ObjectivesTo evaluate the effectiveness of non-pharmacological interventions for managing post-stroke depression and identify the characteristics of optimal interventions.Data SourcesEight English databases and two Chinese databases were searched from inception to February 2025, alongside grey literature.MethodsTwo reviewers independently screened studies and extracted data from randomised controlled trials (RCTs) or pilot/feasibility RCTs. Study quality was evaluated with the Cochrane Risk of Bias 2 tool. Meta-analyses used Review Manager 5.3 when feasible; otherwise, narrative syntheses were conducted. Certainty of evidence was assessed via the Grading of Recommendations Assessment, Development, and Evaluation system.ResultsSeventeen studies (1297 stroke survivors) were included. Two had a low risk of bias, two had a high risk, and 13 had some concerns. Meta-analyses showed cognitive-behavioural intervention had significant short-term effects (< one month) on depressive symptoms versus control (standardised mean difference SMD: -0.63, 95% CI: -1.00 to -0.26, p < 0.001, I2 = 81%; 7 studies; 693 participants). Cognitive-behavioural interventions without cognitive restructuring showed significant short-term (effect size ES = 0.52-1.08) and medium-term (1-6 months) effects (ES = 0.73-1.71). Preliminary evidence suggested that exercise with music, acceptance and commitment therapy, mindfulness meditation, and aromatherapy also improve depressive symptoms versus control.ConclusionNon-pharmacological interventions, including cognitive-behavioural intervention, exercise, acceptance and commitment therapy, mindfulness meditation, and aromatherapy, could improve post-stroke depressive symptoms. However, with very low evidence certainty, further rigorous RCTs are needed.

Persons with acquired brain injury (ABI) often experience mood problems like depression. While psychotherapy is widely accepted for managing depression in populations without ABI, its effectiveness for post-ABI depression is uncertain. The working mechanisms of psychotherapy in persons with ABI may differ from idiopathic depression. This scoping review aimed to identify studies on psychotherapeutic interventions for post-ABI depression, assess the use of process measures (instruments measuring the mechanisms of psychotherapy), and report effects on both process and primary outcome measures. In the 47 included studies, Cognitive Behavioural Therapy, Problem Solving Therapy, and Third-Wave Therapies were most frequently investigated. Results indicated that less than half of the studies implemented a process measure. Studies into Third-Wave Therapies most frequently implemented process measures. Around half of the studies found significant time or interaction effects on the process measure, while not necessarily finding effects on outcome measures for depression. Moreover, the review could not identify a specific type of intervention effective in improving depressive symptoms and the underlying process. Our findings emphasize that it is still unclear which psychotherapy works for whom, and how. To enhance understanding of effective interventions for post-ABI depression, it is crucial to incorporate process measures in future intervention studies.

Antidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.

To assess antidepressants' efficacy and tolerability in individuals with depression and comorbid physical conditions.

Systematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (https://osf.io/9cjhe/).

Of the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from -1.01 (imipramine) to -0.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was 'low' or 'very low' for most comparisons.

Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.

Background: Polypharmacy is a predictor of adverse outcomes, making its management crucial for improving patient health and recovery. Managing polypharmacy is particularly challenging in patients with stroke with many comorbidities and sequelae. Although reducing inappropriate prescribing is necessary, the number of medications may increase to effectively implement secondary prevention, potentially offsetting any changes in medication count. For patients with stroke undergoing recovery-phase rehabilitation, balancing secondary prevention and optimizing drug use early without hindering recovery of activities of daily living are crucial. This study is aimed at examining the effect of increasing or decreasing the use of polypharmacy on recovery of motor and cognitive function during recovery-phase rehabilitation in patients with stroke. Methods: The study was conducted from July 2010 to June 2019 among patients with stroke discharged from the convalescent rehabilitation ward during the study period. Patients who were using more than five drugs on admission and had either an increase or decrease in the number of drugs used on discharge were compared. Propensity score matching (PSM) was used to control for background variables such as patient demographics, laboratory values, and functional independence measure (FIM) scores at baseline. The primary outcomes were motor, cognition, and total FIM gain. Results: Of the 226 patients initially enrolled, 156 were matched on propensity score. The total motor FIM gain, total cognitive FIM gain, and total FIM gain were significantly higher in the decreased group than in the increased group (p = 0.0139, p = 0.0377, and p = 0.0077, respectively). Conclusion: In patients with stroke, reducing rather than increasing the number of drugs administered during recovery-phase rehabilitation could improve rehabilitation outcomes. Therefore, it is important to consider whether the drugs are essential for the patient and proactively revise the drug regimen to ensure rapid rehabilitation of patients with stroke.

To evaluate the efficacy and safety of acupuncture combined with five-element music (FEM) as an therapeutic strategy for the physical and mental state of Post-stroke depression patients.

Multicenter, randomized clinical trial conducted at 3 hospitals in China and enrolling 237 patients with PSD between June 2019 and April 2021. Participants mild/moderate PSD (17-item GRID Hamilton Depression Scale (HAMD) score 7-24) were randomly assigned (1:1) to acupuncture combined with FEM (AFEM) group or cognitive behavioral therapy (CBT) group.

The primary outcome was change and differences between the groups in HAMD-17 from baseline to week 12. Secondary outcomes included Fugl-Meyer Assessment Scale score and Stroke-Specific Quality of Life Scale (SS-QOL) score.

The 237 patients in this intention-to-treat analysis were randomized into either the AFEM group (n=119) or the cognitive behavioral therapy (CBT) group (n=118). Of these 237 participants, 225 (94.9 %) completed all outcome measurements at week 12. The AFEM and CBT groups both showed significant improvement in HAMD-17 from baseline to week 12. Patients in the AFEM group had significantly lower HAMD-17 scores of -3.56 at week 8 (95 % CI,-4.59 to -2.53; p <.001) and -3.50 at week 12 (95 % CI,-4.53 to -2.46; p<.001) than patients in the CBT group. The SS-QOL score improved significantly at week 12. The Fugl-Meyer score was significantly lower in the AFEM group than in the CBT group at week 4, but this difference was not statistically significant upon follow-up at weeks 8 and 12. The incidence of treatment-related adverse events was 2.1 % in the AFEM group, with no serious adverse events reported.

The results suggest that acupuncture and five-element music significantly improve the depressive symptoms in this cohort of Chinese PSD patients, and the toxicities were similar with CBP group.

This study registered with the ClinicalTrials.gov Identifier: ChiCTR1900023741.

Post-stroke depression (PSD) is a common and debilitating condition affecting stroke survivors, significantly impacting their recovery and overall quality of life.

To assess the effects of early PSD screening on functional outcomes, quality of life, and mortality.

From an initial pool of 1065 articles, 6 studies met the inclusion criteria and were selected for analysis. Functional outcomes were measured using the functional independence measure (FIM).

The analysis revealed a significant improvement in FIM scores for a PSD screening group compared to controls [standardized mean difference (SMD) = 8.90, 95% confidence interval (CI): 4.65-13.15, P < 0.01]. Quality of life was assessed using the Stroke-Specific Quality of Life Scale, with the screening group showing significantly higher scores (SMD = 20.83, 95%CI: 15.27-26.38, P < 0.01). Mortality analysis indicated a reduction in five-year mortality rates for the PSD screening group.

Early PSD screening enhances functional recovery, improves quality of life, and reduces mortality rates in stroke survivors. Thus, integrating PSD screening into routine stroke care improves long-term outcomes for patients.

Nearly one-third of all stroke patients develop depression at any time after a stroke, and its presence is associated with unfavorable outcomes. This narrative review aims to provide a synopsis of possible pharmacological and non-pharmacological treatment modalities for post-stroke depression (PSD). Several studies have demonstrated the efficacy and safety of selective serotonin reuptake inhibitors in treating the symptoms of this clinical condition. The treatment of PSD has been recently enhanced by innovative approaches, such as cognitive-behavioral therapy, virtual reality, telehealth, repetitive transcranial magnetic stimulation, and non-conventional therapies, which might improve depression treatment in stroke survivors. Future high-quality randomized controlled trials are necessary to confirm this hypothesis.

Depression is the most frequent psychiatric disorder following stroke, affecting about one-third of stroke survivors. Patients experience poorer recovery, lower quality of life and higher mortality compared with stroke survivors without depression. Despite these well-known malign consequences, poststroke depression (PSD) is regarded underdiagnosed and undertreated. Evidence of beneficial effects of psychotherapy to treat PSD remains scarce and inconclusive and is limited by heterogeneity in design, content and timing of the intervention. This pilot study aims to assess the feasibility of a newly developed integrative-interpersonal dynamic PSD intervention in an outpatient setting and provide a first estimation of the potential effect size as basis for the sample size estimation for a subsequent definite trial.

Patients will be recruited from two German stroke units. After discharge from inpatient rehabilitation, depressed stroke survivors will be randomised to short-term psychotherapy (12 weeks, ≤16 sessions) or enhanced treatment as usual. The manualised psychotherapy integrates key features of the Unified Psychodynamic and Cognitive-Behavioural Unified Protocol for emotional disorders and was adapted for PSD. Primary endpoints are recruitment feasibility and treatment acceptability, defined as a recruitment rate of ≥20% for eligible patients consenting to randomisation and ≥70% completion-rate of patients participating in the treatment condition. A preliminary estimation of the treatment effect based on the mean difference in Patient Health Questionnaire-9 (PHQ-9) scores between intervention and control group six months poststroke is calculated. Secondary endpoints include changes in depression (PHQ-9/Hamilton Depression Scale) and anxiety (Generalised Anxiety Disorder 7) of all participants across all follow-ups during the first year poststroke.

The INID pilot study received full ethical approval (S-321/2019; 2022-2286_1). Trial results will be published in a peer-reviewed journal in the first half of 2025. One-year follow-ups are planned to be carried out until summer 2025.

DRKS00030378.

Depression is an important morbidity associated with stroke that impacts on recovery, yet is often undetected or inadequately treated.

To evaluate the benefits and harms of pharmacological intervention, non-invasive brain stimulation, psychological therapy, or combinations of these to treat depression after stroke.

This is a living systematic review. We search for new evidence every two months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. We searched the Specialised Registers of Cochrane Stroke, and Cochrane Depression Anxiety and Neurosis, CENTRAL, MEDLINE, Embase, five other databases, two clinical trials registers, reference lists and conference proceedings (February 2022). We contacted study authors.

Randomised controlled trials (RCTs) comparing: 1) pharmacological interventions with placebo; 2) non-invasive brain stimulation with sham stimulation or usual care; 3) psychological therapy with usual care or attention control; 4) pharmacological intervention and psychological therapy with pharmacological intervention and usual care or attention control; 5) pharmacological intervention and non-invasive brain stimulation with pharmacological intervention and sham stimulation or usual care; 6) non-invasive brain stimulation and psychological therapy versus sham brain stimulation or usual care and psychological therapy; 7) pharmacological intervention and psychological therapy with placebo and psychological therapy; 8) pharmacological intervention and non-invasive brain stimulation with placebo and non-invasive brain stimulation; and 9) non-invasive brain stimulation and psychological therapy versus non-invasive brain stimulation and usual care or attention control, with the intention of treating depression after stroke.

Two review authors independently selected studies, assessed risk of bias, and extracted data from included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE.

We included 65 trials (72 comparisons) with 5831 participants. Data were available for: 1) 20 comparisons; 2) nine comparisons; 3) 25 comparisons; 4) three comparisons; 5) 14 comparisons; and 6) one comparison. We found no trials for comparisons 7 to 9. Comparison 1: Pharmacological interventions Very low-certainty evidence from eight trials suggests pharmacological interventions decreased the number of people meeting the study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; P = 0.002; 8 RCTs; 1025 participants) at end of treatment and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with inadequate response to treatment (RR 0.47, 95% CI 0.32 to 0.70; P = 0.0002; 6 RCTs; 511 participants) compared to placebo. More adverse events related to the central nervous system (CNS) (RR 1.55, 95% CI 1.12 to 2.15; P = 0.008; 5 RCTs; 488 participants; very low-certainty evidence) and gastrointestinal system (RR 1.62, 95% CI 1.19 to 2.19; P = 0.002; 4 RCTs; 473 participants; very low-certainty evidence) were noted in the pharmacological intervention than in the placebo group. Comparison 2: Non-invasive brain stimulation Very low-certainty evidence from two trials show that non-invasive brain stimulation had little to no effect on the number of people meeting the study criteria for depression (RR 0.67, 95% CI 0.39 to 1.14; P = 0.14; 2 RCTs; 130 participants) and the number of people with inadequate response to treatment (RR 0.84, 95% CI 0.52, 1.37; P = 0.49; 2 RCTs; 130 participants) compared to sham stimulation. Non-invasive brain stimulation resulted in no deaths. Comparison 3: Psychological therapy Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; P = 0.01; 521 participants) compared to usual care/attention control. No trials of psychological therapy reported on the outcome inadequate response to treatment. No differences in the number of deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Comparison 4: Pharmacological interventions with psychological therapy No trials of this combination reported on the primary outcomes. Combination therapy resulted in no deaths. Comparison 5: Pharmacological interventions with non-invasive brain stimulation Non-invasive brain stimulation with pharmacological intervention reduced the number of people meeting study criteria for depression at end of treatment (RR 0.77, 95% CI 0.64 to 0.91; P = 0.002; 3 RCTs; 392 participants; low-certainty evidence) but not the number of people with inadequate response to treatment (RR 0.95, 95% CI 0.69 to 1.30; P = 0.75; 3 RCTs; 392 participants; very low-certainty evidence) compared to pharmacological therapy alone. Very low-certainty evidence from five trials suggest no difference in deaths between this combination therapy (RR 1.06, 95% CI 0.27 to 4.16; P = 0.93; 487 participants) compared to pharmacological therapy intervention and sham stimulation or usual care. Comparison 6: Non-invasive brain stimulation with psychological therapy No trials of this combination reported on the primary outcomes.

Very low-certainty evidence suggests that pharmacological, psychological and combination therapies can reduce the prevalence of depression while non-invasive brain stimulation had little to no effect on the prevalence of depression. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.

The incidence of posttraumatic stress disorder (PTSD) following stroke ranges from 6.5 % to 25 %. Presently few studies have focused on its treatment. Repetitive transcranial magnetic stimulation (rTMS) is often applied as a rehabilitation method after stroke, and it also represents a novel approach to PTSD. The aim of this study was to explore the effect of rTMS (or combined with a brief stroke re-exposure) on treating post-stroke PTSD. Sixty participants with post-stroke PTSD were randomly assigned into three groups (rTMS + brief exposure group, TMS + BE; rTMS alone group, TMS; sham treatment group, ST) and received 10 sessions of treatment accordingly over two weeks. Changes in PTSD symptoms (Impact of Event Scale-Revised, IES-R) were evaluated at pre-treatment (T1), the end of the first (T2), and the end of the second treatment week (T3). At the three-month follow-up (T4), a PTSD interview and IES-R assessment were given. Results showed that from T1 to T3, IES-R (and its intrusion subscale) scores of TMS + BE group and TMS group were significantly lower than the ST group, and the effect remained at three-month follow-up. The treatment effect was comparable between TMS + BE group and TMS group at T3, however, it was better for TMS + BE group than TMS group at T2, indicating a brief exposure promotes the effect of rTMS. At follow-up, the rates of PTSD were lower in TMS + BE group and TMS group than ST group. In conclusion, rTMS can effectively treat post-stroke PTSD and the effects may be accelerated by combining a brief exposure procedure. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100043444.

Post-stroke depression (PSD) is a biopsychosocial disorder that affects individuals who have suffered a stroke at any point. PSD has a 20 to 60 percent reported prevalence among stroke survivors. Its effects are usually adverse, can lead to disability, and may increase mortality if not managed or treated early. PSD is linked to several other medical conditions, including anxiety, hyper-locomotor activity, and poor functional recovery. Despite significant awareness of its adverse impacts, understanding the pathogenesis of PSD has proved challenging. The exact pathophysiology of PSD is unknown, yet its complexity has been definitively shown, involving mechanisms such as dysfunction of monoamine, the glutamatergic systems, the gut-brain axis, and neuroinflammation. The current effectiveness of PSD treatment is about 30-40 percent of all cases. In this review, we examined different pathophysiological mechanisms and current pharmacological and non-pharmacological approaches for the treatment of PSD.

(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.

CBT has a beneficial effect on depression and anxiety; however, the number of cases where therapy was used in patients with stroke was rare. In addition, there is still a lack of research on the effects of occupation-based training and the effects of bilateral upper limb training that provides an intervention based on patients' state of hemiplegic upper limb function. This study investigated the effects of combining CBT and occupation-based bilateral upper limb training on the depression, anxiety, upper limb function, and occupational performance. The experimental group was given 30-min cognitive behavioral therapy and occupation-based bilateral upper limb training, while the control group was given 30-min conventional occupational therapy and occupation-based bilateral upper limb training. For both groups, the intervention was given as a 30-min session once a day and five times a week for 4 weeks. Following intervention, the experimental group showed significant within-group variance for automatic thoughts, depression, anxiety, upper limb function, and occupational performance only (p < 0.01). For between-group variance, a significant difference was found for automatic thoughts, depression, anxiety, and occupational performance (p < 0.01), however, not for upper limb function (p > 0.05). In this study, it is meaningful that this author provided good guidelines for therapists and caregivers by organizing and providing actual programs in a very rare situation where cognitive behavioral therapy was applied to stroke patients.

Background Several studies investigated the role of selective serotonin reuptake inhibitors (SSRIs) in improving poststroke recovery; thus, we have decided to conduct this systematic review and meta-analysis to investigate the efficacy and safety of SSRIs in poststroke recovery. Methods and Results In this meta-analysis we searched the following databases: PubMed, Cochrane, Scopus, and Google Scholar. The studies were included if they were placebo-controlled trials in design and reported SSRIs' effects on poststroke depression, anxiety, disability, dependence, motor abilities, and cognitive functions. The quality of the included studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The search yielded 44 articles that included 16 164 patients, and about half of the participants were treated with SSRIs. Our results showed that SSRIs had a significant effect on preventing depression (weighted mean difference [WMD], -7.05 [95% CI, -11.78 to -2.31]), treating depression according to the Hamilton Rating Scale for Depression score (WMD, -1.45 [95% CI, -2.77 to -0.14]), anxiety (relative risk, 0.23 [95% CI, 0.09-0.61]), dependence (WMD, 8.86 [95% CI, 1.23-16.48]), motor abilities according to National Institutes of Health Stroke Scale score (WMD, -0.79 [95% CI, -1.42 to -0.15]), and cognitive functions (WMD, 1.00 [95% CI, 0.12-1.89]). On the other hand, no significant effect of SSRIs on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (relative risk, 1.44 [95% CI, 1.13-1.83]), whereas there was no difference in the incidence of gastrointestinal symptoms or bleeding between SSRIs and a placebo. Conclusions Our study showed that SSRIs are effective in preventing and treating depression, and improving anxiety, motor function, cognitive function, and dependence in patients after stroke. These benefits were only reproducible with the citalopram subanalysis but not fluoxetine. Further well-conducted placebo-controlled trials are needed to investigate the safety and efficacy of citalopram among patients after stroke. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021285766.

Stroke is the fifth leading cause of death and as healthcare intervention improves, the number of stroke survivors has also increased. Furthermore, there exists a subgroup of younger adults, who suffer stroke and survive. Given the overall improved survival rate, bettering our understanding of long-term stroke outcomes is critical. In this review we will explore the causes and challenges of known long-term consequences of stroke and if present, their corresponding sex differences in both old and young survivors. We have separated these long-term post-stroke consequences into three categories: mobility and muscle weakness, memory and cognitive deficits, and mental health and mood. Lastly, we discuss the potential of common preclinical stroke models to contribute to our understanding of long-term outcomes following stroke.

Post-stroke depression (PSD) is the most common and serious sequelae of stroke. Approximately 33% of stroke survivors were affected by PSD. However, many issues (e.g., incidence, diagnostic marker, and risk factor) related to PSD remained unclear. The "monoamine hypothesis" is a significant hypothesis for depression, which suggests that three monoamines play a key role in depression. Therefore, most current antidepressants are developed to modulate the monoamines on PSD treatment, and these antidepressants have good effects on patients with PSD. However, the potential mechanisms of three monoamines in PSD are still unclear. Previously, we proposed "three primary emotions," which suggested a new model of basic emotions based on the three monoamines. It may provide a new way for PSD treatment. In addition, recent studies have found that monoamine-related emotional intervention also showed potential effects in the treatment and prevention of PSD. This study discusses these issues and attempts to provide a prospect for future research on PSD.

Stroke is the leading cause of human death and disability. After a stroke, many patients may have some physical disability, including difficulties in moving, speaking, and seeing, but patients may also exhibit changes in mood manifested by depression, anxiety, and cognitive changes which we call post-stroke mood disorders (PSMDs). Astrocytes are the most diverse and numerous glial cell type in the central nervous system (CNS). They provide structural, nutritional, and metabolic support to neurons and regulate synaptic activity under normal conditions. Astrocytes are also critically involved in focal ischemic stroke (FIS). They undergo many changes after FIS. These changes may affect acute neuronal death and brain damage as well as brain recovery and PSMD in the chronic phase after FIS. Studies using postmortem brain specimens and animal models of FIS suggest that astrocytes/reactive astrocytes are involved in PSMD. This chapter provides an overview of recent advances in the molecular base of astrocyte in PSMD. As astrocytes exhibit high plasticity after FIS, we suggest that targeting local astrocytes may be a promising strategy for PSMD therapy.

Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019.

To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects.

We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers.

We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta-analysis. The primary analysis included studies at low risk of bias.

We extracted data on demographics, stroke type and, our pre-specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria.

We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow-up. Thirty-eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD -0.0; 95% CI -0.05 to 0.05; 5 studies, 5436 participants, high-quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high-quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high-quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high-quality evidence). Cognition was slightly better in the control group (MD -1.22, 95% CI -2.37 to -0.07; 4 studies, 5373 participants, moderate-quality evidence). Only one study (n = 30) reported neurological deficit score (SMD -0.39, 95% CI -1.12 to 0.33; low-quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, -0.02 to 0.08; 6 studies, 5518 participants, moderate-quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high-quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate-quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high-quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD -0.06; 95% CI -1.24 to 1.11; 4 studies, 5524 participants, moderate-quality of evidence), nor in quality of life (MD 0.00; 95% CI -0.02 to 0.02, 3 studies, 5482 participants, high-quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta-analysis of outcomes at end of follow-up. Several small ongoing studies are unlikely to alter conclusions.

There is high-quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk.

Post-stroke depression (PSD) is one of common and serious sequelae of stroke. Approximately, one in three stroke survivors suffered from depression after stroke. It heavily affected functional rehabilitation, which leaded to poor quality of life. What is worse, it is strongly associated with high mortality. In this review, we aimed to derive a comprehensive and integrated understanding of PSD according to recently published papers and previous classic articles. Based on the considerable number of studies, we found that within 2 years incidence of PSD has a range from 11 to 41%. Many factors contribute to the occurrence of PSD, including the history of depression, stroke severity, lesion location, and so on. Currently, the diagnosis of PSD is mainly based on the DSM guidelines and combined with various depression scales. Unfortunately, we lack a unified mechanism to explain PSD which mechanisms now involve dysregulation of hypothalamic-pituitary-adrenal (HPA) axis, increased inflammatory factors, decreased levels of monoamines, glutamate-mediated excitotoxicity, and abnormal neurotrophic response. At present, both pharmacotherapy and psychological therapies are employed in treating PSD. Although great advance has been made by researchers, there are still a lot of issues need to be addressed. Especially, the mechanism of PSD is not completely clear.

There is currently insufficient evidence for the clinical effectiveness and cost-effectiveness of psychological therapies for post-stroke depression.

To evaluate the feasibility of undertaking a definitive trial to evaluate the clinical effectiveness and cost-effectiveness of behavioural activation (BA) compared with usual stroke care for treating post-stroke depression.

Parallel-group, feasibility, multicentre, randomised controlled trial with nested qualitative research and a health economic evaluation.

Acute and community stroke services in three sites in England.

Community-dwelling adults 3 months to 5 years post stroke who are depressed, as determined by the Patient Health Questionnaire-9 (PHQ-9) or the Visual Analogue Mood Scales 'Sad' item. Exclusions: patients who are blind and/or deaf, have dementia, are unable to communicate in English, do not have mental capacity to consent, are receiving treatment for depression at the time of stroke onset or are currently receiving psychological intervention.

Participants were randomised (1 : 1 ratio) to BA or usual stroke care. Randomisation was conducted using a computer-generated list with random permuted blocks of varying sizes, stratified by site. Participants and therapists were aware of the allocation, but outcome assessors were blind.

The intervention arm received up to 15 sessions of BA over 4 months. BA aims to improve mood by increasing people's level of enjoyable or valued activities. The control arm received usual care only.

Primary feasibility outcomes concerned feasibility of recruitment to the main trial, acceptability of research procedures and measures, appropriateness of baseline and outcome measures, retention of participants and potential value of conducting the definitive trial. Secondary feasibility outcomes concerned the delivery of the intervention. The primary clinical outcome 6 months post randomisation was the PHQ-9. Secondary clinical outcomes were Stroke Aphasic Depression Questionnaire - Hospital version, Nottingham Leisure Questionnaire, Nottingham Extended Activities of Daily Living, Carer Strain Index, EuroQol-5 Dimensions, five-level version and health-care resource use questionnaire.

Forty-eight participants were recruited in 27 centre-months of recruitment, at a recruitment rate of 1.8 participants per centre per month. The 25 participants randomised to receive BA attended a mean of 8.5 therapy sessions [standard deviation (SD) 4.4 therapy sessions]; 23 participants were allocated to usual care. Outcome assessments were completed by 39 (81%) participants (BA, n = 18; usual care, n = 21). Mean PHQ-9 scores at 6-month follow-up were 10.1 points (SD 6.9 points) and 14.4 points (SD 5.1 points) in the BA and control groups, respectively, a difference of -3.8 (95% confidence interval -6.9 to -0.6) after adjusting for baseline PHQ-9 score and centre, representing a reduction in depression in the BA arm. Therapy was delivered as intended. BA was acceptable to participants, carers and therapists. Value-of-information analysis indicates that the benefits of conducting a definitive trial would be likely to outweigh the costs. It is estimated that a sample size of between 580 and 623 participants would be needed for a definitive trial.

Target recruitment was not achieved, although we identified methods to improve recruitment.

The Behavioural Activation Therapy for Depression after Stroke trial was feasible with regard to the majority of outcomes. The outstanding issue is whether or not a sufficient number of participants could be recruited within a reasonable time frame for a definitive trial. Future work is required to identify whether or not there are sufficient sites that are able to deliver the services required for a definitive trial.

Current Controlled Trials ISRCTN12715175.

This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 47. See the NIHR Journals Library website for further project information.

Depression is an important morbidity associated with stroke that impacts on recovery yet often undetected or inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and updated in 2008.

Primary objective • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce the prevalence of diagnosable depression after stroke Secondary objectives • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce levels of depressive symptoms, improve physical and neurological function and health-related quality of life, and reduce dependency after stroke • To assess the safety of and adherence to such treatments SEARCH METHODS: We searched the Specialised Registers of Cochrane Stroke and Cochrane Depression Anxiety and Neurosis (last searched August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), in the Cochrane Library, MEDLINE (1966 to August 2018), Embase (1980 to August 2018), the Cumulative Index to Nursing and Alllied Health Literature (CINAHL) (1982 to August 2018), PsycINFO (1967 to August 2018), and Web of Science (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) to August 2018; ClinicalTrials.gov to August 2018), and conference proceedings, and we contacted study authors.

Randomised controlled trials comparing (1) pharmacological interventions with placebo; (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; (3) one of various forms of psychological therapy with usual care and/or attention control; (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control; (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care; (6) pharmacological intervention and one of various forms of psychological therapy with placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation with placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy, with the intention of treating depression after stroke.

Two review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE.

We included 49 trials (56 comparisons) with 3342 participants. Data were available for: (1) pharmacological interventions with placebo (with 20 pharmacological comparisons); (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care (with eight non-invasive brain stimulation comparisons); (3) one of various forms of psychological therapy with usual care and/or attention control (with 16 psychological therapy comparisons); (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control (with two comparisons); and (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care (with 10 comparisons). We found no trials for the following comparisons: (6) pharmacological intervention and various forms of psychological therapy interventions versus placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation versus placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy. Treatment effects observed: very low-certainty evidence from eight trials suggests that pharmacological interventions decreased the number of people meeting study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; 1025 participants) at end of treatment, and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with less than 50% reduction in depression scale scores at end of treatment (RR 0.47, 95% CI 0.32 to 0.69; 511 participants) compared to placebo. No trials of non-invasive brain stimulation reported on meeting study criteria for depression at end of treatment. Only one trial of non-invasive brain stimulation reported on the outcome <50% reduction in depression scale scores; thus, we were unable to perform a meta-analysis for this outcome. Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; 521 participants) compared to usual care/attention control. No trials of combination therapies reported on the number of people meeting the study criteria for depression at end of treatment. Only one trial of combination (non-invasive brain stimulation and pharmacological intervention) therapy reported <50% reduction in depression scale scores at end of treatment. Thus, we were unable to perform a meta-analysis for this outcome. Five trials reported adverse events related to the central nervous system (CNS) and noted significant harm in the pharmacological interventions group (RR 1.55, 95% CI 1.12 to 2.15; 488 participants; very low-certainty evidence). Four trials found significant gastrointestinal adverse events in the pharmacological interventions group (RR 1.62, 95% CI 1.19 to 2.19; 473 participants; very low-certainty evidence) compared to the placebo group. No significant deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Non-invasive brain stimulation interventions and combination therapies resulted in no deaths.

Very low-certainty evidence suggests that pharmacological or psychological therapies can reduce the prevalence of depression. This very low-certainty evidence suggests that pharmacological therapy, psychological therapy, non-invasive brain stimulation, and combined interventions can reduce depressive symptoms. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.

Early rehabilitation after stroke is essential to help reduce disability.

To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke.

English-language searches of multiple electronic databases from April 2009 through July 2018; targeted searches to December 2018 for studies of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors.

19 systematic reviews and 37 randomized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke.

One investigator abstracted the data, and quality and GRADE assessment were checked by a second investigator.

Most interventions (for example, SSRIs, mental practice, mirror therapy) did not improve motor function. High-quality evidence did not support use of fluoxetine to improve motor function. Moderate-quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living (ADLs). Low-quality evidence supported use of robotic arm training to improve ADLs. Low-quality evidence indicated that antidepressants may reduce depression, whereas the frequency and severity of antidepressant-related adverse effects was unclear. Low-quality evidence suggested that cognitive behavioral therapy and exercise, including mind-body exercise, may reduce symptoms of depression and anxiety.

Studies were of poor quality, interventions and comparators were heterogeneous, and evidence on harms was scarce.

Cardiorespiratory training, repetitive task training, and transcranial direct current stimulation may improve ADLs in adults with stroke. Cognitive behavioral therapy, exercise, and SSRIs may reduce symptoms of poststroke depression, but use of SSRIs to prevent depression or improve motor function was not supported.

U.S. Department of Veterans Affairs, Veterans Health Administration.

In June 2019, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved an update of the joint clinical practice guideline for rehabilitation after stroke. This synopsis summarizes the key recommendations from this guideline.

In February 2018, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and stroke survivors and conformed to the National Academy of Medicine (formerly the Institute of Medicine) tenets for trustworthy clinical practice guidelines. The guideline panel identified key questions, systematically searched and evaluated the literature, and developed 2 algorithms and 42 key recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Stroke survivors and their family members were invited to share their perspectives to further inform guideline development.

The guideline recommendations provide evidence-based guidance for the rehabilitation care of patients after stroke. The recommendations are applicable to health care providers in both primary care and rehabilitation. Key features of the guideline are recommendations in 6 areas: timing and approach; motor therapy; dysphagia; cognitive, speech, and sensory therapy; mental health therapy; and other functions, such as returning to work and driving.

Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence.

To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects.

For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers.

We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early).

We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria.

We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow-up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta-analysis of these three trials found little or no effect of SSRI on either disability score: SMD -0.01 (95% CI -0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate-quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate-quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate-quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate-quality evidence), with no evidence of heterogeneity (I2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants.

We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta-analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta-analysis of large ongoing trials will be required to determine the generalisability of these findings.

Mood disorder after stroke is common but drug and psychosocial treatments have been assessed with disappointing results. Preventing mood disorder from developing in the first place could be a better approach and might reduce the need for pharmacotherapy in this predominantly older patient group. We used a brief problem-solving therapy and evaluated its effect in reducing mood disorder in the 12 months after stroke.

A 3-group, parallel, randomised controlled trial. Four hundred fifty patients with stroke were randomised within 1 month of hospital admission to problem-solving therapy from a psychiatric nurse, non-specific support given by volunteers or treatment-as-usual. Follow up took place at 6 and 12 months after stroke. Standardised measures of mood (Present State Examination, GHQ-28), cognitive state (mini-mental state examination) and function (Barthel ADL index, Frenchay Activities Index) were taken at baseline, 6 and 12 months after randomisation. Satisfaction with care was recorded at follow up.

At 6 months, all psychological and activity measures favoured problem-solving therapy. At 12 months, patients in the problem-solving therapy group had significantly lower GHQ-28 scores and lower median Present State Examination symptom scores. There were no statistically significant differences in activity. The problem-solving therapy group were more satisfied with some aspects of care.

The results are encouraging and suggest it is possible to prevent mood disorder in stroke patients using a psychological intervention. The differences between the groups at 12 months may indicate a sustained impact of psychological therapies, by comparison with non-specific support.

ISRCTN: ISRCTN33773710 Registered: 23/01/2004 (Retrospectively).

Cognitive behavioral therapy (CBT) has been widely used for post-stroke depression (PSD), but the findings have been inconsistent. This is a meta-analysis of randomized controlled trials (RCTs) of CBT for PSD.

Both English (PubMed, PsycINFO, Embase) and Chinese (WanFang Database, Chinese National Knowledge Infrastructure and SinoMed) databases were systematically searched. Weighted and standardized mean differences (WMDs/SMDs), and the risk ratio (RR) with their 95% confidence intervals (CIs) were calculated using the random effects model.

Altogether 23 studies with 1,972 participants with PSD were included and analyzed. Of the 23 RCTs, 39.1% (9/23) were rated as high quality studies, while 60.9% (14/23) were rated as low quality. CBT showed positive effects on PSD compared to control groups (23 arms, SMD = -0.83, 95% CI: -1.05 to -0.60, P < 0.001). Both CBT alone (7 arms, SMD = -0.76, 95% CI: -1.22 to -0.29, P = 0.001) and CBT with antidepressants (14 arms, SMD = -0.95, 95% CI: -1.20 to -0.71, P < 0.00001) significantly improved depressive symptoms in PSD. CBT had significantly higher remission (6 arms, RR = 1.76, 95% CI: 1.37-2.25, P < 0.00001) and response rates (6 arms, RR = 1.41, 95% CI: 1.22-1.63, P < 0.00001), with improvement in anxiety, neurological functional deficits and activities of daily living. CBT effects were associated with sample size, mean age, proportion of male subjects, baseline depression score, mean CBT duration, mean number of CBT sessions, treatment duration in each session and study quality.

Although this meta-analysis found positive effects of CBT on depressive symptoms in PSD, the evidence for CBT is still inconclusive due to the limitations of the included studies. Future high-quality RCTs are needed to confirm the benefits of CBT in PSD.

This was a longitudinal study which investigated the relationship between serum uric acid (SUA) and total bilirubin (Tbil) upon admission in elderly stroke patients and the occurrence of postischemic stroke depression (IPSD) at 3, 6, and 9 months of post-stroke follow-up.

Data were analyzed for 525 acute ischemic stroke patients. Beck Depression Inventory (BDI) scores >17 and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were used separately to screen and diagnose IPSD at 3, 6, and 9 months post-stroke. Once IPSD was diagnosed, follow-up activities were terminated.

High levels of SUA (odds ratio [OR]=2.08, P<0.01) and Tbil (OR=2.31, P<0.01) in the first 3 months post-stroke and low levels of SUA (OR=2.05, P=0.03) and Tbil (OR=2.79, P<0.01) from 3 to 6 months post-stroke were identified as risk factors for major IPSD. At 3 months, patients with SUA levels ≥406.5 μmol/L (males with SUA levels of ≥409.5 μmol/L and females with SUA levels ≥385.5 μmol/L) and Tbil levels ≥23.65 μmol/L were more likely to develop major IPSD. At 6 months, both SUA (area under curve [AUC]=0.625, P=0.005, cutoff =194.0 μmol/L) and Tbil (AUC=0.681, P=0.004, cutoff =6.75 μmol/L) had minor diagnostic values (AUC<0.700), although SUA levels ≤214.5 μmol/L (AUC=0.756, P=0.001) in female patients had a good diagnostic value (AUC=0.722, P=0.006) for major IPSD. At 9 months, major IPSD showed no statistical relationship with either SUA (χ²=2.33, P=0.13) or Tbil (χ²=0.41, P=0.84).

Higher levels of SUA and Tbil on admission were closely related to the occurrence of major IPSD within 3 months of stroke. Lower levels of these two biomarkers on admission were characteristic for the occurrence of major IPSD between 3 and 6 months post-stroke, while 6 months after stroke, there was no relationship between major IPSD and these two biomarkers.

Post-stroke depression (PSD) is a common and serious complication after stroke, occurring in nearly one third of stroke survivors, and affecting mortality rate, functional outcome, rehabilitation results and quality of life. However, in the common clinical practice only a minority of patients are properly treated. A relatively small number of scientific reports are available on clinical usefulness and safety of antidepressants (ADs) in PSD. Areas covered: This report provides an updated review about pharmacological state of art of PSD, including efficacy and safety of different drugs and their role on prevention, treatment and functional outcome. Expert opinion: Even if currently an antidepressant treatment can improve depressive symptoms, neither the optimal drug nor the optimal lengths of treatment, have been identified. Serotonergic drugs are preferable because of their better safety profile, but in the recent years there has been an important debate on possible association between selective serotonin reuptake inhibitor use and increased mortality. Another issue is the potential role of ADs for improving functional recovery. Newer ADs have interesting properties, in particular vortioxetine, due to its properties of enhancing cognitive functions, but further research is needed to clarify its/their role in treatment of PSD.