Selective Serotonin Receptor Inhibitors Research Articles

THE TREATMENT OF ACUTE ANGLE CLOSURE WITH HISTORY OF PSYCHOTROPIC AGENTS : A CASE REPORT

Introduction : Psychotropic agents may precipitate Acute Angle Closure (AAC) either by inducing pupil block via adrenergic or anticholinergic mechanisms, or via an idiosyncratic non-pupillary block mechanism. This is a serious condition that can diminished aquous humor (AH) outflow and increased intraocular pressure
 Case Illustration : A 60-year-old female complained of a sudden onset of a severe painful red eye on the right eye (RE)2 weeks ago and there was an IOP elevation. Anti-glaucoma medications were given with no succcess. The patient regularly consumed psychotropic drugs Trihexyphenidyl, Risperidone, and Chlopromazine since 2005 and Escitalopram since 2 years ago
 Discussion : Several classes of centrally acting drugs, including antidepressants such as selective serotonin receptor inhibitors (SSRIs) and antipsychotics have been implicated in precipitate AAC in individuals with pre-existing narrow angels. Rapid lowering of the IOP including medical treatment and relieved relative pupillary block with laser peripheral iridotomy (LPI) is an important initial step in treating AAC. Because the media is not clear due to corneal edema, trabeculectomy + 5 Fluorouracil can be considered for IOP control to prevent further damage.
 Conclusion : Trabeculectomy + 5 FU procedures may be a valuable and effective option in cases where LPI is too risky due to unclear visualization because of corneal edema. Trabeculectomy has been shown to effectively reduce IOP. Closed monitoring is necessary to assess ocular side effects due to the use of psychotropic agents

Palliative care and end of life care in decompensated cirrhosis.

Palliative care and end of life care in decompensated cirrhosis.

(037) Hypersexuality with the Use of Selective Serotonin Receptor Inhibitors

Abstract Introduction We present two cases of hypersexuality in perimenopausal women evaluated, diagnosed, and being managed at this time for what seems to be a sexual dysfunction recently described as a consequence of the use of a combination of 2 kinds of medications: Bupropion, a Norepinephrine Dopamine Reuptake Inhibitor (NDRI), and Sertraline/Fluoxetine, a Selective Serotonin Receptor Inhibitor (SSRI), used as an anti-depressant and anxiolytics for psychiatric conditions. Both cases arrived at our centers referred by their primary care physicians or a psychiatrist for sexual therapy and sexological evaluation. Objective To show a new sexual dysfunction related to the use of SSRI medications. Methods The analysis of 2 cases of a new described sexual dysfunction related with the use of SSRI medications: Bupropion at 150 mg PO bid, and Fluoxetine at 125 mg PO qd. Results The first case, one week after the initiation of Fluoxetine, having been taking Bupropion for months, started to develop uncontrolled need for sex, having sex with multiple men, in addition to her husband. Her husband accepted to have sexual relationships in trios, a situation that lasted for several months. However, after 4-6 weeks, she started to look for additional partners other than her husband. He left. She arrived with extreme anxiety during her first visit. Neither her, nor the psychiatrist understood why this was happening. At that moment, she was having sex with several men on a daily basis. She wanted to preserve her marriage but her sexual compulsion was an impediment. The second patient decided to be unfaithful to her husband of 10 years. In this case, she decided to have hidden sexual relations with several men at the same time with just one. She was also undergoing psychiatric treatment with both medications, Fluoxetine and Bupropion. There was a temporal correlation between the initiation of Fluoxetine and the appearance of the sexual dysfunction. We suspended both medications and around 10 days after this therapeutic step, there was a frank decline in the compulsive sexual behavior. However, due to depression and anxiety symptoms, the psychiatrist decided to restart only Bupropion without the Fluoxetine that was the medication with which the appearance of symptoms have been related. Now, she is okay. Conclusions We describe the possible pharmacological mechanisms involved in the pathophysiology of this disorder and the way in which we have managed the two cases up to now. This condition needs to be differentiated from the hyperactive sexual arousal disorder, previously described in the sexological literature and we need to determine if this is a variant of that kind of syndrome. We have never encountered this kind of reaction before and have only found one publication describing a similar case. Disclosure No

Case 312: Dercum Disease

A 29-year-old woman was referred for US of bilateral breasts during evaluation for noncyclical mastalgia predominantly in the left breast of 8 months duration. She had been taking selective serotonin receptor inhibitors for the past 6 months for a clinical diagnosis of generalized anxiety disorder. A detailed medical history revealed breast cancer in the patient's mother and grandmother. There was no history of weight loss or appetite loss, nor was there a history of any altered bowel or bladder habits. The patient was overweight, with a body mass index of 26.8 kg/m2, and appeared anxious during the general physical examination, with an increased pulse (102 beats per minute) and normal blood pressure (118/82 mm Hg). Local examination revealed multiple small mobile painful lesions that were palpable in all quadrants of the bilateral breasts, anterior abdominal wall, and forearm. On further questioning, the patient reported similar painful lesions were present in her mother and one brother. Laboratory investigations showed a normal hemoglobin level (12.4 g/dL; normal range, 12-15 g/dL), a total leukocyte count of 9000 cells per microliter (9 cells × 109/L) (normal range, 4500-11 000 cells per microliter [4.5-11 cells × 109/L]), a normal differential leukocyte count (74% neutrophils [normal range, 40%-80%], 24% lymphocytes [normal range, 20%-40%], and 2% eosinophils [normal range, 1%-4%]), and an erythrocyte sedimentation rate of 5 mm per hour (normal range, 0-29 mm per hour). High-frequency US of bilateral breasts was performed in conjunction with Color Doppler US and shear-wave elastography of representative lesions in the breasts. Similar lesions were also found in the subcutaneous plane of the right forearm and the anterior abdominal wall.

Hormone-Related and Drug-Induced Osteoporosis: A Cellular and Molecular Overview.

Osteoporosis resulting from an imbalance of bone turnover between resorption and formation is a critical health issue worldwide. Estrogen deficiency following a nature aging process is the leading cause of hormone-related osteoporosis for postmenopausal women, while glucocorticoid-induced osteoporosis remains the most common in drug-induced osteoporosis. Other medications and medical conditions related to secondary osteoporosis include proton pump inhibitors, hypogonadism, selective serotonin receptor inhibitors, chemotherapies, and medroxyprogesterone acetate. This review is a summary of the cellular and molecular mechanisms of bone turnover, the pathophysiology of osteoporosis, and their treatment. Nuclear factor-κβ ligand (RANKL) appears to be the critical uncoupling factor that enhances osteoclastogenesis. In contrast, osteoprotegerin (OPG) is a RANKL antagonist secreted by osteoblast lineage cells. Estrogen promotes apoptosis of osteoclasts and inhibits osteoclastogenesis by stimulating the production of OPG and reducing osteoclast differentiation after suppression of IL-1 and TNF, and subsequent M-CSF, RANKL, and IL-6 release. It can also activate the Wnt signaling pathway to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts rather than adipocytes. Estrogen deficiency leads to the uncoupling of bone resorption and formation; therefore, resulting in greater bone loss. Excessive glucocorticoids increase PPAR-2 production, upregulate the expression of Dickkopf-1 (DKK1) in osteoblasts, and inhibit the Wnt signaling pathway, thus decreasing osteoblast differentiation. They promote osteoclast survival by enhancing RANKL expression and inhibiting OPG expression. Appropriate estrogen supplement and avoiding excessive glucocorticoid use are deemed the primary treatment for hormone-related and glucocorticoid-induced osteoporosis. Additionally, current pharmacological treatment includes bisphosphonates, teriparatide (PTH), and RANKL inhibitors (such as denosumab). However, many detailed cellular and molecular mechanisms underlying osteoporosis seem complicated and unexplored and warrant further investigation.

Impact of selective serotonin receptor inhibitors on gastric histopathology in patients with depression

Objective: Antidepressant medications such as Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) are used in the psychopharmacological treatment for various types conditions. This study aimed to investigate whether SSRIs and SNRIs could reduce gastric intestinal metaplasia. Material Methods: A total of 212 patients who underwent upper gastrointestinal endoscopy plus biopsy in our clinic and were using selective serotonin reuptake inhibitors and other potent serotonin reuptake inhibitors were included in the study. A control group was created with a total of 230 age and gender matched patients who underwent upper gastrointestinal endoscopy plus biopsy but had no SSRI or SNRI usage. Patients’ endoscopic and pathologic findings were recorded retrospectively and compared between the groups. Results: The patient group consisted of 180 (84.9%) male and 32 (15.1%) female patients, while the control group included 175 (76.1%) male and 55 (23.29%) female patients. There was a statistically significant difference between the groups in terms of gender (p=0.020). The rates of erythematous antral gastritis (p<0.001), peptic ulcer (p=0.019), erosive gastropathy (p=0.001) and duodenitis (p=0.002) were statistically significantly lower in the patient group compared to the control group. The rates of H.Pylori(p=0.002), intestinal metaplasia (p=0.013), neutrophil activity (acute inflammation) (p<0.001) and chronic inflammation (p<0.001) were lower in the case group compared to the control group. Conclusion: SSRIs/SNRIs may potentially be used in treating gastrointestinal inflammation and metaplasia. However, further prospective randomised studies with larger series are needed to support our findings.

Case 312.

A 29-year-old woman was referred for US of bilateral breasts during evaluation for noncyclical mastalgia predominantly in the left breast of 8 months duration. She had been taking selective serotonin receptor inhibitors for the past 6 months for a clinical diagnosis of generalized anxiety disorder. A detailed medical history revealed breast cancer in the patient's mother and grandmother. There was no history of weight loss or appetite loss, nor was there a history of any altered bowel or bladder habits. The patient was overweight, with a body mass index of 26.8 kg/m2, and appeared anxious during the general physical examination, with an increased pulse (102 beats per minute) and normal blood pressure (118/82 mm Hg). Local examination revealed multiple small mobile painful lesions that were palpable in all quadrants of the bilateral breasts, anterior abdominal wall, and forearm. On further questioning, the patient reported similar painful lesions were present in her mother and one brother. Laboratory investigations showed a normal hemoglobin level (12.4 g/dL; normal range, 12-15 g/dL), a total leukocyte count of 9000 cells per microliter (9 cells × 109/L) (normal range, 4500-11 000 cells per microliter [4.5-11 cells × 109/L]), a normal differential leukocyte count (74% neutrophils [normal range, 40%-80%], 24% lymphocytes [normal range, 20%-40%], and 2% eosinophils [normal range, 1%-4%]), and an erythrocyte sedimentation rate of 5 mm per hour (normal range, 0-29 mm per hour). High-frequency US of bilateral breasts (Figs 1, 2) was performed in conjunction with Color Doppler US (Fig 3) and shear-wave elastography of representative lesions in the breasts (Fig 4). Similar lesions were also found in the subcutaneous plane of the right forearm (Fig 5) and the anterior abdominal wall (Fig 6).

A systematic review and meta-analysis on the effect of selective serotonin reuptake inhibitors on endothelial function

Abstract Background Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also reported in patients with depression. Emerging evidence suggests that selective serotonin receptor inhibitors (SSRIs) may improve endothelial function. However, clinical studies assessing flow-mediated dilation (FMD), the gold-standard method to evaluate conduit artery endothelial function, in response to SSRIs treatment included limited number of patients and did not provide consistent results. Purpose In the present study we aim to evaluate the effect of SSRIs treatment on endothelial function assessed by longitudinal changes in FMD. Methods We performed a systematic review to retrieve and subsequently meta-analyze eligible studies in patients with depression who received SSRIs and had available measurements of FMD change before and after treatment. Results In 5 studies and 323 individuals in total, SSRIs were associated with increased FMD at the end of follow-up compared to baseline measurement (pooled mean change 1.97%, 95% CI 0.17, 3.77, P=0.032, I2=87.4%). These results did not substantially change when analysis was restricted to patients with history of atherosclerotic cardiovascular disease (ASCVD). Similarly, FMD changes were higher in individuals receiving SSRIs compared to not-treated subjects (pooled mean difference 2.5%. 95% CI 0.7, 4.2, P<0.001, I2=82.7%). Substantial heterogeneity regarding with respect to follow-up duration, demographics, and SSRIs agents. Conclusion SSRIs significantly improve FMD, the gold-standard marker of endothelial function. Further investigation is warranted for the role of FMD as a possible therapeutic biomarker in patients with depression and established or subclinical ASCVD. Prospero registration: CRD42021252241 Funding Acknowledgement Type of funding sources: None.

Does prescribing SSRI alone effective to prevent relapse in panic disorder?

Psychological and pharmacological modalities have been proposed by studies to be adapted for treatment of panic disorder. Selective Serotonin Receptor Inhibitors (SSRI), a group of antidepressant is the first-line drug recommended by National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology for their more desired profile of adverse effect over other classes of antidepressants such as tricyclic antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs). However, the efficacy of SSRI as a monotherapy to prevent relapse in panic disorder has not being widely studied, hence, this review.

Gender differences in Parkinson's disease with dementia and dementia with Lewy bodies

BackgroundGender differences for dementia with Lewy bodies (DLB), usually considered an intermediate disease between Alzheimer disease (AD), Parkinson disease (PD), and Parkinson disease with dementia (PDD), is controversial. The present study investigated gender differences in DLB and PDD using demographic and pharmacologic treatment strategies in a retrospective data analysis. MethodData of confirmed cases of DLB and PDD between 2015 and 2020 were collected from the PRISMA dementia data-base registry. Data from 7594 PDD patients and 608 DLB patients were analyzed using logistic regression analysis to determine demographic and pharmacologic factors associated with DLB and PDD patients. ResultIn the adjusted analysis, central acetylcholinesterase inhibitors (ChEIs) including donepezil, galantamine, rivastigmine were associated with DLB. Second generation antipsychotics (SGAs) such as risperidone (odd ratio(OR)=1.900, 95% confidence interval (CI),1.192–3.030, P = 0.007) was associated with females with DLB while aripiprazole (OR=0.195,95% CI,0.06–0.631, P<0.006), and a selective serotonin receptor inhibitor (SSRIs) including escitalopram (OR=0.651, 95% CI,0.468–0.906, P = 0.011), and demographic factors including tobacco use (OR=0.620, 95% CI,0.444–0.866, P<0.005) and increasing age (OR =1.042, 95% CI, 1.025–1.058, P<0.001), were associated with females that present with PDD. Olanzapine (OR=2.871, 95% CI, 1.902–4.334, P<0.001), escitalopram (OR=1.444, 95% CI, 1.079–1.932) and tobacco use (OR=1.424, 95%CI, 1.075–1.887, P = 0.014) were associated with males with DLB. African American males (OR= 0.249, 95% CI, 0.088–0.703, P = 0.009) with a history of ethyl alcohol (ETOH) use (OR= 0.371, 95% CI, 0.260–0.531, P<0.001) treated with aripiprazole (OR=0.581, 95%CI, (0.302–1.118), P = 0.004) were associated with PDD. ConclusionOur findings reveal similarities and differences in demographic and pharmacologic factors associated with DLB and PDD. Investigating the effect of identified factors on DLB or PDD in future studies can help improve the care of DLB and PDD patients.

Selective serotonin reuptake inhibitor (SSRI) antidepressants reduce COVID-19 infection: prospects for use.

PurposeThe absence of specific treatments for COVID-19 leads to an intense global effort in the search for new therapeutic interventions and better clinical outcomes for patients. This review aimed to present a selection of accepted studies that reported the activity of antidepressant drugs belonging to the selective serotonin receptor inhibitor (SSRI) class for treating the novel coronavirus.MethodsA search was performed in PubMed and SciELO databases using the following search strategies: [(coronavirus) OR (COVID) OR (SARS-CoV-2) AND (antidepressant) OR (serotonin) OR (selective serotonin receptor inhibitors)]. In the end, eleven articles were included. We also covered information obtained from ClinicalTrials.gov in our research.ResultsAlthough several clinical trials are ongoing, only a few drugs have been officially approved to treat the infection. Remdesivir, an antiviral drug, despite favorable preliminary results, has restricted the use due to the risk of toxicity and methodological flaws. Antidepressant drugs were able to reduce the risk of intubation or death related to COVID-19, decrease the need for intensive medical care, and severely inhibit viral titers by up to 99%. Among the SSRIs studied so far, fluoxetine and fluvoxamine have shown to be the most promising against SARS-CoV-2.ConclusionIf successful, these drugs can substantially reduce hospitalization and mortality rates, as well as allow for fully outpatient treatment for mild-to-moderate infections. Thus, repositioning SSRIs can provide benefits when faced with a rapidly evolving pandemic such as COVID-19.

Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study

BackgroundThis study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database.Methods6306 patients identified as having CFS during the 2000–2012 period and 6306 controls (with similar distributions of age and sex) were analyzed.ResultThe patients with CFS were predominantly female and aged 35–64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn’s disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group.ConclusionThis large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems.

Hormonal Imbalances Association to Persistent Genital Arousal Disorder in Females

ABSTRACT Introduction The etiology of the uncommon presentation of persistent genital arousal disorder (PGAD) can provide an insight into the hormonal imbalances that effect sexual function and dysfunction in females. We examine, review, and analyze the correlation of the known cases of PGAD that involved hormonal imbalances with a focus on hormone imbalances (HI) from a urological perspective. Objective To review the literature regarding hormonal imbalances in females with PGAD with a focus on HI. Methods A literature review of articles and clinical studies was performed to define the diagnosis, etiology, and treatment outcomes of PGAD. Search terms included hormone imbalances and/or, persistent genital arousal disorder, diagnosis of persistent genital arousal disorder, defining persistent genital arousal disorder, as well as treatment of persistent genital arousal disorder. Results We found the of onset of PGAD on average was 49.2± 13.1 years with the average length of symptoms 4.7± 11.2 years. The common etiology of cases presented as hormonal imbalances with most individuals experiencing this as their only etiology. Overall, individuals who underwent treatment had a 72.2% rate of symptoms being resolved. The treatments administered involved pharmacological, clinical intervention, diet modification, and hypnotherapy. Clinical intervention was used the less than pharmacological treatment but was more successful. Conclusions There was a high frequency of PGAD presentation and treatment involving dopamine medications such as selective serotonin receptor inhibitors (SSRI). When evaluating for this rare disease it is important to keep in consideration the effect of hormone imbalances. Further studies are needed to get a more thorough understanding of the effects of dopamine may have on sexual dysfunction disorders such as PGAD. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast and Boston Scientific

Is hypoglycemia really observed in pediatric beta-blocker intoxications? A case–control study

BackgroundBeta-blocker (BB) intoxications are common in both childhood and adulthood. In the case of poisoning, bradycardia, hypotension, ventricular dysrhythmias, mental status changes, seizures, hypoglycemia, and bronchospasm may occur. Effects on the cardiovascular system are commonly seen, but hypoglycemia is not frequently observed in clinical practice. In this study, we aimed to answer the question, “Is hypoglycemia more commonly observed in BB intoxications than in other intoxications?” MethodThis was a case–control study conducted in a pediatric emergency department of a university hospital. The case group (Group 1) consisted of cases with BB poisonings and the control group (Group 2) consisted of cases with selective serotonin receptor inhibitor (SSRI) poisonings. Data were obtained from patient files. We recorded the blood glucose levels (BGLs) of all patients on admission to the emergency department and at the 1-, 6-, and 24-h follow-up. The amounts of BBs received by the cases were compared with the specific toxic doses of each drug. The data obtained were analyzed using the Statistical Package for the Social Sciences 22 (SPSS.22) program. Mean and standard deviation for numerical values and frequency for categorical data are reported; at test, chi-square test, and ANOVA tests were used for the analysis. ResultsThe study comprised 40 patients (Group 1) and 40 controls (Group 2). The mean serum BGLs of patients in Group 1 at admission and at the 1-, 6-, and 24-h follow-up were 107.2 ± 46.3 mg/dl, 86.3 ± 20.1 mg/dl, 88.6 ± 28.4 mg/dl, and 86.5 ± 23.7 mg/dl, respectively. The mean values of Group 2 cases were 100 ± 39.5 mg/dl, 92.1 ± 30 mg/dl, 91±28 mg/dl, and 127.8 ± 60.7 mg/dl, respectively, at admission and at the 1-, 6-, and 24-h follow-up (p = 0.4, p < 0.001, p = 0.7, and p < 0.001, respectively). The mean BGLs of patients who were exposed to propranolol at admission and at the 1-, 6-, and 24-h follow-up were significantly lower than those of the patients who had taken different BBs in Group 1. No linear correlation was found between the percentage of exposure to BB toxic doses and BGLs. ConclusionOur study showed that the BGLs of patients receiving BBs could be lower, but they were not at a level that would have serious consequences. Nevertheless, the BGLs of all cases of intoxication should be monitored closely.

Association between Adherence to SSRI Treatment and Mortality among Individuals with Metabolic Syndrome Components.

Depression and anxiety have been associated with type 2 diabetes mellitus and metabolic syndrome, major causes of cardiovascular morbidity and mortality. The effect of antidepressants in this association is unknown. This study aimed to examine the association between adherence to selective serotonin receptor inhibitors (SSRIs) and all-cause mortality among individuals with metabolic syndrome components (hypertension, obesity, and diabetes mellitus). Data on 201 777 patients who were prescribed SSRIs during the years 2008-2011 were analyzed retrospectively. Adherence was measured using prescription purchase records. The moderating effect of SSRI and statin adherence on the association between metabolic syndrome load and mortality hazard risk (HR) during the study period were analyzed. The Cox-proportional hazard model adjusted to background variables was used to this end. During the study period, the maximal metabolic load was associated with mortality HR=1.89 (95% CI: 1.79-2) compared to participants without metabolic risk factors. A slight reduction in mortality HR was demonstrated among those with low and moderate SSRI adherence rates. Adherence to statins was negatively associated with the risk of mortality across all levels of adherence. A significant association (r=0.214, p<0.01) was found between adherence to statins and adherence to SSRIs, with higher rates of adherence to statins across all metabolic load categories. While a high metabolic load is associated with a higher risk of mortality, adherence to SSRIs only partially moderated the risk of mortality, in contrast to the protective effect of statins. Adherence differences to statins and SSRIs among individuals prescribed both medications merit further investigation.

Xiaoyao-san, a traditional Chinese herbal formula, for the treatment of irritable bowel syndrome: A protocol for a systematic review and meta-analysis.

Background:Irritable bowel syndrome (IBS) is a disorder which has considerable effect to patient's quality of life and social functioning. Its main symptoms include recurrent abdominal pain and/or bloating associated with abnormal stool form or frequency. The recommendable treatment of IBS is a medication including loperamide, cimetropium, tricyclic antidepressants, and selective serotonin receptor inhibitors, but it has limited effects and several side effects dissatisfy IBS patients. As an alternative therapy, Xiaoyao-san (XYS) is gaining interest for IBS patients. XYS, a traditional Chinese medicine (TCM), has wide scope of indications and it can be prescribed for various gastrointestinal disorders in TCM syndromes but there has been no systematic review on IBS. Therefore, this review aims on systematically validating the curative effect of XYS on IBS.Methods:Electronic databases, manual search, and contact to author e-mail will be used for searching randomized controlled trials about the use of XYS for IBS. We will select studies by the predefined criteria and collect the data on study participants, interventions, control groups, outcome measurement, adverse events, and risk of bias. Primary outcome will be the efficacy rate, and secondary outcomes will be the IBS-centered indices (abdominal pain score, abdominal distension score, diarrhea or constipation score, bowel symptom severity scale), index about quality of life, and adverse events. Review Manager software and Cochrane Collaboration “risk of bias” tools will be used for meta-analysis and assessment of risk of bias.Results:This review will identify the clinical evidence of XYS's effectiveness and safety for IBS according to formal evaluation aspects.Conclusion:This review will further support the evidence-based usage of XYS for IBS treatment.Ethics and dissemination:No ethical approval is required since there is no personal information collection and patient recruitment.Trial registration number:Research Registry; reviewregistry986.

The case for and against selective serotonin reuptake inhibitors in rapid cycling bipolar disorder

Patients affected by the rapid cycling variant of bipolar disorder often experience significant functional difficulties. Physicians caring for affected patients face many challenges managing the turbulent course of this disorder, complicated at times by psychiatric comorbidities (including substance use disorders), polypharmacy, risk management (of suicidality and aggression), and difficulties with community functioning. There is some controversy about the use of selective serotonin receptor inhibitors (SSRIs) in managing bipolar depression, particularly in the rapid cycling variant. The potential benefit of SSRIs in reducing depressive symptoms must be balanced against the risks of mood phase switching and overall worsening of the rapid cycling course. This case report highlights challenges inherent in the application of SSRIs in a case of treatment-refractory rapid cycling bipolar disorder, and discusses the controversy of their use.

Increased Risk of Falls, Fall-related Injuries and Fractures in People with Type 1 and Type 2 Diabetes - A Nationwide Cohort Study.

People with diabetes could have an increased risk of falls as they show more complications, morbidity and use of medication compared to the general population. This study aimed to estimate the risk of falls and to identify risk factors associated with falls in people with diabetes. The second aim was to estimate fall-related injuries, such as lesions and fractures, including their anatomic localization in people with diabetes compared with the general population. From the Danish National Patient Register, we identified people with Type 1 Diabetes (T1D) (n=12,975) Type 2 Diabetes (T2D) (n=407,009). The cohort was divided into two groups, with respective control groups matched on age and sex (1:1). All episodes of people hospitalized with a first fall from 1996 to 2017 were analyzed using a Cox proportional-hazards model. Risk factors such as age, sex, diabetic complications, a history of alcohol abuse and the use of medication were included in an adjusted analysis. The incidence rate, incidence rate difference and incidence rate ratio (IRR) of falls and the anatomic localization of fall-related injuries as lesions and fractures were identified. The cumulative incidence, of falls requiring hospital treatment, was 13.3% in T1D, 11.9% in T2D. In the adjusted analysis, T1D and T2D were associated with a higher risk of falls [T1D, Hazard Ratio (HR): 1.33 (95% CI: 1.25 - 1.43), T2D, HR: 1.19 (95% CI:1.16 - 1.22), respectively]. Women [group 1, HR 1.21 (CI:95%:1.13 - 1.29), group 2, HR 1.61 (CI:95%:1.58-1.64)], aged >65 years [groups 1, HR 1.52 (CI:95%:1.39 - 1.61), group 2, HR 1.32 (CI:95%:1.58-1.64)], use of selective serotonin receptor inhibitors (SSRI) [group 1, HR 1.35 (CI:95%:1.1.30 - 1.40), group 2, HR 1.32 (CI:95%:1.27-1.38)], opioids [group 1, HR 1.15 (CI:95%:1.12 - 1.19), group 2, HR 1.09 (CI:95%:1.05-1.12)] and a history of alcohol abuse [group 1, HR 1.77 (CI:95%:1.17 - 2.15), group 2, HR 1.88 (CI:95%:1.65-2.15)] were significantly associated with an increased risk of falls in both groups. The IRR of fall-related injuries as hip, radius, humerus and skull/facial fractures were higher in people with T2D than controls [IRR 1.02 (CI:95%:1.01-1.04), IRR 1.39 (CI:95%: 1.18-1.61), IRR 1.24 (CI:95%: 1.12-1.37) and IRR 1.15 (CI:95%:1.07-1.24)]. People with T1D had a higher IRR of hip fractures than controls [IRR: 1.11 (CI:95%:1.02 - 1.23)]. People with diabetes have an increased risk of first fall and a higher incidence of fall- related injuries, including fractures. Advanced aging and sex are non-modifiable risk factors, whereas diabetes, the use of SSRIs and opioids and alcohol abuse could be potentially modifiable risk factors for falls. Gaining information on risk factors for falls could guide the management of diabetes treatment, i.e., choice of drugs, which enables us to improve treatment, particularly in people with a high risk of falls and fractures associated with high mortality.

The Gut-Brain Axis and Its Role in Depression.

The gut microbiota in humans communicates to the central nervous system through the gut-brain axis, and this communication functions in a bidirectional manner. The backbone of this axis is via the vagus nerve allowing the communication. Research on the functionality of the gut-brain axis is present; however, analysis of the diversity and stratification of the gut microbiota is in its infancy. Through the exploration of various studies focusing on the role of the gut microbiota and its effects on the efficacy of selective serotonin receptor inhibitors (SSRIs) in depression management, many promising alterations in constructive changes have emerged. It has become evident that a set of quantifiable microbial markers have been identified as consistent in the stools of depressive subjects that can be further used to determine the severity of disease progression - the presence of certain bacterial species being a common thread amongst the therapeutic bacteria for depression management. The vagus nerve's role in the gut-brain axis, which is vital to carry out any constructive alterations in the gut microbiota, has been strengthened through evidence of SSRIs depending on the vagus to execute therapeutic effects. This review will focus on the interaction between the diversity of the gut microbiota and investigate its link with depression.

Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder

Background: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. Purpose: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. Patients and Methods: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. Results: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. Conclusion: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.