Use Of Serotonin Reuptake Inhibitors Research Articles

FRI262 Can Selective Serotonin Reuptake Inhibitors Unmask Underlying Polyglandular Autoimmune Syndrome Type II?

Abstract Disclosure: S. Dehghani: None. S. Kalik: None. J. Zaidan: None. A. Nisar: None. Background: Patients with chronic use of SSRIs are at increased risk of developing hyponatremia secondary to SIADH but a full work up to exclude other etiologies might still be warranted if patient has risk factors. Clinical Case: 63-year-old female with past medical history of rheumatoid arthritis and hypothyroidism secondary to Hashimoto thyroiditis presented to the hospital for evaluation of syncopal episodes associated with dizziness, loss of consciousness and weight loss. She was started three weeks prior to presentation on Escitalopram 10 mg for mild depression. On exam she had orthostatic hypotension, she looked tanned but there was no buccal or palmar pigmentation. Admission blood work showed Na level of (111 mmol/L, n:135-145 mmol/L), Potassium of (5.7 mmol/L, n: 3.5-5 mmol/L), Creatinine of (0.8 mg/dL, n:0.7-1.5 mg/dL). Urine Sodium was (59 mEq/L, n: 20 mEq/L) and Urine osm (306 mOsm/Kg, n:50-1200 mOsm/kg). TSH was normal and 8 AM cortisol level was (6.0 ug/dL, n: 6.0-18.4 ug/dL). Initially Hyponatremia was attributed to SIADH secondary to use of Selective Serotonin Reuptake inhibitors, however her autoimmune comorbidities, orthostatic hypotension and physical exam findings warranted more work up to rule out Adrenal insufficiency. The 250 mcg Cosyntropin Stimulation test was done with baseline cortisol of (4.6 ug/dL, n: 6-18.4 ug/dL) and cortisol at 30 minutes and 60 minutes of (5.2 ug/dL and 5.1 ug/dL respectively) confirming failure to respond to ACTH and diagnosis of adrenal insufficiency. She denied taking exogenous steroids. Later her ACTH came back very high (956 pg/mL, n:7-63 pg/mL), aldosterone was (5.3 ng/dL, n<23 ng/dL), plasma renin activity was high at (20.095 ng/mL/hr, n:0.1-1.3ng/mL/hr) and anti-adrenal antibodies were positive confirming the diagnosis of Addison disease. Patient was started on IV hydrocortisone with slow resolution of hyponatremia and symptoms. She was discharged on maintenance hydrocortisone and fludrocortisone. Given the presence of Hashimoto thyroid disease and Rheumatoid arthritis, patient was diagnosed as having polyglandular autoimmune Syndrome type II. Conclusion: The signs and symptoms of adrenal insufficiency are often nonspecific, resulting in long delays in diagnosis or even misdiagnosis. Hyponatremia is one of the manifestations of adrenal insufficiency which can be inevitably missed or misdiagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) as both can manifest as euvolemic hyponatremia and inappropriate urinary Na concentration. This case demonstrates the importance of thorough investigation of underlying etiologies of patients with symptomatic hyponatremia who are also at risk SIADH secondary to SSRIs use. Presentation: Friday, June 16, 2023

Medication and Road Test Performance Among Cognitively Healthy Older Adults

Older adults are increasingly prescribed medications that have adverse effects. Prior studies have found a higher risk of motor vehicle crashes to be associated with certain medication use. To determine whether specific medication classes were associated with performance decline as assessed by a standardized road test in a community sample of cognitively healthy older adults, to evaluate additional associations of poor road test performance with comorbid medical conditions and demographic characteristics, and to test the hypothesis that specific medication classes (ie, antidepressants, benzodiazepines, sedatives or hypnotics, anticholinergics, antihistamines, and nonsteroidal anti-inflammatory drugs or acetaminophen) would be associated with an increase in risk of impaired driving performance over time. This was a prospective cohort study of 198 cognitively healthy adults 65 years and older with a valid driver's license who were followed up annually, with rolling enrollment. Data were collected from participants in St Louis, Missouri, and neighboring Illinois who were enrolled in the Knight Alzheimer's Disease Research Center. Data were collected from August 28, 2012, to March 14, 2023, and analyzed from April 1 to 25, 2023. Participants with healthy cognition, defined as a Clinical Dementia Rating score of 0 at baseline and subsequent visits, who had available clinical, neuropsychological, road tests, and self-reported medication data were included. Potentially driver-impairing medication use. The primary outcome measure was performance on the Washington University Road Test (pass or marginal/fail). Multivariable Cox proportional hazards models were used to evaluate associations between potentially driver-impairing medication use and road test performance. Of the 198 included adults (mean [SD] baseline age, 72.6 [4.6] years; 87 female [43.9%]), 70 (35%) received a marginal/fail rating on the road test over a mean (SD) follow-up of 5.70 (2.45) years. Any use of antidepressants (adjusted hazard ratio [aHR], 2.68; 95% CI, 1.69-4.71), serotonin and norepinephrine reuptake inhibitors (aHR, 2.68; 95% CI, 1.54-4.64), sedatives or hypnotics (aHR, 2.70; 95% CI, 1.40-5.19), or nonsteroidal anti-inflammatory drugs (aHR, 2.72; 95% CI, 1.31-5.63) was associated with an increase in risk of receiving a marginal/fail rating on the road test compared with control individuals. Conversely, participants taking lipid-lowering agents had a lower risk of receiving a marginal/fail rating compared to control individuals. There were no statistically significant associations found between anticholinergic or antihistamines and poor performance. In this prospective cohort study, specific medication classes were associated with an increase in risk of poor road test performance over time. Clinicians should consider this information and counsel patients accordingly when prescribing these medications.

P-Glycoprotein-Mediated Interaction Is a Risk Factor for QT Prolongation in Concomitant Use of Antipsychotics and SSRIs as P-Glycoprotein-Mediated Inhibitors: Analysis of the Japanese Adverse Drug Event Report Database.

The inhibition of human ether-a-go-go-related gene (hERG) channels is a known cause of QT prolongation triggered by antipsychotic drugs. Our previous studies suggest that P-glycoprotein (P-gp)-mediated drug interactions may lead to increased gastrointestinal absorption of pimozide and its accumulation in cardiomyocytes, thereby enhancing the inhibitory effect of hERG channels. There is a paucity of epidemiological studies examining the risk of QT prolongation by antipsychotic drugs in terms of P-gp-mediated interactions with concomitant drugs. Therefore, using the Japanese Adverse Event Reporting Database, we investigated whether the risk of QT prolongation triggered by antipsychotic drugs associated with hERG inhibition is affected by the concomitant use of selective serotonin reuptake inhibitors (SSRIs) associated with P-gp inhibition. The results showed that the frequency of QT prolongation increased when the antipsychotic drugs quetiapine and sulpiride, which are P-gp substrates, were combined with SSRIs with P-gp inhibition. In contrast, no association with QT prolongation was observed in patients on non-P-gp-substrate antipsychotics, irrespective of the P-gp inhibitory effect of the concomitant SSRI. These results suggest that P-gp-mediated interactions are a risk factor for antipsychotic-induced QT prolongation. There is a need for further investigation into the risks of specific drug combinations.

Selective serotonin reuptake inhibitor use, age-related neuropathology and cognition in late-life

The objective of this study was to evaluate an association of selective serotonin reuptake inhibitor (SSRI) use with late life cognitive decline and further investigate the association with brain pathology. Using the data are from two harmonized clinical-pathologic cohort studies with annual cognitive testing we found that SSRI use was associated with significantly faster global cognitive decline and this association was present in those with and without pre-existing cognitive impairment at the time of SSRI initiation. In separate analyses of persons who died during the study and underwent neuropathologic examination, SSRI use was related to higher level of paired helical filament tau tangles and faster rate of global cognitive decline. However, when SSRI use and tangles were included in the same model, the association of SSRI use with rate of global cognitive decline was reduced by more than 50% and no longer statistically significant. SSRI use was associated with higher postmortem level of tau tangles, possibly because SSRI are being used to treat neurobehavioral symptoms associated with dementia, and this relationship appears to partly account for the association of SSRI use with more rapid cognitive decline.

Plasma Serotonin and Cardiovascular Outcomes in Chronic Kidney Disease.

Background Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. Methods and Results In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross-sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension. We also analyzed whether serotonin was associated with time-to-event cardiovascular outcomes, including heart failure hospitalization and atherosclerotic cardiovascular disease (ASCVD) events, in addition to mortality. Because selective serotonin reuptake inhibitors decrease plasma serotonin levels, we specifically evaluated the influence of selective serotonin reuptake inhibitor use in the relationship between serotonin and outcomes. Plasma serotonin level inversely correlated with estimated glomerular filtration rate and directly correlated with blood pressure. High plasma serotonin was associated with left ventricular hypertrophy (adjusted odds ratio, 2.74 [95% CI, 1.11-7.41]). In contrast, undetectable plasma serotonin level was associated with the highest risk of heart failure (adjusted hazard ratio [HR], 2.26 [95% CI, 1.40-3.66]) and ASCVD events (adjusted HR, 1.96 [95% CI, 1.15-3.32]). Conclusions In a large chronic kidney disease cohort, plasma serotonin levels correlated with blood pressure, and elevated serotonin levels were associated with left ventricular hypertrophy. In contrast, undetectable plasma serotonin was associated with the highest risk of heart failure and ASCVD events.

Association between constipation and major depression in adult Americans: evidence from NHANES 2005-2010.

Current studies on the association between constipation and depression is still insufficient. In this study, we investigated the detailed association between constipation and major depression among American adults. In this cross-sectional study, 12,352 adults aged 20 and older were selected from the National Health and Nutrition Examination Survey 2005-2010 for the sample. Constipation was defined as fewer than three defecation frequencies per week. For the assessment of major depression, the validated Patient Health Questionnaire-9 was used. Adjusted odds ratios (ORs) were calculated using multivariate logistic regression models. A subgroup analysis was carried out to ensure that the results were stable. Of the 12,352 participants, 430 reported constipation, with a prevalence of 3.5%. Depression was reported in 1030 cases, indicating a prevalence rate of 8.3%. Patients with constipation were significantly more likely to have major depression (20.9%) than those without it (7.9%, p < 0.001). After adjusting for age, sex, race/ethnicity, marital status, education level, body mass index, vigorous physical activity, alcohol consumption, smoking status, poverty income ratio, diabetes, selective serotonin reuptake inhibitor use, liver disease, heart disease, pulmonary disease, hypertension, arthritis, cancer, dietary fiber intake, moisture intake, total fat intake, carbohydrates intake, and protein intake, constipation is significantly associated with major depression (OR: 2.20, 95%CI: 1.68-2.87, p < 0.001). Subgroup analyses by age, sex, dietary intake, risk behaviors, and common complications showed no statistically significant interactions (p > 0.05). In conclusion, this study showed that constipation were significantly associated with depression. When treating patients with constipation, it is necessary for clinicians to screen and evaluate depression, and provide timely and effective intervention for patients with depression to avoid further deterioration of the condition.

Evidence of Hematoma Prevention After Facelift.

Hematoma is a common complication after facelift procedures. Multiple factors have been shown to increase the risk of hematoma formation such as male gender, anticoagulant medication use, perioperative hypertension, increased intrathoracic pressure, and operative technique. The purpose of this manuscript is to provide an overview of existing literature to provide surgeons with evidence-based recommendations on how to minimize hematoma risk during facelift surgery. A literature search for hematoma and facelift surgery was performed which identified 478 unique manuscripts. Abstracts were reviewed, excluding articles not describing facelift surgery, those written before 1970, studies with a sample size less than 5 patients, non-English studies, and those that did not provide postoperative hematoma rates. Forty-five articles were included in this text with their recommendations. Measures such as the prophylactic management of pain, nausea, and hypertension, the use of fibrin glue tissue sealants, the use of local anesthesia over general anesthesia, and strict blood pressure control of at least <140mmHg were found to significantly reduce hematoma formation. The use of quilting sutures has shown benefit in some high-risk patients. Measures such as drains, compression dressings, perioperative use of selective serotonin reuptake inhibitors (SSRIs), and perioperative steroids had no significant effect on hematoma formation. In addition to appropriate patient selection and careful intraoperative hemostasis, many adjunctive measures have been shown to reduce post-operative hematoma formation in facelift procedures.

Safety of lactational exposure to venlafaxine on the rat mammary gland development and carcinogenesis in F1 female offspring

The chronic use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SNRIs) may result in human gynecomastia, mammoplasia, galactorrhea, and elevated breast cancer risk. As antidepressants are frequently used for postpartum depression (PPD) treatment, this study investigated the adverse effects of lactational exposure to venlafaxine (VENL, a selective SNRI) on mammary gland development and carcinogenesis in F1 female offspring. Thus, lactating Wistar rats (F0) received VENL by oral gavage at daily doses of 3.85, 7.7, or 15.4 mg/kg (N = 9, each group) from lactational day (LD 1) until the weaning of the offspring (LD 21). F1 female offspring were euthanized for mammary gland, and ovary histological analyses on the post-natal day (PND) 22 and 30 (1 pup/litter/period, N = 9, each group). At PND 22, other females (2 pups/litter, N = 18, each group) received a single dose of carcinogen N-methyl-N-nitrosourea (MNU, 50 mg/kg) intraperitoneally (i.p.) for tumor susceptibility assay until PND 250. Tumor incidence and latency were recorded and representative tumor samples were collected for histopathology. The results indicate that lactational exposure to VENL did not alter the development of the mammary gland (epithelial ductal tree or the mean number of terminal end buds), or the ovary (weight and primary, secondary, tertiary, and Graafian follicles) in prepubertal F1 female offspring. In addition, VENL exposure did not influence tumor incidence or tumor latency in adult female offspring that received MNU. Thus, the findings of this animal study indicated that lactational VENL exposure, a period similar to human PPD, did not exert an adverse effect on the mammary gland development at the prepubertal phase or on chemically induced mammary tumorigenesis in adult F1 female rats.

Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery.

A retrospective cohort study. Venous thromboembolism (VTE) is a potentially high-risk complication for patients undergoing spine surgery. Although guidelines for assessing VTE risk in this population have been established, development of new techniques that target different aspects of the medical history may prove to be of further utility. The goal of this study was to develop a predictive machine learning (ML) model to identify nontraditional risk factors for predicting VTE in spine surgery patients. A cohort of 63 patients was identified who had undergone spine surgery at a single center from 2015 to 2021. Thirty-one patients had a confirmed VTE, while 32 had no VTE. A total of 113 attributes were defined and collected via chart review. Attribute categories included demographics, medications, labs, past medical history, operative history, and VTE diagnosis. The Waikato Environment for Knowledge Analysis (WEKA) software was used in creating and evaluating the ML models. Six classifier models were tested with 10-fold cross-validation and statistically evaluated using t tests. Comparing the predictive ML models to the control model (ZeroR), all predictive models were significantly better than the control model at predicting VTE risk, based on the 113 attributes ( P <0.001). The Random Forest model had the highest accuracy of 88.89% with a positive predictive value of 93.75%. The Simple Logistic algorithm had an accuracy of 84.13% and defined risk attributes to include calcium and phosphate laboratory values, history of cardiac comorbidity, history of previous VTE, anesthesia time, selective serotonin reuptake inhibitor use, antibiotic use, and antihistamine use. The J48 model had an accuracy of 80.95% and it defined hemoglobin laboratory values, anesthesia time, beta-blocker use, dopamine agonist use, history of cancer, and Medicare use as potential VTE risk factors. Further development of these tools may provide high diagnostic value and may guide chemoprophylaxis treatment in this setting of high-risk patients.

Anxiety and substance abuse disorders-Focus on alcohol and cannabis

Anxiety disorders are frequent, with a12-month prevalence of 14%, tend to be chronic, and display ahigh comorbidity with substance abuse disorders. Anxiety and substance abuse disorders are associated with apronounced individual as well as socioeconomic burden. This article reviews the epidemiological, etiological, and clinical aspects of the dual diagnosis of anxiety and substance abuse disorders, with aparticular focus on alcohol and cannabis. The treatment comprises nonpharmacological strategies, mainly cognitive behavioral therapy combined with elements of motivational interviewing (MI) and pharmacological management with antidepressants; however, the use of selective serotonin reuptake inhibitors (SSRI)/serotonin and noradrenaline reuptake inhibitors (SNRI) is not unreservedly recommended. The use of gabapentinoids requires careful risk-benefit consideration because of their potential for abuse and dependence in substance abuse disorders. Benzodiazepines are reserved exclusively for crisis management. Rapid diagnosis and treatment initiation targeting both disorders are essential for successful treatment of comorbid anxiety and substance abuse disorders.

Serotonin syndrome-A focused review.

Serotonin syndrome is a potentially life-threatening syndrome with manifestations spanning from mild adverse effects to life-threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation. This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis and treatment, as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for the detection and management of serotonin syndrome. Focused review based on a literature search using the PubMed database. Serotonin syndrome can occur through therapeutic use or overdose of a single serotonergic drug or as a drug interaction between two or more serotonergic drugs. Central clinical features consist of neuromuscular excitation, autonomic dysfunction and altered mental status, occurring in a patient undergoing new or altered serotonergic therapy. Early clinical recognition and treatment are crucial to prevent significant morbidity.

Pregnancy, Delivery, and Neonatal Outcomes Associated With Maternal Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is associated with adverse health-related outcomes. However, pregnancy and neonatal outcomes among women with OCD have been sparsely studied. To evaluate associations of maternal OCD with pregnancy, delivery, and neonatal outcomes. Two register-based cohort studies in Sweden and British Columbia (BC), Canada, included all singleton births at 22 weeks or more of gestation between January 1, 1999 (Sweden), or April 1, 2000 (BC), and December 31, 2019. Statistical analyses were conducted between August 1, 2022, and February 14, 2023. Maternal OCD diagnosis recorded before childbirth and use of serotonin reuptake inhibitors (SRIs) during pregnancy. Pregnancy and delivery outcomes examined were gestational diabetes, preeclampsia, maternal infection, antepartum hemorrhage or placental abruption, premature rupture of membranes, induction of labor, mode of delivery, and postpartum hemorrhage. Neonatal outcomes included perinatal death, preterm birth, small for gestational age, low birth weight (<2500 g), low 5-minute Apgar score, neonatal hypoglycemia, neonatal jaundice, neonatal respiratory distress, neonatal infections, and congenital malformations. Multivariable Poisson log-linear regressions estimated crude and adjusted risk ratios (aRRs). In the Swedish cohort, sister and cousin analyses were performed to account for familial confounding. In the Swedish cohort, 8312 pregnancies in women with OCD (mean [SD] age at delivery, 30.2 [5.1] years) were compared with 2 137 348 pregnancies in unexposed women (mean [SD] age at delivery, 30.2 [5.1] years). In the BC cohort, 2341 pregnancies in women with OCD (mean [SD] age at delivery, 31.0 [5.4] years) were compared with 821 759 pregnancies in unexposed women (mean [SD] age at delivery, 31.3 [5.5] years). In Sweden, maternal OCD was associated with increased risks of gestational diabetes (aRR, 1.40; 95% CI, 1.19-1.65) and elective cesarean delivery (aRR, 1.39; 95% CI, 1.30-1.49), as well as preeclampsia (aRR, 1.14; 95% CI, 1.01-1.29), induction of labor (aRR, 1.12; 95% CI, 1.06-1.18), emergency cesarean delivery (aRR, 1.16; 95% CI, 1.08-1.25), and postpartum hemorrhage (aRR, 1.13; 95% CI, 1.04-1.22). In BC, only emergency cesarean delivery (aRR, 1.15; 95% CI, 1.01-1.31) and antepartum hemorrhage or placental abruption (aRR, 1.48; 95% CI, 1.03-2.14) were associated with significantly higher risk. In both cohorts, offspring of women with OCD were at elevated risk of low Apgar score at 5 minutes (Sweden: aRR, 1.62; 95% CI, 1.42-1.85; BC: aRR, 2.30; 95% CI, 1.74-3.04), as well as preterm birth (Sweden: aRR, 1.33; 95% CI, 1.21-1.45; BC: aRR, 1.58; 95% CI, 1.32-1.87), low birth weight (Sweden: aRR, 1.28; 95% CI, 1.14-1.44; BC: aRR, 1.40; 95% CI, 1.07-1.82), and neonatal respiratory distress (Sweden: aRR, 1.63; 95% CI, 1.49-1.79; BC: aRR, 1.47; 95% CI, 1.20-1.80). Women with OCD taking SRIs during pregnancy had an overall increased risk of these outcomes, compared with those not taking SRIs. However, women with OCD not taking SRIs still had increased risks compared with women without OCD. Sister and cousin analyses showed that at least some of the associations were not influenced by familial confounding. These cohort studies suggest that maternal OCD was associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. Improved collaboration between psychiatry and obstetric services and improved maternal and neonatal care for women with OCD and their children is warranted.

Pre-intensive care unit use of selective serotonin reuptake inhibitors and mortality in critically ill adults with mental disorders: analysis from the MIMIC-IV database

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mental disorders in critically ill patients. We performed a retrospective cohort study to investigate the association between pre-ICU use of SSRIs and mortality in critically ill adults with mental disorders. We identified critically ill adults with mental disorders based on the Medical Information Mart in Intensive Care-IV database. The exposure was the use of SSRIs during the period after hospital admission and before ICU admission. The outcome was in-hospital mortality. Time-dependent Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) with 95% confidence interval (CI). To further test the robustness of the results, we performed propensity score matching and marginal structural Cox model estimated by inverse probability of treatment weighting. The original cohort identified 16601 patients. Of those, 2232 (13.4%) received pre-ICU SSRIs, and 14369 (86.6%) did not. Matched cohort obtained 4406 patients, with 2203 patients in each group (SSRIs users vs. non-users). In the original cohort, pre-ICU use of SSRIs was associated with a 24% increase in the hazard for in-hospital mortality (aHR, 1.24; 95% CI, 1.05–1.46; P = 0.010). The results were robust in the matched cohort (aHR, 1.26; 95% CI, 1.02–1.57; P = 0.032) and the weighted cohort (aHR, 1.43; 95% CI, 1.32–1.54; P < 0.001). Pre-ICU use of SSRIs is associated with an increase in the hazard for in-hospital mortality in critically ill adults with mental disorders.

CO12 Evaluation of Hyponatremia Risk Among Geriatric Patients Exposed to Selective Serotonin Reuptake Inhibitors (SSRIS) and Thiazide Diuretics

Hyponatremia is a common electrolyte disorder among the elderly that can cause serious adverse effects. The purpose of this study was to assess the risk of hyponatremia and the concurrent use of selective serotonin reuptake inhibitors (SSRIs) and thiazide diuretics in a geriatric population.

Association between the type of hypnotic drug and in-hospital fractures in older patients with neurocognitive disorders: A case-control study using a nationwide database.

Hypnotics might increase the risk of falls and fractures in older patients with neurocognitive disorders. Orexin receptor antagonists have recently been approved, but the relationship between the new drugs and fractures remains unclarified. This study aimed to evaluate the association between the type of hypnotic and in-hospital fractures in older patients with neurocognitive disorders using a nationwide inpatient database. Using the Japanese Diagnosis Procedure Combination database, we collected information on inpatients aged ≥65 years with neurocognitive disorders between April 2014 and March 2021. We examined trends in the prescription patterns of benzodiazepine drugs, Z-drugs, orexin receptor antagonists and melatonin receptor agonists. We also carried out a 1:4 matched case-control analysis of in-hospital fractures. The odds ratio of each hypnotic drug was estimated using a generalized estimating equation with adjustment for walking ability, comorbidities, osteoporosis, dialysis, selective serotonin reuptake inhibitor use and anti-dementia drug use. The prescription of benzodiazepine hypnotics decreased and that of orexin receptor antagonists increased. This case-control analysis included 6832 patients with fractures and 23 463 controls. Ultrashort-acting benzodiazepines, short-acting benzodiazepines and Z-drugs were associated with an increased risk of bone fracture (odds ratio [95% confidence interval] 1.38 [1.08-1.77], 1.38 [1.27-1.50], 1.49 [1.37-1.61], respectively). Orexin receptor antagonists were not associated with an increased risk of bone fracture (1.07 [0.95-1.19]). In contrast to other types of hypnotics, orexin receptor antagonists were not associated with in-hospital fractures in older patients with neurocognitive disorders. Geriatr Gerontol Int 2023; 23: 500-505.

(016) Pharmacological Treatment of Men with Compulsive Sexual Behaviour Disorder - Randomized, Double-blind, Placebo-controlled Trial of Paroxetine and Naltrexone

Abstract Introduction Psychotherapy is considered as first-line therapy for compulsive sexual behaviour disorder (CSBD). “Off-label” use of selective serotonin reuptake inhibitors and opioid antagonists was reported as effective but the evidence-based data on pharmacological interventions remains very scarce. Objective The purpose of the study was to compare safety and efficacy of naltrexone and paroxetine in the treatment of CSBD. Methods Double-blind, randomized study comparing naltrexone, paroxetine and placebo was performed in a group of 73 treatment-seeking, heterosexual males meeting the ICD-11 criteria of CSBD. During 5 months treatment, the safety and efficacy of the medication was assessed by clinical examinations and clinical scales including Sexual Addiction Screening Test (SAST), Hypersexual Behavior Inventory (HBI), the Brief Pornography Screen (BPS), as well as in the Ecological Momentary Assessment. Results Symptoms of CSBD significantly improved in all three treatment arms but receiving active treatment was related to better satisfaction with the therapy and self-reported decrease of problematic sexual behavior. Sexual and porn craving decrease was pronounced the most in the paroxetine group. Adverse effects were relatively seldom and mild. All-cause discontinuation rate was 15.1%. Conclusions The study has shown that paroxetine and naltrexone represent safe treatment options for CSBD male patients. However, due to mixed results, their clinical efficacy should be confirmed in future trials that should also include women and non-heterosexual groups of patients. Disclosure No

Late-life depressive symptoms and white matter structural integrity within older Black adults.

Older Black adults experience a high burden of depressive symptoms and cerebrovascular disease but the specific neurobiological substrates underlying the association between late-life depressive symptoms and brain integrity are understudied, particularly in within-group designs. Using the Center for Epidemiologic Studies Depression Scale and diffusion-tensor imaging, within-Black variation in the association between late-life depressive symptoms and white matter structural integrity was examined in 297 older Black participants without dementia that were enrolled across three epidemiological studies of aging and dementia. Linear regression models were used to test associations with DTI metrics (fractional anisotropy, trace of the diffusion tensor) as the outcomes and depressive symptoms as the predictor, while adjusting for age, sex, education, scanner, serotonin-reuptake inhibitor use, total volume of white-matter hyperintensities normalized by intracranial volume, and presence of white-matter hyperintensities at the voxel level. Higher level of self-reported late-life depressive symptoms was associated with greater diffusion-tensor trace (reduced white matter integrity) in connections between commissural pathways and contralateral prefrontal regions (superior and middle frontal/dorsolateral prefrontal cortex), association pathways connecting dorsolateral prefrontal cortex with insular, striatal and thalamic regions, and association pathways connecting the parietal, temporal and occipital lobes and the thalamus. This study demonstrated a discernable pattern of compromised white matter structural integrity underlying late-life depressive symptoms within older Black adults.

Unsubstantiated use of Selective serotonin reuptake inhibitors as an alternative for the treatment of depression

Unsubstantiated use of Selective serotonin reuptake inhibitors as an alternative for the treatment of depression

Diagnosis and therapy of obsessive-compulsive spectrum disorders in general medical and neurological practice

Obsessive-compulsive spectrum disorders are widely represented in the population and often encountered in clinical practice, but they are not well diagnosed and many patients do not receive proper treatment. This review discusses the prevalence of obsessive-compulsive spectrum disorders, their negative impact on the level of functioning of patients, comorbidity with other mental disorders, diagnosis and differential diagnosis. The emphasis is put on changes in approaches to the diagnosis of obsessive-compulsive disorders that will occur after the introduction of the International Classification of Diseases of the 11th revision (ICD-11). Approaches to the treatment of obsessive-compulsive spectrum disorders are discussed in accordance with the principles of evidence-based medicine, and the use of selective serotonin reuptake inhibitors and cognitive behavioral therapy as first-line therapy is justified.

Effect of self-reported clinician experience level on perceptions of the relative rankings of risk factors for biological complications with dental implant therapy

Statement of problemThe effect of clinician experience on the perception of risks for biological complications associated with dental implant therapy is unknown. PurposeThe purpose of this study was to determine whether clinician experience levels, as assessed by the number of implants placed and/or restored, as well as by type of clinical experience (restorative/prosthodontic and/or surgical), influence the perception of risk for biological complications with dental implant therapy. Material and methodsA 10-item survey instrument was developed that asked participants from a convenience sample to rank different risk factors for peri-implant complications in the areas of patient history, clinical findings, and clinician choices and postimplant placement findings. Information about participant experience (number of implants placed and restored and type of experience) was also captured. The Kruskal-Wallis and Mann-Whitney U test statistical analyses were performed to determine the degree, if any, to which the level of clinician experience influenced risk factor rankings (α=.05). ResultsClinicians with more experience viewed the use of selective serotonin reuptake inhibitor (SSRI) medications and clinician inexperience as more important risk factors than did less experienced clinicians. Clinicians with less experience viewed treated moderate or severe chronic periodontitis and thin tissue biotype as more important risk factors than did more experienced clinicians. Clinicians with predominantly surgical experience viewed a heavy plaque index as a more important risk factor than clinicians with predominantly restorative experience. ConclusionsThe data indicate that the level of clinical experience influences how risk factors associated with biological complications of dental implant therapy are viewed by clinicians.