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Depression and Antidepressant Use After Stroke and

Transient Ischemic Attack
Nada El Husseini, MD, MHS; Larry B. Goldstein, MD; Eric D. Peterson, MD, MHS; Xin Zhao, MHS;
Wenqin Pan, PhD; DaiWai M. Olson, RN, PhD; Louise O. Zimmer, MA;
John W. Williams, Jr, MD, MHS; Cheryl Bushnell, MD, MHS; Daniel T. Laskowitz, MD, MHS
Background and Purpose—Patients with stroke and transient ischemic attack (TIA) often have comparable comorbidities,
but it is unclear whether they have similar rates of depression or antidepressant use.
Methods—This study was a secondary analysis of a prospective cohort registry that enrolled subjects from 2006 to 2008 in the
United States. Depression (defined by the Patient Health Questionnaire-8 score ⱖ10) and medication use were prospectively
assessed 3 and 12 months after hospitalization in 1450 subjects with ischemic stroke and 397 subjects with TIA.
Results—The proportional frequency of depression after stroke and TIA was similar at 3 months (17.9% versus 14.3%,
P⫽0.09) and at 12 months (16.4% versus 12.8%, P⫽0.08). The rates of newly identified depression between 3 and 12
months were also similar (8.7% versus 6.2%, P⫽0.12). Persistent depression (defined as Patient Health Questionnaire-8
score ⱖ10 at both 3 and 12 months) was present in 134 (9.2%) of those with stroke and in 30 (7.6%) of those with TIA.
Younger age, greater stroke-related disability, and inability to work at 3 months were associated with persistent
depression in subjects with stroke. Among subjects with persistent depression, 67.9% of those with stroke and 70.0%
of those with TIA were not using antidepressants at either time point (P⫽0.920).
Conclusions—Stroke and TIA subjects had a similar frequency of depression at 3 and 12 months after hospitalization and
similar rates of newly identified depression between 3 and 12 months. A high proportion of those with persistent
depression was untreated. (Stroke. 2012;43:1609-1616.)
Key Words: behavioral neurology 䡲 cerebral infarct 䡲 cerebrovascular disease 䡲 neuropsychology 䡲 stroke care
䡲 transient ischemic attack

D

epression is the most common psychiatric disorder
affecting patients with stroke and may contribute to
poststroke morbidity and mortality.1 The frequency of poststroke depression varies considerably across studies depending on cohort characteristics and diagnostic criteria but is
considerably higher than control populations matched for age
and sex.2– 4 The pathophysiology of poststroke depression is
likely multifactorial and influenced by the location and extent
of brain injury, vascular comorbidities, and reaction to new
functional disability.5–7 Patients with transient ischemic attack (TIA) share comorbid conditions with those who have
had an ischemic stroke, and although approximately 30% to
40% may have radiographically demonstrated brain injury, by
definition, a TIA is not associated with a long-lasting functional impairment. Nonetheless, there is a paucity of studies
assessing the proportional frequency of depression and antidepressant use among patients with TIA.8,9 Furthermore,

there are little patient-level longitudinal data reflecting the
presence or absence of depression and antidepressant use
within the year after hospitalization for stroke or TIA. Such
analyses are needed to inform screening recommendations
and to assess the adequacy of current treatment approaches.
Various reports on depression care in the general US
population suggest racial and ethnic disparities in the use of
psychiatric resources, including the use of antidepressants.10 –12 Other factors such as financial stress, lack of health
insurance coverage, and the presence of concurrent medical
conditions may also affect antidepressant use.11,12 It is not
clear whether the same factors affect antidepressant use in
patients with stroke and depression.
The primary objectives of the current study were to compare
the proportional frequency of depression, newly identified depression between 3 and 12 months and antidepressant use in the
year after hospitalization for stroke or TIA. The secondary

Received November 3, 2011; final revision received January 17, 2012; accepted February 1, 2012.
From the Department of Medicine (N.E.H., L.B.G., E.D.P., D.M.O., J.W.W., D.T.L.), Division of Neurology (N.E.H., L.B.G., D.M.O., D.T.L.), and
Duke Clinical Research Institute (E.D.P., X.Z., W.P., D.M.O., L.O.Z., D.T.L.), Duke University Medical Center, Durham, NC; Durham Veterans Affairs
(L.B.G., J.W.W.), Durham, NC; and the Department of Neurology (C.B.), Wake Forest University Health Sciences, Winston-Salem, NC.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.111.
643130/-/DC1.
Correspondence to Nada El Husseini, MD, MHS, Duke University Medical Center, Department of Medicine, Division of Neurology, Bryan Research
building, Research Drive, Suite 201A, Durham, NC 27710. E-mail nada.elhusseini@duke.edu
© 2012 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org

DOI: 10.1161/STROKEAHA.111.643130

Downloaded from http://stroke.ahajournals.org/
by guest on August 23, 2015
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to have less than a college education (63. The AVAIL study methodology has been previously published.5 years. Depression at 3 months was included only as a predictor variable for depression at 12 months.17 Undertreatment was identified when subjects were not using antidepressants at 3 or 12 months but had PHQ-8 ⱖ10 at both time points. Fourth Edition for diagnosis of major depressive disorder. interquartile range.6% in the Northeast. Medication use was subject-reported and ascertained through a series of questions aimed at comparing current and previous use. The frequency of newly identified depression was calculated by dividing the number of those with both PHQ-8 ⱖ10 at 12 months and PHQ-8 ⬍10 at 3 months by the sample size within each group.0001). a sensitivity analysis was performed by redefining depression as PHQ-8 ⱖ10 and/or the use of antidepressants at an appropriate dose. or the subject died before 12 months (Figure) leaving a total of 1847 AVAIL subjects from 99 hospitals. to be living in an institution at 3 months (2. 2015 .3% were in the Midwest. the proportional frequency of depression was also compared between stroke and TIA after excluding subjects with a history of cerebrovascular events. All probability values are 2-sided with P⬍0. To address this possibility. 30.15. if antidepressant doses were missing.3%. 0 –5).4% versus 52.16 Persistent depression was defined as PHQ-8 ⱖ10 at both 3 and 12 months regardless of antidepressant use.1 was performed in both models. use of antidepressants at 3 months.13. previous history of stroke/TIA. The 12-month follow-up was completed in August 2009.004).4%. to report their work status as “home not by choice” (13.ahajournals.or 12-month PHQ-8 was not completed. patient or legally authorized representative consent to participate. The PHQ-8. The enrolling sites were both academic (73. direct admission based on physician evaluation or arrival through the emergency department.4%.1610 Stroke June 2012 objectives were to identify factors associated with undertreatment of depression. 58 – 80 years. Outcome Sciences.2. Methods Study Population and Design This is a secondary analysis of a multicenter prospective cohort registry (Adherence eValuation After Ischemic stroke Longitudinal [AVAIL] study).0001). age.4% versus 10. The association of prespecified variables with undertreatment of persistent depression was assessed with univariate logistic analysis. and 18.org/ by guest on August 23. and history of smoking using multivariable logistic regressions. P⬍0. To account for the possible confounding effect of previous stroke/TIA on the frequency of depression. to report that household income did not meet needs (7. P⬍0. The Duke Clinical Research Institute served as the data analysis center for both GWTG and AVAIL. P⬍0.2%. Subject-level longitudinal data about depression and antidepressant medications were described. includes 8 of the 9 criteria from the Diagnostic and Statistical Manual of Mental Disorders. Ninth Edition Codes. work status at 3 months (work. Duke Clinical Research Institute research personnel conducted telephone interviews at 3 months and 12 months after hospital discharge using standardized scripts. Backward selection of covariates with a probability value of ⬍0. disability (mRS). The observed proportional frequency of depression was compared between stroke and TIA at 3 and 12 months before and after adjusting for gender. and persistent depression (depression at both 3 and 12 months) in patients with stroke. Antidepressants used at an approved dosage were identified based on a previously validated algorithm (online-only Data Supplemental Table I).19 Statistical Analysis Frequency distribution was used for categorical variables. to have a Downloaded from http://stroke. age. AVAIL subjects were excluded from the present analysis if baseline data were missing.15 This cutoff has a sensitivity and specificity of 88% and positive predictive value of 57% for major depression.7% versus 26. and inclusion in the GWTG–Stroke program. Chi-squared tests were used to compare categorical variables and Wilcoxon rank-sum tests to compare continuous variables. mRS at 3 months (range.2% in the West. P⬍0. based on symptoms within the prior 2 weeks.13 The modified Rankin Scale (mRS) was scored at each follow-up based on the standardized telephone interview.3% versus 0.9%.05 considered statistically significant.0001). versus 65 years. The rate of missing covariate data was low with the values imputed. Each participating site obtained Institutional Review Board approval before enrolling patients into AVAIL. and history of coronary artery disease/myocardial infarction at baseline. 55–74. Subjects who were excluded were more likely to be older (median age. or if the subject died before 12 months.001). subjects using antidepressants may carry a diagnosis of “depression” even if symptoms are adequately controlled by treatment. race/ethnicity (white versus other). Time-dependent subject characteristics were self-reported by subjects on follow-up at each time point as part of the AVAIL protocol. Median and interquartile ranges were calculated for continuous variables. The modified Wald method was used to calculate CIs. 23.3%) and nonacademic (26. P⬍0. P⬍0. Trained hospital personnel abstracted baseline time-independent demographic characteristics from inpatient medical records as part of the GWTG–Stroke admission. the 3. because a mRS ⬍3 is usually associated with the ability to maintain independent living. Subjects The inclusion criteria for the AVAIL registry were: age ⱖ18 years. antidepressant doses were missing. 1042 (36%) were excluded from the present analysis because baseline data were missing. depression at 12 months posthospitalization. P⬍0. Results Comparison of Included and Excluded Subjects Of AVAIL subjects (n⫽2889). 25. hospitalization with a primary diagnosis of acute ischemic stroke or TIA based on the GWTG–Stroke identified International Classification of Diseases.13 Briefly.4% versus 38. the 3.13 Outcomes and Covariates The primary outcomes for this analysis were depression (assessed with the PHQ-8) and antidepressant use (at doses at or above those recommended for treatment of depression). which was designed to assess adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or TIA. living situation at 3 months (with someone versus other).3%) hospitals. A similar analysis in subjects with TIA was not performed because the number in the TIA group was too small to support a valid multivariate analysis. to have been discharged to an institution (45.3% in the South. 2889 patients with stroke or TIA were recruited from hospitals participating in the Get With The Guidelines (GWTG)–Stroke program from July 2006 through July 2008. Key demographic variables were compared between included and excluded subjects. The variables included: sex.001). All analyses were performed using SAS software Version 9. Although the primary end point was based on self-reported symptoms of depression.0001). home by choice. Multivariate logistic modeling was used to assess the association of prespecified variables with persistent depression and depression at 12 months in subjects with stroke.9% versus 5.8%.or 12-month Patient Health Questionnaire-8 (PHQ-8) was not completed.14 The PHQ-8 yields a score from 0 to 24 with a score of ⱖ10 indicating a clinically significant depressive disorder. interquartile range. a multivariable logistic regression was not planned because of sample size limitations for this outcome.18 A cutoff of 3 was used to differentiate mild from moderate/severe stroke. Incident depression was defined as having a PHQ-8 ⱖ10 at 12 months in those with PHQ-8 ⬍10 at 3 months. Inc served as the data collection and coordinating center for GWTG–Stroke. to be unmarried (44. 69 years. versus home not by choice).

296). respectively. P⫽0. P⫽0. TIA indicates Transient Ischemic Attack. P⬍0.2%). P⫽0. Table 1). P⫽0. continued to have depressive symptoms and/or were treated with antidepressants at 12 Downloaded from http://stroke. The frequency of newly identified depression between 3 and 12 months was similar after stroke and TIA (8.4% versus 23. P⫽0. P⫽0.4% versus 45.4% versus 12. Get With The Guidelines–Stroke Program.9% versus 14.038) but The pattern of depression and antidepressant use was similar after stroke and TIA (online-only Data Supplemental Figures I–II). Patient Health Questionnaire. Of the 134 subjects with stroke and 30 subjects with TIA who were persistently depressed (PHQ-8 ⱖ10 at both 3 and 12 months). younger (median age. P⫽0.237) were similar between stroke and TIA (Table 2). P⫽0.ahajournals.7% versus 6.444). and baseline demographic variables (Table 2). the proportional frequency of depression was higher after stroke compared with TIA at 3 months (17.7% in stroke.0001).003).9% of subjects with stroke and 70. P⫽0. peripheral vascular disease (3.3% versus 7. AVAIL.1%.0% versus 80.3%.108) or medical history of carotid stenosis (4.org/ by guest on August 23.2% in TIA).3% versus 21.6%.7% versus 79.005). 2) Follow-up not done at 3 or 12 months (N = 315) 3) Died before 12 months interview (N = 84) 4) Proxy records-PHQ-8 not done (N = 526) Stroke 5) PHQ-8 missing at 3 or 12 months (N=46) N=1450 TIA N=397 6) Antidepressant dose missing at 3 or 12 months (N=62) history of previous stroke/TIA (29. was not different at 12 months (15.0% versus 26. P⫽0.0% versus 14. hypertension (78. P⫽0. history of smoking.4%.0% versus 14. P⫽0. 2015 .920).09) and at 12 months (16. P⫽0. P⫽0. respectively. smokers (27.12). diabetes mellitus (28. Adherence eValuation After Ischemic stroke Longitudinal study. respectively. those with aphasia or significant cognitive impairments were more likely to be excluded.734). or dyslipidemia (48.0003.4% versus 12. When depression was redefined as PHQ-8 ⱖ10 and/or use of antidepressants. even after adjustment for disability.9%]) and TIA (6 [1. 67. P⫽0.5%]) had persistent depression despite antidepressant use. P⫽0.100).1% versus 3.4%. respectively.1% versus 8.8% versus 6.254). P⫽0.9% versus 12.9%.2%. The proportional frequency of depression over the year after stroke and TIA was constant due to a similar proportion of subjects who had resolving depression and subjects who had new-onset depression between 3 and 12 months (resolving versus new onset: 7.El Husseini et al Depression and Antidepressant Post Stroke and TIA 1611 Stroke/TIA Initial AVAIL cohort N=2889 Stroke N=2417 TIA N=472 Exclusions: 1) Without GWTG enrollment admission (N = 9) Figure. 64 versus 68 years.3%. history of stroke/TIA.7% versus 5.1%. PHQ.227). After excluding subjects with previous stroke/TIA in both groups. respectively. GWTG.6% versus 15. P⫽0. and to have a history of coronary artery disease/ myocardial infarction (29.2%.50) and new antidepressant use between 3 and 12 months (5. Study cohort. P⫽0.0001) and have a mRS ⱖ3 at 3 months (23.6%.2%. P⫽0.5%. Comparison of Stroke and TIA Subjects Longitudinal Follow-Up of Depression and Antidepressant Medications in Subjects With Stroke and TIA Subjects with stroke (N⫽1450) were more likely than those with TIA (N⫽397) to be men (55% versus 45%. Of the 205 subjects with stroke and 43 with TIA who were depressed and not using antidepressants at 3 months.2%.4691).088).6%) and 22 subjects (51.8%.0% of subjects with TIA were not using antidepressants at either time point (P⫽0. Subjects with TIA were more likely to have a history of stroke/TIA (30. P⫽0. race (white versus nonwhite 83.7% versus 31. the proportional frequency of depression and the frequency of newly identified depression between 3 and 12 months (11. The proportion of antidepressant use at 3 months (13.08). smoking (25. Proportional Frequency and Frequency of Newly Identified Depression and Antidepressant Use in Subjects With Stroke and TIA The proportional frequency of depression was similar in subjects with stroke and TIA at 3 months (17. respectively. P⫽0.6%.5% versus 45. The excluded group did not differ with respect to sex (female 46.9% versus 15. 6.7% versus 4. Only a minority of subjects with stroke (N⫽28 [1.08) remained comparable (Table 2).1% versus 24.0%.6%. In addition.6%.8%. 112 (54.45) and 12 months (16. because subjects rather than a proxy had to complete the PHQ-8. P⫽0.0002).6%.002).2%.

org/ by guest on August 23.1%) 4 (1.8%) 272 (68.6%) Refused 19 (1.2%) 8 (2.8%) 9 (2.5%) With spouse/significant other and/or children 983 (67.631 873 (60.0002 White 1194 (82.4%) 9 (2.0%) 0.5%) 203 (51. yes Medical history prestroke Atrial/fibrillation/flutter 142 (10. 3 mo Home not by choice 153 (10.2%) Asian 11 (0.0003 CAD/prior MI 308 (23.3%) 0.3%) 2 (0.1%) 0.396 54 (4.1%) 7 (2.1%) ⬍0.3%) 182 (52.5%) 38 (9.8%) Do not know 31 (2.7%) 0 (0%) Discharge status Left against medical advice or discontinued care Transfer to acute care facility Rehabilitation 395 (27.6%) 288 (85.7%) 1 (0.4%) 0.1612 Stroke June 2012 Table 1.3%) 0.8%) 35 (10.9%) 0.5%) 0.672 Education (baseline) College or above.062 Peripheral vascular disease 1020 (77.2%) 69 (17.453 Household income meets needs.ahajournals.7%) 187 (47.0001 24 (1.0%) 0.2%) 248 (62.0) 68.6%) 53 (15. 3 mo More than adequate 246 (17. median (IQR) Sex Female Race/ethnicity 161 (11.0%) 94 (23.117 Diabetes mellitus 384 (29.0 –74.1%) Somewhat 264 (18.162 Work status.8%) Hispanic 36 (2.4%) 5 (1.0001 Dyslipidemia 622 (47.0) 0.049 Smoker Hypertension 363 (27.2%) In nursing home/hospice 5 (0.1%) 0.2%) Other/undetermined/missing 40 (2.3%) 339 (85.3%) 663 (45.4%) Not at all 76 (5.2%) 217 (54.5%) Alone 336 (23.424 0.3%) 959 (66. y.1%) 94 (23.5%) Home by choice 659 (45.2%) With relative(s) 98 (6.1%) 0 (0%) ⬍0.7%) In rehabilitation institution 0 (0%) 1 (0. Characteristics of Subjects With Stroke and TIA Stroke (N⫽1450) TIA (N⫽397) P Value* 64.5%) Skilled nursing facility Home Living situation at 3 mo With friend(s) 21 (1. baseline Married.2%) 106 (30.0 (56.4%) 203 (51.2%) 20 (5. 2015 .139 (Continued) Downloaded from http://stroke.3%) 3 (0.1%) 384 (96.1%) 0.0%) 63 (4.112 2 (0.1%) 39 (9.8%) 0.5–76.2%) 94 (26.3%) 5 (1.7%) 0.5%) 0.0 (55.737 Black Age.4%) 96 (27.3%) 154 (38.1%) Working 628 (43.7) Adequately 789 (54.003 641 (44. yes Marital status.0%) Previous stroke/TIA 279 (21.7%) 22 (5.

63 (0.41) 238 51 1. Factors Associated With Lack of Antidepressant Medication Use in Subjects With Stroke and Persistent Depression Among subjects with stroke who were persistently depressed and not using antidepressants (N⫽91).6% (11.4%) 0. living situation (P⫽0.56) 1.2% of subjects with TIA were not depressed at either time point (P⫽0. and being depressed at 3 months (P⬍0. CAD.092).2% (20.4%) 0⫽no symptoms at all 345 (23.5% of TIA (P⫽0.7% of subjects with stroke and 4.23) 0.1–19. *P values were calculated by ␹2 tests for categorical variables and Wilcoxon rank-sum test for continuous variables. Proportional Frequency of Depression.94–1.75–1. Patient Health Questionnaire-8.862).6–18. whereas the rest had spontaneous resolution of depressive symptoms.0% (25.0% (14. N/A indicates not applicable because multivariate analyses were not performed for antidepressant use. Depression and Antidepressant Post Stroke and TIA 1613 Continued Stroke (N⫽1450) TIA (N⫽397) P Value* ⬍0.89 13.El Husseini et al Table 1.3 0.8%) 2⫽slight disability 513 (35.0–20.84) 232 58 1.7%) 1⫽no significant disability 254 (17. and Depression and/or Use of Antidepressant in Subjects With Stroke and TIA at 3 and 12 Mo PHQ-8 ⱖ10 at 3 mo Antidepressant use at 3 mo PHQ-8 ⱖ10 and/or use of antidepressant at 3 mo PHQ-8 ⱖ10 at 12 mo Stroke (N⫽1450.274). there was no association between the lack of antidepressant use and age (P⫽0.8%) 180 (45.21 27.77–1.82–1.8–30.50 0.96–1. suggesting a low rate of depression recognition and treatment. mRS. only 18.4) Antidepressant use at 12 mo PHQ-8 ⱖ10 and/or use of antidepressant at 12 mo 12.67 (0.9–1. inability to work (P⬍0.65–1.516).1–30.3%) 1112 (76.844) when compared with those who were depressed and untreated at 3 months but using antidepressants by 12 months (N⫽21).6) (0.4% (14.2) 24. 62.6–30. IQR.215).5%) 69 (17. age.9% (16.3) (0. smoking.363) or a neurologist (P⫽0.09 1.33 16.2–15.42) TIA indicates transient ischemic attack.8%) 335 (84.0%) 43 (10.0001).79 17.7%) 339 (85.894).05 0. interquartile range.46) 0.09 0.7) 15.5% of subjects with stroke and 65.004).85–1.2) (0.001 mRS at 3 mo 5⫽severe disability 26 (1.8) 201 61 0. Of those subjects who did not have spontaneous resolution of depressive symptoms.5–18. Downloaded from http://stroke.4% (12. Antidepressant Use. modified Rankin Scale at 3 mo. Table 2.ahajournals.2% (22. 2015 . 95% CI P Value Multivariate OR.04) were using antidepressants at 12 months.2–18. months.45 N/A N/A 0.4% (11. higher mRS at 3 months (P⬍0.4) (0. sex (P⫽0.8%) 1 (0.0001).47 0.72–1.11 16. *Multivariate ORs represent the odds of subjects with stroke of having depression compared with those with transient ischemic attack after adjusting for gender.4%) 0.0) 14. Proportional Frequency.2–28.031).3%) 4⫽moderately severe disability 74 (5.9–16.1%) 12 (3.94 0. Factors Associated With Depression at 12 Months and Persistent Depression in Subjects With Stroke Univariate analyses showed that depression at 12 months (N⫽238) in subjects with stroke was associated with younger age (P⬍0.9% (25.4) 26.2–18. medication insurance status (P⫽0.58 (0. All P values were calculated by comparing only nonmissing row values. and history of stroke/transient ischemic attack at baseline. or interim follow-up with a primary care physician (P⫽0.14 N/A N/A 1.21) 406 104 1.0%) 3⫽moderate disability 232 (16.031).0001 1157 (79.08 0. modified Rankin Scale.0001). mRS (P⫽0. MI.8% (9.09 28.4%) 90 (22.9% (12. 95% CI) TIA (N⫽397. race (P⫽0.0) 14. Among those using antidepressants at both 3 and 12 months (N⫽168 with stroke versus 46 with TIA).55) 0.* 95% CI P Value 260 57 1. using an antidepressant at 3 months (P⫽0. nonwhite race (P⫽0. coronary artery disease.0001).08 (0. myocardial infarction. Proportional Frequency.7) (0. PHQ-8.5) (0.612).81–1. female sex (P⫽0. 95% CI) Univariate OR.org/ by guest on August 23.04 mRS at 3 mo mRS ⬍3 mRS at 12 mo mRS ⬍3 TIA indicates transient ischemic attack.52) 404 96 1.

Discussion In this large longitudinal study. history of stroke/TIA. 95% CI. the proportional frequency and the frequency of newly identified depression between 3 and 12 months posthospitalization were similar after stroke and TIA when assessed with the PHQ-8 scale or by the PHQ-8 and/or use of antidepressants. not applicable.53 0. depression at 3 months was associated with depression at 12 months.1614 Stroke June 2012 Table 3. y (per 10-y increase) Persistent Depression (N⫽134) Adjusted OR 95% CI 0.7–9. and approximately 15% of subjects with TIA had severe disability (mRS ⱖ3). The frequency of poststroke depression varies between published studies depending on the setting. the frequency of depression was higher after stroke compared with TIA at 3 months indicating that prior cerebrovascular events partly explained the high frequency of depression after TIA.2 None of the included studies used the PHQ-8 scale.2 In light of the higher frequency of depression at 3 and 12 months. The similar frequency of depression after stroke and TIA could be explained by the nature of the stroke and TIA cohorts included in the current study.93 1.3).61 0. Persistent depression (N⫽134) was associated with the same variables.001 ⬍0. and inclusion and exclusion criteria. diagnostic criteria.001 1.5–10. The pooled frequencies varied when grouped by method of mood assessment. depression.139) or living situation at 3 months (P⫽0.org/ by guest on August 23. suggesting that other factors play a more important role in late (12 months) versus early depression (3 months). respectively). younger age.40–0.8% (95% CI. the Behavioral Risk Factor Surveillance Survey data from 2006 and 2008 indicated that the overall frequency of “current” depression in the general population using the PHQ-8 diagnostic algorithm was 9. 9.ahajournals. 8.81.98 ⬍0.62–2. it was lowest in studies that used a single simple question to determine depression status (14%. Consistent with previous reports. the pooled frequency of depressive symptoms among stroke survivors at any time during follow-up was 33% (95% CI.21 The longitudinal data from AVAIL demonstrate.20 We further found that the same variables were associated with persistent depression. the frequency of depression remained comparable between the 2 groups even after adjusting for disability. the rates were 10.5) in the 45.0% (95% CI. a higher mRS at 3 months.014 Adjusted OR 95% CI P Value 0. Although depression at 3 months was a strong predictor of depression Downloaded from http://stroke. 23%– 60%).94 – 0. 6.56 … … … … 6.84 0.49 1. In addition.55 4. and inability to work at 3 months were associated with depression at 12 months and with persistent depression (Table 3). similar to previous studies.2) in those ⱖ65 years old. There was no association with a history of coronary artery disease/myocardial infarction (P⫽0. patient population.73 ⬍0. or other comorbidities. 30.001 Work status at 3 mo Working 0.8 For example. the frequency of depression after excluding previous cerebrovascular events was similar after stroke and TIA.66–9. 29%–36%). 2015 .6.96 0.30 ⬍0. time period.93 0.19–0. these results also indicate that the risk of depression after even mild stroke or TIA was higher than the general population with a comparable age distribution.29–1. Consistent with previous reports.53 Home by choice 0. presumably related to previous or intercurrent stroke. and baseline demographic factors.96 – 0. OR Estimates of Depression at 12 Months and Persistent Depression (3 and 12 Months) in Subjects With Stroke (Nⴝ1450) After Multiple Logistic Regression Depression at 12 Mo (N⫽238) Variable Age.19 ⬍0. Multivariate analysis confirmed that younger age. 14%–15%) and highest when using standardized questionnaires such as the Montgomery Asberg depression rating scale (41%.3% of subjects with TIA had also a history of stroke/TIA. According to a meta-analysis published in 2005. 95% CI.19–0. However. N/A.98 0. poor functional outcome.9 At 12 months. that the frequency of depression is constant in the year after stroke and TIA.4 –7.8.001 N/A N/A N/A 1.009 0. After excluding subjects with a history of stroke/TIA.to 65-year-old population and 6.001 Home not by choice (reference) Depression at 3 mo mRS at 3 mo 5⫽severe disability 4⫽moderately severe disability (Per 1-unit increase) (Per 1-unit increase) 3⫽moderate disability 2⫽slight disability 1⫽no significant disability 0⫽no symptoms Only final results of the models are provided.292). and inability to work at 3 months were associated with poststroke depression at 12 months. mRS indicates modified Rankin Scale.32 0.33–0. which argues against the hypothesis that the increased risk of depression is limited to the first few months after a cerebrovascular event.82 and C⫽0. The majority of subjects with stroke had only mild disability (mRS ⬍3).0% (95% CI.32 0.99 P Value 0. Both models had good discriminate validity (C⫽0. screening for depression appears to be warranted in the first year after stroke or TIA at both time points.

Subjects with stroke who are young. we cannot exclude the possibility that some of the antidepressant drugs were being used for other purposes besides depression. reaction to new functional disability and overall health status. However. however. there are several limitations. because radiographic data were not readily available.5. Conclusions Both subjects with stroke and those with TIA had a similarly high proportional frequency and frequency of newly identified depression between 3 and 12 months after hospitalization. unable to work. even in patients with minor disability. was missing in a large proportion of GWTG–Stroke subjects and therefore was not included in our analyses. and have significant disability may need more vigilance because of their higher risk for long-term and persistent depression.28 Overall 36% of AVAIL subjects were excluded from the present analysis (Figure). Potential inception cohort bias is always a concern when consent is required. a lower level of depression severity at baseline. The demographics of the AVAIL population. depressed mood. Various hypotheses regarding the etiology of poststroke depression include the relative contribution of brain injury related to stroke. the frequency of depression was high after stroke or TIA. Undertreatment was not associated with any of the study’s prespecified variables. It is possible.” which includes major depression.30 Given this limitation. we were able to determine the frequency of newly identified depression between 3 and 12 months by using the 3-month assessment as the baseline. a study of the representativeness of the GWTG–Stroke registry indicates that the data are generally representative of national fee-for-service Medicare ischemic stroke populations providing support for external validity. the frequency of newly identified depression between the 3. that contributors to depression may differ between patients with stroke and TIA. because more than two thirds of those with persistent depression were not appropriately treated with antidepressants. we cannot exclude the possibility that a proportion of subjects in the cohort had a history of depression.29 Prestroke depression. limiting the cerebrovascular event to a subset of events that were serious enough to warrant hospitalization. however. However. Other nonpharmacological treatments for depression such as cognitive behavioral therapy were not captured in this study. GWTG–Stroke hospitals do tend to be larger. but a high proportion of persistent depression in these 2 groups was not appropriately treated. Despite these differences. This was possibly due to the self-limited nature of depressive symptoms.26 However. Instead we used the mRS as an indication of functional outcome. Some of the subjects with “depression” in this study may not have needed treatment with antidepressants. did not differ substantially from the overall GWTG–Stroke cohort.25 The majority of subjects using antidepressants did not have symptoms of depression. these factors would not be anticipated to play a significant role in the TIA cohort except in those with previous or intercurrent stroke.20 In addition. which correlates well with stroke severity but can be confounded by depression. These differences need to be considered and limit the generalizability of the results. The strengths of this study were the large cohort with complete follow-up that prospectively and longitudinally evaluated both depressive symptoms and antidepressant use in both subjects with stroke and those with TIA. or antidepressant use in the interim that was stopped before the 12-month follow-up.27.24. AVAIL subjects were recruited from geographically diverse hospitals participating in the American Heart Association GWTG– 1615 Stroke program. other depressive disorders.ahajournals. it is very likely that those who were characterized as persistently depressed may have had clinically significant depression that warranted treatment. this study reveals that. An important finding from the current study is that undertreatment of depression was common in subjects with either stroke or TIA. In the current study. thus possibly overestimating the frequency of “undertreatment. functional disability and inability to work were independently associated with depression among stroke subjects. Previous studies found a comparable incidence of depression among patients with stroke and those with similar vascular comorbidities (eg. 2015 . The baseline data of subjects who were excluded from this analysis do differ in several ways. as determined by National Institutes of Health Stroke Scale. Because subjects rather than proxies were required to complete the PHQ-8. For example. this method of medication assessment has good concordance with claims records and is likely to be valid for assessing current antidepressant use for depression therapy. Additional studies are needed to investigate determinants of depression among patients with TIA. in our study. it had resolved by 12 months in approximately half of the subjects without the use of antidepressants.23 Our finding that the frequency of depression was similar between subjects with stroke and TIA is also consistent with this hypothesis. we were not able to correlate depression with stroke location or volume. this conclusion is limited by the small sample size of subjects for this outcome and warrants replication.22. which implies that depression in subjects with stroke and TIA is amenable to treatment or. All participants were discharged from hospitals for a stroke or TIA.and 12-month follow-up was also significant. however. Nonetheless. antidepressant use was similar for both subjects with stroke and those with TIA and higher than the reported rates in the general population (approximately 10%). however. alternatively. a baseline assessment of stroke severity. or anhedonia. Despite these limitations. was not assessed in our study. Because TIA is not associated with residual functional impairment.El Husseini et al Depression and Antidepressant Post Stroke and TIA at 12 months. Lastly. shown to be strongly associated with poststroke depression. because a PHQ-8 score of ⱖ10 reflects “current depression.15 However. the results are also likely biased toward those with mild disability including those without aphasia or significant cognitive impairments. including vascular comorbidities. myocardial infarction) but a higher prevalence of depression among patients with stroke compared with those with orthopedic disease with the same level of physical disability and suggested a “vascular etiology” of depression.org/ by guest on August 23. that antidepressants are used nonselectively in this population. urban and teaching centers. Systematic evaluation Downloaded from http://stroke.” Antidepressant use was self-reported based on structured interviews and not confirmed by alternative methods.13.

Stroke. Jia H. 22. 1991. Hackett ML. The adherence evaluation after ischemic stroke longitudinal (AVAIL) registry: design. Zimmer L. Pei Y. Merck. Chang CM. 23. Civilian Noninstitutionalized Population. 2003. Stroke. et al. Zimmer LO. 2006. Maryland. Br J Psychiatry.e422. Am J Geriatr Psychiatry. Dieguez S. 7. Strik J. 2005. Trends in Antidepressant Use by the U. Mood disorder as a specific complication of stroke. Mt Sinai J Med. Wang X. Bungay KM.67:1456 –1463. Disparity in depression treatment among racial and ethnic minority populations in the United States. Vroomen PC. 24. Lodder J. Stroke. Smith EE. Antidepressant use in a nationally representative sample of community-dwelling US Latinos with and without depressive and anxiety disorders. 1988. Neuropsychiatric disorders following vascular brain injury. Eriksson M. Shuman M. 11. Veterans’ Affair. Goldstein LB. et al. 30. AVAIL analyses were also supported in part by the Agency for Healthcare Research and Quality cooperative agreement U18HS016964. Jones L. Spitzer RL. Alegria M.114:163–173. Int J Geriatr Psychiatry. Breteler MM. Bowen ME. Olfson M. 2010. J Neurol Neurosurg Psychiatry. Bushnell C. Psychiatr Ann. Berry JT. BoheringerIngelheim.61:16 –21. Sources of Funding Dr El Husseini was fully supported and Dr Goldstein and Dr Laskowitz were partially supported by an American Stroke Association-Bugher Foundation Stroke Prevention Research Center award. Wells K. Cao Z. Croghan TW. Agency for Healthcare Research and Quality. Department of Defense (FIMDM).pdf. 2004. Tueth M. Cameon R. 2005. Bruggimann L. Rogers WH. Stroke. et al. and Steering Committee for the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial (Pfizer). Van Swieten JC. 19. Bogousslavsky J. Hawton K. Koudstaal PJ. Depress Anxiety. and BMS. He has obtained funding from (National Institutes of Health) 1D43TW008308-01 “Training for the prevention and treatment of stroke. AGA Medical Corporation).50:563–569. 16.” Dr Goldstein serves as a consultant for Allergan. Statistical Brief #76. Smith EE. Wieberdink RG. Strine TW. 1977. West BT. Does prestroke depression impact poststroke depression and treatment? Am J Geriatr Psychiatry. 10.43:44 – 49. Damush TM. Stroke. Takeuchi D. and baseline patient characteristics. et al. Saver JL. 28. Hackett ML. 36:1330 –1340. Wu KY. Zhao X. 13. Folstein MF. Qin H. Br J Psychiatry. 21. Anderson CS. Characteristics. 29. 2010. Dr Bushnell was a co-Principal Investigator of AVAIL and received research salary support from Bristol Myers Squibb-Sanofi Joint Partnership for her role. The PHQ-8 as a measure of current depression in the general population. The Veterans Affairs and are on mental health topics including depression but not directly related to the article. Olson DW.151:200 –205. and the Foundation for Informed Medical Decision Making. 8. 20.1616 Stroke June 2012 for depression in patients with stroke or TIA may improve detection and treatment of this condition. Honig A.36:2296 –2301. Persistence with stroke prevention medications 3 months after hospitalization. 2009. House A. 4. Koudstaal PJ. Med Care. Olson D. 2006 and 2008. Poynter B.66:848 – 856. Croghan TW. Lousberg R. 2009.org/ by guest on August 23. American Psychiatric Association. Dennis M.36: 1984 –1987. Optimizing cutoff scores for the Barthel Index and the modified Rankin Scale for defining outcome in acute stroke trials.35:936 –941. DC: American Psychiatric Association. Racial variation in antidepressant treatment in a Medicaid population. et al.ahajournals. and in-hospital outcomes of the first one million stroke and transient ischemic attack admissions in Get With The Guidelines–Stroke. 6. Mogridge L. 2009. Yapa C. Schwamm L. Anderson CS. May 2005. Disclosures Dr Laskowitz serves as an associate editor for the Critical Care research and Practice from 2009 to the present (no compensation).32:509. 18. Stricker BH. Hewer RA. Arch Gen Psychiatry. 15. 2010.18:624 – 633. Legh-Smith J. Sex differences in the prevalence of post-stroke depression: a systematic review. et al. Kroenke K. Terent A. Stroke. Pan W.73:1006 –1014. Circ Cardiovasc Qual Outcomes. Transient ischemic attack and incident depression.S. Zhao X. Chatterji P. Antidepressant use: concordance between self-report and claims records. Mood disorders in the year after first stroke. J Affect Disord. Kroenke K. 2011. 2004. et al. J Clin Psychiatry. Tarraf W. McHugh PR. Hernandez AF. Ried LD. Levine SR. 1994. Asymptomatic Carotid Trial (Abbott).74: 581–585. 17. Williams JB. 2015 . Psychosomatics. Bushnell CD. Depressed mood after stroke. Zhou Q. 2010. J Neurol Neurosurg Psychiatry. 1997 and 2002. Stewart RE. 3. Pan W. Self-reported depression and use of antidepressants after stroke: a national survey. Luijckx GJ. 25.gov/mepsweb/data_files/publications/st76/stat76. http://meps. Stegmayr B. Feng H. Kapral M. Verhey F. Interobserver agreement for the assessment of handicap in stroke patients. Frequency of depression after stroke: a systematic review of observational studies. Van Gijn J. Chemerinski E. Melfi CA. Marcus SC. Staub F. Hofman A. Warlow C. et al. Liu CY. Fonarow GC. The AVAIL project was supported by unrestricted funds from Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and conducted through collaboration with the American Heart Association and the “Get With The Guidelines–Stroke” program.26:674 – 681. Stagnitti MN. Norrving B.3: 291–302.18:382–387. Pfizer.59:1264 –1272. Luijendijk HJ. Representativeness of the Get With The Guidelines–Stroke registry: comparison of patient and hospital characteristics among medicare beneficiaries hospitalized with ischemic stroke. et al. performance measures. Dr Williams received funds for other research from the Agency for Healthcare Research and Quality. Visser MC. 2003.41:368 –374. 9. 2000. 2. He also served on the Neurology Executive Committee RESPECT Trial (Patent foramen ovale closure. A community study of its frequency. Schouten HJ. Clapp-Channing N. et al. Wilson IB. Arch Neurol. 27. Current depression among adults—United States. Psychiatr Serv. Parag V. Harding T. MMWR Morb Mortal Wkly Rep. Am Heart J. Fonarow GC. 1987. Cao Z.226:53–58.ahrq. Plue L. but the funding ended in 2009. 2009. Wade DT. Casefinding algorithm for post-stroke depression in the Veterans Health Administration. Stewart DE. Reeves MJ. Olson DM. Uyttenboogaart M. The PHQ-9: a new depression diagnostic and severity measure. Stroke. 2002. Reeves MJ. Gonzalez HM. De Keyser J. 12. Washington.42:1857–1861. Diaz-Granados N. Maiberger R. Robinson RL. 14.40: 1018 –1020. Asplund K.59:1229 –1235. Hanna MP. Chau YL. Grace SL. 2008. 5.158:83–92. 2009. IV ed. References 1. 2008. Predictors of depression after stroke: a systematic review of observational studies. A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction. Mokdad AH. Meteleva T.23:517–522. Rockville. Is poststroke depression a vascular depression? J Neurol Sci. Cameon R. Aben I. Jia H. Diagnostic and Statistical Manual of Mental Disorders. Glader EL.157:428 – 435. Chen CN. Downloaded from http://stroke. 2005. rationale. Spitzer RL. Site Oversight Committee.19:604 – 607. Kwon A. 2010. Ried LD. 2012. Transient ischemic attack and incidence of depression in old age: evidence from a population-based analysis in Taiwan. National patterns in antidepressant medication treatment. 26.

eFigure2: Longitudinal follow-up of depression and antidepressant* use in TIA patients (N=397).STROKE/2011/643130 El Husseini 1 SUPPLEMENTAL MATERIAL Depression and Antidepressant use after Stroke and Transient Ischemic Attack 1 eTable: Antidepressants algorithm 2 eFigures eFigure 1: Longitudinal follow-up of depression and antidepressant* use in stroke patients (N=1450). .

Cameon R. Jia H. Int J Geriatr Psychiatry. Case-finding algorithm for post-stroke depression in the veterans health administration. et al. the minimum daily dosage for these medications was derived from expert consensus. 2008). . Antidepressant medications algorithm Antidepressants Sertraline Paroxetine Citalopram Escitalopram* Fluoxetine Fluvoxamine Amitriptyline Doxepin Imipramine Nortriptyline Clomipramine Trazodone Bupropion Venlafaxine Mirtazapine Duloxetine* Patient age≥65 years 25 10 20 10 10 100 Not recommended 30 30 30 75 25 50 50 15 40 Patient age<65 years 50 20 20 10 20 100 50 75 75 75 75 150 200 75 15 40 Antidepressants and their guideline-recommended minimum daily dosage (mg/day) (adapted with permission from Damush et al. Ried LD. 2008. *These antidepressants were not featured in the paper by Damush et al.23:517-522. Qin H. Plue L. Ref: Damush TM.STROKE/2011/643130 El Husseini 2 eTable.

1%) 24(16.6%) Antidepressant (-) (N=1046) Numbers and percentages within each arrow represent the number and percentages of patients who moved from each category.6%) 3(2.4%) PHQ8<10 Antidepressant (-) (N=1044) PHQ8<10 925(88.9%) PHQ8<10 Antidepressant (+) (N=146) PHQ8<10 Antidepressant (+) (N=166) 105(71.9%) 11(1.3%) 4 (7. .6%) 21 (38.2%) 13 (6. Longitudinal follow-up of depression and antidepressant* use in stroke patients (N=1450).STROKE/2011/643130 El Husseini 3 eFigure 1.4%) 76(7.3%) PHQ8≥10 PHQ8≥10 Antidepressant (-) ( N=205) 91 (44.0%) 93 (44. 3 months 12 months PHQ8≥10 PHQ8≥10 Antidepressant(+) (N=55) Antidepressant (+) (N=66) 28 (50. *Antidepressant at or above the minimal age appropriate dose.4%) Antidepressant (-) (N=172) 14(9.9%) 2 (3.3%) 32(3.1%) 8 (3.

3%) 1 (7.8%) Antidepressant (-) (N=38) 5 (10.8%) 1 (0.4%) 9(19. 3 months 12 months PHQ8≥10 PHQ8≥10 Antidepressant (+) (N=14) Antidepressant (+) (N=13) 6 (42.9%) 2 (14.1%) PHQ8<10 Antidepressant (-) (N=293) PHQ8<10 270(92.STROKE/2011/643130 El Husseini 4 eFigure2.3%) 5 (35.8%) 12(4.1%) Antidepressant (-) (N=301) Numbers and percentages within each arrow represent the number and percentages of patients who moved from each category.3%) 21 (48.1%) PHQ8≥10 PHQ8≥10 Antidepressant (-) (N=43) 21 (48.7%) 1 (2.6%) 3(6. *Antidepressant at or above the minimal age appropriate dose.1%) 10(3.4%) 0(0%) PHQ8<10 Antidepressant (+) (N=47) PHQ8<10 Antidepressant (+) (N=45) 30(63. . Longitudinal follow-up of depression and antidepressant* use in TIA patients (N=397).

org/content/suppl/2012/03/29/STROKEAHA. TX 75231 Copyright © 2012 American Heart Association. 2012. a service of the Copyright Clearance Center. Laskowitz Stroke. or portions of articles originally published in Stroke can be obtained via RightsLink.Depression and Antidepressant Use After Stroke and Transient Ischemic Attack Nada El Husseini. originally published online March 29. Williams.ahajournals. 2012. Jr. Online ISSN: 1524-4628 The online version of this article. Print ISSN: 0039-2499. Larry B.111. Louise O. John W.ahajournals.html Permissions: Requests for permissions to reproduce figures. Once the online version of the published article for which permission is being requested is located. Goldstein.43:1609-1616. All rights reserved.111.org//subscriptions/ Downloaded from http://stroke. tables.DC2.org/content/43/6/1609 Data Supplement (unedited) at: http://stroke. Cheryl Bushnell and Daniel T. click Request Permissions in the middle column of the Web page under Services. is located on the World Wide Web at: http://stroke.ahajournals. Olson. along with updated information and services. Dallas.643130.1161/STROKEAHA.643130 Stroke is published by the American Heart Association. Further information about this process is available in the Permissions and Rights Question and Answer document.ahajournals. doi: 10. 2015 . Inc. Xin Zhao. Eric D. Zimmer. Reprints: Information about reprints can be found online at: http://www. Wenqin Pan.org/ by guest on August 23.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke. 7272 Greenville Avenue. DaiWai M.lww. Peterson. not the Editorial Office.