Serotonin-norepinephrine Reuptake Inhibitors Research Articles

Distinct Effects of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors on Soluble Biomarkers in Blood and Cerebrospinal Fluid of People With HIV.

Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immunomodulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH. Cross-sectional single-center (United States) analysis in 184 PWH on ART with plasma HIV RNA < 200 copies/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and clinical conditions. Participants were mostly middle-aged men, with median CD4+ T cells of 620/µL. In adjusted models, SSRI use was associated with 3 PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=.14, P = .040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=-.12, P = .042); and higher plasma sCD14 with lower sCD40L (aβ=.15, P = .042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=.22, P = .004). Statins and ACEIs showed no association. SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation, and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH.

Pediatric anxiety disorders: Basic concepts for primary care.

Anxiety disorders in children and adolescents often present in primary care, and many clinicians will need to guide families on treatment. The purpose of this article is to give a brief overview of assessment and treatment principles for clinicians in primary care. Anxiety and its expression are heavily influenced by children's developmental progression and capabilities. Anxiety disorders have multiple underlying etiologies including temperament, environmental exposure to stressors, and childhood trauma. All anxiety disorders are strengthened by an operant process known as escape conditioning. The most effective treatments for child and adolescent anxiety begin with behavioral-based interventions including exposure with response prevention (ERP) and cognitive behavioral therapy (CBT). Medication can be effective in combination with CBT and ERP, or as a standalone treatment when behavioral interventions are not available. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors have been evaluated by randomized clinical trials for the treatment of childhood anxiety, but most are not approved by the Food and Drug Administration. When anxiety is severe and functional impairment is high, referral for psychiatric care and multimodal treatment reduces the likelihood of poor outcomes.

Trends in the treatment of fibromyalgia in South Korea between 2011 and 2018: a retrospective analysis of cross-sectional health insurance data

ObjectivesFibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea.DesignRetrospective, observational study...

The dynamic interaction between symptoms and pharmacological treatment in patients with major depressive disorder: the role of network intervention analysis

IntroductionThe Major Depressive Disorder (MDD) is a mental health disorder that affects millions of people worldwide. It is characterized by persistent feelings of sadness, hopelessness, and a loss of interest in activities that were once enjoyable. MDD is a major public health concern and is the leading cause of disability, morbidity, institutionalization, and excess mortality, conferring high suicide risk. Pharmacological treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Noradrenaline Reuptake Inhibitors (SNRIs) is often the first choice for their efficacy and tolerability profile. However, a significant percentage of depressive individuals do not achieve remission even after an adequate trial of pharmacotherapy, a condition known as treatment-resistant depression (TRD).MethodsTo better understand the complexity of clinical phenotypes in MDD we propose Network Intervention Analysis (NIA) that can help health psychology in the detection of risky behaviors, in the primary and/or secondary prevention, as well as to monitor the treatment and verify its effectiveness. The paper aims to identify the interaction and changes in network nodes and connections of 14 continuous variables with nodes identified as "Treatment" in a cohort of MDD patients recruited for their recent history of partial response to antidepressant drugs. The study analyzed the network of MDD patients at baseline and after 12 weeks of drug treatment.ResultsAt baseline, the network showed separate dimensions for cognitive and psychosocial-affective symptoms, with cognitive symptoms strongly affecting psychosocial functioning. The MoCA tool was identified as a potential psychometric tool for evaluating cognitive deficits and monitoring treatment response. After drug treatment, the network showed less interconnection between nodes, indicating greater stability, with antidepressants taking a central role in driving the network. Affective symptoms improved at follow-up, with the highest predictability for HDRS and BDI-II nodes being connected to the Antidepressants node.ConclusionNIA allows us to understand not only what symptoms enhance after pharmacological treatment, but especially the role it plays within the network and with which nodes it has stronger connections.

Approaches towards Anxiety due to Post Traumatic Stress Disorder : A Review

Post-traumatic stress disorder (PTSD) is a mental health condition caused by witnessing or experiencing a terrifying event The anxiety disorder known as post-traumatic stress disorder (PTSD) is very common and has been linked to a higher risk of hypertension and cardiovascular disease. Types of PTSD are Normal Stress Response, Acute Stress Disorder, Uncomplicated, Complex, Comorbid. There are many factors that can contribute to someone developing posttraumatic stress disorder. Flashbacks, nightmares, excruciating anxiety, and uncontrollable thoughts about the incident are all possible symptoms. The amygdala is a component of the neural circuitry involved in emotional learning, fear, and anxiety. is a diverse disorder that has an impact on a person's behaviour, physical health, and mood as well as biological, psychological, and environmental factors. Anxiety types- Panic Disorder or OCD. There may be a feeling of disconnection between your mind and body that makes you feel out of control. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are frequently used in the treatment of PTSD and anxiety disorders, sertraline (Zoloft), paroxetine (Paxil), and fluoxetine (Fludac) approval for the treatment of PTSD. Many PTSD patients may turn to alcohol, drugs, or even suicide during this time in an effort to cope with the agoraphobia, depression, and nightmares.

Exploring venlafaxine effects on chronic vulvar pain: Changes in mood and pain regulation networks

The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake inhibitor (SNRIs) in modulating vulvar pain led to the hypothesis that PV might involve central mechanisms. Here, we investigate whether vulvar pain is associated with gene-expression changes in mood, stress and pain systems, including amygdala (Amg), medial prefrontal cortex (mPFC), and periaqueductal gray matter (PAG). Additionally, we examined the analgesic and anxiolytic effects of venlafaxine. We found that the development of chronic vulvar pain in an animal model of PV is associated by overexpression of genes related to neuronal-activity and neuroinflammation in the Amg, mPFC, and PAG. Additionally, changes in the expression of GABA and serotonin synthesis, and reuptake were noted in the Amg and mPFC. Unsurprisingly, anxiety-like behavior and emotional-disorder were observed in rats with chronic vulvar pain. Nevertheless, treatment with venlafaxine (37.5 mg/kg) for one month significantly improves the vulvar hypersensitivity, as well as reduces the anxiety level. More critically, the long-term gene expression adaptation in serotonin receptor and synthesis, GABA synthesis, neuroplasticity, and neuroinflammation in the Amg, mPFC, and PAG, were modulated by venlafaxine in rats with vulvar pain. Our findings suggest that vulvar allodynia induced by inflammation might associated with gene expression changes in brain areas that are involved in mood, stress and pain regulation. These changes probably play a role in central sensitization, and anxiety. Strikingly, enhancing the activity of serotonin and noradrenaline via venlafaxine treatment in rats with vulvar pain induces analgesic and anxiolytic effects.

Antidepressants as Autophagy Modulators for Cancer Therapy.

Cancer is a major global public health problem with high morbidity. Depression is known to be a high-frequency complication of cancer diseases that decreases patients' life quality and increases the mortality rate. Therefore, antidepressants are often used as a complementary treatment during cancer therapy. During recent decades, various studies have shown that the combination of antidepressants and anticancer drugs increases treatment efficiency. In recent years, further emerging evidence has suggested that the modulation of autophagy serves as one of the primary anticancer mechanisms for antidepressants to suppress tumor growth. In this review, we introduce the anticancer potential of antidepressants, including tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). In particular, we focus on their autophagy-modulating mechanisms for regulating autophagosome formation and lysosomal degradation. We also discuss the prospect of repurposing antidepressants as anticancer agents. It is promising to repurpose antidepressants for cancer therapy in the future.

Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants in ambulatory care: a prospective interventional study in community pharmacies

Abstract Background/Introduction Direct oral anticoagulants (DOACs) are increasingly used but can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Community pharmacists, who have access to patients’ complete medication profiles, including over-the-counter medication and medication from different prescribers, can play a crucial role in detecting and managing DDIs with DOAC in ambulatory care. Purpose This study aimed to detect and manage DDIs with DOAC in ambulatory care, because such real-life clinical practice studies are currently lacking. Methods A prospective interventional study was conducted between October 2021 and August 2022 in 201 community pharmacies in Belgium. On random days, every patient purchasing a DOAC or an interacting drug was screened for the presence of a DDI with DOAC. The pharmacist contacted the physician to discuss the management of the interaction. For the screening and management of DDI with DOAC, a previously developed practice-oriented DDI list for ambulatory care was used [1]. Results In total, 751 patients (74.5±10.7 years) were included, in whom 875 DDIs were identified. The three most commonly involved interacting drugs were (selective) serotonin (norepinephrine) reuptake inhibitors (32.9%), antiplatelets (30.9%), and non-steroidal anti-inflammatory drugs (28.9%). Most DDIs (83.1%) were not new (patients were already using these drugs) and 8.7% of interacting drugs were dispensed over-the-counter. In almost one-third of DDIs (28.0%), the interacting drug and the DOAC were prescribed by different physicians. Prescribers rated the clinical risks of the identified DDIs as high (15.9%), moderate (33.1%), and low (38.7%), whereas 12.3% were unaware of the potential risks. Remarkably, in 18 patients who were concomitantly taking an antiplatelet and DOAC, the prescriber reported forgetting to stop the antiplatelet or not being aware that the patient was taking both medications. Three patients were also found to be using another anticoagulant along with DOAC due to miscommunication between prescribers. When discussing how to manage the DDI, pharmacotherapy was mostly unchanged (60.2%). Physicians cited reasons such as the interacting drug being deemed necessary (37.2%), the patient already using a proton pump inhibitor (PPI) (19.5%), or the patient using both interacting drugs already for a long time without problems (18.6%). However, in 39.8% of cases, the discussion resulted in a pharmacotherapy change. The most common changes included stopping the interacting drug (21.5%), initiating a PPI (17.6%), or replacing the interacting drug with a safer alternative (14.5%). Conclusion This study illustrated that community pharmacists, in collaboration with physicians, can contribute to reducing avoidable patient harm from DDIs with DOACs.

Indirect adjusted comparison of 6-month clinical outcomes between esketamine nasal spray and other real-world polypharmacy treatment strategies for treatment resistant depression: results from the ICEBERG study.

The efficacy of esketamine nasal spray (NS) as a rapid-acting agent for treatment resistant depression (TRD) was demonstrated in comparisons with placebo, when both were given in addition to a newly initiated selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI). How esketamine NS compares with commonly used real-world (RW) polypharmacy treatment strategies is not known. ICEBERG was an adjusted indirect treatment comparison that analysed data from SUSTAIN-2 (NCT02497287; clinicaltrials.gov), a long-term, open-label study of esketamine NS plus SSRI/SNRI, and the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov), an observational study of routine clinical practice. Data were compared between patients receiving esketamine NS (SUSTAIN-2) and those from the EOTC treated with polypharmacy treatment strategies, either combination or augmentation. Analyses were adjusted for potential confounders, using rescaled average treatment effect among treated estimates. Threshold analyses were conducted to assess potential impact of unmeasured confounders on the robustness of analyses where esketamine NS was found to be significantly superior. Sensitivity analyses were used to understand the impact of analysis method selection and data handling. Esketamine NS treatment resulted in a higher probability of 6-month response (49.7% [95% confidence interval (CI) 45.6-53.9]) and remission (33.6% [95% CI 29.7-37.6]) versus RW polypharmacy (26.8% [95% CI 21.0-32.5] and 19.4%, [95% CI 14.2-24.6], respectively). Relative risk calculations showed esketamine NS was 1.859 (95% CI 1.474-2.345; p < 0.0001) times as likely to result in response and 1.735 (1.297-2.322; p = 0.0002) times as likely to result in remission versus RW polypharmacy at 6 months. Threshold and extensive sensitivity analyses supported that analyses of esketamine NS superiority were robust. ICEBERG supports esketamine NS being superior to current RW individualized polypharmacy strategies, including augmentation, with benefits extending beyond acute use, to improved chance of 6-month response and remission. While unobserved confounding factors may certainly impact results of an indirect comparison, threshold analysis supported a low likelihood of this affecting the conclusions.To view an animated summary of this publication, please click on the Supplementary video.

ICEBERG study: an indirect adjusted comparison estimating the long-term benefit of esketamine nasal spray when compared with routine treatment of treatment resistant depression in general psychiatry.

Treatment resistant depression (TRD) affects 10-30% of patients with major depressive disorder. In 4-week trials, esketamine nasal spray (NS) was efficacious vs. placebo when both were initiated in addition to a new selective serotonin or serotonin norepinephrine reuptake inhibitor. However, comparison with an extended range of real-world treatments (RWT) is lacking. ICEBERG was an adjusted indirect treatment comparison using propensity score-based inverse probability weighting, performed on 6-month response and remission data from patients receiving esketamine NS plus oral antidepressant from the SUSTAIN-2 (NCT02497287; clinicaltrials.gov) study, compared with patients receiving other RWT from the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov) study. SUSTAIN-2 was a long-term open-label study of esketamine NS, while the EOTC was conducted at a time when esketamine NS was not available as RWT. Threshold and sensitivity analyses were conducted to assess how robust the primary analyses were. Patients receiving esketamine NS had a higher probability of 6-month response (49.7% [95% confidence interval (CI) 45.6-53.9]) and remission (33.6% [95% CI 29.7-37.6]) vs. patients receiving RWT (26.4% [95% CI 21.5-31.4] and 18.2% [95% CI 13.9-22.5], respectively), according to rescaled average treatment effect among treated estimates. Resulting adjusted odds ratios (OR) and relative risk (RR) favoured esketamine NS over RWT for 6-month response (OR 2.756 [95% CI 2.034-3.733], p < 0.0001; RR 1.882 [95% CI 1.534-2.310], p < 0.0001) and remission (OR 2.276 [95% CI 1.621-3.196], p < 0.0001; RR 1.847 [95% CI 1.418-2.406], p < 0.0001). Threshold analyses suggested that differences between the two studies were robust, and results were consistent across extensive sensitivity analyses. ICEBERG supports that, at 6 months, esketamine NS has a substantial and significant benefit over RWT for patients with TRD. While results may be affected by unobserved confounding factors, threshold analyses suggested these were unlikely to impact the study conclusions.To view an animated summary of this publication, please click on the Supplementary video.

Beyond the Pain: A Systematic Narrative Review of the Latest Advancements in Fibromyalgia Treatment.

Fibromyalgia is a complex chronic pain disorder that significantly impacts the quality of life of affected individuals. The etiology of fibromyalgia remains elusive, necessitating effective treatment options. This review aims to provide an overview of current treatment options for fibromyalgia and highlight recent updates in managing the condition. The methodology employed in this systematic review comprised the following key steps. We conducted a comprehensive search across various databases to identify pertinent studies published between 2000 and 2023. Inclusion criteria were defined to specifically target studies involving adult individuals diagnosed with fibromyalgia, with a focus on both pharmacological and non-pharmacological interventions for managing the condition. The review encompassed a range of study types, including randomized controlled trials, observational studies, and systematic reviews. To ensure the quality of the selected studies, we employed appropriate assessment tools, and data extraction and synthesis adhered to established guidelines. This rigorous approach allowed for a robust analysis of the literature on fibromyalgia management. In the course of our review, it became evident that a spectrum of treatment approaches holds significant promise in the management of fibromyalgia. Specifically, pharmacological interventions, including selective serotonin-norepinephrine reuptake inhibitors, anticonvulsants, cannabinoids, tropisetron, and sodium oxybate, have exhibited substantial potential in alleviating fibromyalgia symptoms. Concurrently, non-pharmacological strategies, such as cognitive-behavioral therapy, exercise regimens, and complementary and alternative therapies, have yielded positive outcomes in improving the condition's management. Recent developments in the field have introduced innovative pharmacological agents like milnacipran and pregabalin, in addition to non-pharmacological interventions like mindfulness-based stress reduction and aquatic exercise, expanding the array of options available to enhance fibromyalgia care and alleviating patient symptoms. Fibromyalgia necessitates a multidisciplinary approach to treatment, encompassing both pharmacological and non-pharmacological interventions. Recent updates in fibromyalgia management offer additional options to alleviate symptoms and improve the quality of life for individuals with fibromyalgia. Healthcare professionals should remain informed about these advancements to provide evidence-based care, addressing the complex symptoms associated with fibromyalgia and enhancing patient outcomes.

Review On Synthetic Vs Herbal Drugs, Its Various Extraction Methods And Animal Models Related To Depression

Depression is a neuropsychiatric disorder The focus of the current review article is on the most recent antidepressants drugs , their mechanisms of action, their pathophysiology, their side effects, and the methods for preventing drug-induced toxicity. There is also a description of phytochemicals that have been found to have antidepressant effects. Widely used synthetic drugs are, i. tricyclic antidepression ii. Selective serotonin reuptake inhibitors iii. monoamine oxidase inhibitors, iv. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) It has been reported that most antidepressants have negative health effects. An account of phytochemicals found to be acting as antidepressant is also included. Their beneficial effects to the human body have been attributed to the presence of active phytochemical ingredients with some efficiency for disease treatment as well as for beauty and health enhancement. Public awareness on the adverse effects of synthetic chemical products also increased the demand for herbal products. Highly efficient herbal processing and extraction technologies have been developed to obtain the optimal amounts of active ingredients from herbs Soxhlet extraction, supercritical fluid extraction cold Maceration Extraction, steam distillation, Hot Water Extraction, microwave assisted extraction. This review focuses on recent findings regarding some of the most widely employed animal models used currently to predict antidepressant potential. Here we, studies the assessment behavioral test by using various animal models force swimming test, tail suspension Test, rotarod test. In that for study of synthetic and herbal drugs in treatment of depression. Their advantageous effects on the human body have been related to the existence of active phytochemical components that are effective in treating certain diseases as well as enhancing attractiveness and health. The demand for herbal items increased as a result of growing public knowledge of the negative consequences of synthetic chemical products.

Probable fluoxetine-induced hepatomegaly: a case report

Depressive disorder is a common behavioural, psychiatric disorder. Among various antidepressants selective serotonin reuptake inhibitors (SSRIs) are preferred drugs for the treatment of depression. When second-generation antidepressants SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat depression, 0.5–1% of patients develop mildly altered liver function without any symptoms. Various degrees of organ dysfunction are linked with drug-induced liver injury, which is unpredictable and might result from exposure to a drug. We reported suspected fluoxetine-induced hepatomegaly secondary to nine weeks of treatment with an SSRI fluoxetine. Upon cessation of the agent, the patient recovered symptomatically. The evidence is vital that the hepatomegaly in this patient was caused by fluoxetine.

Alzheimer's disease and epilepsy: shared neuropathology guides current and future treatment strategies.

Epilepsy is a cause of profound disability in patients with Alzheimer's disease (AD). The risk of being diagnosed with AD increases the risk for epilepsy, and in parallel, a history of epilepsy increases the likelihood of the development of AD. This bi-directional relationship may be due to underlying shared pathophysiologic hallmarks, including decreased cerebrospinal fluid amyloid beta 42 (Aβ42), increased hyperphosphorylated tau protein, and hippocampal hyperexcitability. Additionally, there are practical treatment considerations in patients with co-morbid AD and epilepsy-namely, there is a higher risk of seizures associated with medications commonly prescribed for Alzheimer's disease patients, including antidepressants and antipsychotics such as trazodone, serotonin norepinephrine reuptake inhibitors (SNRIs), and first-generation neuroleptics. Anti-amyloid antibodies like aducanumab and lecanemab present new and unique considerations in patients with co-morbid AD and epilepsy given the risk of seizures associated with amyloid-related imaging abnormalities (ARIA) seen with this drug class. Finally, we identify and detail five active studies, including two clinical trials of levetiracetam in the respective treatment of cognition and neuropsychiatric features of AD, a study characterizing the prevalence of epilepsy in AD via prolonged EEG monitoring, a study characterizing AD biomarkers in late-onset epilepsy, and a study evaluating hyperexcitability in AD. These ongoing trials may guide future clinical decision-making and the development of novel therapeutics.

Exploring the human gut microbiota targets in relation to the use of contemporary antidepressants

BackgroundAntidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed for depression treatment. Animal studies have shown that antidepressants can influence gut microbiota composition and specific bacterial taxa. We aimed to investigate the association between antidepressant use and human gut microbiota composition and functional pathway. MethodsWe collected information on antidepressant use, demographic, food patterns, and clinical characteristics through questionnaires and medical records. The gut microbiota profiles of 271 depressive patients were carried out through 16S rRNA gene sequencing. Patients were categorized based on different types of antidepressant use groups for gut microbiota comparisons. MaAsLin2 was performed to evaluate microbiota composition across groups. PICRUSt2 was used to predict microbiota functional pathways. ResultsPatients taking SSRIs or SNRIs had a lower microbiota diversity. We found seven taxa abundances (Turicibacter, Barnesiella, Lachnospiraceae_ND3007_group, Romboutia, Akkermansia, Dialister, Romboutia and Fusicatenibacter) differed in patients with various types of antidepressants compared with those without antidepressant treatments (p < 0.05). Turicibacter inversely correlated with depression severity in SSRIs or SNRI users (r = −0.43, p < 0.05). Top identified pathways were related to compound fermentation and biosynthesis in microbiota function. ConclusionAntidepressant usage, especially SSRIs and SNRIs, associates with changes in gut microbiota composition and specific taxa. Given our study's preliminary cross-sectional nature, further research is warranted to comprehend the relationship between antidepressant use, treatment response, and gut microbiota, aiming to enhance therapeutic interventions in the future.

Real-World Evidence on Clinical Outcomes of Commonly Used Antidepressants in Older Adults Initiating Antidepressants for Depression: A Nationwide Cohort Study in Denmark.

The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes. This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders. The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years). This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.

Patient journey before and after a formal post-traumatic stress disorder diagnosis in adults in the United States – a retrospective claims study

Objective To describe post-traumatic stress disorder (PTSD)-related symptoms and frequent psychiatric comorbidities, treatments received, healthcare resource utilization (HRU), and healthcare costs pre- and post-PTSD diagnosis among adults in the United States. Methods Adults with PTSD who received a PTSD-related pharmacological treatment (selective serotonin reuptake inhibitor [SSRI], serotonin-norepinephrine reuptake inhibitor [SNRI], atypical antipsychotic [AA]) within 24 months of the first observed PTSD diagnosis (index date) were identified using MarketScan Commercial Database (2015–2020). Study outcomes were assessed during the 6-month pre-diagnosis and 24-month post-diagnosis periods. Subgroup analyses included patients treated or not treated with AAs post-PTSD diagnosis. Results Of the overall patients (N = 26,306; mean age at diagnosis 39.5 years; 73.3% female), 85.9% had PTSD-related symptoms and frequent psychiatric comorbidities during the 6 months pre-diagnosis. Patients treated with AAs post-PTSD diagnosis (N = 9,298) tended to have higher rates of PTSD-related symptoms and comorbidities at diagnosis than those not treated with AAs (N = 7,011). Following diagnosis, the most commonly observed first-line treatments were SSRI (67.4%), AA (23.4%), and SNRI (22.6%). The rate of PTSD-related symptoms and comorbidities, psychotherapy and pharmacological treatments received, HRU, and healthcare costs increased during the 6 months post-diagnosis relative to the 6 months pre-diagnosis and then declined over time during the 24 months post-diagnosis. Conclusions The PTSD diagnosis was associated with increased rates of symptoms and frequent psychiatric comorbidities, psychotherapy and pharmacological treatments received, HRU, and healthcare costs, pointing to increased patient monitoring. Within 6 to 12 months after the PTSD diagnosis, these outcomes tended to reduce, perhaps as patients were obtaining targeted and effective care.

Temporal trends of antidepressant utilization patterns in children and adolescents in Hong Kong: A 14-year population-based study with joinpoint regression analysis

BackgroundThere is limited research on real-world antidepressant utilization patterns in children and adolescents, particularly in non-western countries. We aimed to examine temporal trends of antidepressant prescribing practice among Chinese children and adolescents in Hong Kong over 14-year period. MethodsThis population-based study identified 9566 patients aged 5–17 years who had redeemed at least one antidepressant prescription within 2005–2018, using data from health-record database of Hong Kong public healthcare services. We calculated annual prescription rates (per 1000 persons) for any antidepressant, antidepressant drug classes, and individual antidepressants. Joinpoint-regression analyses were performed to assess temporal antidepressant prescription trends, quantified by average annual-percent-change (AAPC), with 95 % confidence-intervals (CIs). ResultsOverall antidepressant prescription rate significantly increased over time (AAPC: 7.30 [95 % CI: 6.70–7.90]), from 3.883 in 2005 to 9.916 in 2018. The use of selective-serotonin-reuptake-inhibitors (SSRIs), serotonin-norepinephrine-reuptake-inhibitors (SNRIs), and other antidepressants significantly increased over 14 years, while tricyclic-antidepressants remained stable. SSRI represented the most commonly-prescribed drug class. Fluoxetine and sertraline constituted the two most frequently-prescribed individual antidepressants, while desvenlafaxine (AAPC: 55.68 [30.74–85.39]) and bupropion (AAPC: 35.28 [23.68–47.98]) exhibited the sharpest increase in prescription rates over the study period. LimitationsMedication adherence could not be assessed and actual drug use may be overestimated. ConclusionsOur results affirm a significant rising trend of antidepressant prescriptions among Chinese children and adolescents over time. All antidepressant drug-classes, except TCA, demonstrated significantly increased use, with SSRI being the most frequently-prescribed drug class. Future investigation should clarify indications, hence off-label use, of antidepressant initiation in this vulnerable population.

Anxiety in subjects with cardiovascular disease: Current diagnostic strategies and therapeutic options. A review

Anxiety and anxiety disorders are important modifiable risk factors for cardiovascular and other common chronic non-communicable diseases and complications. Anxiety disorders significantly reduce the motivation and adherence of patients to lifestyle changes and drug therapy, significantly worsen the quality of life, and increase the risk of disability and the costs of the health care system. The issues of diagnosis and therapy of anxiety are relevant for the practice of physicians and cardiologists due to the high incidence of anxiety disorders in patients with cardiovascular diseases, a decrease in the quality of life and an increase in adverse outcomes, and also due to the insufficient awareness of the risks associated with the psycho-emotional state of patients. Therapy of anxiety disorders includes both drug and non-drug methods. The first-line drugs in treating most anxiety disorders are selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors. The risk of possible side effects of these agents in patients with cardiovascular diseases should be considered. Sedative and anti-anxiety drugs, including non-benzodiazepine tranquilizers, are more commonly used. The most studied drug from this class in therapeutic and cardiological practice is fabomotizole. The efficacy and safety of fabomotizole, including long-term use, have been studied in numerous studies in patients with cardiovascular diseases and a wide range of anxiety disorders.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

BackgroundIn treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown.MethodsIn an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery–Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures.ResultsOverall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P=0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments.ConclusionsIn patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.)