The Impact of Depression on the Functional Outcome of the Elderly Stroke Victim from a Gender Perspective: A Systematic Review

(1) Background: The aim of this systematic review focused on analyzing the impact of depression on the functional outcome of the elderly stroke victim and how this disorder affects both the female and the male population. (2) Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered in PROSPERO (ID 346284). The systematic search for clinical trials was performed in the databases Pubmed, Otseeker, Scopus, Web of Science, Psycinfo, Medline Complete, ScienceDirect, SciELO, and Dialnet. Articles were selected according to the inclusion and exclusion criteria, including those dealing with post-stroke depression in adults whose psychological status had changed. Studies that only assessed the psychological state of caregivers were excluded. (3) Results: In total, 609 articles were identified, of which 11 randomized controlled trials were finally included in the review. The results indicate that post-stroke depression influences the recovery of functionality and quality of life. In addition, the need to detect the mood of the adult population after the stroke and to provide individualized treatment according to the characteristics of the person is highlighted. (4) Conclusions: This systematic review shows how early detection of post-stroke depressive symptoms can improve the degree of disability and quality of life of the person, especially in women.


Introduction
Cerebrovascular Accident (CVA), also known as stroke, occurs when the blood vessels leading to the brain are affected. The World Health Organization (WHO) considers this pathology to be the second leading cause of death in the world and the third leading cause of physical disability in adults [1].
The World Stroke Organization (WSO) declares that 15 million people suffer a stroke each year and six million of whom do not survive the episode [2]. In Spain, the prevalence of people who have suffered a stroke is estimated to be approximately 7% of the population over 65 years of age. This figure is expected to increase by 35% by 2035 [3].
According to the "IBERICTUS" study by Díaz-Guzmán et al. [4] carried out in Spain in 2006, 10% of strokes occur in young people and 54% in women. It is established as the first cause of death in women and the third in men, with greater severity, mortality, and worse evolution in women.
Two out of every three people who survive a stroke have some type of sequelae, which can even be disabling [5]. This event is frequently associated with depression [6]. It was

Problem Statement
Post-stroke depression is the most frequent disorder and the main factor limiting patients' recovery and rehabilitation [7][8][9][10][11][12]. It occurs in one out of three stroke patients and more than half go undiagnosed and consequently untreated [13,14]. The study "Secondary Prevention of Small Subcortical Strokes" examined the prevalence of depression and it was associated with lower occurrence in older males without cognitive impairment [21,22].
It is difficult to distinguish those signs and symptoms that belong to stroke or depression [23]. Some symptoms are common or not recognized as consequent to this mental disorder and the diagnosis is underestimated [24]. In addition, questions remain as to what the best time is to initiate treatment and whether the only use of antidepressants has a direct effect on cognition and motor function [7,17]. These two areas, together with effectivity, play an important role in the impact of cerebrovascular disease.
Beyond pharmacological treatment, a rehabilitation program is necessary to recover functional capacity, independence, and reintegration of the individual into his or her family, social and work environment. Rehabilitation is adjusted to the level of disability, sequelae, and severity of the individual. If it starts in the first weeks, it leads to better long-term results [8,23,24].

Importance of Occupational Therapy
Stroke can be addressed by the clinical practice of Occupational Therapy at both physical and psychological levels to achieve the promotion of people's health, prevention of permanent disability status, and participation in the environment towards engagement in occupation [25][26][27][28].
The framework for Occupational Therapy practice defines the characteristics that make up the client as a dynamic interaction between psychological aspects, bodily functions, and the surrounding environment. The balance in these three aspects determines the commitment toward optimal occupational performance [29].
The illness process and the adaptation to a new situation can lead to a deficit in performance skills, loss of old habits, routines or roles, and alteration of the contexts and environments in which the individual used to relate [29].
Occupational therapy theory and practice can create a person-centered clinical rationale to support the recovery process. It provides the opportunity to develop a plan according to the client's needs, to adapt the rehabilitation process, and to offer counseling guidelines, both in the hospital setting and in the personal environment [29].
The lack of an Occupational Therapy service in the hospital context leads to late detection of functionality and psychological aspects such as depression suffered in the disease process [30].
This service can provide an opportunity for a type of intervention such as a counseling process to work with the clients to identify their problems, consider possible solutions, and modify the new situation they are facing [31].
Therefore, Occupational Therapists can assist other professionals in the early detection of post-stroke depression and they can offer different intervention approaches to prevent the disability and the reduced functionality that is perceived in people who suffer a stroke causing them long-term problems and high healthcare costs [24,25] So, the main objective of this systematic review is to analyze the effect of depression on the functional outcome and long-term recovery of patients who have suffered a stroke.
In turn, two secondary objectives are set: to analyze the impact of this mental disorder in the female versus male elderly population; to highlight the need for occupational therapy to address both the physical and psychological rehabilitation of this pathology during the period of admission and discharge.

Materials and Methods
The development of this systematic review was guided by the "PRISMA 2020" statement and its registration information is available [32].

Information Sources
This systematic review was conducted through an advanced search between February and April 2022 in the following databases: 'Pubmed', 'Scopus', 'Web of Science', 'Psycinfo', 'Medline Complete', 'Science Direct', 'OTseeker', 'SciELO' and 'Dialnet' (see Table 1). At this stage, it was checked that no other review had been carried out on the same topic. Then, the registration was completed in PROSPERO (ID 346284).

Search Strategy
To carry out this systematic review, an exhaustive search was performed in the databases: Pubmed, Otseeker, Scopus, Web of Science, Psycinfo, Medline Complete, Sci-enceDirect, SciELO, and Dialnet to identify controlled clinical trials or randomized clinical trials, published in the last ten years (see Table 2). A figure was developed according to the PRISMA regulation and the trial selection was attached (see Figure 1). The search for all published studies was conducted in December 2021 and updated in May 2022. Limit-to2012-2022, English, Spanish "stroke" AND "depression" AND "treatment outcome" 402
The full search strategy for all databases was: ('stroke' AND 'depression' AND 'treatment outcome') and the search filters selected were 'last 10 years'/'2012-2022', 'English', 'Spanish'. Except for 'Pubmed' and 'OTseeker' a manual reading was carried out to select those studies that were randomized or controlled clinical trials (Table 2).

Selection Criteria
Only studies that met the following criteria were included in this systematic review: controlled clinical trials or randomized clinical trials, published in the last 10 years, involving women and/or men over 18 years of age who had suffered an ischemic or hemorrhagic stroke and highlighting the change in their psychological state through assessment scales such as the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAM-D) or Hospital Anxiety and Depression Scale (HADS). The languages included were English and Spanish.
Exclusion criteria were: the rest of the types of studies that are not exposed in the inclusion criteria and studies that focused on the psychological state of caregivers and did not focus the research on the psychological state of users were excluded. Records deleted before screening:

Registers automatically marked as ineligible by years and language (n=10355)
Pubmed (n=130) Otseeker (n= 1) Records manually flagged as ineligible by type of study (n=779) Manually excluded records by title The quality assessment of the selected studies was carried out by two independent researchers using PEDro Scale [33].
The full search strategy for all databases was: ('stroke' AND 'depression' AND 'treatment outcome') and the search filters selected were 'last 10 years'/'2012-2022', 'English', 'Spanish'. Except for 'Pubmed' and 'OTseeker' a manual reading was carried out to select those studies that were randomized or controlled clinical trials (Table 2).

Selection Criteria
Only studies that met the following criteria were included in this systematic review: controlled clinical trials or randomized clinical trials, published in the last 10 years, involving women and/or men over 18 years of age who had suffered an ischemic or hemorrhagic stroke and highlighting the change in their psychological state through assessment scales such as the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAM-D) or Hospital Anxiety and Depression Scale (HADS). The languages included were English and Spanish.
Exclusion criteria were: the rest of the types of studies that are not exposed in the inclusion criteria and studies that focused on the psychological state of caregivers and did not focus the research on the psychological state of users were excluded.

Search Results
In May, the search results were checked after performing the same strategy. Figure 1 was developed according to the PRISMA regulation.

Characteristics of Included Trials
The 11 resulting clinical trials are summarized in Table 3 (see Table 3). Patients with hemiplegia due to stroke divided into a study group with conventional rehabilitation and a robotic-based rehabilitation system (n = 17) and a control group with only conventional rehabilitation (n = 20). The group exposed to natural light had a significant decrease in post-stroke depression and an increase in well-being at discharge (p = 0.046). Post-stroke anxiety was also reduced (p = 0.045). There were no significant differences in cognition.
3.5 months (group A: 9 sessions; group B: 9 sessions; group C: waiting list for care).

BDI, LESS
Cognitive rehabilitation therapy has a greater effect on post-stroke depression (p < 0.001) than psychoeducation and usual care. It is suggested that the type of intervention is influential in detecting post-stroke depression both at baseline and after treatment.

BDI, HAMD, STAI
The forest group showed a decrease in BDI, HAMD, and SATI scores (p < 0.05). See the need to manage psychological conditions (anxiety and depression) in this population.

AMT, MBI, HADS, PTQoLq
The creative art therapy group improved functionality, depression (p < 0.001), and quality of life (p < 0.001) after the intervention. There were no significant differences in anxiety and mental state (p = 0.123).

BI, HADS, TMSE
Barthel (p < 0.03) and HADS (p < 0.01) scores improved after 2 years. Depression was associated with dependency and quality of life. The higher HADS score of the control group showed a lower BI score.

Included Studies
After the search, 779 articles were retrieved and 170 were eliminated as duplicates. Finally, a total of 609 articles were retrieved of which 52 were read in full text. The final sample of the systematic review was composed of 11 clinical trials (see Table 1). The selection of these articles was based on the objectives and the application of the defined inclusion and exclusion criteria. The most relevant information from the articles obtained is summarized in Table 3 (see Table 3).
The identification of included studies was conducted independently in three stages: in the first stage; duplicates were manually removed; in the second stage; the title and abstract were read to select valid studies; and in the third stage; the full text of the resulting studies was assessed.
The following information was extracted independently for all studies, using a template (Table 3): author (main author is written), year of publication, type of study, participants (the total number), the study group (description of the intervention and the sample assigned to each group), characteristics of the intervention (duration of the intervention and the procedure followed by each group), measures (assessment scales used), and outcomes (reflection of the effectiveness of the intervention and possible significant underachievement). At the end of the table, the resulting score after the internal validity analysis (PEDro scale) is presented.

Quality of Trials
To minimize the risk of bias, the PEDro Scale was used to assess the internal validity of the studies in this systematic review. The scoring of the studies is in Table 3. This tool helped to identify randomized clinical trials through 10 items, which assess the specificity of choice criteria, randomization of subjects, blinded allocation, outcome measures, outcome statistics, and variability [45]. It was agreed to score at least five points in the evaluation of the studies to be included in the final review. Table 3 shows how the majority of the studies included have a score above seven, so they have a very good internal validity according to the range of the PEDro scale.
To complete the evidence of this review, the results of randomized clinical trials have to include the Relative Risk (RR). This measure reflects the strength of the association between receiving or not receiving the intervention, indicating if RR > 1 that the intervention is associated with positive recovery outcomes. The measurement of RR is carried out with the following formula [46]: Table 4 shows the Relative Risk of all included studies (see Table 4): The sample size of the included studies is a variable that stands out in this systematic review. Excepting the clinical trial by Taravati et al. [36] with n = 37, the clinical trial by Olukolade and Osinowo [40] with n = 30, and the one by Chun et al. [42] with n = 59, the rest presented a sample size equal to or greater than 60 patients.
Regarding the periodicity of the interventions proposed in the included studies, the majority lasted longer than two months. However, four clinical trials had a shorter duration [28,[30][31][32].
In terms of assessment instruments, all studies have used multiple standardized tests. For the assessment of depression status, the most commonly used tools have been found to be the Hospital Anxiety and Depression Scale (HADS) [31][32][33][34], the Hamilton Depression Scale (HAM-D) [30,33,35,36], and the Beck Depression Inventory (BDI) [29,30,36]. Other aspects such as occupational performance measured through the assessment instrument known as the Barthel Index (BI) were addressed [31,34,36,37].
Regarding the quality of the article, it was found that they achieved a medium-high score excluding one study. This random clinical trial scored below average because it did not present a method of sample randomization as can be seen in Table 3 [39].  The Risk of Bias tool by Cochrane Collaboration [47] was used to assess the methodology of scientific evidence of the RCTs included in this systematic review. The risk of bias assessment for each RCT included and by domain is summarized in Figure 2.

Discussion
The main objective of the present systematic review focused on studying the effect of depression on functional outcomes and long-term recovery after stroke, as shown in the results. Then, the articles were discussed according to how they achieved the objectives of this systematic review. The internal validity of the articles corresponded to the scientific evidence shown by the methodology of the included articles. Figure 2 shows how most articles have a low risk of bias. Three studies present a worrying risk of bias because they do not present much information on the domain of the intervention allocation effect and how it affects the outcome measure. Only one study shows a high risk of bias because the assessors were aware of the intervention assigned to the participant and it could affect the context.

Discussion
The main objective of the present systematic review focused on studying the effect of depression on functional outcomes and long-term recovery after stroke, as shown in the results. Then, the articles were discussed according to how they achieved the objectives of this systematic review.

Impact of Depression on Functionality and Recovery
Olukolade and Osinowo [40], Kongkasuwan et al. [43] and Zhang et al. [34], and Wang et al. [38] highlighted the importance of diagnosing and treating post-stroke depression to improve the rehabilitation process and increasing patients' quality of life, leading to a greater and more effective recovery.
The daylight intervention in inpatient rehabilitation confirmed an improvement in the psychological state of the person leading to reduced depression and increased well-being at the time of discharge [39].
The results of several interventions (Chun et al. [42], Chaiyawat and Kulkantrakorn [44], and Zhang et al. [34]) showed a reduction in depression and anxiety that resulted in less dysfunctionality and dependency. Furthermore, in the article by Chaiyawat and Kulkantrakorn [44] the high score on the HADS assessment of anxiety and depression during the hospital stay resulted in a lower score on the instrument assessing the performance of activities of daily living (Barthel Index).
Several articles confirmed that depression was strongly associated with dependence and quality of life [28,34,38].
The only clinical trial that conducted a virtual reality intervention combined with physical rehabilitation showed in its results a decrease in the depressive mood of the patients who received it, which increased the functionality and muscle strength of the affected and unaffected physical parts [37].
However, several authors such as Taravati et al. [36], Kongkasuwan et al. [43], West et al. [39], and Niu et al. [35], did not show significant changes in the outcomes of the cognitive aspects of their interventions (as assessed by MoCA) or in the long-term functional prognosis of their interventions. Furthermore, changes in depression were also not confirmed by the single use of antidepressants [41].
Sometimes, over time, symptoms were able to improve on their own by restoring neurological function [35].

Impact of Depression on Women versus Men
All of the resulting articles included stroke survivors 55 years through 80 years old, of which five were notable for their large female population [29,32,34,35,38]. All were randomized clinical trials except one, which was a quasi-experimental clinical study [44].
Another study highlighted the importance of presenting anxiety and depression after stroke, beyond the physical and cognitive disability [39]. This was presented as a result of the intervention study by Gao et al. [41] where they assessed patients at discharge, at 2-3 months, and at 6-9 months after discharge [41].
Olukolade and Osinowo [40] indicated that it is important to diagnose and treat depression after stroke to benefit patients' medical condition and quality of life, leading to a reduction in pain and disability and thus greater adherence to treatment.
Mental health may be more vulnerable after a stroke because cognitive impairments (concentration or performance) may interfere with emotional states [36].

The Need for Occupational Therapy Approach in Physical and Mental Rehabilitation
Olukolade and Osinowo highlighted that the type of therapy has a significant influence on post-stroke depression, both at the beginning and at the end of treatment [40].
The discipline of occupational therapy can implement different therapeutic interventions such as the one presented in Kongkasuwan et al. article on creative art therapy [32]. This intervention allowed stroke patients who have suffered a stroke and experienced emotional disturbance with loss of motor skills, to improve their depressive symptoms and quality of life.
Interventions for cognitive training (computer or virtual reality) and learning showed results of improvements in cognitive function, depression, anxiety, sleep quality, and selfcare in patients with moderate cognitive states after stroke [29,31,35]. It was even more effective than psychoeducation and the usual care provided [40].
The combination of physical rehabilitation, patient education to restore daily living functions, problem-solving skills and counseling made patients satisfied and it reduced the feeling of lack of support that they experienced after hospital discharge [44].
In all the trials reviewed, no significant changes were found with the single use of pharmacological therapies. In contrast, the results of a citalopram intervention highlighted the adverse effects of long-term medication [30,36].

Limitations
There are heterogeneous studies in the methodology (number of patients, type of therapy, and duration). The percentage of the sample whose results were striking did not correspond to the original sample size.
The occupational therapy approach has not been studied in depth due to the fact that this profession has difficulties to been recognized in the hospital environment [38,42,45,48].

Conclusions
Based on all the points discussed in this systematic review, it can be concluded that post-stroke rehabilitation should include the prevention of depression to allow greater recovery of functionality and to improve quality of life.
According to the second objective, it is shown that post-stroke depressive disorder may differ by gender. Depressive symptoms are common after stroke and the female gender is associated with them, resulting in a higher level of disability and poorer quality of life.
Therefore, it is necessary to attend to the individuality of the person and to offer treatment according to the different aspects surrounding them (gender, age, background, and family support...). All of this could speed up functional recovery and improve the patient's and their family's quality of life.
Finally, it is important to explore more studies that research the effects of occupational therapy practice on physical and mental recovery in post-stroke patients with depression. There are very little scientific data to support this hypothesis, but the results of the various studies are consistent in showing improvements in all areas that an occupational therapist's knowledge and practice can deal with.