Serotonin Receptor Inhibitors Research Articles

Agomelatine as Antidepressant Treatment in Elderly Patients With Previous Hyponatremia Due To SSRI Use: Case Series.

To evaluate agomelatine treatment in elderly patients with major depressive disorder (MDD) who developed hyponatremia while using selective serotonin receptor inhibitors (SSRIs). Patients (60years or older) with hyponatremia after SSRI treatment for MDD were changed to agomelatine 50mg/day during one month to observe sodium levels during the treatment and change in depressive symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Scale (CGI) of severity were used before and after treatment with agomelatine. The mean age of our sample (five patients) was 75.3 (SD±7.8) years. Sodium levels while using SSRIs were reported with a mean of 122.54 (SD±10.8) mEq/L. Mean MADRS and CGI scores on SSRIs before treatment with agomelatine were 27.8 (SD±3.90) and 5 (SD±0.71) respectively. After 4weeks of treatment with agomelatine 50mg/day, mean scores of sodium were reported at 135.48 (SD±1.6) mEq/L, and mean MADRS and CGI scores were 13.6 (SD±8.35) and 2.4 (SD±1.5). The difference in means of the MADRS scale before and after treatment with agomelatine was found to be statistically significant (27.8 [3.89] versus 13.6 [8.35], p=<0.01). Our open observational study suggests that agomelatine represents a safe and effective treatment option for elderly patients with major depressive disorder and previous SSRIs-induced hyponatremia.

Urinary and gynecologic adverse events associated with SSRI use

Background Selective Serotonin Receptor Inhibitors (SSRIs) are the most prescribed psychiatric drug in the United States. However, the adverse effects of SSRIs related to the genitourinary and reproductive systems in real-world settings remains unclear. The aim of this study is to identify a comprehensive profile of adverse events (AEs) associated with SSRIs in females using data from the FDA Adverse Events Reporting System (FAERS) and variability of adverse events across individual SSRIs. Methods A software designed to analyze adverse drug events, OpenVigil 2.1, was used to query the FAERS data. We defined 445 genitourinary and reproductive system related adverse events related to genitourinary and reproductive systems. Proportional reporting ratio (PRR) was utilized to assess the strength of association between adverse events and SSRIs. Subgroup analysis was conducted to stratify adverse events by age. Results The majority of AEs were related to sexual dysfunction, such as issues of arousal, libido, and orgasm. Additional significant findings were related to gynecologic bleeding, urinary retention and incontinence, and hypersexuality. Citalopram exhibited the strongest signal strengths, as evidenced by the highest proportional reporting ratios (PRRs), particularly in relation to sexual dysfunction. The strongest signals related to sexual dysfunction were found in the 40-59 years age group. Urinary symptoms were most prevalent in the over 60 years age group. Conclusion According to our findings, the potential for genitourinary and reproductive system related AEs of SSRIs warrants further investigation of underlying mechanisms and monitoring in clinical practice. AEs are important considerations for clinical practice as side effects of SSRIs can impact treatment compliance and patient quality of life.

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&#x0D; 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&#x0D; 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.&#x0D; 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

PROTON-PUMP INHIBITORS ARE ASSOCIATED WITH AN INCREASED RISK OF MICROSCOPIC COLITIS: A POPULATION-BASED STUDY AND REVIEW OF THE LITERATURE.

•The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. •The use of PPI represented the highest odds of developing microscopic colitis. Microscopic colitis is a relatively new diagnosis that was first described in the 1980s. Patients usually present with chronic watery and non-bloody diarrhea and are typically characterized by an unremarkable gross appearance of the colon on lower endoscopy while having evidence of lymphocytic infiltration of the lamina propria and the epithelium on histology. Two subtypes have been described in the literature: Collagenous colitis, with marked thickening of the subepithelial layer, and Lymphocytic colitis. Multiple risk factors such as female gender, older age and celiac disease have been associated with this entity. A few studies have found an association between microscopic colitis and proton-pump inhibitor (PPI). The aim of our study was to evaluate the risk of developing microscopic colitis and its subtypes for patients who are on PPI therapy. A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have been diagnosed with any autoimmune disease have been excluded. A multivariate regression analysis was performed to assess risk of developing microscopic, lymphocytic, and collagenous colitis by accounting for potential confounders including female gender, smoking history, and the use of proton pump inhibitor, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). 78,256,749 individuals were screened in the database and 69,315,150 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with microscopic, lymphocytic, and collagenous colitis is seen in table 1. Using a multivariate regression analysis, the risk of developing microscopic, lymphocytic, and collagenous colitis was calculated and illustrated in table 2. Our study showed that the risk of microscopic colitis, lymphocytic colitis and collagenous colitis was higher in females and smokers. Although medications like SSRI and NSAIDs showed a positive correlation with colitis, the highest likelihood of developing this disease was associated with PPIs. Lansoprazole has been documented to be associated with microscopic colitis as it is believed to inhibit colonic proton pumps, and subsequently promote diarrhea and inflammation. Interestingly, the prevalence of lymphocytic colitis and collagenous colitis was similar in the cohort of patients treated with PPIs, indicating no specific predisposition to either subtype. This study further confirms the risk factors associated with microscopic colitis. It can help guide physicians to recognize and eliminate these risk factors prior to initiating treatment for this disease. Future studies can focus on identifying the incidence of microscopic colitis with the different types of PPIs in the market.

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

Pulmonary ILC2-derived serotonin mediates RSV-evoked airway hyperreactivity in mice

Abstract Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, lung epithelial cell-released IL-33 is elevated and promotes group 2 innate lymphoid cells (ILC2s) activation, leading to type 2 cytokines production and asthma development. Serotonin is a neurotransmitter involved in numerous biological functions in the central nervous system as well as peripheral tissues. Previous studies have found elevated serotonin levels in plasma and bronchoalveolar lavage fluid (BALF) from asthma patients, implying that serotonin may involve in the pathogenesis of asthma. Therefore, we aimed to elucidate the role of ILC2-released serotonin in the regulation of RSV-induced airway hyperreactivity (AHR). To investigate whether ILC2 would secrete serotonin upon activation, pulmonary ILC2s were sorted from C57BL/6 mice and then treated with IL-33 in vitro, and we found an increase in the production of serotonin from IL-33-activated ILC2s. Furthermore, elevated BALF serotonin levels were also found in RSV-infected mice. Moreover, we clarified that ILC2 as a major source of serotonin during RSV infection. Next, to determine the role of serotonin in RSV-evoked AHR, we found that the treatment of Clozapine (serotonin receptor inhibitor) significantly attenuated AHR and decreased IL-13 expression. Meanwhile, we demonstrated that the administration of exogenous serotonin exacerbated RSV-caused AHR. Furthermore, serotonin enhanced IL-5 and IL-13 production from IL-33-activated ILC2 in vitro. Taken together, our results indicated that pulmonary ILC2-derived serotonin contributes to RSV-evoked AHR and exacerbates type 2 cytokines through a positive regulation of ILC2 function.

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&lt;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&lt;0.001) and chronic inflammation (p&lt;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.

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&amp;lt;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.

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.

Can miRNA Expression Levels Predict Treatment Resistance to Serotonin Reuptake Inhibitors in Patients with Obsessive-Compulsive Disorder?

Obsessive-compulsive disorder is a psychiatric disorder with different clinical manifestations caused by the interaction of genetic and environmental factors. Recently, it has been shown that microRNAs play a role in the pathogenesis of some psychiatric diseases. We aimed to compare the expression levels of microRNAs between obsessive-compulsive disorder patients and healthy controls and investigate the association between miRNA expression levels and treatment resistance. Twelve miRNA expression levels in venous blood of 100 obsessive-compulsive disorder patients and 50 healthy controls were detected by real-time polymerase chain reaction. Patients were assessed using the Hamilton Depression Rating Scale, Yale-Brown Obsessive-Compulsive Scale, and Yale-Brown Obsessive-Compulsive Symptom Checklist. Each patient was scheduled for a monthly follow-up for a minimum 6-month-period after serotonin receptor inhibitor treatments were initiated. We found that miR-26a-5p (P < .001), miR-21-3p (P < .001), miR-219a-1-3p (P = .016), miR-106b-5p (P = .039), miR-6740-5p (P = .020), miR-320a (P = .001), miR-22-3p, and miR-16b-5p (P = .010) expression levels were statistically higher in obsessive-compulsive disorder patients than healthy controls; miR-135a-5p (P < .001) and miR-129-6b-5p (P < .001) expression levels were statistically lower. Also, it was determined that increased miR-106b-5p levels were associated with treatment-resistance (P = .020) and there was a negative correlation between miR-374b-3p and disease severity (P = .042). In obsessive-compulsive disorder, there may be a potential value in the relationship between various miRNA expression levels and treatment resistance and disease severity, and future studies may be beneficial.

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.

Altered Membrane Mechanics Provides a Receptor-Independent Pathway for Serotonin Action.

Serotonin, an important signaling molecule in humans, has an unexpectedly high lipid membrane affinity. The significance of this finding has evoked considerable speculation. Here we show that membrane binding by serotonin can directly modulate membrane properties and cellular function, providing an activity pathway completely independent of serotonin receptors. Atomic force microscopy shows that serotonin makes artificial lipid bilayers softer, and induces nucleation of liquid disordered domains inside the raft‐like liquid‐ordered domains. Solid‐state NMR spectroscopy corroborates this data at the atomic level, revealing a homogeneous decrease in the order parameter of the lipid chains in the presence of serotonin. In the RN46A immortalized serotonergic neuronal cell line, extracellular serotonin enhances transferrin receptor endocytosis, even in the presence of broad‐spectrum serotonin receptor and transporter inhibitors. Similarly, it increases the membrane binding and internalization of oligomeric peptides. Our results uncover a mode of serotonin–membrane interaction that can potentiate key cellular processes in a receptor‐independent fashion.

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.