Serotonin And Norepinephrine Reuptake Inhibitors Research Articles

Abstract PO5-11-08: Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer

Abstract Background: Treatment with endocrine therapy such as tamoxifen has been identified as one of the most important variables linked with survival among women with hormone receptor-positive breast cancer (BC). There is significant risk reduction of BC recurrence and BC mortality at 15 years among patients treated with tamoxifen for 5 years compared to no endocrine therapy. Tamoxifen is metabolized in the liver via multiple cytochrome P (CYP) isoforms. To ensure optimal efficacy of tamoxifen, consideration must be given to concomitant use of other commonly prescribed drugs such as antidepressants. Some selective serotonin reuptake inhibitors (SSRIs) are potent inhibitors of CYP2D6, an enzyme that metabolizes tamoxifen into its active metabolite, endoxifen, which has anti-tumor effect. Such inhibition can reduce the plasma concentration of endoxifen which could lead to higher rates of BC recurrence. This resulted in an FDA black box warning discouraging concurrent prescriptions of tamoxifen and SSRIs, yet clinical data to support this warning is lacking. Our aim is to describe the practice patterns of concomitant use of tamoxifen and antidepressant medication at our institution. Methods: This is a single institution retrospective study that included adult women, ages 18-99, with stage I-IV BC, who received adjuvant tamoxifen and were taking an antidepressant medication between years 2016-2021. Patients were identified from a tumor registry database. Patient demographics and tumor characteristics were collected via electronic medical record. Results: A total of 419 patients met the inclusion criteria. At the start of tamoxifen therapy, 348 women were on at least one antidepressant, mostly for Major Depressive Disorder (86%). Of those women, 22% were prescribed a strong/moderately potent CYP inhibitor (paroxetine, fluoxetine, duloxetine, or bupropion) and 43% were prescribed weak or non-CYP inhibiting SSRIs (citalopram, escitalopram, fluvoxamine, and sertraline). The most commonly prescribed antidepressants at the start of tamoxifen, alone or in combination with a second antidepressant, were: venlafaxine (30%), escitalopram (17%), sertraline (13%), citalopram (12%) and duloxetine (10%). Main prescribers of antidepressants were primary care physicians (70%), psychiatrists (10%) followed by academic medical oncologists (7%) and regional medical oncologists (6%). Interestingly, the majority of women continued taking the same antidepressant after starting tamoxifen (76%) while, at least 10% of patients changed anti-depressant classes prior to starting tamoxifen, due to concern for drug-drug interaction. When a different class of antidepressant was chosen after starting tamoxifen (22%), serotonin and norepinephrine reuptake inhibitors (SNRIs) were the most frequent class (48%), followed by a different SSRI (42%). The time in which the antidepressant change occurred was variable, but most commonly prior to initiating tamoxifen. Conclusion: Concurrent use of tamoxifen and antidepressant medications is common. Theoretical risk of reduced efficacy of tamoxifen with inhibitors of CYP leads to medication changes for some but not all patients requiring tamoxifen and an antidepressant medication. This can have clinical implications as stability on a specific antidepressant is important for patients and adjustment may impact control of their mood disorder. In some cases, even if a drug-drug interaction was identified, some patients chose to continue their current antidepressant due to concerns of mood de-stabilization, and in other cases, aromatase inhibitors were started as an alternative. These findings highlight differences in practice patterns for which additional guidance may be helpful in bringing awareness and standardization to care. Citation Format: Mariah Ondeck, Bennett Osantowski, Nerea Lopetegui-Lia, Wei Wei, Alexandra Murray, Amanda Maggiotto, Halle Moore, Erin Roesch. Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-08.

Antidepressant treatment in inflammatory bowel disease: a systematic review and meta-analysis.

Around 25% of patients with inflammatory bowel disease (IBD) have depressive symptoms, yet antidepressants have been poorly studied in IBD. We systematically searched IBD studies testing antidepressants in four databases. Outcomes were depressive symptoms, anxiety, IBD disease activity, quality of life (QoL) and adverse events. For randomized controlled trials (RCTs), we performed random-effects meta-analysis of the standardized mean difference (SMD) in posttreatment scores between antidepressant and placebo groups. Risk of bias was assessed using the Cochrane Common Mental Disorders Depression Anxiety and Neurosis Group tool (clinical trials) and Newcastle-Ottawa scale (cohort studies). We included 11 studies ( n = 327): three placebo-controlled RCTs, two nonrandomized trials, and six other study types. In the pooled analysis, antidepressants improved depressive symptoms [SMD = -0.71 (95% confidence interval (CI) -1.32 to -0.10), P = 0.02, I2 = 51%] and QoL [SMD = 0.88 (95% CI 0.30-1.45), P = 0.003, I2 = 44%] more than placebo. Serotonin and noradrenaline reuptake inhibitors (SNRIs) alone improved depressive symptoms [SMD = -0.95 (95% CI -1.45 to -0.45, P < 0.001, I2 = 11%], anxiety [SMD = -0.92 (95% CI 1.72 to -0.13), P = 0.023, I2 = 65%] and QoL [SMD = 1.14 (95% CI 0.66-1.62), P < 0.001, I2 = 0%]. The three RCTs were of good quality. In conclusion, based on three small but good-quality studies, antidepressants improve depressive symptoms and QoL compared to placebo in IBD. SNRI antidepressants may also improve anxiety. A fully powered study of antidepressants in IBD is needed.

Access to a tailored mobile application enhances medication adherence among young users of antidepressants.

Patients' adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence. The study was a single group pre-post intervention design. Data were collected using the validated OsloMet Adherence-to-medication Survey tool (OMAS-37) before and after app access. Pre-app access survey (Survey 1) was conducted via social media and online newspapers, encompassing 445 SSRI/SNRI users aged 18 years and above. Post-app access survey (Survey 2) was sent to 103 SSRI/SNRI users from Survey 1. Wilcoxon Signed Rank Test compared pre- and post-intervention adherence measurements. Pearson's chi-square tests and Fisher's exact tests compared study population categories. Forty-two SSRI/SNRI users, median age 26 (IQR 17), 93% identifying as female, used the app while using the same antidepressant during the 2-month period between gaining access to the app and Survey 2. There was a statistically significant reduction in non-adherence score post-app access (z = 3.57, n = 42, p < 0.001) with medium effect size (r = 0.39), indicating enhanced adherence. Total non-adherence score decreased by 39% from pre-to post-access, and there was a 12% decrease in users scoring equivalent with poor adherence (score <2) post-access. Twenty-nine of 37 non-adherence causes improved, with three showing statistical significance. Of 42 responders, 50% (n = 21) indicated using the app one to two times, while 50% (n = 21) more than three times. Approximately 69% (n = 28) found it useful, and 43% (n = 18) felt safer in their use of antidepressants after access to the app. No significant preference was observed for the app over alternative sources of information. Enhanced medication adherence was observed among antidepressant users following access to the tailored app. Further studies are warranted to evaluate the app applicability to a broader range of antidepressants users or other patient groups, encompassing those in the initiation phase of medication adherence. The app is intended as an easily accessible supplement to the information and advice provided by prescribing physicians and dispensing pharmacists.

Identification of new risk factors for hydroxychloroquine and chloroquine retinopathy in systemic lupus erythematosus patients

BackgroundLong-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3–8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney disease, concurrent tamoxifen therapy and pre-existing retinal or macular disease. However, those factors cannot explain the entire risk of developing antimalarial retinopathy. ObjectiveThis study was undertaken to identify new risk factors associated with HCQ or CQ retinopathy (QRNP) in systemic lupus erythematosus (SLE) patients. MethodsThis case–control (1:2) study compared SLE patients with QRNP (cases) to those without (controls). Controls were matched for sex and known QRNP risk factors: HCQ and/or CQ treatment duration (±1 year) and age (±5 year) at SLE diagnosis. ResultsForty-eight cases were compared to 96 SLE controls. Multivariable logistic-regression analysis retained the following as independent determinants significantly associated with QRNP: concomitant selective serotonin-reuptake inhibitor (SSRI) or serotonin- and norepinephrine-reuptake inhibitor (SNRI) intake (OR [95 % confidence interval] 6.6 [1.2 to 40.9]; p < 0.01); antiphospholipid syndrome (OR=8.9 [2.2 to 41.4] p < 0.01); blood hydroxychloroquine/desethylchloroquine concentration ([HCQ]/[DCQ]) ratio <7.2 (OR 8.4 [2.7 to 30.8]; p < 0.01) or skin phototype ≥4 (OR 5.5 [1.4 to 26.5]; p = 0.02), but not daily HCQ dose, blood [HCQ] or body mass index. ConclusionThe results of this case–control study identified blood [HCQ]/[DCQ] ratio, concurrent SSRI/SNRI therapy, skin phototype ≥4 and antiphospholipid syndrome as new risk factors for QRNP.

Viloxazine: A New Non-Stimulant Treatment for Attention-Deficit/Hyperactivity Disorder (ADHD)

&#x0D; IntroductionViloxazine is an antidepressant medication classified as an SNRI (serotonin and norepinephrine reuptake inhibitor). In April 2021, it received FDA approval in the United States for the treatment of ADHD in children aged 6 to 17. Subsequently, in May 2022, it was also approved for the treatment of adults with ADHD [1]. Viloxazine, available in extended-release capsules, represents novel non-stimulant medication option for patients with ADHD.Aim of the studyOur aim was to review the viloxazine in the fields of ADHD treatment, summarize current knowledge and analyze the first treatment results.&#x0D; &#x0D; &#x0D; Methods and materialsA review of the literature available in the PubMed database was performed, using the key words: „Viloxazine" ; „ADHD treatment" ; „ADHD”, „attention deficit hyperactivity disorder”, „attention deficit hyperactivity disorder treatment”; „ADHD non-stimulant treatment”; „ADHD non-stimulant”; „ADHD non-stimulant drugs”, „SPN-812”&#x0D; &#x0D; &#x0D; ConclusionViloxazine presents a promising non-stimulant alternative for ADHD treatment with more favorable pharmacokinetics, new way of possible administration and fewer adverse effects, particularly within the cardiovascular system, than other available ADHD medication options. While these findings are encouraging, continual research is imperative to establish the long-term safety profile.&#x0D;

Psychopathological symptoms in fibromyalgia and their associations with resistance to pharmacotherapy with SNRI.

Fibromyalgia (FM) is often comorbid with psychiatric disorders. Moreover, several studies show that psychiatric disorders may be linked to the severity and impact of FM. Therefore, the study described in the article had two main goals: (1) to explore various psychopathological symptom dimensions in patients with fibromyalgia and secondly, (2) to examine the links between psychopathology and response to treatment with serotonin and norepinephrine reuptake inhibitors (SNRI). This cross-sectional study was performed between December 2020 and November 2022. The definition of resistance to SNRI was <30% reduction of pain after ≥8 weeks of treatment. 30 FM subjects responsive to SNRI (FM T[+]), 32 patients non-responsive to SNRI (FM T[-]) and 30 healthy controls were enrolled. Participants were examined by physicians and completed self-report tools to evaluate levels of depression (Quick Inventory of Depressive Symptomatology, Hospital Anxiety and Depression Scale), anxiety (State and Trait Anxiety Inventory), anhedonia (Snaith-Hamilton Pleasure Scale), bipolar symptoms (Mood Disorder Questionnaire, Hypomania Checklist), and dissociation (Dissociative Experiences Scale - Revised). ANOVA analysis and a series of simple logistic regressions were used to examine the associations between psychopathological variables and response to SNRI. FM T[-] vs. FM T[+] showed higher levels of: depression, state and trait anxiety and anhedonia as well as higher proportion of scores indicating the presence of anxiety disorder. Increased severity of depression, anxiety and anhedonia were predictors of resistance to SNRI. Modifiable psychopathological symptoms vary in FM T[+] vs. FM T[-] and are predictors of resistance to SNRI. Psychological assessment should be integrated into standard care for FM patients.

Impact of depression and the potential effect of its treatment on semen parameters

BackgroundUp to 30% of male infertility may be idiopathic. Researchers are looking into psychological problems, particularly depression, as possible risk factors for such idiopathic etiology. We aimed to assess how depression affects Egyptian patients’ semen parameters and its indicators for male fertility and to evaluate the potential positive influence of improving the score of depression on these parameters. A prospective observational pilot clinical study included twenty-one male patients with moderate, severe, or very severe depression. They were subjected to baseline semen analysis. All patients were treated by serotonin and norepinephrine reuptake inhibitors (SNRIs). Those who showed improvement in their depression, within the following 6 months, were eligible for a second evaluation of their semen. We compared baseline semen parameters of all patients to 2021-WHO lower normal limit as well as post-improvement values.ResultsOnly 16 patients showed improvement in their depression after treatment with SNRIs and were candidates for the 2nd assessment of semen analysis. No significant improvements could be detected except for volume. Yet, on repeating the comparisons including only patients with abnormal baseline semen parameters, significant improvements were observed in most semen parameters, including semen volume, sperm count per ejaculate, and percentage of sperm motility either progressive or total.ConclusionThe results addressed the potential impact of depression on male fertility in a sample of Egyptian patients through a negative effect on semen parameters. This effect is neither sole nor direct and may require either predisposed individuals or the existence of other co-factors to be manifested. However, the appropriate treatment of depression may reverse such effects and help in the management of male infertility.

The Antidepressant Therapy Selective Norepinephrine Reuptake Inhibitors (SNRIs) Reduces the Risk of Alzheimer’s Disease

AbstractBackgroundDepression has been established as a risk factor for developing Alzheimer’s Disease (AD). Further, depression is a common symptom of the prodromal phase of the disease and acts as an accelerating factor for cognitive decline before and after dementia diagnosis. Based on this association, analyses of real‐world medical data were conducted to determine the impact of anti‐depressive pharmacological therapy, Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), on risk of AD diagnosis. This study aimed to determine the effect of SNRI therapy on AD incidence, as well as determining responder vs non‐responder phenotypes on demographic characteristics, comorbidity burden, and co‐treatment profile.MethodA retrospective analysis was conducted using the Mariner insurance claims dataset and included patients 60 years of age and older with a diagnosis of depression. To minimize bias, a propensity score matching was conducted to adjust for age, gender, cci and comorbidities. The propensity score matched population was surveyed for a diagnosis of AD after at least 1 year of SNRI drug exposure, and different durations of SNRI therapy were analyzed. Responders were detected through sensitivity analyses based on comorbidities and drug combinations.ResultThe propensity score matched group included 307,671 patients exposed to SNRIs and 307,671 patients with no exposure to any antidepressant therapy. SNRI therapy was associated with a significant decrease in risk of AD diagnosis (RR [95%CI]: 0.73 [0.70–0.76]; P&lt;.0001), with women (RR [95%CI]: 0.66 [0.63–0.70]; P&lt;.0001) exhibiting greater risk reduction compared to men (RR [95%CI]: 0.88 [0.82–0.95]; P&lt;.0001). Long‐term SNRI treatment (&gt;6 years) was associated with the greatest AD risk reduction (RR [95%CI]: 0.50 [0.47–0.53]; P&lt;.0001). Responders exhibited higher incidence of obesity and greater use of anti‐inflammatories.ConclusionSNRI therapy was associated with a significant reduction in AD risk. Furthermore, increased duration of SNRI therapy was associated with greater AD risk reduction. Responders displayed fewer comorbidities and co‐treatments although they had a higher incidence of obesity. Clinically, these findings, based on real‐world psychiatric care, provide data regarding long‐term neurological health outcomes of SNRI anti‐depressant therapy. From a mechanistic perspective, data reported herein indicate that sustaining noradrenergic function is a key pathway involved in preventing AD.

Prescription Practices Regarding the use of Systemic Drugs in the Management of Patients with Chronic Pruritus amongst Indian Dermatologists - A Questionnaire Based Survey.

Chronic pruritus poses a significant challenge to treating physicians due to multitude of underlying causes and varying treatment strategies. Several topical, systemic, and physical modalities have been tried with variable success. Prescription practices in chronic pruritus are influenced by differential knowledge and experience of physicians, patient-related factors, and resource availability. The purpose of this survey was to observe the current pattern of practice in Indian dermatologists in the management of chronic pruritus and to identify practice gaps particularly regarding the use of various systemic agents as antipruritics. A previously validated questionnaire was sent to consultant dermatologists across India between January 2020 and July 2020. The questionnaire was comprised of six questions (multiple-choice questions as well as open-ended questions) regarding the use of antidepressants, cyclic gamma-aminobutyric acid (GABA) analogues, opioid antagonists, antihistamines, and alternate therapies in the management of chronic pruritus. A total of 700 dermatologists completed the questionnaire (response rate 70%). Overall, antihistamines were the most common drug prescribed in chronic pruritus (more than 95% respondents). Other systemic agents such as opioid antagonists, gabapentinoids, and antidepressants were prescribed by 22.42%, 71.85%, and 75.29% respondents, respectively, in chronic pruritus as either monotherapy or in combination with antihistamines in specific types of itches. Among antidepressants, tricyclic antidepressants (TCAs) (69.29%) were prescribed most often, followed by selective serotonin reuptake inhibitors (SSRIs) (32.29%) and serotonin and norepinephrine reuptake inhibitors (SNRIs) (9.14%). Other treatment options such as omalizumab, thalidomide, ondansetron, ursodeoxycholic acid (UDCA), and rifampicin were used by 10% respondents to alleviate pruritus in special situations. This survey revealed the redundant practice of prescribing antihistamines in chronic pruritus irrespective of etiology among Indian dermatologists. It also revealed a differential approach regarding use of systemic agents such as gabapentinoids, opioid antagonists, and antidepressants, in academic and non-academic institutions. The survey emphasized a barrier in writing prescription of systemic agents such as opioid antagonist and SNRIs due to lack of knowledge and experience, fear of side effects, and inadequate available evidence.

Maternal exposure to SSRIs or SNRIs and the risk of congenital abnormalities in offspring: A systematic review and meta-analysis.

The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors. A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study. Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56). SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.

Utilization of Pharmacologic and Non-Pharmacologic Therapies for Pain in Sickle Cell Disease: A Cross-Sectional Study

Background: The sickling deformity of red blood cells in sickle cell disease (SCD) results in multisystem sequelae, including severe, acute pain from vaso-occlusive crises (VOCs) and chronic pain from central sensitization. Pain is the main cause of poor quality of life and hospital admissions among patients with SCD. While opioid therapy is an important component of treatment for acute SCD pain, it can be complicated by side effects and toxicities. In contrast, chronic SCD pain is best managed with non-pharmacologic therapies. A multimodal, multidisciplinary approach to pain management that promotes non-pharmacologic therapies can improve the quality of care for patients with SCD by addressing biopsychosocial components of the pain experience and is recommended by the American Society of Hematology (ASH). This study examines current usage of pharmacologic and non-pharmacologic therapies among Adolescents and Young Adults (AYAs) with SCD receiving care at our institution. Methods: The electronic medical record and Sickle Cell Knowledgebase, a customized data visualization platform unique to our institution, were utilized to conduct a retrospective chart review of AYAs, ages 13-21 years of age, with SCD from 2016-2021. Data collected included demographic information, diagnosis of chronic pain, emergency department (ED) visits and inpatient admissions for VOCs, as well as pharmacologic and non-pharmacologic therapies utilized in the ED, inpatient setting, and, for patients with chronic pain, in the outpatient setting. Results: The cohort included 90 AYAs with SCD (73% were 13-17 years old). The most common SCD genotypes were HbSS (n=47, 52%) and HbSC (n=32, 36%). The majority were female (n=53, 49%), Black (n=85, 94%), and non-Hispanic (n=86, 96%). There were 95 ED visits for VOC, where the patient was subsequently discharged home, and 246 admissions for VOC during the study period. There was a high frequency of opioid interventions for VOCs during the 95 extracted ED visits (81.8% in 2016, 91.7% in 2021). During VOC admissions, there was consistent use of opioids in 100% of admissions from 2016-2021 with increasing utilization of patient-controlled analgesia (7.7% in 2016, 45.1% in 2021) and subanesthetic ketamine (0% in 2016, 18.3% in 2021) each year during the study period. Compared to pharmacologic measures, non-pharmacologic therapies (i.e., healing touch, massage, art therapy, child life, music therapy, occupational therapy, physical therapy, psychology) were less utilized during VOC admissions. While healing touch and child life therapy were ordered during approximately 85% of VOC admissions, they occurred &amp;lt;50% of the time. All other integrative therapies were ordered between 5-55% of admissions each year and occurred &amp;lt;50% of the time. There was no correlation between length of hospital stay and use of integrative therapies. Seven patients with a diagnosis of chronic pain were identified. All 7 received non-pharmacologic therapies in the outpatient setting, including cognitive behavioral therapy, guided imagery, and psychology consultation. Six received either a gabapentinoid, serotonin and norepinephrine reuptake inhibitor (SNRI), or tricyclic antidepressant (TCA). Conclusion: Per the ASH SCD guidelines, non-pharmacologic therapies are recommended for SCD-related pain. In our cohort, we found that non-pharmacologic therapies occurred in &amp;lt;50% of VOC admissions and were underutilized for SCD-related pain in AYAs when compared to pharmacologic therapies at our institution. Though we speculate that healing touch and child life were frequently ordered as a default within our admission order set, utilization rates were still low. To better understand barriers to non-pharmacologic therapies in SCD, we are conducting qualitative interviews of patients, caregivers, and healthcare providers using the Consolidated Framework for Implementation Research (CFIR) as a theoretical model. Understanding barriers to the use of non-pharmacologic therapies will be essential to maximizing their implementation and hence maximizing pain control, improving quality of life, and increasing self-efficacy.

4 An Update: Greater Apathy Associated with Selective Serotonin Reuptake Inhibitor Use in Parkinson’s Disease

Objective:Apathy is a primary lack of motivation that is frequently reported in Parkinson’s disease (PD) and often misdiagnosed as depression. In PD, apathy worsens over time with motor symptom progression. Evidence over the past 15 years has documented that use of selective serotonin reuptake inhibitors (SSRIs) is associated with increased apathy in patients with depression, including individuals with PD. In PD, this appears to be related to downregulation of dopaminergic systems by serotonin. Despite increasing evidence, SSRIs continue to be heavily prescribed in individuals with PD— potentially worsening apathy and decreasing quality of life for these individuals. This study is an update, re-examining the relationship between apathy and the use of SSRIs and other antidepressants in a large cohort of individuals with PD.Participants and Methods:Participants included a convenience sample of 387 nondemented individuals with idiopathic PD who were in their mid-60's (mean age=64.9+8.72 years), well-educated (mean=14.95+2.78 years), predominantly male (72.4%), non-Hispanic white (94.5%), and in mid-stage of disease severity (on medication Unified Parkinson Disease Rating Scale motor score=25.3+10.1). All scored above clinical cutoff for dementia on a cognitive screener (Dementia Rating Scale-2 (DRS) &gt; 125). Medications, cognitive, mood, and clinical data were extracted from chart review. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped into SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs) and other. Analyses included bootstrapped Pearson’s correlations, Pearson’s chi-square, and linear regressionsResults:Among 387 individuals with PD, 41.3% (N=160) were taking antidepressant medications. Of these 160, 61.3% were on SSRIs, 24.4% on SNRIs, and the remainder on other antidepressants. Approximately 36.9% of the 387 PD patients exceeded recommended clinical cutoffs for apathy (AS &gt;14) and 23.5% for depression (BDI-II &gt;14) (Starkstein et al., 1992; Beck et al., 1996). Individuals taking SSRIs (N=98, x2=5.14, p=0.023) or SNRIs (N=39; x2=5.43, p=0.020) were more likely to be clinically apathetic than those taking other depression medications (N=23; x2=1.28, p=0.26). Results of a multiple regression with age, education, disease duration, motor severity, DRS-2, BDI-II, and all psychotropic medications (anti-depressants, anti-anxiety, anti-psychotics) as independent variables explained 42.8% of the variance in total apathy scores (F[17,285]=12.550, p&lt;0.001). SSRIs were the only medication to significantly predict greater AS scores (ß=0.110, p=0.020) in this model. Less education (ß=-0.119, p=0.017) worse cognition (ß=-0.128, p=0.009), and greater depressive symptoms (ß=0.561, p&lt;0.001) were also significant predictors of apathy.Conclusions:These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy as a potential adverse effect when determining which anti-depressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative anti-depressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study. Longitudinal studies are also needed to elucidate the relationship of apathy and anti-depressant use over time, specifically to determine potential causality of this observed association. Funding: T32-NS082168

Functional Movement Disorder; Importance of Proper Diagnosis and Treatment: A Case Report

Background: Dystonia is a common movement disorder with a wide range of aetiologies. Delays in the identification and initiation of effective treatments should be minimized to improve patient pain and optimize outcomes. This case report aims to underscore the successful treatment of chronic dystonia with the use of mood-modifying serotonin and norepinephrine reuptake inhibitors (SNRI), and encourage clinicians to consider a diagnosis of functional (psychogenic) movement disorder in patients with dystonia that is refractory to usual treatment.&#x0D; Case Report: This case report describes a 40-year-old woman who presented to a chronic pain clinic for pain related to cervical dystonia with associated head tremor. Her symptoms were refractory to nearly a decade of quarterly botulinum toxin injections. Based on careful evaluation of the patient’s history, a normal neurological examination, increased Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Injustice Experiences Questionnaire (IEQ) scores, and unsuccessful symptom management with botulinum toxin A, a diagnosis of functional movement disorder (FMD) was made. Low-dose Cymbalta was initiated. The patient achieved near complete symptom remission and resolution of her chronic pain within 2 months and achieved near complete resolution in 2 years.&#x0D; Conclusion: A diagnosis of FMD should be considered in all patients with dystonia, but especially in patients who respond inadequately to botulinum toxin injections or other rehabilitation therapies. The treatment of comorbid psychiatric conditions can result in substantial benefits and remission from dystonia due to FMD.

Psychological variables associated with resistance to treatment with serotonin and noradrenaline reuptake inhibitors in fibromyalgia

ObjectiveThe treatment of fibromyalgia (FM) often offers only partial pain relief. Among the most effective drugs for FM pain are serotonin and noradrenalin reuptake inhibitors (SNRI). Few studies investigated the affective temperaments and personality features in FM. Our objective was to explore the associations between the affective temperaments, personality traits, schizotypy and response to SNRI treatment in FM. Methods60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[−] and 30 healthy controls were recruited. Resistance to SNRI was defined as <30% pain reduction during at least 8-week treatment. Subjects were assessed by physician and filled self-report questionnaires: Temperament Scale of Memphis, Pisa and San Diego- autoquestionnaire, Ten Item Personality Inventory, Oxford-Liverpool Inventory of Feelings and Experiences and Fibromyalgia Impact Questionnaire (FIQ). ANOVA analysis and simple logistic regressions were used to examine the links between psychological variables and lack of response to SNRI. ResultsFM T[−] presented higher scores in total FIQ and in physical, work, well-being, pain, fatigue/sleep, stiffness domains than FM T[+]. FM T[−] showed higher levels of: irritable and anxious temperaments, neuroticism, schizotypy than FM T[+]. The levels of depressive, irritable and anxious temperaments, introversion, neuroticism and schizotypy were linked to lack of response to SNRI. ConclusionsFM T[+] and FM T[−] differ in clinical presentation and psychological features. The levels of affective temperaments, personality and schizotypal traits are associated with lack response to SNRI in FM.

Association of serotonin reuptake inhibitors with asthma control.

Background: Clinical trials demonstrated that selective serotonin reuptake inhibitors (SSRI) can improve asthma control in patients with comorbid major depressive disorder (MDD) and that this effect may be greater than the effect of SSRIs on depression. These findings suggest that SSRIs may improve asthma control in patients without MDD. Objective: The current retrospective study examined the effect of SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRI) on asthma control in adult patients. We hypothesized that patients would have fewer asthma exacerbations after treatment with an SSRI or SNRI. Methods: Electronic health record data of adult patients (N = 592) who were seen at a University of Texas Southwestern (UTSW) hospital or clinic and had (1) an SSRI or SNRI prescription, (2) a previous asthma diagnosis, and (3) no mood disorder diagnosis were extracted by using the UTSW Clinical Data Exchange Network. Wilcoxon signed rank tests were used to compare oral corticosteroid prescriptions and asthma-related emergency department (ED) visits and hospitalizations in the 12 months before and after the start of an SSRI/SNRI. Results: Therapy with SSRIs/SNRIs was associated with a significant decrease in oral corticosteroid use (p = 0.003), ED visits (p = 0.002), and hospitalizations (p < 0.001). Conclusion: Results from the current study add to the existing literature by demonstrating a reduced rate of severe exacerbations in patients with asthma by using an SSRI/SNRI without limiting the analytic sample to a high-illness-severity subgroup defined by symptoms of asthma or depression. Future work should include a prospective, placebo controlled study with individuals who have asthma and no comorbid mental health condition, verified by a mental health professional.

Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure-Activity Relationship Studies.

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it as a significant therapeutic target for treating such conditions. Inhibitors of serotoninergic signaling (especially selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)) are prominently selected as first-line therapy for the treatment of depression, which benefits via increasing low serotonin levels and norepinephrine by blocking serotonin/norepinephrine reuptake and thereby increasing activity. While developing newer heterocyclic scaffolds to target/modulate the serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics and an electron-rich environment, ultimately resulting in a diverse range of bioactivities. Therefore, the current manuscript discloses such a specific modification and structural activity relationship (SAR) of attempted derivatization in terms of the serotonergic efficacy of the resultant inhibitor. We also featured a landscape of imidazole-based development, focusing on SAR studies against the serotoninergic system to target depression. This study covers the recent advancements in synthetic methodologies for imidazole derivatives and the development of new molecules having antidepressant activity via modulating serotonergic systems, along with their SAR studies. The focus of the study is to provide structural insights into imidazole-based derivatives as serotonergic system modulators for the treatment of depression.

Antidepressants and their metabolites primarily affect lysosomal functions in the marine mussel, Mytilus galloprovincialis

Antidepressants widely occur as emerging contaminants in marine coastal waters, with concentrations reported in the low ng/L range. Although at relatively lower levels with respect to other pharmaceuticals, antidepressants – fluoxetine (FLX) in particular - have attracted attention because of their striking effects exerted at low doses on marine invertebrates. In this study, the effects of four antidepressants including FLX, sertraline (SER), and citalopram, as members of the selective serotonin reuptake inhibitor (SSRI) class, and venlafaxine (VEN) as a member of the serotonin and norepinephrine reuptake inhibitor (SNRI) class, were evaluated in the mussel Mytilus galloprovincialis. In addition, the effects of two main metabolites of FLX and VEN, i.e., norfluoxetine (NFL) and O-desmethylvenlafaxine (ODV) respectively, were compared to those of the parent compounds. Eight concentrations of each drug (0.5–500 ng/L range) were tested on the early life stage endpoints of gamete fertilization and larval development at 48 h post fertilization (hpf). Egg fertilization was reduced by all compounds, except for VEN. Larval development at 48 hpf was affected by all SSRIs, but not by SNRIs. The above effects were significant but never exceeded 20 % of control values. Adult mussels were exposed in vivo for 7 days to environmental concentrations of the drugs (0.5, 5, and 10 ng/L) and a battery of eight biomarkers was assessed. Antidepressants primarily targeted lysosomal functions, decreasing haemocyte lysosome membrane stability (up to 70 % reduction) and increasing of the lysosome/cytosol ratio (up to 220 %), neutral lipid (up to 230 %), and lipofuscin (up to 440 %) accumulation in digestive gland. Only SER and NFL significantly affected catalase and glutathione-S-transferase activities in gills and digestive gland. NFL and ODV, were effective and sometimes more active than the parent compounds. All compounds impaired mussel health status, as indicated by the low to high stress levels assigned using the Mussel Expert System.

Comparative safety of adding serotonin and norepinephrine reuptake inhibitors (SNRIs) versus nonsteroidal anti-inflammatory drugs (NSAIDs) to short-acting opioids for non-malignant pain in nursing homes.

The comparative safety of serotonin and norepinephrine reuptake inhibitors (SNRIs) as adjuvants to short-acting opioids in older adults is unknown even though SNRIs are commonly used. We compared the effects of SNRIs versus nonsteroidal anti-Inflammatory drugs (NSAIDs) on delirium among nursing home residents when SNRIs or NSAIDs were added to stable regimens of short-acting opioids. Using 2011-2016 national Minimum Data Set (MDS) 3.0 and Medicare claims data to implement a new-user design, we identified a cohort of nursing home residents receiving short-acting opioids who initiated either an SNRI or an NSAID. Delirium was defined from the Confusion Assessment Method in MDS 3.0 assessments and ICD9/10 codes using Medicare hospitalization claims. Propensity score matching balanced underlying differences for initiating treatments on 39 demographic and clinical characteristics (nSNRIs = 5350; nNSAIDs = 5350). Fine and Gray models provided hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for the competing risk of death. Hydrocodone was the most commonly used short-acting opioid (48%). Residents received ~23 mg daily oral morphine equivalent at the time of SNRIs/NSAIDs initiation. The majority were women, non-Hispanic White, and aged ≥75 years. There were no differences in any of the confounders after propensity matching. Over 1 year, 10.8% of SNRIs initiators and 8.9% of NSAIDs initiators developed delirium. The rate of delirium onset was similar in SNRIs and NSAID initiators (HR(delirium in nursing home or hospitalization for delirium):1.10; 95% CI: 0.97-1.24; HR(hospitalization for delirium): 1.06; 95% CI: 0.89-1.25), and were similar regardless of baseline opioid daily dosage. Among nursing home residents, adding SNRIs to short-acting opioids does not appear to increase risk of delirium relative to initiating NSAIDs. Understanding the comparative safety of pain regimens is needed to inform clinical decisions in a medically complex population often excluded from clinical research.

How to treat chronic pain in rheumatic and musculoskeletal diseases (RMDs) – A pharmacological review

IntroductionChronic pain is a common symptom of rheumatic diseases that impacts patients’ quality of life. While non-pharmacological approaches are often recommended as first-line treatments, pharmacological interventions are important for pain management. However, the effectiveness and safety of different pharmacological treatments for chronic pain in rheumatic diseases are unclear. MethodsThis review critically synthesizes the current evidence base to guide clinicians in selecting appropriate pharmacological treatments for their patients, considering the expected benefits and potential risks and side effects. ResultsFor osteoarthritis, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and antidepressants are commonly used, with NSAIDs being the most recommended. In addition, topical agents, such as topical NSAIDs, are recommended for localized pain relief. For fibromyalgia, amitriptyline, serotonin and noradrenaline reuptake inhibitors (SNRIs), and gabapentinoids are commonly used, with SNRIs being the most recommended. For back pain, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids are used only for acute of flare-up pain, whereas neuropathic pain drugs are only used for chronic radicular pain. For inflammatory rheumatic diseases, disease-modifying antirheumatic drugs (DMARDs) and biological agents are recommended to slow disease progression and manage symptoms. ConclusionWhile DMARDs and biological agents are recommended for inflammatory rheumatic diseases, pharmacological treatments for other rheumatic diseases only alleviate symptoms and do not provide a cure for the underlying condition. The use of pharmacological treatments should be based on the expected benefits and evaluation of side effects, with non-pharmacological modalities also being considered, especially for fibromyalgia.

Prevalence of the use of antidepressants in patients with venous thromboembolism

To estimate the prevalence of Antidepressant use in patients with a history of venous thromboembolism (VTE). Describe the patient's characteristics and which drugs are the most prescribed. A cross-sectional study involving a consecutive sample of patients included in the Registro de Enfermedad Tromboembólica (RIET) from the Hospital Italiano de Buenos Aires in a period between 01/01/2014 to 01/09/2018. All patients presented symptomatic VTE and confirmed diagnosis. Drugs considered included in this study were: Selective Serotonin Reuptake Inhibitors (SSRI), Dopamine and Norepinephrine Reuptake Inhibitors (NDRI), Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) and Tricyclic antidepressants (TCA). From a total of 2373 patients with VTE, 472 were active users of antidepressants, showing a prevalence of antidepressant use of 19.9% (CI 95%). The most frequently prescribed drugs by drug classification were: SSRI 83.9%, TCA 20.5%, ISRN 14.6%, and NDRI 2.5%. Patients presented a median age of 76 years, predominantly women (71.4%), with several comorbidities: 52.24% arterial hypertension, 37.29% overweight, and 34.75% history of smoking. Concerning relevant history, we observed: 29.03% active oncologic disease, 26.27% major surgery before the VTE, and 21.61% previous VTE. The prevalence of antidepressant use in patients with VTE is 19.9%, superior by far to that of the general population. Depression is a major cause of morbidity worldwide, and its prevalence is increasing over the years.