Treatment Of Post-stroke Depression Research Articles

Comparison of the Incidence and Magnitude of Hyponatremia Among Patients With Poststroke Depression Receiving Either Escitalopram or Sertraline.

Depression is the most frequent psychiatric condition experienced in stroke survivors. Selective serotonin reuptake inhibitors (SSRIs) are frequently used as first-line antidepressants; however, they have been strongly associated with hyponatremia which, in poststroke patients, can worsen outcomes. This study aims to determine and compare the incidence and magnitude of hyponatremia and potential risk factors in patients receiving either escitalopram or sertraline for the management of poststroke depression (PSD). A retrospective observational study involving all hospitalized patients who received either escitalopram or sertraline for the treatment of PSD. Electronic medical records were reviewed over a 5-year period with data collected on various demographic, laboratory, comorbidity, and medication-related variables. Data were analyzed using multivariate logistic regression. A total of 401 patients met the inclusion criteria. Overall, 36.7% of patients experienced hyponatremia, with 67 (38.3%) cases in patients receiving escitalopram and 76 (33.6%) in sertraline group. The median drop in sodium level from baseline was 5 mmol/L in both groups; with the majority of cases being of mild nature (73.1% and 69.7% for escitalopram and sertraline, respectively). Findings from the multivariate logistic regression did not yield a model with significant association (p = 0.353). Escitalopram and sertraline were both associated with an increased risk of hyponatremia in poststroke patients, with most cases being mild. There was no significant difference between treatment arms regarding the incidence or magnitude of hyponatremia. Caution should be exercised when prescribing escitalopram or sertraline.

Hippocampal exosomes from stroke aggravate post-stroke depression by regulating the expression of proBDNF and p75NTR and altering spine density

Post-stroke depression (PSD) affects millions of patients who suffer cerebral stroke. However, the molecular mechanisms and pathophysiology are poorly understood. Previous studies have shown that exosomes have been proven to be involved in neuropsychiatric disorders such as stroke and post-stroke depression in neurotransmitter release, neuronal remodeling, and neuron angiogenesis. Here we extracted and purified hippocampal exosomes from stroke mouse model to investigate mechanisms of hippocampal exocytosis in PSD assessed by using behavioral tests and biochemical methods. Aiming at the effect of hippocampal exosomes from stroke on the development of PSD, behavioral test was compared including sugar water preference experiment, open fields, forced swimming test, to explore it in depth. Further, the expression of depression-related protein (proBDNF and p75NTR) and synapse-associated proteins (Synaptotagmin and PSD95) was evaluated by Western blotting, RT-qPCR or immunofluorescence staining. Density of dendritic protrusions of neurons was assessed by Golgi staining to measure changes in spine density after the treatment of hippocampal exosomes from stroke. Our results revealed that injection of exosomes from stroke models significantly aggravated depressive-like behaviors, increase of depression-related protein (proBDNF and p75NTR) expression and deficiency of synapse-associated proteins (Synaptotagmin and PSD95) expression, and the decreased number of spin density. Our findings together suggest that hippocampal exosomes from stroke cause exacerbation of depressive-like behavior in mice, possibly resulting from the regulation of neurogenesis by its depression-associated proteins (proBDNF and p75NTR). Therefore, hippocampal exosomes from stroke are promising targets for the diagnosis and treatment of PSD.

Association of Vitamin B12 and Polymorphism of TCN2 with Early-Onset Post-Stroke Depression.

Post-stroke depression (PSD) is a common neuropsychiatric complication after a stroke with complex mechanisms. However, few studies have identified the role of vitamin B12 and folate in the occurrence and pathophysiology of PSD. The aim of our study is to investigate the relationship among vitamin B12, folate, their transporter genes, and early-onset PSD. A total of 173 ischemic stroke patients were recruited in Xiangya Hospital of Central South University. We collected peripheral blood samples, clinical data, and demographics at admission. The 17-item Hamilton Depression Scale was used for screening for the existence of depression at 2weeks after stroke onset. Serum vitamin B12 and folate level were measured based on double-antibody sandwich enzyme-linked immune-sorbent assay. Four single nucleotide polymorphisms (SNP) of transcobalamin 2 (TCN2) and solute carrier family 19 member 1 were genotyped using SNPscanTM multiplex SNP typing Kit. Eighty-four patients were diagnosed with PSD at 2weeks after stroke onset, and the incidence rate was 48.6%. Serum vitamin B12 level in PSD group was significantly lower than those in the non-PSD group (p=0.018). Binary logistic regression revealed that TCN2 rs1801198 GG genotype and G allele were associated with an increased risk of PSD after adjustment for confounding factors (for GG genotype, OR = 4.253, 95% CI = 1.711~10.572, p = 0.002; for G allele, OR = 2.134, 95% CI = 1.362~3.343, p = 0.001). Moreover, individuals with the rs1801198 G allele in the PSD group exhibited lower vitamin B12 level than those with the rs1801198 G allele in the non-PSD group (p=0.045). TCN2 rs1801198 and vitamin B12 are associated with the risk of early-onset PSD, and they may be involved in the development of PSD. Our study presents a novel standpoint for the treatment of PSD and gains insights into the mechanistic underpinnings of PSD.

Non-Invasive Brain Stimulation Progression in Post-Stroke Depression Treatment: A Systematic Review.

Post-stroke depression (PSD) is the most common psychological disorder in patients with stroke. It not only seriously affects the patient's functional recovery, quality of life, and ability to return to society but also increases stroke recurrence rate and mortality. However, the effectiveness of drug treatment is unpredictable and associated with certain side effects and low compliance. Pharmacological therapy is limited. The field of noninvasive brain stimulation (NIBS) has recently made great progress in developing specific stimulation protocols to alleviate the symptoms of patients with PSD and might offer valid, alternative strategies. We systematically searched PubMed, Embase, and the Cochrane Library for investigating the use of NIBS in the treatment of PSD. The methodological quality of selected studies was assessed according to the Risk of Bias 2 (ROB2). We identified 814 references in 3 databases. After excluding irrelevant and duplicate studies, 14 studies were included. According to the PRISMA checklist, 4 studies were overall comprehensive, 6 had some problems, and 4 had considerable problems with the presented information. The evidence was evaluated using ROB2, with 5 "low-risk" studies, 5 "some concerns" studies, and 4 "high-risk" studies included. This review provides a comprehensive overview of the clinical trials reported in PSD. Noninvasive brain stimulation is a potentially promising treatment strategy. However, an optimal stimulation protocol needs to be formulated, and much work is required before NIBS can be widely applied in the clinic.

Research Progress of Acupuncture in the Treatment of Post-Stroke Depression

Post-stroke depression (PSD) is a prevalent complication in stroke survivors, characterized by persistent mood disorders that hinder rehabilitation and reduce quality of life. This study examines recent scholarly endeavors focusing on acupuncture (AC) as a feasible therapeutic approach for PSD. By analyzing contemporary literature, it elucidates the Traditional Chinese Medicine (TCM) perspective on PSD and evaluates AC's effectiveness. AC stands out as a promising modality of treatment owing to its potency and negligible side effects, with mechanisms including neurotransmitter modulation, neurotrophic factor regulation, neuronal apoptosis inhibition, inflammatory response modulation, and so on. This review offers valuable insights into PSD from a TCM perspective and highlights AC's potential as a therapeutic intervention, contributing to knowledge advancement and informing clinical practice in PSD management.

EEG microstate as a biomarker of post-stroke depression with acupuncture treatment.

Post-stroke depression (PSD) is a prevalent psychiatric complication among stroke survivors. The PSD researches focus on pathogenesis, new treatment methods and efficacy prediction. This study explored the electroencephalography (EEG) microstates in PSD and assessed their changes after acupuncture treatment, aiming to find the biological characteristics and the predictors of treatment efficacy of PSD. A 64-channel resting EEG data was collected from 70 PSD patients (PSD group) and 40 healthy controls (HC group) to explore the neuro-electrophysiological mechanism of PSD. The PSD patients received 6 weeks of acupuncture treatment. EEG data was collected from 60 PSD patients after acupuncture treatment (MA group) to verify whether acupuncture had a modulating effect on abnormal EEG microstates. Finally, the MA group was divided into two groups: the remission prediction group (RP group) and the non-remission prediction group (NRP group) according to the 24-Item Hamilton Depression Scale (HAMD-24) reduction rate. A prediction model for acupuncture treatment was established by baseline EEG microstates. The duration of microstate D along with the occurrence and contribution of microstate C were reduced in PSD patients. Acupuncture treatment partially normalized abnormal EEG microstates in PSD patients. Baseline EEG microstates predicted the efficacy of acupuncture treatment with an area under the curve (AUC) of 0.964. This study provides a novel viewpoint on the neurophysiological mechanisms of PSD and emphasizes the potential of EEG microstates as a functional biomarker. Additionally, we anticipated the therapeutic outcomes of acupuncture by analyzing the baseline microstates, which holds significant practical implication for the PSD treatment.

Effectiveness of acupuncture plus music therapy for post-stroke depression: Systematic review and meta-analysis.

Post-stroke depression (PSD) is a prevalent complication of stroke that adversely affects patient outcomes. The etiology of PSD is complex, and no universally effective treatment exists. Acupuncture, with its historical use, combined with music therapy, presents a novel approach for PSD treatment. This study aims to systematically evaluate the clinical efficacy of combining acupuncture with music therapy for PSD through a meta-analysis. We systematically searched both Chinese and English literature in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and the Chinese Science and Technology Periodical Database (VIP Database) for randomized controlled trials evaluating acupuncture combined with music therapy for PSD. Two independent evaluators conducted quality assessments and data extraction. Statistical analyses were performed using RevMan 5.4 and Stata 18.0 software. This article contains 11 studies, involving a total of 698 patients. The results of the meta-analysis showed that, compared with the control group, the test group showed significant improvement on multiple outcome measures: HAMD score [mean difference (MD) = -3.18, 95% confidence interval (CI) (-3.61, -2.76), P < .00001], Self-Rating Depression Scale score [MD = -5.12, 95% CI (-6.61, -3.63), P < .00001], Pittsburgh sleep quality index score [MD = -2.40, 95% CI (-2.96, -1.84), P < .00001], BI score [MD = 14.16, 95% CI (4.37, 23.94), P = .005] were all significantly lower, significantly higher effectiveness [risk ratio = 1.21, 95% CI (1.11, 1.33), P < .0001]. These differences were also statistically significant. The use of acupuncture combined with music therapy is effective in reducing depression in PSD patients.

Neuro-endocrine-immune network mechanism of acupuncture for post-stroke depression

The nervous, endocrine and immune systems are interconnected through neurotransmitters, endocrine hormones and cytokines, forming a neuro-endocrine-immune (NEI) network that outputs effect information to target organs in a multi-level and multi-system manner. The effects of acupuncture can be amplified through the NEI network, causing local microenvironment responses at acupoints to treat post-stroke depression (PSD). This paper systematically elucidates the mechanisms of acupuncture treatment for PSD from three aspects: nervous, endocrine and immune, and reveals the potential mechanisms and biological pathways of acupuncture treatment for PSD from an overall perspective based on the NEI network, aiming to provide a reliable theoretical basis for fundamental research on acupuncture treatment for PSD.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the risk of post-stroke depression: A cross-sectional study

BackgroundLimited observational research has explored the relationship between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and the risk of post-stroke depression (PSD). This study aims to investigate the potential associations between NHHR and PSD. MethodsA cross-sectional study was conducted using data from stroke participants aged 20 and older, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018. Depression was assessed using the PHQ-9 questionnaire. The association between NHHR and PSD risk was evaluated through weighted multivariate logistic regression and restricted cubic spline (RCS) models. Subgroup and sensitivity analyses were performed to validate the findings. ResultsIn the continuous model, the NHHR value for the PSD group (3.23±1.84) was significantly higher than that of the non-PSD group (2.79±1.40, p=0.015). Logistic regression analysis in the fully adjusted model revealed a positive association between NHHR and PSD (OR 1.16, 95 % CI 1.03-1.30, p=0.016). Interaction tests showed no significant differences across strata (p > 0.05 for interaction). Restricted cubic spline results indicated a linear dose-response relationship between NHHR and PSD risk (P for non-linearity = 0.6). This association persisted in various subgroup analyses. ConclusionNHHR was significantly correlated with an increased risk of PSD among U.S. adults. Further re-search on NHHR could contribute to the prevention and treatment of PSD.

Evidence-based nursing interventions in the prevention and treatment of post-stroke depression

Evidence-based nursing interventions in the prevention and treatment of post-stroke depression

Acupuncture ameliorates depression-like behavior of poststroke depression model rats through the regulation of gut microbiota and NLRP3 inflammasome in the colon.

This study was conducted to examine the effects of acupuncture on gut microbiota and expression of NLRP3 inflammasome in the colon in poststroke depression (PSD) model rats. Sprague-Dawley male rats were randomized into four groups: sham surgery group, poststroke depression group, acupuncture group, and probiotics group. Acupuncture therapy at Baihui (GV20), Shenting (GV24), bilateral Zusanli (ST36) acupoints in the acupuncture group and probiotic gavage therapy in the probiotics group were performed once per day for 2 weeks. Behaviors of depression were assessed by using weight measurements, sucrose preference test, open field test, and forced swimming test. Histopathological alterations in the colon were determined by hematoxylin-eosin staining, the expression of NLRP3/ASC/caspase-1 pathway-related proteins was analyzed by western blotting. Serum levels of IL-1β and IL-18 were derived from ELISA. The 16S rRNA gene sequencing was performed to examine and analyze the differences of gut microbiota of rats among all groups. Acupuncture was effective to increase weight and ameliorate depressive-like behaviors in PSD rats. Acupuncture increased the diversity of gut microbiota, upregulated the abundance of Bifidobacteriaceae and Lactobacillaceae, and decreased the relative abundance of Peptostreptococcaceae, Rikenellaceae, Eggerthellaceae, and Streptococcaceae at family level. Acupuncture effectively improved the pathological changes in the colon. Meanwhile, acupuncture reduced NLRP3, ASC, caspase-1 protein expressions in the colon, and serum levels of IL-18 and IL-1β. Acupuncture may reduce depressive-like behaviors of PSD by regulating the gut microbiota and suppressing hyperactivation of NLRP3 inflammasome in the colon. Microbiota-gut-brain axis may be an effective target pathway for acupuncture treatment of PSD.

Research Progress in the Treatment of Post-stroke Depression with Traditional Chinese Medicine

In recent years, the incidence rate of stroke has increased year by year. Post stroke depression is one of its main complications, which seriously affects the recovery of physiological functions and quality of life of stroke patients. Traditional Chinese medicine has significant therapeutic effects in treating this disease. This article provides a classification and review of traditional Chinese medicine treatment methods for post-stroke depression, and looks forward to the current problems.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Three-needle electroacupuncture ameliorates depressive-like behaviors in a mouse model of post-stroke depression by promoting excitatory synapse formation via the NGL-3/L1cam pathway

Three-needle electroacupuncture (TNEA) has shown promise as a non-pharmacological treatment for post-stroke depression (PSD). However, the underlying mechanisms of its therapeutic effects remain unclear. In this study, we investigated the potential molecular and synaptic mechanisms by which TNEA ameliorates depressive-like behaviors in a mouse model of PSD. Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) to induce PSD and subsequently treated with TNEA for three weeks at specific acupoints (GV24 and bilateral GB13). Through a combination of behavioral tests, neuronal activation assessment, synaptic function examination, transcriptomic analysis, and various molecular techniques, we found that TNEA treatment significantly improved anxiety and depressive-like behaviors in PSD mice. These improvements were accompanied by enhanced neuronal activation in the medial prefrontal cortex (mPFC) and primary somatosensory cortex (PSC), as well as the promotion of excitatory synapse formation and transmission function in the mPFC. Transcriptomic analysis revealed that TNEA upregulated the expression of Netrin-G Ligand-3 (NGL-3), a postsynaptic cell adhesion molecule, in the mPFC. Further investigation showed that the extracellular domain of NGL-3 binds to the presynaptic protein L1cam, promoting the formation of Vesicular Glutamate Transporter 1 (vGluT1) puncta on neuronal dendrites. Notably, cortical neuron-specific knockout of NGL-3 abolished the antidepressant-like effects of TNEA in PSD mice, confirming the crucial role of the NGL-3/L1cam pathway in mediating the therapeutic effects of TNEA. These findings provide novel insights into the molecular and synaptic mechanisms underlying the therapeutic effects of acupuncture in the treatment of PSD and highlight the potential of targeting the NGL-3/L1cam pathway for the development of alternative interventions for PSD and other depressive disorders.

CRHR1 antagonist alleviated depression-like behavior by downregulating p62 in a rat model of post-stroke depression

Post-stroke depression (PSD) is a complication of cerebrovascular disease, which can increase mortality after stroke. CRH is one of the main signaling peptides released after activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. It affects synaptic plasticity by regulating inflammation, oxidative stress and autophagy in the central nervous system. And the loss of spines exacerbates depression-like behavior. Therefore, synaptic deficits induced by CRH may be related to post-stroke depression. However, the underlying mechanism remains unclear. The Keap1-Nrf2 complex is one of the core components of the antioxidant response. As an autophagy associated protein, p62 participates in the Keap1-NrF2 pathway through its Keap1 interaction domain. Oxidative stress is involved in the feedback regulation between Keap1-Nrf2 pathway and p62.However, whether the relationship between CRH and the Keap1-Nrf2-p62 pathway is involved in PSD remains unknown. This study found that serum levels of CRH in 22 patients with PSD were higher than those in healthy subjects. We used MCAO combined with CUMS single-cage SD rats to establish an animal model of PSD. Animal experiments showed that CRHR1 antagonist prevented synaptic loss in the hippocampus of PSD rats and alleviated depression-like behavior. CRH induced p62 accumulation in the prefrontal cortex of PSD rats through CRHR1. CRHR1 antagonist inhibited Keap1-Nrf2-p62 pathway by attenuating oxidative stress. In addition, we found that abnormal accumulation of p62 induces PSD. It alleviates depression-like behavior by inhibiting the expression of p62 and promoting the clearance of p62 in PSD rats. These findings can help explore the pathogenesis of PSD and design targeted treatments for PSD.

What are the effects of pharmacological, non-invasive brain stimulation and psychological interventions, and their combination, in the treatment of post-stroke depression? A Cochrane Review summary with commentary.

Post-stroke depression (PSD) is a prevalent condition that can significantly influence the recovery process. To assess the effects of pharmacological, non-invasive brain stimulation and psychological interventions, and their combination on PSD. A summary of the Cochrane Review by Allida et al. (2023), with comments from a rehabilitation perspective. Sixty-one studies with 5831 participants were included in the Cochrane Review. Very low-certainty evidence indicated favorable treatment effects of pharmacological interventions, psychological therapies, and the combination of pharmacological intervention and non-invasive brain stimulation on PSD. Pharmacological intervention has resulted in increased side effects associated with the central nervous system and gastrointestinal system, with very low-certainty evidence. Evidence for the effectiveness of pharmacological, psychological, and combination therapies for the management of PSD is uncertain, as the quality of the evidence has been assessed as very low. Therefore, further studies with improved methods should investigate pharmacological and non-pharmacological interventions for the treatment of depression in stroke survivors.

The oxytocin receptor is essential for the protective effect of pair housing on post-stroke depression in mice

The beneficial effect of social interaction in mitigating the incidence of post-stroke depression (PSD) and ameliorating depressive symptoms has been consistently demonstrated through preclinical and clinical studies. However, the underlying relationship with oxytocin requires further investigation. In light of this, the present study aimed to explore the protective effect of pair housing on the development of PSD and the potential relationship with oxytocin receptors. The PSD model was induced by middle cerebral artery occlusion (MCAO) for 50 min, followed by 4-week isolated housing and restrained stress. Subsequently, each mouse in the pair-housing group (PH) was pair-housed with an isosexual healthy partner. Another group was continuously administrated fluoxetine (10 mg/Kg, i.p, once a day) for 3 weeks. To elucidate the potential role of oxytocin, we subjected pair-housed PSD mice to treatment with an oxytocin receptor (OXTR) antagonist (L368,889) (5 mg/Kg, i.p, once a day) for 3 weeks. At 31 to 32 days after MCAO, anxiety- and depressive-like behaviors were assessed using sucrose consumption, forced swim test, and tail-suspension test. The results showed that pair housing significantly improved post-stroke depression to an extent comparable to that of fluoxetine treatment. Furthermore, pair housing significantly decreased corticosterone in serum, increasing OXT mRNA expression in the hypothalamus. Treatment with L368,889 essentially reversed the effect of pair housing, with no discernible sex differences apart from changes in body weight. Pair housing increased hippocampal serotonin (5-HT), but treatment with L368,889 had no significant impact. Additionally, pair housing effectively reduced the number of reactive astrocytes and increased Nissl's body in the cortex and hippocampal CA3 regions. Correspondingly, treatment with L368,889 significantly reversed the changes in the Nissl's body and reactive astrocytes. Moreover, pair housing downregulated mRNA levels of TNF-α, IL-1β, and IL-6 in the cortex caused by PSD, which was also reversed by treatment with L368,889. In conclusion, pair housing protects against the development of PSD depending on OXT and OXTR in the brain, with no significant divergence based on sex. These findings provide valuable insights into the potential of social interaction and oxytocin as therapeutic targets for PSD. Further research into the underlying mechanisms of these effects may contribute to the development of novel treatments for PSD.

Analysis of radiological features in patients with post-stroke depression and cognitive impairment.

Post-stroke depression (PSD) and post-stroke cognitive impairment (PSCI) are common complications following a stroke, significantly impacting the quality of life and survival time of survivors. Currently, the comorbidity of PSCI and PSD is receiving increasing attention, as they share some common clinical characteristics, mechanisms, risk factors, radiological features, and treatment strategies. They influence each other, with the clinical prevalence of PSD comorbid with PSCI reaching as high as 26.15 %. The prevention, screening, diagnosis, and treatment of PSD and PSCI require collaboration across clinical, radiological, and neuropsychological evaluations. This paper aims to summarize the common radiological features of both conditions from a radiological perspective, which may aid in identifying early screening and predictive imaging biomarkers.

Post-Stroke Depression in Older Adults: An Overview.

Detailed data on post-stroke depression (PSD) in older adults are limited in spite of the high vulnerability of this population to stroke. In fact, PSD prevalence in older adults ranges from 16.0 to 43.9%; however, timing and instruments of evaluation often differ significantly across all available studies. The etiology, genetic and inflammatory factors, as well as structural brain alterations, are claimed as part of a multifaceted mechanism of action in PSD onset. Thus, the aim of this narrative review was to further elaborate on the prevalence, etiology, diagnosis, consequences and treatment of PSD in older adults. The consequences of PSD in older adults may be devastating, including a poor functional outcome after rehabilitation and lower medication adherence. In addition, lower quality of life and reduced social participation, higher risk of new stroke, rehospitalization, and mortality have been reported. In this scenario, treating PSD represents a crucial step to prevent these complications. Both pharmacological and non-pharmacological therapies are currently available. The pharmacological treatment utilizes antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TAs) and new multimodal antidepressants (NMAs). Non-pharmacological therapies include psychological interventions and non-invasive brain stimulation techniques, while excluding drug administration. In the general population experiencing PSD, SSRIs (sertraline in particular) are the most prescribed, whereas the combination of antidepressants and psychotherapy is underused. Furthermore, about one-third of patients do not receive treatment for PSD. In regard to older adults with PSD, the possibility of more adverse effects or contraindications to antidepressant prescription due to comorbidities may limit the therapeutic window. Although drugs such as citalopram, escitalopram, sertraline, venlafaxine, and vortioxetine are usually well tolerated by older patients with PSD, the few randomized controlled trials (RCTs) specifically considering older adults with PSD have been conducted with fluoxetine, fluvoxamine, reboxetine, citalopram and nortriptyline, often with very small patient samples. Furthermore, data regarding the results of non-pharmacological therapies are scarce. High-quality RCTs recruiting large samples of older adults are needed in order to better manage PSD in this population. In addition, adequate screening and diagnosis instruments, with reliable timing of evaluation, should be applied.

Effects and central mechanism of electroacupuncture and MRI-navigated rTMS for PSD: study protocol for an fMRI-based single-center, randomized, controlled, open-label trial.

Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life for stroke patients. Antidepressants are the first-line treatment for PSD; however, many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture (EA) or rTMS have a positive effect on PSD. However, there are few clinical studies on EA and MRI-navigated rTMS for PSD that explore the fMRI-based central mechanism in depression. In this randomized, controlled, open-label trial, 64 patients with PSD will be randomly allocated into the experiment group (n = 32) or control group (n = 32). The experiment group will receive EA and MRI-navigated rTMS and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, 10 healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome will be the change from baseline in the Hamilton Depression Scale-24 item (HAMD-24) scores at week 4. The primary analysis of the central mechanism will mainly involve cortical morphology, local spontaneous brain activity, and the default mode network (DMN) functional connectivity based on fMRI at 0 and 4 weeks. Secondary outcomes will include the neuro-patho-physiological and quality of life changes in cortical excitability, determined using the motor evoked potential test (MEP), National Institutes of Health Stroke Scale (NIHSS), EuroQol Five Dimensions Questionnaire (EQ-5D) Scale, Modified Barthel Index (MBI) Scale, and Health Scale of Traditional Chinese Medicine (HSTCM). Additional indicators will include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess the acceptability and economic practicality of the treatment under study. Outcomes will be assessed at baseline and post intervention. EA and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and a potential central mechanism for the future use of EA and MRI-navigated rTMS for PSD. NCT05516680, ClinicalTrials.gov (registered in August 2022).