Incidence of post-stroke depression in hospitalized patients after ischemic stroke

Summary

Background: Stroke is the second most common cause of death in the Czech Republic. Ischemic stroke accounts for more than ¾ of all strokes. In 2020, the incidence of ischemic stroke was 211 cases per 100,000 people per year, and the prevalence is estimated at 240,000 cases. Post-stroke depression (PSD) affects approximately one third of patients after ischemic stroke and significantly affects rehabilitation and quality of life. The aim of our work was to determine the frequency of PSD after the first ischemic stroke in our department and to evaluate the interest of patients in drug and experimental treatments. Methodology: The study included patients hospitalized after the first ischemic stroke without previous depression and aphasia. Depression screening was performed using the Beck Depression Inventory (BDI-II) first after 3 months in the outpatient clinic, and later during hospitalization after protocol modification. Results: 40 patients were examined in the outpatient phase, out of whom 12 (30%) were depressed. Only 3 patients agreed to a psychiatric examination. After the protocol change, 300 patients were examined during hospitalization, 51 (17%) were screened as depressed, and 43 patients (14.3%) were treated with antidepressants. Conclusions: The prevalence of PSD reached 17–30% depending on the timing of screening. A fundamental problem is the low compliance of patients with psychiatric care due to stigmatization. Screening during hospitalization appears to be more practical than outpatient monitoring.

Keywords:

ischemic stroke – pharmacotherapy – post-stroke depression – Beck Depression Scale

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

 

Introduction

Cerebrovascular accident has traditionally been considered a disease affecting primarily motor performance and speech. The approach to rehabilitation and follow-up has focused almost exclusively on improving these areas. However, studies and our own experience show that other functions, such as cognition, behavior, and emotions, are also affected. These changes also have a significant impact on the life of patients after ischemic stroke (IS). One of the determining factors is depression, which is the most common neuropsychological complication of IS [2].

Depression arising after a stroke is an organically conditioned affective disorder and is referred to in the literature as post-stroke depression (PSD) [3]. It manifests itself in a depressed mood and a loss of feelings of joy and interest (anhedonia). In addition, at least five secondary symptoms must be present –⁠ sleep disturbance (insomnia, hypersomnia), appetite disorder (usually decreased appetite), slowed psychomotor speed and increased fatigue, impaired attention, difficulty thinking, feelings of failure, remorse, decreased self-esteem, impaired will and initiative, thoughts of death, and suicidal behavior. Side effects may include reluctance to talk, irritability, negativity, tearfulness, feelings of hopelessness, absence of meaningful daily activities, non-cooperation with treatment, or refusal of help from others [4].

Depression is an important predictor of functional outcome after IS. It is associated with poorer functional and cognitive recovery, limitations in daily living activities, social and interpersonal activities, poorer quality of life, and higher mortality (up to 10 times higher than in patients without PSD) [5]. Many other neuropsychological symptoms may be present after IS –⁠ anxiety, irritability, agitation, and emotional incontinence; changes in emotional experience; sleep disorders; behavioral disorders (such as disinhibition); apathy, fatigue –⁠ even psychotic symptoms, such as delusions and hallucinations. All of these conditions can affect the quality of recovery and quality of life [3,5].

There are many risk factors for the development of depression, including more severe motor deficits, higher levels of disability, and poorer social support networks. Identifying these factors allows for the early application of prevention and treatment strategies [2]. However, although the prevalence of depression after IS is high, it is generally underdiagnosed and usually undertreated. Therefore, it is necessary to identify it in at-risk patients as early as possible.

Methodology

The aim of our study was to determine the frequency of PSD after the first IS at KCC FN Ostrava. Another aim was to determine whether patients are interested in drug treatment for PSD and, in suitable patients, in experimental treatment using repetitive transcranial magnetic stimulation (rTMS).

The study was conducted in two phases with different methodologies due to practical problems with the original protocol:

 

First phase (11/2021–12/2022)

Patients were examined 3 months after discharge at the cerebrovascular outpatient clinic using the Beck Depression Inventory (BDI-II). Patients without fatigue disorders, with a modified Rankin Scale (mRS) score ≤ 3, and able to sit for > 30 min were included. Patients with a history of depression and those taking antidepressants prior to IS were excluded from the study. The survey was conducted in the form of a BDI-II depression screening questionnaire. The evaluation was performed according to the methodology of Preiss and Vacíra [6]. Based on the number of points obtained, patients were divided into groups without depression, with mild, moderate, and severe depression. Depressed patients were offered psychiatric care with further examination using the Hamilton Depression Rating Scale (HDRS). Patients with mild depression were offered rTMS. Patients with moderate to severe depression were prescribed antidepressants.

 

Second phase (1/2023–8/2024)

After the protocol was changed, patients were examined during their hospitalization at our clinic. All patients after their first IS without previous depression and without aphasia were included. Patients with aphasia were again excluded. All patients also underwent cognitive function screening using the Mini Mental States Exam (MMSE) test.

 

Results

In the first phase, 40 suitable patients were examined between November 2021 and December 2022. Twelve patients (30%) were assessed as depressed. Ten patients were mildly depressed, and two were moderately depressed. No cases of severe depression were diagnosed in the patients examined. Patients were offered further examination by a psychiatrist with the option of undergoing rTSM or classic drug therapy. To our disappointment, only 3 patients were willing to undergo psychiatric examination. Other patients refused the examination for personal and family reasons. These patients were offered antidepressants. Only one patient accepted the treatment, while the others refused it. Thus, 2 patients underwent additional psychiatric examination. One patient canceled the examination by a psychiatrist due to illness and did not return for another examination. The remaining two patients were examined using a structured interview and HDRS. One patient was assessed as a suitable candidate for rTSM, which he subsequently underwent, but the treatment was ineffective at the follow-up. Another patient, whose biggest problem was insomnia following IS, preferred treatment with trazodone, which was administered with good effect.

In the second phase, all patients hospitalized at our clinic after their first IS without a previous history of depression and without aphasia were included. From January 2023 to August 2024, 300 patients hospitalized after IS were examined. A total of 51 patients (17%) were screened as depressed according to the BDI-II self-assessment scale. Patients were offered antidepressants. Eighteen patients with moderate to severe depression underwent psychiatric examination. Eight patients refused treatment. Finally, antidepressants were prescribed to 43 patients (14.33%). In 18 cases ( ), the patients were men, and in 25 cases, they were women. The medications prescribed were sertraline (10 cases), citalopram (13 cases), and mirtazapine/trazodone (10 cases). Another 55 patients (18.33%) had positive cognitive screening (MMSE 25 and below) and were referred for further examination (Figs. 1, 2). No further follow-up of the examined patients was performed. Most patients were then monitored by outpatient neurologists, and follow-up examinations using BDI questionnaires after 3 months were not performed by the monitoring physicians. No patients were referred for rTMS.

The strongest predictors of depression appear to be the degree of disability after IS (53.9% of patients with depression), female gender (49% of patients with depression), and social isolation –⁠ individuals living alone (46.5% of patients with depression).

 

Limitations

Although the chosen protocol seemed easy to implement, we discovered its significant limitations during the study. The main limitation of the study is the modification of the study protocol during data collection, which does not allow for a direct comparison of the two phases. Of the patients in the first phase, i.e., those who had suffered an IS, only a fraction of patients –⁠ those who had undergone mechanical recanalization or those with unknown stroke etiology –⁠ were referred to the cerebrovascular outpatient clinic. Given the size of our catchment area, a proportionate number are referred to cerebrovascular clinics at stroke centers in the catchment area. In addition, some patients were hospitalized in inpatient rehabilitation or at spas at the time of the scheduled check-up, or did not come for the check-up at all. The number of patients after their first IS (mRS score of 3 or lower, without cognitive deficit and without a previous history of depression) who came to our cerebrovascular clinic 3 months after the event is therefore relatively low.

Another limitation was patients' reluctance to undergo psychiatric examinations. Even today, these examinations are stigmatizing for middle-aged and older patients. Therefore, rTMS was not even proposed to them.

In the second phase of the protocol, more patients were examined. The examination took place during hospitalization and was not performed at a later date, so some patients may have escaped screening. Screening during hospitalization may therefore underestimate the incidence of PSD, as the acute phase may not reflect the actual incidence of depression. The monocentric nature and lack of long-term follow-up reduce the generalizability of the results. These limitations were partially predictable at the time of study design.

The usual limitations of these studies include the uneven representation of men (183) and women (117), different representation of age groups, and different comorbidities of subjects.

 

Discussion

The incidence of depression after IS is high. The highest incidence of depression is observed in the first year after the event [7]. Clinically significant depression may occur as a single episode or recurrently with a risk of chronicity. Less than half of patients achieve remission within 6 months [7]. Studies investigating predictors of depression have not yielded clear results. However, gender (only a slight predominance of women), age (older age is not associated with a higher risk), risk factors for IS (arterial hypertension, hyperlipidemia, diabetes mellitus), recurrence of IS, type of CMP, education, or social background (family situation) do not appear to be risk factors. Family history of depression, occurrence of depression before IS, severity and extent of IS, and poorer functioning in daily activities appear to be risk factors. The association between the degree of disability and the severity of depression is not very strong and explains only 10% of the variability [4]. The relationship between the location of IS and the development of depression is also unclear [8]. The influence of psychosocial factors cannot be ruled out either. The absence of social support is a risk factor for the early onset of depression after IS and its severity, but not for the development of depression in general [9]. This corresponds to our findings –⁠ the strongest predictive factor appears to be patient isolation (46.5% of depressed patients).

There is no consensus in the literature on PSD screening methods. Czech psychiatric literature recommends structured interviews and various questionnaires –⁠ the Center for Epidemiological Studies Depression Scale (CES-D), HDRS, and Patient Health Questionnaire (PHQ-9) [4]. The Canadian Best Stroke Practices provide detailed recommendations. Its website recommends screening all patients who have undergone IS and are able to undergo the examination for the presence of depression. The recommended tests are the Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), PHQ-9, BDI, CES-D, or Depression, Obstructive Sleep Apnea, and Cognitive Impairment Screen (DOC) [10]. The American Heart Association/American Stroke Association mentions that the optimal test for determining depression may vary depending on the timing of the examination. In principle, it prefers similar questionnaires –⁠ HDRS, CES-D, HADS-D, and BDI [11].

The BDI-II screening questionnaire we have chosen is very similar to the PHQ-9 questionnaire in terms of test questions. It reflects the patient's current feelings [12]. Based on the number of points obtained, we distinguish between normal (0–13), mild (14–19), moderate (20–39), and severe depression (40–63). It is easy to administer and does not require training of the evaluator.

There is also no consensus on the period during which the patient should be examined for depression. Given that depression most commonly occurs between 2 and 5 months after IS, this period seems to be the most appropriate [13]. However, data collection during this period is complicated. In our case, changing the protocol to screening during hospitalization proved to be a more practical solution.

Our findings on the prevalence of PSD (17–30%) correspond with the published literature (25–79%) [2,3,5,9,13]. The difference between the phases of the study can be explained by different timing.

However, screening alone is not enough. According to a randomized study by Whooley et al., although screening in primary care leads to improved diagnosis, it does not lead to an improvement in patients' depressive symptoms. Patients' unwillingness to undergo pharmacological treatment or targeted interventions also contributes to this situation [14]. A key finding of our work is the extremely low compliance with psychiatric care (25% in the first phase). This reflects the stigmatization of psychiatry in the Czech population, which represents a major barrier to the treatment of PSD.

Again, there is no global consensus on the treatment of depression. The most commonly studied drugs include selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). Studies focusing on the treatment of depression after IS tested nortriptyline [15], citalopram [16], fluoxetine [17,18], or compared nortriptyline with fluoxetine and placebo [19,20]. These studies were conducted on a small number of patients and the results did not provide clear recommendations. Ried et al. found that SSRI treatment was associated with higher survival rates and therefore recommend initiating or resuming SSRI treatment as soon as possible after IS [21]. According to Jorge et al., patients taking escitalopram after IS showed improvement in verbal and visual memory functions compared to patients taking placebo [22]. In addition, some stimulants, such as amphetamines and methylphenidate [23], or the calcium antagonist nimodipine [24], have been investigated. None of these drugs has gained acceptance in the treatment of depression, and antidepressants are still preferred.

Selective serotonin reuptake inhibitors appear to be safe, cause fewer side effects than other drugs studied, act relatively quickly, with a latency period of 7–10 days, and also have an anxiolytic effect. Caution should be exercised when used concomitantly with anticoagulants (SSRIs increase the anticoagulant effect), antiepileptics (SSRIs lower the seizure threshold), and in patients taking antiulcer drugs (omeprazole increases plasma levels of escitalopram) [25].

Our choice of SSRIs as first-line drugs is therefore in line with international recommendations.

Repetitive transcranial magnetic stimulation is a non-invasive physical method that mimics neuronal excitation or inhibition and has a neuromodulatory effect on the cerebral cortex. It is assumed that biochemical changes occur (correction of catecholamines and their receptors, improvement of cortex nutrition, and reduction of inflammatory factors), local blood flow improves, and the mutual inhibitory mechanism between the hemispheres is disrupted. All of this should lead to the restoration of neurological functions after IS.

The method is generally considered safe. The most common side effects include headache, pain at the stimulation site, and tinnitus. Patients with cardiovascular instability, epilepsy or at risk of epileptic seizures, and patients with implanted metal devices, pacemakers, or drug pumps are not suitable for treatment. Since 2014, the Food and Drug Administration has approved its use in combination with antidepressants for the treatment of depression. Currently, 54 randomized studies have been published on the treatment of depression after IS using rTMS. Some studies focus purely on the effect of rTMS, some combine the effect of conventional antidepressants with rTSM and rehabilitation, and others combine the effect of rTMS with traditional Chinese medicine. Some studies involved repeated stimulation, while others involved single stimulation. Individual protocols differ in terms of the frequency used, the number of pulses and series, the interval between individual series, the intensity used, and the application sites. All studies report rTMS as more effective than the control group [26]. Unfortunately, these studies are not consistent in the parameters monitored –⁠ improvement in motor skills, improvement in cognitive parameters, improvement in daily activities. Neuromodulation methods such as rTMS may be effective in some refractory patients, but further studies are needed to prove their effectiveness [11].

 

Conclusion

Depression after IS remains a significant and often underdiagnosed problem. The prevalence of depression in our cohort ranged from 17% during hospitalization to 30% at the 3-month follow-up after IS. These data are consistent with the published literature, which reports a range of 25–79% [27], with most studies reporting a prevalence of around 30%. The difference in prevalence between the two phases of our study may be due to both different screening timing and different patient selection methods. The literature reports the highest incidence of depression between 2 and 5 months after IS, which would explain the higher detection rate in our 3-month cohort.

A key finding of our study is the very low compliance of patients with follow-up psychiatric care. This phenomenon reflects the persistent stigma attached to psychiatric care among the Czech population, especially among older patients. This attitude represents a significant barrier to the provision of adequate care and requires a systematic solution in the form of education for both patients and healthcare personnel.

The choice of SSRI treatment is in line with international recommendations, which prefer SSRIs as first-line drugs due to their favorable safety profile and minimal interactions. Another important aspect is their anxiolytic effect and relatively rapid onset of action (7–10 days), which is important for patient compliance with treatment.

Screening during hospitalization appears to be more practical than outpatient monitoring. For future research, we therefore recommend a multicenter study with a uniform protocol and longer follow-up. One option is to introduce two -⁠ to three-stage screening for depression after IS: the first upon discharge from the hospital, the second after 3 months, and possibly the third after 6 months from the event (Fig. 3).

The BDI-II questionnaire has proven to be a useful screening tool in the Czech environment. The limitation of the BDI is that it cannot be used in patients with aphasia or cognitive impairment. It will therefore be necessary to develop or validate a screening tool for patients with aphasia and cognitive impairment, who are currently excluded from screening. An economic analysis of the cost-effectiveness of systematic screening for depression after IS could provide further arguments for its implementation into routine clinical practice.

 

Ethical aspects

The work was carried out in accordance with the 1975 Helsinki Declaration and its revisions in 2004 and 2008. Approval by the Ethics Committee was granted as part of the approval of institutional grant 25/RVO-FNOs/2021. Approval was granted on April 29, 2021.

 

Grant support

The work was supported by grant 25/RVO-FNOs/2021.

 

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study.