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The Natural History of Depression up to

15 Years After Stroke
The South London Stroke Register
Luis Ayerbe, MSc; Salma Ayis, PhD; Siobhan Crichton, MSc;
Charles D.A. Wolfe, FFPH; Anthony G. Rudd, FRCP
Background and Purpose—Evidence on the natural history of depression after stroke is still insufficient to inform prognosis
and treatment strategies. This study estimates the incidence, cumulative incidence, prevalence, time of onset, duration,
and recurrence rate of depression up to 15 years after stroke.
Methods—Data from patients registered in the South London Stroke Register between 1995 and 2009 were used (N=4022
at registration. Maximum number of participants for these analyses n=1233). Depression was assessed in all patients with
the Hospital Anxiety and Depression Scale (scores >7=depression) 3 months after stroke, 1 year after stroke, and annually
thereafter up to 15 years after stroke. Inverse probability weighting was used to calculate the estimates accounting for
missing data.
Results—The poststroke incidence of depression ranged from 7% to 21% in the 15 years after a stroke, with cumulative
incidence of 55% and prevalence ranging from 29% to 39%. Most episodes of depression started within a year of stroke,
with 33% of the cases starting in the 3 months after a stroke, and none from year 10 onward. Fifty percent of the patients
with depression at 3 months had recovered 1 year after stroke. The proportion of recurrent episodes of depression after
stroke increased gradually from 38% in year 2 to 100% in years 14 and 15.
Conclusions—The natural history of depression after stroke is dynamic. Depression affects most of the stroke patients with
episodes that have a short duration but a high risk of recurrence in the long term.   (Stroke. 2013;44:1105-1110.)
Key Words: cohort studies

depression

A

lthough depression is a recognized outcome of stroke,1
most studies investigating depression after stroke have
limitations, including selection bias, short follow-up, and
small sample size.2,3 The prevalence of depression in the first
few years after stroke has been reported in several studies.2
Nonetheless, evidence is poor or lacking on other estimates of
the long-term natural history of depression, such as the poststroke incidence, cumulative incidence, time of onset, duration, and recurrence rate.2 Interventions for depression after
stroke only show limited effect. Whether these interventions
had been started at the right time after stroke and given for an
adequate length of time to obtain maximal sustained response
has been questioned.4
In this article, the poststroke incidence, cumulative incidence, prevalence, time of onset, duration, and recurrence rate
of depression up to 15 years after stroke are estimated in a
population-based study.

incidence

natural history

prevalence

stroke

Methods
First in a lifetime stroke patients were recruited from the South
London Stroke Register (SLSR), a prospective population-based
stroke register covering an inner-city population of 271 817.5 Data
from patients, registered in the SLSR between January 1, 1995, and
December 31, 2009, and followed up between April 1, 1995 (first 3
months of follow-up assessments), and August 31, 2010, were used
(patients at registration, N=4022).
Patients were registered during the acute phase of stroke and were
then followed up for 3 months after stroke, 1 year after stroke, and annually thereafter. The World Health Organization definition of stroke
was used.6 Follow-up was by postal questionnaire or interview, depending on the capacity of patient to fill in the questionnaire. Such
capacity was judged by the patient, the next of kin, or the field worker
in a preceding follow-up assessment. Patients unable to complete
the follow-up questionnaire, and those not returning them by post,
were telephoned to arrange face-to-face interviews or have another
follow-up questionnaire posted. Patients who could not be followed
up at one time point remained registered and were contacted again
for the following annual assessment. At follow-up, patients were

Received October 4, 2012; final revision received December 21, 2012; accepted December 28, 2012.
From the Division of Health and Social Care Research, King’s College London, London, United Kingdom (L.A., S.A., S.C., C.D.A.W., A.G.R.);
National Institute for Health Research (NIHR) Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
(C.D.A.W.); and Stroke Unit, Guy’s and St. Thomas’ NHS Foundation Trust, St. Thomas’ Hospital, London, United Kingdom (A.G.R.).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
111.679340/-/DC1.
Correspondence to Luis Ayerbe, 7th Floor, Capital House, 42 Weston Street, London SE1 3QD, United Kingdom. E-mail luis.ayerbe_garcia-mozon@
kcl.ac.uk
© 2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org

DOI: 10.1161/STROKEAHA.111.679340

Downloaded from http://stroke.ahajournals.org/
by guest on August 23, 2015
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therefore. therefore.ahajournals. all estimates were obtained only from patients with complete data (ie. all information was collected directly from patients. online-only Data Supplement III). estimates obtained from CC analysis may be biased if the excluded individuals are systematically different from those included.1106  Stroke  April 2013 assessed for depression using the Hospital Anxiety and Depression Scale (HADS). sex.2. Ethics Patients or their relatives gave written informed consent. No cases of depression at 3 months recovering after year 9 were observed (Table 4). Data on HADS were. Variables included in the models were those considered to be associated with completeness: age. and paresis). ethnicity. The maximum number of participants available for analysis was 1233. The cumulative incidence of depression was calculated among patients assessed for depression at any time point. a variable of completeness was created for each estimate.1.org/ by guest on August 23. 1 year after stroke. the SLSR registered 4022 patients. which are largely stable throughout the follow-up.9%– 60.4% (53. particularly those obtained with small number of patients toward the end of the follow-up. The study was approved by the ethics committees of Guy’s and St Thomas’ Hospital NHS Foundation Trust. optimum performance when HADS subscales scores >7 are used to identify depression. As a first step. The poststroke incidence of depression after stroke ranged between 7% and 21% per year during the 15-year follow-up (Table 1. was 33%. between 3 months and 15 years after stroke. and this proportion gradually decreased to 4% in year 9. The prevalence of depression ranged from 29% to 39% during the follow-up period (Table 2.13 The prevalence and poststroke incidence observed in this study.7 Despite its good performance. had confidence intervals with values >1 or <0. only CC estimates are presented because IPW can also introduce error when weights are very large. The proportion of patients depressed at 3 months who recovered each year was calculated among patients with complete follow-up until each time point. IPW was not possible. incontinence. online-only Data Supplement IV). the follow-up time for survivors ranged from 3 months to 15 years. Up to 10 years after stroke. the arcsine correction was used. was calculated among patients who had ≥3 follow-up assessments. Sociodemographic and clinical characteristics of survivors completing and not completing HADS were compared using χ2 test because these variables were categorical. is presented in the online-only Data Supplement I. The other half recovered gradually between years 2 and 9. those who had had more severe strokes were less likely to be assessed (onlineonly Data Supplement III). Finally.12. Weighted and CC estimates of prevalence. The number of patients registered in each period. becoming depressed in the following one and having a previous episode of depression reported. To weight the probability of being complete. Poststroke incidence of depression 3 months after stroke was not calculated because there were no depression assessments before that point. The prevalence of depression was calculated among survivors assessed at each time point.5%) on CC analysis and 58. 2015 . complete case [CC] analysis). Because HADS cannot be answered by proxy. the proportion of patients not depressed at one time point. was calculated among patients with complete follow-up until each time point. and Chelsea and Westminster Hospital. cases were weighted by the inverse of their probability of being a CC. Thirty-three percent of the assessed patients had their first detected episode of poststroke depression 3 months after the acute event. cumulative incidence. at each time point.6). Patients registered in 1995 (n=299) and 1996 (n=350) received their first HADS assessment in 1997.2. HADS is not a diagnostic scale but a screening tool that indicates risk of depression. Discussion These analyses and estimates show that the natural history of depression after stroke is dynamic. or the patient’s next of kin in case of postal questionnaire. assessed for depression or lost to follow-up. only CC estimates were reported. first cases after stroke. However.9 Using IPW.5%) using IPW. The proportion of patients who became depressed for the first time at each assessment. Weighted and CC estimates are presented. no data could be collected from patients with severe cognitive or communication impairment that the field worker. and specificity: 81. National Hospital for Neurology and Neurosurgery. are estimates suggesting a persisting risk of depression among Downloaded from http://stroke. Results Between 1995 and 2009. stroke severity measures (Glasgow Coma Scale.7 Scores >7 in the HADS depression subscale were considered depression. Therefore. to estimate recurrence rate. estimates were calculated on weighted data. with a stable prevalence of ~30% up to 15 years after stroke. There were no observations of patients having their first episode of depression from year 10 onward (Table 3). St George’s Hospital. to allow for a stable model of completeness to be built. Finally. HADS has been validated in stroke patients showing a good performance both when it is used in a face-to-face interview and when it is self-administered8 (Cronbach’s alpha > 0.3 Poststroke incidence is an estimate of natural history that has been scarcely investigated. prevalence of depression at 3 months is 1=observed and 0=missing. and disability at baseline. not included from these patients in the respective estimates for early rates of depression. The proportion of patients depressed at 3 months.11 When this correction was used. In these cases.2% (52.10 Some estimates. For cases with weight >25. the term depression will be used in this article for succinctness in patients with scores >7. between 1 and 68. estimates were calculated using inverse probability weighting (IPW). Few differences were observed between sociodemographic characteristics of patients who were and those who were not assessed for depression (online-only Data Supplement II). poststroke incidence. Although patients with some degree of cognitive or communication impairment can respond to HADS.80. A logistic regression model was built to identify predictors of completeness. in a second step. However. Depression affects more than half of all stroke patients at some point. This study shows a prevalence of depression similar to the one previously reported in other studies. Cumulative incidence of depression was 55. The inverse of the probability of being a CC was calculated and applied to individuals with available data. with most patients recovering from depression after a few years and having a significant risk of recurrent episodes in the long term. although the follow-up is substantially longer. King’s College Hospital Foundation. and duration were consistent at all time points. HADS was routinely collected between 1997 and 2010.9 IPW was not used to estimate rate of recurrences because the number of patients available each year was too low. judged would give invalid responses. sensitivity: 73. When the follow-up period finished in August 2010. Queen’s Square Hospital. For example. Statistical Methods The poststroke incidence of depression was calculated among patients assessed at each time point who were also assessed and not depressed in the previous follow-up. The proportion of recurrent cases rose from 38% in year 2 to 100% in years 14 and 15 (Table 5). Half of the patients who were depressed at 3 months had recovered from depression at 1 year.3%–57. time of onset.

Other studies following stroke patients for up to 3 years published similar results.8) 15.8 (30. y 116 37 31.6 (31.8–34.9 (27.4) 7.3–40.8 (14.7 (27.6 (28.6) 2 488 93 19.9 (8.0–33.5) NR† 12 66 12 18.5) 13.6) 9.4 (18.9) 17.4) 1.6–24.5) 8.2 (9.1 (27.1 (15. y 46 14 30.2 (5. y 72 28 38.3 (12.6–33.1)* NR‡ Because patients who were lost to follow-up for 1 year remained registered and were contacted again the following year. minus the number of incident cases.8 (24.12–14 The increase in recurrent episodes observed during the 15-year follow-up explains why depression starting shortly after stroke and having short duration has a stable prevalence. therefore it was not possible to know whether estimates of depression were different from the ones in general population.6) 33. ‡Estimate not reported as arcsine correction cannot be used.0 (11.5 (23.9 (24. †Weights >25 were considered too high.11 (9.5) 30. CI indicates confidence interval.8 (27.8 (25.6–27. the number of patients at risk may be higher than the number of patients at risk.0) 3.6 (27.8–19. y 234 81 34. y Patient at Risk Depression Poststroke Incidence (95% CI) Weighted Poststroke Incidence (95% CI) 1 518 85 16.9 (10.2) 5 356 58 16. y 600 179 29. y 392 113 28.3–41.7–20.9 (23. y 475 151 31. and NR.2–33.8 (30.5–37.1) 14.6–36.0–24.4)* NR‡ 15 7 1 14.2) 34.4) CI indicates confidence interval. y 296 106 35.3 The duration of the episodes of depression is relatively short.8) 16.6) 8 205 27 13.2 (30.5 (13.1) 34.5–50.5 (26.8–23.8) 32.2–62. Downloaded from http://stroke.6 (28.0–20.0) 30.2–19.6 (11.1) 31.2–26.3 (2.8–36.2) 5. y 658 194 29.9 (28.7) 11.7–43. Two previous studies observed that significantly more stroke survivors were depressed than controls.5) 30.3) 37.5 (22.0–36.6–44.3) 29.1) 6 281 42 14.5) 3 423 69 16.4–31.1–28. y 183 54 29.5) 4.  Poststroke Incidence of Depression up to 15 Years After Stroke Follow-up.0–26.8 (26.6–36.5 (26.4 (16.0 (27.15.5–40.4–20.9 (11.0–40.3 (16. y 16 5 31.2) 30.7–21.2–33.1) 18.5 (25.16 Studies observing general population report lower frequency of depression than that observed among stroke patients with a cumulative incidence Table 2.2 (8.5 (16.5) 31.6) 12.1) 9 159 27 17.  Prevalence of Depression up to 15 Years After Stroke Follow-up Patients Assessed at Each Time Point Prevalence (95% CI) Weighted Prevalence (95% CI) 3m 1101 Patients Depressed 361 32. y 1233 357 28.4–21.4) 35.7–34.6–40.2) 11 94 15 15.5) 29.9) 14.9 (13.5–17. y 1100 340 30.7) 7 268 52 19.3 (0.2.2 (8. 2015 .7–56.9–31.5 (13.1) 6.4–34. in the previous assessment. stroke patients and a dynamic natural history of depression in the long term after stroke.9 (26.Ayerbe et al   Natural History of Depression After Stroke   1107 Table 1.0–34.4 (14.3) 15. and weighted estimates included CIs with values >1 or <0.3–33.4 (26. y 901 266 29.6) 31.9 (8.1–33.5 (12.0–21.3 (12.1 (13.5 (22.4) 10. not reported.3–33.9) 21.7–34.5) 2.7 (0.org/ by guest on August 23.4 (28.1–22.0) 32.ahajournals.7–19.0–47.7) NR† 13 43 9 20.6–22. *Proportions calculated using arcsine correction.5–18.4 (13. The SLSR does not have a control arm.7–33. The cumulative incidence of depression in stroke cohorts has been so rarely reported in previous studies that the overall importance of depression among stroke patients has probably been underestimated.2) 22.6–24.4) 17.1 (27.6) 20.4–23.6) 17.6) NR† 14 15 1 6.5–32.0–35.8) 4 498 85 17. y 890 268 30.3–50.3–50.9) 10 113 22 19.

y No observations§ … … … 14.0–35.0–13.6) 33.3 (43.2–16.3) 4.3–20. *Proportions calculated using arcsine correction.4–12.2 (2.5–56.4) 3 92 7 7.0) 5. *Proportions calculated using arcsine correction. ‡Estimate not reported as arcsine correction cannot be used.4 (3.9 (6.3–50.5) 9. ‡Estimate not reported as arcsine correction cannot be used.4 (6.3 (0. y 44 4 8. of depression between 13% and 17% during patient’s lifetime and incidence between 5% and 10%. y 750 85 11.1) 8. and weighted estimates included CIs with values >1 or <0.6) 2 139 19 13.0 (0. y 450 40 8.17–19 It has been reported that medical illness.9 (7. §No patients had complete follow-up from registration to >12 years. and weighted estimates included confidence intervals with values >1 or <0.0–36.ahajournals.1–57.9 (0.6 (2.8 (0.1108  Stroke  April 2013 Table 3.8–8.0 (9.4–4. y 11 0 0 NR† 12.2 (30.20 The World Health Organization World Health Survey reported from observations in 60 countries that up to 23% of patients with chronic physical diseases had comorbid depression. y Patients With Depression at 3 mo With Complete Follow-up Patients With Depression at 3 mo Recovered for the First Time Proportion of Patients Depressed at 3 mo Recovered for the First Time (95% CI) Weighted Proportion of Patients Depressed at 3 mo Recovered for the First Time (95% CI) 1 232 116 50. not reported.9)* NR‡ 6. y 5 0 0 NR† 13. y 154 3 1.3)* NR‡ 6 26 1 3. increases the risk of depression. unpleasant treatments.5–8.3 (0. y 36 0 0 NR† 9.9)* NR‡ 7 12 0 0 NR† 8 9 0 0 NR† 9 7 1 14.org/ by guest on August 23.09–15.0 (43.3 (9.5) 50. y No observations§ … … … 15.  Recovery After Depression After Stroke Recovery Time.1 (1.8 (30.1)* NR‡ 10 5 0 0 NR† 11 5 0 0 NR† 12 2 0 0 NR|| 13 0 … … … 14 0 … … … 15 0 … … … CI indicates confidence interval. y 87 0 0 NR† 7. Downloaded from http://stroke. †Weights >25 were considered too high.7) 4 74 3 4.8–7.1)* NR‡ 5 41 1 2.2 (2.9–10. 2015 .1–13.3–9. y 329 17 5.6 (2.  Proportion of Patients (With Complete Follow-up) With New Cases of Depression Annually Follow-up Patients With Complete Follow-up and Depression First Detected Number of Patients With Complete Follow-up to Each Time Point Proportion of Patients With Complete Follow-up and Depression First Detected Weighted Proportion of Patients With Complete Follow-up and Depression First Detected 3 mo 1101 361 32. ||Number of observations too low to build a model of completeness.06–10. y No observations§ … … … NR indicates not reported. y 27 1 3. y 249 16 6.4) 13.7 (0.7) 2.2–11.3) 3.9–19. †Weights >25 were considered too high.21 Life-threatening illness.4) 1. y 14 0 0 NR† 11.4–14. and NR.7 (7.4)* NR† 10.6–14.4) NR‡ 8.4 (0. not only stroke.1–15.5) 5.6) 12.6) 5. and drugs causing depression as a side Table 4.

6) 8 26 20 76.7 (46. The exclusion of patients with cognitive and communication impairment is a limitation affecting most studies of depression in stroke cohorts.4) 10 22 17 77. Hackett ML.A. Parag V. Rudd AG. such as sedentary lifestyle. 2008. Wolfe C.19 It would have also been better to assess depression with a diagnostic tool as well. Cochrane Database Syst Rev. Charles D. Anderson CS. of Incident Cases With ≥3 Assessments No.6–54. Wolfe CD.7) 5 54 31 57. Wolfe is an NIHR Senior Investigator.0 (43.8:e1001033. To assess the natural history of depression.9–74.6) 3 57 26 45. of Cases With ≥1 Previous Episode of Depression Proportion of Recurrent Cases 2 65 25 38.  Proportion of Recurrent Cases of Depression After Stroke Follow-up. Toschke AM. Particular thanks to field workers and the team working since 1995 for the South London Stroke Register and the Stroke Research Team at King’s College London.0)* 12 12 10 83.7)* 14 1 1 100 15 1 1 100 *Proportions calculated using arcsine correction. there are some missing data in this study.5 (26.5–82. this had little impact on the estimates of the natural history of depression after stroke. This article presents independent research commissioned by the National Institute for Health Research (NIHR) under its Program Grants for Applied Research funding scheme (RP-PG-0407-10184). Hackett ML.3 (58. The other authors have no conflicts to report.5 (52. Ayerbe L. Toschke AM. Sources of Funding The study was funded by Guy’s and St Thomas’ Hospital Charity.3–82.2 A capture–recapture analysis conducted with the data on incident strokes registered in the SLSR concluded that 88% of the strokes occurring in the study area were being registered. 2008:CD003437. (3) depression is a secondary psychological reaction to stroke.6 (32. 2015 . This suggests that although part of the sociodemographic groups are more likely to be missing than others. y No. With the exception of those patients who do not become depressed shortly after stroke. Heuschmann PU. UK. and (5) stroke has a direct pathophysiological effect on the brain (eg. (2) depression and stroke have risk factors in common.3–58. the NIHR. The Stroke Association.5 (54.8–71. McKevitt CJ. This was not only attributable to the difficulty in following up patients for so long but also to the difficulty of some patients in responding to the HADS. Therefore. References 1.20 Most of these apply to stroke patients. it cannot adjust for unmeasured factors.0)* 13 8 7 87. it should be acknowledged that weighted and CC estimates were always consistent. 2005. the increased prevalence of depression specifically among stroke patients may also be attributable to other causes. and outcomes. such as the SLSR. Grieve AP. depression requires periodic clinical attention in the long term. The HADS shows a good performance detecting depression in patients with no psychiatric conditions according to a systematic review. 5. Assuming that a patient recovering from depression is a closed case could lead to a late diagnosis or an overlooking of a further episode. Acknowledgments We thank all patients and healthcare professionals involved. Estimates of outcomes up to ten years after stroke: analysis from the prospective South London Stroke Register. Wolfe CD.6–94. Department of Health HQIP grant. such as cognitive impairment. The views expressed in this article are those of the authors and not necessarily those of the National Health Service. Frequency of depression after stroke: a systematic review of observational studies. et al. Xia J. It provides the least biased sampling frame and good statistical power in the analyses of data collected in the long term after stroke. Ethnic group disparities in 10-year trends in stroke incidence and vascular risk factors: the South London Stroke Register (SLSR). A systematic review and metaanalysis of depression after stroke. predictors.Ayerbe et al   Natural History of Depression After Stroke   1109 Table 5. these limitations are common in large epidemiology studies. Wolfe acknowledges financial support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Center award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. (4) depression is secondary to other outcomes of stroke.9–99. including the following: (1) depression is a risk factor for stroke.23 However.A. even when stroke seems to be completely settled and many other medical issues may have presented. Crichton SL. However. Stroke.org/ by guest on August 23. its natural history. PLoS Med.9 (59.22 As in almost all cohort studies.0 (55.202:14–21. the validity of results from CC analysis should be considered.3–50. The high rate of recurrence of depression should be noted.ahajournals.4 (43.24 Clinicians should acknowledge that depression remains a frequent active problem long after stroke.2–96. it would have been ideal to followup patients more frequently because the average duration of episodes of depression is shorter than 1 year. effect may explain this association.3 (56. who seem to be at lower risk. Although IPW adjusts for differences in characteristics of patients with complete and incomplete follow-up. Interventions for treating depression after stroke. Yapa C. Disclosure Charles D.9) 4 68 29 42. Heuschmann PU.7–100.36:1330–1340. missing data were handled using IPW.0) 6 40 27 67.7 The SLSR is probably the largest population-based cohort of stroke patients followed up for so long. House A.2 Nonetheless. therefore the proportion of patients at risk of depression may be increased among stroke patients. 3. Stroke. Downloaded from http://stroke. Rudd A. increase of cytokine levels). such as the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. which may result in some patients being more likely to have incomplete follow-up. 2. 2011.39:2204–2210.3) 9 27 17 63. or the Department of Health. National Institute for Health Research Program Grant (RPPG-0407-10184). 2013. and to obtain maximum robustness. both the results of IPW and CC analysis are presented.7) 7 51 31 60.6 (30. Br J Psychiatry. 4. However.3) 11 15 12 80. in contrast with previous studies. Ayis S. Grieve AP.0–100. Anderson CS.

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3%) 1995-1999 N=1502 12 year Dead <12y=966 LTF=99 FU=128 HADS=116 (51.1%) 1995-1998 N=1193 13 year Dead <13y=704 LTF=63 FU=96 HADS=72 (45. Number of participants included in the analysis at each follow up time point N= number of patients registered.1%) 1995-2002 N=2288 9 year Dead <9y= 1451 LTF=211 FU=356 HADS=296 (52.0%) Supplement 1.SUPPLEMENTAL MATERIAL Follow up time Registration period since stroke 3 months Dead <3m=1064 LTF=1015 FU=1943 # HADS=1101** (37.5%) 1995-2000 N=1726 11 year Dead <11y=1165 LTF=134 FU=203 HADS=183 (54.3%) 1995-1997 N=863 14 year Dead <14y=451 LTF=40 FU=51 HADS=46 (47.2%) 1995-2001N=2018 10 year Dead <10y=1297 LTF=167 FU=262 HADS=234 (54. .0%) 1995-1996 N=204 LTF=558 FU=1858 HADS=1233## (51.8%) 1995-2007 N=3524 4 year Dead <4y=1695 LTF=498 FU=1094 HADS=890 (55.3%) 1995-2004 N=2807 7 year Dead <7y=1664 LTF=330 FU=568 HADS=475 (52.9%) 1995-2006 N=3287 5 year Dead <5y=1728 LTF=517 FU=820 HADS=658 (49.9%) 1995-2003 N=2562 8 year Dead <8y=1563 LTF=251 FU=474 HADS=392 (54.6%) 1995-2008 N=3740 3 year Dead<3y =1652 LTF=556 FU=1316 HADS=1100 (58.4%) 1995-1996 N=542 15 year Dead<15y =172 LTF=16 FU=16 HADS=16 (50.2%) ¶ 1995-2009 N=4022 1 year Dead<1y=1541 1995-2009 N=3957 2 year Dead<2y=1523 LTF=954 FU=1263 HADS=901 (40.2%) 1995-2005 N=3065 6 year Dead <6y=1702 LTF=395 FU=710 HADS=600 (54.

. FU= Number of patients followed up at each time point. # Note that some patients who were followed up could not be assessed with HADS due to cognitive or communication impairment.HADS=number of patients completing the depression scale. ¶ Proportion of patients assessed with HADS over the total patients followed up and lost to follow up ##The 299 patients registered in 1995 were not assessed for depression at this time point as HADs was routinely collected from 1997. **The 649 patients registered in 1995 and 1996 were not assessed for depression at this point as HADs was routinely collected from 1997. LTF=Number of patients lost to follow up at each time point.

7 43.7 68.6/30.7 38.6/40.0 66.2/39.2/43.7/50.3/64.HADS completed / HADS not completed †† Age>65(%) Female gender (%) White ethnicity (%) Black ethnicity (%) 3m 64.1 22.4 45.2/29.1 24.6/44.4/28.3 26.3/59.1/24.1 39.5 Supplement 2 Comparison of sociodemographic characteristics of the survivors assessed.8 2y 59.8/55.4 41. with the HADS at each time point ‡‡ p<0.7/37.1/30.1/47.8/30.8/35.9/58.7/69.3 25.3/64.9 41.2 38.1/61.4/55.2 27.5 44.1/37.2/61.4 71.0‡‡ 22.4 69.1 66.7/35.8/30.6‡‡ 24.7/56.8/46.7/50 56.8/44.0 66.2/25.0/55.3‡‡ 44.1/68.0 9y 38.8§§ 23.9/44.0 3y 57.6/61.4‡‡ 7y 49.2 70.2 71.4 15y 43.2 42.1 36.7/24.4/41.3 6y 50.5‡‡ 13y 33.2‡‡ 5y 49.2 64.5 11y 44.8/27.6/46.1/44.2 36.9‡‡ 25.5 23.0 31.5/40.2 70.9/60.2 69.0/65.3 22.1/70.05 §§ p<0.8 67.6 42.4/38.2 1y 61.2/31.6/43.8 68.6/62.5‡‡ 24.4 23.8 29.7 10y 37.2/63.7‡‡ 8y 44.4/27.0/47.8/42.2 26.5/62.3/48.7 68. and not assessed.0/39.6 14y 37.8 67.7/23.7/63.8/33.7 12y 39.6/45.7/28.7/56.9/59.8/42.7§§ 4y 54.01 †† Survivors who did not complete the HADS were either lost to follow up or unable complete the HADS due to cognitive or communication impairment .8 68.3‡‡ 41.9 46.3/40.

9 13y 81.6 31.9/85.6 §§ 30.1 80.2/29.5/27.7/24.2/25.2 79.9/78.7 §§ 5y 89.0 §§ 26.9 6y 90.4 70. . Comparison of the stroke clinical characteristics of survivors assessed.6 ‡‡ 33.6 ‡‡ 33.6 25.8 81.1 §§ 75.3 8y 90.9 32.2/68.9/28.0/91.7/18.3 ‡‡ 76.4/34.05 §§ p<0.0/72.3 §§ 33.8/25.6 §§ 43.8/69.7/35.1 §§ 33.0/32.3/71.8/24.9/36.4/71.9/87. with HADS at each time point ‡‡ p<0.1/36.9/25.7/84.2/72.0 37.9 ‡‡ 11y 88.4 ‡‡ 40.0 9y 89.3 §§ 32.1/86.7/29.7 §§ 3y 88.3 §§ 7y 90.5 75.8/67.8 ‡‡ 32.3 42.1/25.2 12y 85.0/71.3 §§ 73.1/25.8 14y 87.6/27.7 ‡‡ 44.6/33.01 †† Survivors who did not complete the HADS were either lost to follow up or unable complete the HADS due to cognitive or communication impairment.3 73.4 §§ 10y 87.2 Supplement 3.3 17.6/85.3 §§ 37.3/64.HAD completed / HADS not completed †† GCS>12 Urine continence No paresis Barthel Index=20 (%) (%) (%) (%) 3m 90.8/28.3/68.7/71.3 27.1 83.7 ‡‡ 4y 90. and not assessed.2/22.4/19.1/38.7/93.4/87.9/72.6/69.2 74.4 §§ 41.8 18.7/86.0/28.1 §§ 30.5/86.2 33.3/32.0/65.7/88.1 §§ 1y 90.2/86.7 79.8/26.4/32.2/75.7 40.2/28.1/85.2 §§ 30.6/86.6 15y 93.4 44.2 §§ 28.8/35.9/26.0/84.7 81.5/29.0 18.8 80.0/56.2 38.3 §§ 2y 89.5 ‡‡ 41.4 78.8 ‡‡ 77.6 46.3 41.7/88.

Incidence of Depression up to 15 years after stroke 12 15 .60 50 40 30 Post stroke Incidence (%) 20 10 0 1 3 6 9 Time (years) Supplement 4.

60 50 40 30 Prevalence % 20 10 0 1 3 6 Time (years) 9 Supplement 5. Prevalence of Depression up to 15 years after stroke 12 15 .

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