstroke onset. Our review, conversely, showed consistency inthe overall frequency of depression across the 3 differenttypes of studies and in relation to the time periods from strokeonset, thus raising doubts about specific biological theories

related to an acute stroke lesion as the major cause ofdepression in this condition. In addition, we found that fewstroke patients receive effective management (antidepressantsor psychotherapy) for their depression, although the limiteddata would suggest that these symptoms are self-limited inmost after several months.

Because the design of observational studies, by their verynature, may differ in a number of important ways,61 it isuseful to explore and quantify the reasons for such heteroge-neity. We identified variation in the cut-points used todetermine caseness in the standardized mood scales as onekey source of variability in the data. It would appear thatmany studies failed to consider that older people, and thosewith physical illnesses, might require higher cut-points onthese scales. Two other problems were that multiple methodswere often used to diagnose depression, with few investiga-tors clearly identifying an a priori primary endpoint in theirstudy, so that the endpoints reported varied between anydepression, first-ever depression, and severity of de-pression. Without greater uniformity or standardization ofsuch methodological issues, it will remain difficult to deter-mine whether heterogeneity in study findings represent truedifferences in characteristics of populations or simply artifactcaused by measurement bias and other error.

Of course, heterogeneity across studies can also be attrib-

uted to differences in case mix, including variation in strokefeatures, clinical characteristics, source of patient recruit-




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ment, and the timing of assessment. In this review, we haveattempted to minimize heterogeneity by grouping studies bysource of case selection. It is particularly noteworthy that anumber of studies excluded patients at the greatest risk fordepression, that is those with a history of depression. Al-though a systematic review with meta-analysis can overcomesome of the shortcomings of unstructured examination ofindividual studies, the gold standard review would include anindividual patient data analysis with adjustment for potentialconfounding factors to calculate frequency estimates, but thisis complex and challenging to undertake.

There are other problems of study design that limit thereliability of the comparisons of frequency estimates betweenstroke patients and controls. It is important to note that strokepatients are generally older, female, and more likely to haveconcomitant illnesses and to have experienced some bereave-ment or other major life event than that of the generalpopulation.62 In this respect, controls need to be matched byage and sex, because these factors are associated with

depression at any age. Yet the selection of controls in 3 of the5 case-control studies did not account for such factors.Although it may appear likely that stroke-associated depres-sion is no more common than other types of depression in thegeneral population, there have been no direct comparisonsbetween stroke patients and people with other disabling andpotentially life-threatening illnesses.

Although we attempted to adhere to the guidelines forreporting meta-analyses of observational studies,61 this re-view does have several limitations. First, we did not hand-search journals and made no attempt to identify unpublishedstudies, raising the possibility that some studies have beenmissed. Second, only one person extracted most of the data.Ideally, 2 people should complete data extraction to reducethe possibility of errors when transcribing study results. Evenso, all the data were checked for accuracy on multipleoccasions and all analyses were conducted twice. Finally, it ispossible that some multiple publications have been mis-coded or missed altogether. We have paid particular attentionto addressing this source of publication bias, because the lackof cross-referencing of data from some cohorts has onlyserved to mislead the research community, specifically inreference to the amount of information available on thedevelopment of depression after stroke.

AcknowledgmentsMaree Hackett holds a Senior Health Research Scholarship, andChaturangi Yapa was in receipt of a Faculty of Medical and HealthSciences Summer Studentship, of The University of Auckland. Thefunding body had no role in the conduct or reporting of the review.

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