Abstract
Background:
Post-stroke depression (PSD) affects one-third of stroke patients and is linked with higher stroke morbidity, mortality, and recurrence. Current guidelines do not direct when to screen for PSD, and predictors of PSD are not well understood. We sought to understand progression of PSD symptoms early after ischemic stroke, identify predictors of PSD, and describe the use of antidepressants in PSD.
Methods:
We collected demographic, clinical, and PSD (Patient Health Questionnaire-9; PHQ-9) data from ischemic stroke patients hospitalized at our Comprehensive Stroke Center and followed up in our clinic. PHQ-9 was obtained during hospitalization and again in clinic within 180 days of discharge. We performed univariate analysis and logistic regression to detect variables associated with PSD.
Results:
Among 201 patients, PSD symptoms (PHQ-9 > 4) were identified in 30% of patients during hospitalization and 46% during follow-up (54% of which had no symptoms during hospitalization). At follow-up, 36% were worse by PHQ-9 category. In univariate analysis, follow-up modified Rankin Scale (mRS) ≥2 (p=0.03) and antidepressant prescription (p<0.001) were associated with worsening PHQ-9 category. In logistic regression analysis, follow-up mRS ≥2 (p=0.02), posterior circulation stroke (p=0.03), and antidepressant prescription (p<0.01) were associated with worsening PHQ-9 category.
Conclusion:
Almost half of ischemic stroke patients develop PSD symptoms and more than one-third worsen between hospitalization and follow-up. Post-stroke disability (mRS ≥2) and posterior circulation stroke were associated with worsening PSD. Worsening PSD symptoms prompted treatment change in 29% of patients. Screening for PSD during hospitalization should be repeated during early follow-up.
Keywords: Ischemic Stroke, Depression, Secondary Prevention, Prediction, Progression
Introduction:
Every year, more than 795,000 people in the United States will have a stroke, about 130,000 will die while over 400,000 will have motor, cognitive or speech disabilities.[1,2] Depression is the most common mood disorder after stroke with a prevalence of 30% - 50%.[3] Symptoms of PSD vary in severity, frequency and duration.[4] Depressive symptoms may occur weeks, months or even years after a stroke and can inhibit progress of recovery and rehabilitation, which can negatively impact quality of life.[5] PSD has important long-term psychosocial consequences and is associated with increased morbidity, mortality, and stroke recurrence.[3]
PSD can be a chronic, relapsing disorder.[6] Thirteen to 52% of individuals with stroke are depressed at the first assessment and about 15% of individuals without depression at initial depression assessment will develop PSD within the first year.[3,7] In a large observational study, of the 36% of patients who developed PSD, 80% developed depression within the first 3 months after stroke.[8] In a longitudinal study of 142 acute stroke patients, over one-third of patients not depressed during the acute in-hospital evaluation developed signs of PSD between 3 months to 2 years after stroke.[9]
The sudden nature and effect of stroke including executive dysfunction, spasticity and/or aphasia predispose to PSD. PSD inhibits recovery and is an independent predictor of poor long-term functional outcome[10]. Previous studies have examined whether patient demographics, including age and sex, play a role in development of PSD, and most have not shown an association.[11–13] There is conflicting evidence whether lesion location is a predictor of PSD.[12,14–16] Social factors, cognitive dysfunction, functional impairment and severity of stroke have been identified as predictors of PSD.[12]
Few studies have investigated the progression and predictors of progression of PSD symptoms from hospitalization to the early post-acute period. Identification and treatment of PSD during the early period is important because it is also a critical time period for stroke recovery.
We utilized the Patient Health Questionnaire-9 (PHQ-9), a validated depression screening tool in the stroke population, to understand the progression, specifically the worsening, of PSD from hospitalization to outpatient clinic follow-up.[17–19] Next, we evaluated the impact of demographic and clinical factors on progression of PSD symptoms during this early post-acute stroke period.[17] Finally, we determined whether use of the PHQ-9 in the outpatient setting was associated with a change in patient management.
Materials and Methods:
We reviewed all ischemic stroke patients who followed-up at our Stroke Transitions Education and Prevention (STEP) Clinic between January 2014 and November 2016. The STEP Clinic is a specialized stroke prevention clinic where stroke patients receive standardized assessments after hospital discharge.[20] Patients seen in the STEP Clinic are included in a prospectively obtained, Institutional Review Board (IRB)-approved clinical registry. Patient data not available in the STEP registry were retrieved from our Comprehensive Stroke Center (CSC) or clinic electronic health records.
Study inclusion criteria were as follows: age 18 years or older; hospitalized for acute ischemic stroke; and followed-up at the STEP Clinic within 180 days of discharge. Patients were excluded if they were not hospitalized at our CSC or if they did not complete an inpatient and outpatient clinic PHQ-9. A PHQ-9 at any point during hospitalization was collected by a social worker as part of our CSC routine stroke care, and the follow-up PHQ-9 was collected on the initial STEP Clinic visit.
Patient baseline factors from hospitalization included demographic and social characteristics: age, sex, race, marital status, employment status; functional impairment as measured by the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS); baseline antidepressant use; stroke circulation location (anterior, posterior or both) and stroke side (right, left or bilateral hemispheres); and baseline depressive symptoms (PHQ-9 scores). Anterior and both anterior and posterior circulation strokes were combined for analysis given evidence supporting an association between PSD and anterior circulation strokes.[21–23] Right-sided and bilateral strokes were combined for analysis since more recent studies have shown association between right hemispheric strokes and PSD.[13–17,21,24] NIHSS was categorized as mild (score 0–4), moderate (score 5–15) and severe (score 16–42).[25] On clinic follow-up, variables recorded included antidepressant prescription and use, which were defined as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tetracyclic or tricyclic antidepressants, mRS and PHQ-9 scores.
The PHQ-9 instrument is a brief, 9-item, self-administered questionnaire that measures depression symptom severity. The instrument scores each of the 9 universally accepted criteria for depression. Scores range from 0 to 27 and are categorized as no depressive symptoms (numerical score 0–4), mild (numerical score 5–9), moderate (numerical score 10–14), moderately severe (numerical score 15–19) and severe depression symptoms (numerical score 20–27).[26] For this study, the moderately severe and severe categories were combined since few patients fell into the severe category. A recent meta-analysis of stroke patients found that the PHQ-9 instrument had a sensitivity of 86% and specificity of 79% for PSD, which was superior to other screening tools.[27] The American Heart Association recommends the PHQ-9 instrument as a valid screening tool for PSD.[28]
Data were analyzed to identify the predictors of development of PSD symptoms and change in PHQ-9 scores within 180 days post-stroke. The change in depressive symptoms measured by the PHQ-9 between hospitalization and clinic follow-up was dichotomized into two categories: stable/improved or worse. A PHQ-9 score at follow-up that reflected either the same category level or lower level of depressive symptoms than the baseline hospitalization score was categorized as stable/improved. A PHQ-9 score at follow-up that reflected a higher level of depressive symptoms than the baseline score was categorized as worse.
Univariate association with PHQ-9 outcome was conducted by using the two-sample t test for continuous characteristics and Fisher’s exact test for categorical characteristics. A logistic regression model was built to identify factors associated with worse PHQ-9 category on follow up. The following variables were considered in logistic regression analysis: age, gender, race (white, black, Hispanic), marital status, stroke location (anterior, posterior only), stroke side, NIHSS on admission, mRS at follow up (0/1, ≥2), on antidepressant at admission and at follow up, antidepressant prescribed at discharge and at follow up. Employment status was not included in multivariable logistic regression analysis because of a large amount of missing data (26%). A forward stepwise algorithm was implemented to select variables using the 5% significance threshold. Interaction between selected variables was tested and none was significant. Two-sided p-values were reported and p-values less than 0.05 were considered significant. All statistical analyses were performed using the SAS software (version 9.4, the SAS Institute, Cary NC). The study protocol was reviewed and approved by the institution’s Committee for the Protection of Human Subjects (IRB).
Results:
Participants
We identified 350 potentially eligible ischemic stroke patients from the STEP clinic registry. We excluded 15 patients who were hospitalized outside of our CSC, 30 patients who did not follow-up within 180 days, and 103 patients who were missing inpatient or outpatient PHQ-9, and one patient with duplicate registry entries. Only 16 patients were excluded for a missing outpatient PHQ-9. The final number of patients for inclusion in the study was 201.
Median time to clinic follow-up was 45 days (IQR 10–131). Patient demographics are illustrated in Table 1. Study participants had an average age of 61.8 years (SD 14.8), and 58% were male. Non-Hispanic white participants and non-Hispanic black participants were 47% and 28% of the study population, respectively. Hispanic patients made up 17% of participants. The remaining were Asian or unknown race. Among participants, 58% were married, 20% were single, 10% were widowed, 7% were divorced, and 5% were of unknown marital status. There were 65 patients (32%) who were employed and 59 (29%) who were retired. Ischemic stroke location was anterior circulation in 59% of cases and both posterior and anterior circulation in 6%. Stroke was right-sided in 47% of participants and left-sided in 46% of participants, and the remaining patients suffered bilateral strokes.
Table 1.
Patient demographics, clinical variables, and PHQ-9 scores.
| Patient Demographics | N=201 |
|---|---|
| Age, mean ± SD | 61.82 ± 14.84 |
| Male sex | 116 (58%) |
| Race | |
| Non-Hispanic White | 94 (47%) |
| Non-Hispanic Black | 56 (28%) |
| Hispanic | 35 (17%) |
| Asian | 4 (2%) |
| Unknown | 12 (6%) |
| Marital Status | |
| Single | 40 (20%) |
| Married | 116 (58%) |
| Divorced | 14 (7%) |
| Widowed | 21 (10%) |
| Unknown | 10 (5%) |
| Employment Status | |
| Employed | 65 (32%) |
| Unemployed | 11 (6%) |
| Retired | 59 (29%) |
| Disabled | 14 (7%) |
| Unknown | 52 (26%) |
| Stroke Circulation Location | |
| Anterior | 119 (59%) |
| Posterior | 70 (35%) |
| Both Anterior and Posterior | 12 (6%) |
| Stroke Side | |
| Right | 94 (47%) |
| Left | 92 (46%) |
| Bilateral | 15 (7%) |
| NIHSS * on Hospital Admission | |
| Mild (0–4) | 117 (58%) |
| Moderate (5–15) | 70 (35%) |
| Severe (≥16) | 13 (6.5%) |
| unknown | 1 (0.5%) |
| mRS† at Clinic Follow-Up | |
| 0–1 | 96 (48%) |
| ≥2 | 103 (52%) |
| Antidepressants | |
| On Antidepressant at Admission | 21 (10%) |
| Prescribed Antidepressant at Discharge | 18 (9%) |
| Continued Antidepressant at Discharge | 20 (10%) |
| On Antidepressant at Follow up | 42 (21%) |
| Prescribed Antidepressant at Follow-Up | 36 (18%) |
| Depressive Symptoms by Admission PHQ-9‡ Score | |
| None (Score 0–4) | 141 (70%) |
| Mild (Score 5–9) | 43 (21%) |
| Moderate (Score 10–14) | 15 (8%) |
| Moderately Severe to Severe (Score 15–27) | 2 (1%) |
| Depressive Symptoms by Follow-Up PHQ-9 Score | |
| None (Score 0–4) | 109 (54%) |
| Mild (Score 5–9) | 46 (23%) |
| Moderate (Score 10–14) | 27 (13%) |
| Moderately Severe to Severe (Score 15–27) | 19 (10%) |
| PHQ-9 Score Change on Clinic Follow-Up | |
| Stable or Improved | 128 (64%) |
| Worse | 73 (36%) |
National Institutes of Health Stroke Scale
modified Rankin Scale
Patient Health Questionnaire-9
One participant did not have a documented NIHSS. Among study patients, 58% had a mild NIHSS, 35% had a moderate NIHSS, and 6.5% had a severe score, and NIHSS ranged from 0 – 32. mRS at follow-up was ≥2 in 52% of study patients, and mRS ranged from 0 – 5. There were 47 patients with mRS 0, 49 with mRS 1, 35 with mRS 2, 53 with mRS 3, 12 with mRS 4, 3 with mRS 5, and 2 with missing mRS scores.
Progression of post-stroke depression
There were 60 patients (30%) with depressive symptoms (PHQ-9 score >4) during hospitalization. This increased to 92 patients (46%) at clinic follow-up. Among 141 patients free from depressive symptoms on hospital admission, 50 (35%) had developed depressive symptoms (PHQ-9 >4) on follow-up screening (Table 2). Among 43 patients with mild depressive symptoms (PHQ-9 5–9) during hospitalization, 18 (42%) developed moderate or severe PSD symptoms (PHQ-9 >10) on follow-up. Among 15 patients with moderate depressive symptoms (PHQ-9 10–14) initially, 5 (33%) developed moderately severe to severe depression symptoms (PHQ-9 ≥15) on follow-up. There were 2 patients with severe depressive symptoms during hospitalization, one had improved to only mild symptoms at follow-up, and one continued to have severe depression, despite antidepressant initiation during hospitalization. Overall, PHQ-9 score change from admission to follow-up was stable in 52% of study patients, worse in 36% of study patients, and improved in only 12%.
Table 2.
PHQ-9 category shifts from hospitalization to clinic follow-up.
| PHQ-9* Category | Hospitalization | Follow-up | |
|---|---|---|---|
| Baseline | Stable/Improved | Worsened | |
| No Depressive Symptoms | 141 (70%) | 91 (65%) | 50 (35%) |
| Mild | 43 (21%) | 25 (58%) | 18 (42%) |
| Moderate | 15 (8%) | 10 (67%) | 5 (33%) |
| Moderately Severe to Severe | 2 (1%) | 2 (100%) | 0 (0%) |
Symptoms defined by PHQ-9 score category: PHQ-9 score 0–4: no depressive symptoms, PHQ-9 score 5–9: mild, PHQ-9 score 10–14: moderate, PHQ-9 score 15–27: moderately severe to severe. By univariate analysis, there was no difference among category shifts (p=0.72).
Patient Health Questionnaire-9
Variables associated with post-stroke depression
Univariate analysis of age, sex, race, marital status, and NIHSS on admission were not associated with worsening PSD at clinic follow-up (Table 3). However, by employment status at follow-up, the highest proportion of patients in the stable/improved category were employed (40%), and the highest proportion of patients in the worse PHQ-9 category were retired (27%) (p=<0.001). Follow-up mRS ≥2 was associated with worse PHQ-9 category (p=0.03). In the worsening PHQ-9 group, 62.5% of patients had mRS ≥ 2 as compared to only 46% in the stable/improved group. In logistic regression analysis, patients with follow-up mRS ≥2 were two times more likely to have a worsening PHQ-9 category (OR 2.05, 95% CI 1.11–3.79) (Table 4).
Table 3.
Ischemic stroke patient demographics and clinical variables by PHQ-9 score change at follow-up clinic visit.
| Entire Cohort | Stable/Improved PHQ-9* Score | Worse PHQ-9 Score | Univariate analysis P value | |
|---|---|---|---|---|
| N | 201 | 128 | 73 | |
| Age, mean ± SD | 61.82 ± 14.84 | 62.63 ± 15.66 | 60.40 ± 13.27 | 0.31 |
| Male sex | 116 (58%) | 54 (42%) | 31 (42%) | 1.0 |
| Race | ||||
| Non-Hispanic White | 94 (47%) | 62 (48%) | 32 (44%) | 0.47 |
| Non-Hispanic Black | 56 (28%) | 32 (25%) | 24 (33%) | |
| Hispanic | 35 (17%) | 21 (16%) | 14 (19%) | |
| Asian | 4 (2%) | 3 (2%) | 1 (1%) | |
| Unknown | 12 (6%) | 10 (8%) | 2 (3%) | |
| Marital Status | ||||
| Single | 40 (20%) | 27 (21%) | 13 (18%) | 0.82 |
| Married | 116 (58%) | 74 (58%) | 42 (57%) | |
| Divorced | 14 (7%) | 7 (5%) | 7 (10%) | |
| Widowed | 21 (10%) | 14 (11%) | 7 (10%) | |
| Unknown | 10 (5%) | 6 (5%) | 4 (5%) | |
| Employment Status | ||||
| Employed | 65 (32%) | 51 (40%) | 14 (19%) | <0.001 |
| Unemployed | 11 (6%) | 7 (6%) | 4 (6%) | |
| Retired | 59 (29%) | 39 (30%) | 20 (27%) | |
| Disabled | 14 (7%) | 3 (2%) | 11 (15%) | |
| Unknown | 52 (26%) | 28 (22%) | 24 (33%) | |
| Stroke Circulation Location | ||||
| Anterior or Both | 131 (65%) | 89 (70%) | 42 (58%) | 0.093 |
| Posterior | 70 (35%) | 39 (30%) | 31 (43%) | |
| Stroke Side | ||||
| Right or Bilateral | 109 (54%) | 63 (49%) | 46 (63%) | 0.077 |
| Left only | 92 (46%) | 65 (51%) | 27 (37%) | |
| NIHSS† on Hospital Admission | ||||
| Mild (Score 0–4) | 117 (58%) | 73 (57%) | 44 (60%) | 0.77 |
| Moderate (Score 5–15) | 70 (35%) | 44 (34%) | 26 (36%) | |
| Severe (Score 16–42) | 13 (6.5%) | 10 (8%) | 3 (4%) | |
| Unknown | 1 (0.5%) | 1 (1%) | 0 (0%) | |
| mRS‡ at Clinic Follow-Up | ||||
| 0–1 | 96 (48%) | 69 (54%) | 27 (37.5%) | 0.027 |
| ≥2 | 103 (52%) | 58 (46%) | 45 (62.5%) | |
| Use of Antidepressants | ||||
| On Antidepressant at Admission | 21 (10%) | 11 (9%) | 10 (14%) | 0.34 |
| Prescribed Antidepressant at Discharge | 18 (9%) | 10 (8%) | 8 (11%) | 0.26 |
| Continued Antidepressant at Discharge | 20 (10%) | 10 (8%) | 10 (14%) | |
| On Antidepressant at Follow up | 42 (21%) | 22 (17%) | 20 (27%) | 0.11 |
| Prescribed Antidepressant at Follow-Up | 36 (18%) | 15 (12%) | 21 (29%) | 0.004 |
Patient Health Questionnaire-9
National Institutes of Health Stroke Scale
modified Rankin Scale
Table 4.
Important clinical variables identified by change in PHQ-9 score at follow-up clinic visit by logistic regression.
| Entire Cohort | Stable/Improved PHQ-9* Score | Worse PHQ-9 Score | Multivariate analysis | |||
|---|---|---|---|---|---|---|
| OR | 95% CI | P value | ||||
| Stroke Circulation Location | ||||||
| Anterior or Bilateral | 131 (65%) | 89 (70%) | 42 (57%) | 2.03 | 1.08–3.83 | 0.029 |
| Posterior Only | 70 (35%) | 39 (30%) | 31 (43%) | |||
| mRS† at Clinic Follow-Up | ||||||
| 0–1 | 96 (48%) | 69 (54%) | 27 (37.5%) | 2.05 | 1.11–3.79 | 0.022 |
| ≥2 | 103 (52%) | 58 (46%) | 45 (62.5%) | |||
| Use of Antidepressants | ||||||
| Prescribed Antidepressant at Follow-Up | 36 (18%) | 15 (12%) | 21 (29%) | 3.45 | 1.60–7.45 | 0.002 |
Patient Health Questionnaire-9
modified Rankin Scale
When evaluating the relationship between PSD symptom severity and stroke circulation, there was a higher proportion of patients with posterior circulation stroke in the worsening PHQ-9 category compared to anterior or both anterior and posterior circulation stroke, but this did not reach significance (p=0.09). However, in logistic regression analysis, patients with posterior circulation strokes were twice as likely to have worsening PHQ-9 category compared to patients with anterior circulation strokes or both (OR 2.03, 95% CI 1.08–3.83) (Table 4). There was a higher proportion of patients with worsening PHQ-9 category with right-hemisphere or bilateral strokes as compared to left-hemisphere strokes, but this did not reach significance in univariate analysis (p=0.08).
Antidepressant use
Among all study patients, 10% were taking an antidepressant medication on hospital admission, and 9% were prescribed an antidepressant at discharge. One patient’s antidepressant was not continued on discharge from the hospital. By clinic follow-up, 21% of patients were taking an antidepressant. Of those 42 patients already on an antidepressant by the follow-up visit, 20 patients (48%) still had worsening of PHQ-9 category. An additional 36 patients or 18% were prescribed an antidepressant at the follow-up clinic visit. Among these 36 patients prescribed an antidepressant in the clinic, 15 were in the stable/improved PHQ-9 group, and 21 were in the worse PHQ-9 group. On follow-up, patients were more likely to receive a prescription for an antidepressant with a worsening PHQ-9 category (p= <0.001). Notably, in logistic regression analysis, patients were nearly 3.5 times more likely to receive a clinic antidepressant prescription with worsening PHQ-9 category (OR 3.45, 95% CI 1.60–7.45) (Table 4).
Discussion:
In our study, 30% of patients had depressive symptoms while hospitalized with stroke, and 46% had depressive symptoms at follow-up, consistent with previously reported data.[3] Over one-third of clinic patients had a worsening PHQ-9 score from hospitalization. Other studies have examined the presence of PSD in the early period after stroke, but very few have documented how patients’ depressive symptoms progress from the acute, in-hospital period to the outpatient follow-up clinic visit.[29,30]
The high prevalence of depressive symptoms in stroke patients both in-hospital and at the follow-up visit highlights the importance of screening for this mood disorder early during hospitalization and recognizing PSD for potential treatment. Our study identifies the importance of the follow-up visit for PSD screening since we have shown high rates of PSD worsening between hospitalization and follow-up. We believe standardized stroke care needs to expand to include strong transitions of care for stroke patients after the acute stage of illness and in follow-up.
In our study, we sought to identify risk factors for developing PSD in the hopes that early identification will lead to early treatment and improved outcomes and recovery. A combination of factors have been associated with development of PSD, including disability, history of depression, cognitive impairment, stroke severity, anxiety, and poor social support.[7,31] Other potential risk factors, such as age, gender, educational status, etiology and lesion location, have conflicting evidence.[11,12] Interpretation of findings related to employment status is limited because of the amount of missing data. It appears that a higher proportion of employed patients had stable or improved depressive symptoms, while a higher proportion of retired patients had worse depressive symptoms at follow-up. This is consistent with prior studies that found employed patients have less PSD. Financial burden may play a role.[32,33]
We found that patients with mRS ≥2 were twice as likely to have worsening depressive symptoms. The mRS is a well-known, widely used metric for evaluating stroke disability outcomes.[34] However, very few other studies have relied on the mRS to capture a relationship with progression of PSD. The relationship of mRS to PSD may be related to the inability to perform all daily activities. Higher levels of cognitive impairment might also play a role, consistent with prior studies.[12,22] Patients react to their new baseline functional state, and mood changes subsequently develop. Much debate remains about the pathophysiology of PSD; whether PSD is related to neurochemical changes in the brain, psychosocial dysfunction or both.[28] Our finding of an association between depressive symptoms and poor functional outcome supports previous studies that showed a relationship between physical disability and mood.[7,11–13,22,35–37] Knowledge that patients with a higher degree of disability may be more vulnerable to PSD should prompt providers to aggressively screen and treat PSD in these patients.
In our study, patients with posterior circulation ischemic strokes were more likely to experience worsening depressive symptoms on clinic follow-up. This is inconsistent with recent evidence that supports an association with anterior circulation strokes.[21,23,24] Older studies showed association of PSD with left hemisphere strokes, but subsequent studies and systematic reviews have failed to show any association and have conflictingly shown association with right hemisphere strokes.[12,14–16,21,24] Few studies have evaluated the relationship between anterior or posterior circulation ischemic strokes and PSD. A recent study showed that patients with frontal lobe strokes were at higher risk for PSD.[23] One study evaluating lesion characteristics did show an association with larger stroke lesion volume and worse depression, but was not successful in identifying other associations.[37] Much debate still remains on the influence of lesion location on development of PSD. A limitation of our study is that we did not measure specific clinical variables that are dependent on lesion location and could play a role in the development of PSD, such as aphasia, dizziness, visual disturbance, or gait impairment. Patients who could not complete a PHQ-9 due to aphasia were excluded from our study, which limits our understanding of depression in the aphasic population and the generalizability of the results.
We found that patients in the worsening PHQ-9 category were nearly 3.5 times more likely to receive an antidepressant prescription during their follow-up visit. All patients in the STEP Clinic registry undergo PHQ-9 screening, which is not standard practice. Our approach to depression screening identified patients with worsening depressive symptoms which prompted treatment with an antidepressant medication. PHQ-9 screening both during hospitalization and follow-up in the clinic enabled us to identify a change in depressive symptom severity. Our data suggest that if repeated screening for depression with a PHQ-9 were standard management of post-stroke patients, PSD would likely be more recognized and treated.
Selection bias is an important limitation of our study. We only included patients who were able to follow-up in clinic, which includes only approximately 25% of our patient population. This had a clear impact on our study population. First, our sample represents patients with milder strokes with better overall outcomes. The median mRS score of our sample was 2 (IQR 1 to 3), and the median NIHSS was 4 (IQR 1 to 7). Only about 7% of the sample population had mRS >4 or severe NIHSS. However, our findings are still relevant. Not only do our results indicate that PSD occurs in relatively mildly affected stroke patients, but also worse mRS is associated with more PSD. If patients with milder strokes are still developing PSD, providers should recognize that patients with more severe strokes are probably more likely to develop PSD.
As mentioned above, patients with aphasia who could not complete both a PHQ-9 while hospitalized and again on follow-up were excluded from the study, and those patients typically have worse outcomes. Aphasic patients are often excluded from depression screening due to inability to participate. These results may not be generalizable to patients with moderate to severe aphasia. Only patients hospitalized at our single CSC were included, so the results might not be applicable to patients managed in populations with different hospital or patient characterstics. Discharge disposition was not included in this analysis and may have played a role in PSD. Hospital discharge mRS was not included in our study, so mRS cannot be assessed as a predictor of PSD. As mentioned, only patients who were able to follow-up in clinic were included, and the majority of these patients were insured (93%). This limits generalizability. Finally, the time to clinic evaluation was broad, up to 6 months, and a shorter period, such as 3 months, may have offered different results.[8] Our study findings should be validated with a multicenter study in the future.
Summary and Conclusion:
Over one-third of ischemic stroke patients develop depression or have worsening depressive symptoms from hospitalization to follow-up. Worse post-stroke disability, assessed as mRS ≥2, is associated with worsening depressive symptoms at clinic follow-up within 6 months post-stroke. Posterior circulation ischemic stroke location is also independently associated with worsening depression symptoms, conflicting with previous evidence which has failed to show stroke circulation as a reliable predictor of PSD. Patients with worsening depressive symptoms are more likely to be treated with antidepressants, highlighting the importance of screening for PSD in the follow-up clinic as well as during acute stroke hospitalization.
Acknowledgments
Dr. Fournier was supported by the following National Institutes of Health grant: 5T32NS007412-20
Footnotes
This work was conducted at The Institute for Stroke and Cerebrovascular Disease and The Department of Neurology at The University of Texas Health Science Center at Houston.
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