Neuroinflammation as a key target in the treatment of post-stroke depression

Post-stroke depression (PSD) is a common and clinically significant complication of stroke, associated with worse rehabilitation potential and increased mortality risk. The prevalence of PSD varies from 25% to 59%, depending on the duration of follow-up, peaking in the first years after the stroke event. The pathogenesis of PSD results from a complex interplay of biological and psychological factors, extending far beyond monoamine deficiency. Key roles are played by damage to monoaminergic pathways, neuroinflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, reduced neuroplasticity (including BDNF deficit), and impaired integrity of neuronal networks. The clinical picture is characterized by a complex of affective (apathy, anhedonia), cognitive (executive dysfunction), and dyssomnic disorders. Although selective serotonin reuptake inhibitors remain the first-line treatment, the modern therapeutic approach to PSD requires targeting all components of its pathogenesis. A promising direction is the use of antidepressants with a multimodal mechanism of action, such as the original drug fluvoxamine, which combines serotonergic effects with anti-inflammatory and neuroprotective properties via sigma-1 (σ1) receptor agonism. Optimizing PSD treatment is achievable through the implementation of a personalized approach, including long-term screening and comprehensive management of the identified disorders.

Objective To explore the role of event-related potential P300 in early diagnosis and treatment of post-stroke depression. Methods Hamilton depression rating scale(HAMD) assessment was adopted to assess 67 patients of first time stroke at 2 weeks.The patients with stroke were divided into four groups: mild post-stroke depression group (n=15), moderate post-stroke depression group (n=11), severe post-stroke depression group (n=4) and non-depression group(n=37).30 patients of post-stroke depression were divided into two groups randomly: treatment with fluoxetine 3 months(n=15) and unused anti-depression drugs(n=15). At 3 months, P300 was executed again in all of patients of post-stroke depression. Results The P300 latency of the patients of the post-stroke depression group[(351.30±22.48)ms] was significantly prolonged than the patients of the non-depression group[(320.92±15.45)ms](t=-6.295, P<0.01), and the P300 amplitude of the patients of the post-stroke depression group [(5.09±1.47)μV] was also reduced significantly compared with the patients of the non-depression group[(6.47±1.74)μV](t=3.475, P<0.01). The P300 latency among the patients of the four gourps had significant difference(F=24.484, P<0.01). While the means of P300 latency of the patients in the moderate post-stroke depression group[(362.73±20.56)ms] and the severe post-stroke depression group[(369.75±22.54)ms] were obviously prolonged than that in the mild post-stroke depression group[(338.00±15.70)ms] and the non-depression group[(320.92±15.45)ms](all P<0.05), but there was no difference in the P300 latency between the moderate post-stroke depression group and the severe post-stroke depression group.The mean score of P300 latency after treatment with fluoxetine in the post-stroke depression group[(326.40±24.42)ms] was significantly shorten compared with (356.13±25.76)ms of before treatment(t=5.173, P<0.01), and also obviously shorten than (342.07±21.24)ms of the unused anti-depression drugs group(t=2.058, P<0.05). Conclusion P300 latency and amplitude may be used as an indicator in early diagnosis and treatment of post-stroke depression. Key words: Depression; Stroke; Event-related potentials, P300; Fluoxetine

Review question / Objective: To evaluate the efficacy and safety of scalp acupuncture for poststroke depression for the first time, and the results of this systematic review will be helpful for clinicians to use scalp acupuncture in the treatment of PSD. Condition being studied: Post-stroke depression (PSD) is one of the most common psychological sequelae of stroke, which is a state characterized by low mood and aversion to activity. It is one of the main obstacles in the process of stroke rehabilitation, which has a detrimental impact on functional recovery and quality of life and even increases mortality. Although the pathogenic factors of PSD are complex and diverse, it is now widely believed to involve complex interactions between neurobiological dysfunctions, psychosocial distress and biological factors. Despite increasing awareness and clinically based research on PSD, drugs to relieve and treat symptoms have made only limited gains. The use of antidepressants is accompanied by various unavoidable adverse effects, including headache, nausea, restlessness, and sexual dysfunction. A previous meta-analysis demonstrated that acupuncture can be safe and effective for the treatment of post-stroke depression. However, there is a lack of systematic reviews to evaluate the efficacy and safety of scalp acupuncture, which is a commonly used acupuncture modality in the treatment of PSD. Consequently, this study will assess the efficacy and safety of scalp acupuncture therapy for PSD compared to other treatments.

Depression occurs in approximately one-third of patients following stroke based on studies that screen entire stroke populations. Less is known about the detection and treatment of post stroke depression (PSD) in routine clinical practice. This was a prospective cohort study of 7643 consecutive stroke patients >66 years of age, from 13 designated stroke centres in Ontario, Canada. PSD was defined as (a) presence of strong evidence of depression documented in the patient chart plus a prescribed antidepressant and a psychiatric consult, or (b) prescription of a new antidepressant following admission. The prevalence of PSD was determined and patients with and without PSD were compared on a variety of measures. Patients admitted to specialized stroke units were compared to patients admitted to standard units in order to determine if PSD detection and treatment rates differed. PSD was diagnosed in 4.8%, and 6.7% were treated with a new antidepressant. Patients with PSD had more severe strokes, more functional handicap, longer hospital stays and were less likely to be discharged home (all p < 0.001). Patients admitted to specialized stroke units were more likely to be diagnosed with depression (5.2% vs 4.0%, p < 0.014) and were more likely to receive a new prescription for an antidepressant (7.8% vs 4.5%; p < 0.001). Rates of diagnosed and treated PSD in routine clinical practice are low and appear significantly lower than those from studies that utilize active screening of entire stroke populations. These results support the routine screening of all patients for PSD using validated instruments. Specialized stroke unit care may improve PSD detection and treatment rates.

Stroke is one of the public health problems widely concerned by many countries in the modern world. It is a kind of cerebrovascular disease with high risk. Most patients will have sequelae after stroke, such as hemiplegia, speech impairment, limited walking, etc. Depression is also one of the common sequelae. Patients are mainly characterized by low mood, unwilling to communicate with others, insomnia, and even negative thoughts of suicide. Post-stroke depression has adverse effects on patients and society, which greatly affects the normal life and work of patients and affects social stability. Western medicine treatment of post-stroke depression is mainly based on oral drugs, but it will bring many adverse reactions, such as drug resistance, dependence, and drug toxicity. Long-term medication treatment brings certain economic pressure. Traditional Chinese medicine (TCM) is a medicine with rich experience accumulated for a long time in China. It has a positive effect on the treatment of stroke and post-stroke depression. It has the characteristics of simplicity, low price and low toxicity, and is widely accepted by society and patients. There are various treatment methods of traditional Chinese medicine. This article reviews a large number of clinical observations to clarify the effectiveness of traditional Chinese medicine in the treatment of post-stroke depression.

Background and Purpose: Although Canadian best practice recommendations regarding assessment and management of poststroke depression (PSD) have been established, the degree to which these evidence-based guidelines have been translated into practice is not known. The objectives of the present study are to compare current and recommended best practice and examine possible reasons for identified care gaps. Methods: Practice audit by chart review was performed to identify recorded screening, assessment, and treatment for PSD in patients discharged from a specialized inpatient rehabilitation program over a 6-month period. A questionnaire was administered to all clinical staff addressing current screening practices as well as opinions regarding the importance and feasibility of identification and treatment of PSD. Results: Of 123 patients, 40 (32.5%) had been prescribed antidepressants at discharge. However, evidence of screening was found for 4.9% of patients; another 9.8% were referred for psychological consult. Treatment was associated with previous antidepressant use or history of depression, but not screening or assessment. Of the survey respondents, 56.2% were not aware of best practice recommendations. However, most felt screening and assessment to be important and treatment was regarded as both simple and effective. Conclusions: Despite potential benefit associated with identification and treatment of PSD and the availability of evidence-based best practice recommendations, PSD may remain unrecognized and undertreated. Given the juxtaposition of perceived importance with the lack of documented best practice, education regarding standardized screening and the development of consistent clinical protocols including roles and responsibilities in the identification, diagnosis, and treatment of PSD are underway.

Stroke is the leading cause of disability in adults. Depression after a stroke is detected in one third of patients, complicating physical rehabilitation, worsening functional outcome, increasing mortality rates. The question of the use of antidepressants in the treatment of post-stroke depression is currently not completely resolved, there is no consensus on the most optimal drug. The drugs of choice are selective serotonin reuptake inhibitors, the use of tricyclic antidepressants is possible. A number of clinical studies indicate the effectiveness of selective serotonin reuptake inhibitors in the treatment of post-stroke depression, including through mechanisms including increased neuroplasticity and stimulation of neurogenesis, while others disprove their effectiveness. The article presents a clinical case of the use of vortiroxetin in the patient’s neurorehabilitation in the early recovery period of a stroke, its safety and positive effect are shown.

To review the best current evidence on heterocyclic and serotonin-reuptake inhibitor (SSRI) treatments of poststroke depression (PSD). A literature review using multiple databases was conducted to identify randomized, controlled trials of the treatment or prevention of PSD. Odds ratios were used to test for significant treatment response between the treatment arms for dichotomous outcomes. Continuous outcome measures were evaluated using weighted mean difference and 95% confidence intervals. Literature review. Patients with stroke enrolled in the study of PSD of each selected article. Frequency of patients with and without depression; frequency of patients who responded to treatment. Nine articles were reviewed. Six investigated use of antidepressant therapy on treatment of PSD, and three examined the prevention of PSD. There was evidence to suggest that patients responded to treatment with antidepressants and significantly improved on depression scales, but treatment, especially with heterocyclic antidepressants, led to a significant number of dropouts due to side effects. There were insufficient data to pool the results of the prevention-based studies. Treatment with heterocyclic antidepressants and SSRIs appears to be a viable option for PSD, but their absolute or relative efficacy has yet to be fully established. The effectiveness of early initiation of antidepressants in the prevention of PSD is not clear.

The post-stroke depression refers to a affective disorders within 2 to 3 years after stroke in patients with stroke. Its main features are depressed mood, decreased interest, irritability, pessimism, and slow thinking, etc. Usually the symptoms will last for more than 2 weeks. It is one of the most common complications of stroke and may seriously affect the rehabilitation and quality of life of patients. Some patients even have suicidal tendency. Early intervention is very important for late neurological recovery in patients with stroke. It can not only improve cognitive function, but also reduce the morbidity and mortality. This article reviews the treatment of post-stroke depression. Key words: Stroke; Depression; Antidepressive Agents

The paper reviews the data available in the literature on the prevalence, pathogenesis, diagnosis, treatment, and prevention of poststroke depression. Depression develops in nearly one in every three patients, who have experienced stroke, and can negatively affect the rehabilitation process. The role of psychological factors, genetic predisposition, brain lesion location, monoamine deficiency in the pathogenesis of depression is considered. Poststroke depression is frequently diagnosed although it is detected using simple studies (Beck depression inventory, Hamilton rating scale). Psychotherapy is effective in preventing poststroke depression; the efficacy of antidepressants is actively being investigated. When depression develops, there is a positive result of treatment with antidepressants; a combination of psychotherapy and antidepressants produces even a more pronounced effect. The long-term (6-month or more) use of tricyclic antidepressants and selective serotonin reuptake inhibitors is noted to have a positive effect; there are data on the high efficacy and good tolerability of escitalopram in poststroke depression. It is stressed that the prevention and treatment of depression may substantially improve the rehabilitation process and quality of life.

Objective To evaluate the efficacy of deanxit in treatment of post-stroke depression (PSD).Methods60 patients with PSD were randomly divided into treatment group ( plus with deanxit) and control group (plus with estazolam necessarily). At the baseline and at 2 weeks,4 weeks, 8 weeks after the treatment, the efficacy was assessed with HAMD, SSS, and ADL rating scale respectively. Results After 2,4,8 weeks treatment, HAMD and SSS scores of the treatment group significantly decreased compared with the control group ( all P ＜ 0. 01 ), and ADL scores of the treatment group increased significantly compared with the control group ( P ＜ 0. 01 ). Conclusion Deanxit could effectively relieve depressing symptoms and neurological impairment of PSD, and clinical side effects of deanxit were less. Deanxit was suitable for acute phase and long-term maintenance therapy in PSD. Key words: Flupentixol/melitracen; Depression; Cerebrovascular accident

Background and Purpose: Post-stroke depression is common, with an estimated prevalence of 30-35%. This study assessed the null hypothesis that PHQ-9 screening is equivalent to standard care (suicide screening + provider assessment) in detection of post-stroke depression. A secondary outcome was to assess the optimal timing and setting to perform PHQ-9 screening after stroke. Methods: PHQ-9 screenings and modified Rankin Scales were conducted in a prospective study population (n=49) at three time points - inpatient within 48 hours of admission for stroke, 7 days after discharge at the outpatient stroke clinic, and by telephone at 90 days. Actionable treatment of depression defined as psychiatry referral and/or initiation of antidepressants were recorded. A retrospective control group (n=125), prior to initiation of the PHQ-9, was reviewed to determine baseline rates for treatment of depression. Results: PHQ-9 screening increased actionable treatment of depression over standard methods from 5.6% to 18.4% (p=0.009, 95% CI 1.6-25% increase) with similar baseline characteristics of age (p=0.406), gender (p=0.9), and antidepressant therapy prior to admission (p=0.377) between groups. 20.4% of the study population had a score of ≥ 10 (depression) at one time point and 59% of the study population had a score of ≥5 signifying minimal symptoms of depression at one time point. 51% experienced an increase in their PHQ-9 from inpatient screening to the outpatient stroke clinic. A significant number, 28.6%, were lost to follow-up at 90 days. In multivariate analysis, predictors of high PHQ-9 scores in stroke patients were young age (p=0.015) and trend with prior antidepressant use (p=0.06). Gender was insignificant (p=0.266). Conclusions: PHQ-9 screening significantly increased our detection and treatment of post-stroke depression and sub-optimally treated pre-morbid depression. The outpatient stroke clinic seems to be the optimal time point for screening due to increased scores and the difficulty in obtaining scores at 90 days. Young age and prior antidepressant use predispose high PHQ-9 scores post-stroke.

Post stroke depression has a huge impact on the rehabilitation and recurrence of patients with stroke.Its specific pathogenesis is unknown.Monoamine transmitters, inflammatory cytokines, hypothalamic pituitary adrenal axis function and neural plasticity are involved.Because of the uncertainty and side effects of drug therapy, non-drug therapy, especially behavioral intervention, is attracting more and more attention from clinicians.At present, behavioral intervention methods commonly used in clinical practice include: cognitive behavioral therapy, motivational interviewing, sports, music, and so on.Although a large number of clinical studies have shown that behavioral intervention has a clear therapeutic effect on post stroke depression, there is still no high level of recommendation for the prevention and treatment of post-stroke depression due to the lack of large sample and high quality multicenter randomized controlled studies. Key words: Post stroke depression; Behavioral intervention; Prevention; Treatment

Appropriate treatment of post-stroke depression (PSD) is critically important, considering the negative impact of PSD. Data regarding the treatment efficacy of antidepressants in patients with PSD are conflicting, and the time-dependent effects of antidepressant treatment in this population are unknown. To systematically assess treatment effects of antidepressants in patients with PSD, incorporating data from recent studies. A meta-analysis of randomized placebo-controlled trials (RCTs) of antidepressants in patients with PSD was conducted, using published studies from 1984 to 2006. Outcome measures of antidepressant treatment included response rate, depression rating scale scores, recovery of neurologic impairments, and improvements in activities of daily living (ADLs) after stroke. The effect size was presented as rate difference (RD) and weighted mean difference for dichotomous outcomes and continuous outcomes, respectively. Pooled effect sizes were calculated by both fixed-effects and random-effects models. A total of 1320 patients who met inclusion criteria were identified from 16 RCTs. The pooled response rates in the active and placebo groups were 65.18% (234/359) and 44.37% (138/311), respectively. The pooled RD was 0.23 (95% CI 0.03 to 0.43), indicating a significantly higher response rate in the active group compared with the placebo group. From baseline to endpoint, patients in the active group had significantly greater improvement in depressive symptoms compared with patients in the placebo group. Longer duration of treatment was positively correlated with the degree of improvement in depressive symptoms (Spearman's correlation, [rho] = -0.93, p = 0.001). No consistent evidence was found for positive antidepressant effects on the recovery of neurologic impairments and improvements in ADLs. The results of this meta-analysis suggest that use of antidepressants among patients with a diagnosis of PSD is associated with improvement in depressive symptoms. Longer durations of antidepressant treatment may be associated with greater reductions in depressive symptoms.

Depression is an important complication of stroke. Although antidepressants are widely used for the treatment of poststroke depression (PSD), prescription is critically influenced by their safety, tolerability and by the impact on co-morbidities. The authors reviewed the literature on the use of antidepressants after stroke. Selective serotonin re-uptake inhibitors are effective and have a good profile of safety and tolerability in PSD. They are, therefore, used as first-line drugs in the treatment of PSD, although potential cardiovascular and cerebrovascular effects, drug–drug interactions and intolerability in a minority of patients have to be considered. Other antidepressants appear to be safe and effective in selected patients. PSD patients should be classified according to their clinical profile for the selection of the drug of choice in particular sub-groups of patients.