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Background: Women with menopausal transition (MT) have an elevated risk of experiencing common mental health diagnoses (CMHD: depression or anxiety). There is no recent data comparing the rate, and treatment, of CMHD between men and women., Methods: In this population-based study, incidence rates (IR) per 100 person-years-at-risk (PYAR) for men and women ≥45 years registered with an UK primary care practice between 2010 and 2021 were estimated. Incidence rate ratios (IRR) with 95 % confidence intervals (CIs) of CMHD were estimated using men as a reference. We measured first prescriptions for psychotropic medications received within 12 months after CMHD. For selective serotonin reuptake inhibitors (SSRIs) /selective norepinephrine reuptake inhibitors (SNRIs), we measured the IR of prescribing per 100 PYAR, by 10-year bands. Proportion of SSRIs/SNRIs prescribing was estimated per 100 persons., Results: Rates of anxiety and depressive disorders were 1.68 and 1.69 per 100 PYAR in women aged 45-54 years-old compared to 0.91 and 1.20 per 100 PYAR in men, with IRR of 1.84 (95 % CI 1.72-1.97) and 1.44 (1.35-1.53) respectively. SSRIs/SNRIs were the most prescribed medication; in 2021, IRs for SSRIs/SNRIs were 13.4 per 100 PYAR in both sexes. In 2021, the proportion of SSRIs/SNRIs prescribing was 50.67 per 100 women and 41.91 per 100 men., Limitations: MT is assumed based on women's age as menopause onset is rarely recorded in primary care databases., Conclusions: Women ≥45 years experienced more CMHD compared to men, especially 45-54 years-olds, which coincides with MT. The proportion of SSRIs/SNRIs prescribing was higher in women., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dana Alsugeir reports financial support was provided by Saudi Arabian Cultural Bureau. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In a population-based cohort study of menopausal women with common mental health diagnoses, SSRIs/SNRIs were associated with a 32% increased risk of osteoporotic fractures. The risk of osteoporotic fractures was particularly increased for longer periods of treatment with SSRIs/SNRIs (> 5 years) and in younger menopausal women (< 50 years old)., Purpose: To investigate the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of osteoporotic fractures (OF) in menopausal women with common mental health diagnoses (CMHD)., Methods: We conducted the study with two designs (cohort and self-controlled case series [SCCS]), using the IQVIA Medical Research Database (IMRD) UK. The source population comprised women aged ≥ 50 years and women with a record indicating menopause (< 50 years). All women had a recorded CMHD. For the cohort analysis, the risk of OFs was estimated by comparing women prescribed SSRIs/SNRIs (exposed) to those not exposed. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). For the SCCS, women acted as their own controls; periods of exposure to SSRIs/SNRIs were compared to periods of non-exposure using conditional Poisson regression to estimate incidence rate ratios (IRR) with 95% CIs., Results: We identified 292,848 women, of whom 35,222 experienced OFs within a median follow-up of 6.01 years. We found strong evidence of an association between SSRIs/SNRIs and the risk of OFs (adjusted HR = 1.32, 95% CI:1.29-1.35). Compared to periods of no exposure, SSRIs/SNRIs increased the risk of OFs during the first 30 days (IRR = 1.38, 95% CI:1.26-1.51), during the first 90 days (IRR = 1.58, 95% CI: 1.48-1.69), and the remaining exposure (IRR = 1.42, 95% CI:1.37-1.48)., Conclusions: In a population of menopausal women with CMHDs, the prescribing of SSRIs/SNRIs antidepressants was associated with a higher risk of OFs. Careful assessment of osteoporosis risk needs to be considered when treating menopausal women with SSRIs/SNRIs antidepressants., (© 2024. The Author(s).)

Importance: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are consistently reported to be discontinued by approximately half of pregnant women. Little is known about how this may be associated with postpartum psychiatric health., Objective: To investigate associations of SSRI or SNRI discontinuation in pregnant women with depression or anxiety and psychiatric health and sick leave absence after childbirth., Design, Setting, and Participants: This population-based cohort study was conducted between 2006 and 2019 using data from Swedish population-based registers. Pregnant women with a filled prescription of an SSRI or SNRI in the 90 days before pregnancy without recorded comorbid or severe psychiatric conditions were included. Analyses were performed in November 2023., Exposures: K-means for longitudinal data was used to cluster trajectories of SSRI and SNRI use during pregnancy, resulting in 2 trajectory groups based on the number of days covered, defined as continued and discontinued use groups., Main Outcomes and Measures: The primary outcome was psychiatric-related hospitalizations by 90 days after childbirth. Secondary outcomes included psychiatric-related outpatient visits, self-harm and suicide, and any-cause mortality by 90 days after childbirth and all outcomes plus sick leave absence by 1.5 years after childbirth., Results: Among 27 773 pregnant women (17 241 aged ≥30 years [62.1%] at childbirth), 13 184 women (47.5%) had discontinued SSRI or SNRI use and 14 589 individuals (52.5%) had continued use. Individuals in the discontinued compared with continued use group were younger (5588 women [42.4%] vs 4944 women [33.9%] aged <30 years), less educated (4281 women [32.5%] vs 5821 women [39.9%] who completed postsecondary education or above), and more likely to have smoked in early pregnancy (1445 individuals [11.0%] vs 1180 individuals [8.1%]), been born in a non-Nordic country (1641 individuals [12.4%] vs 975 individuals [6.7%]), and used anxiolytics (1301 individuals [9.9%] vs 1119 individuals [7.7%]) and hypnotics and sedatives (1609 individuals [12.2%] vs 1510 individuals [10.4%]). Psychiatric-related hospitalizations occurred in 49 individuals (0.4%) in the discontinued vs 59 individuals (0.5%) in the continued use group in the 90 days after childbirth, with an adjusted hazard ratio (aHR) of 1.28 (95% CI, 0.85-1.91), while at 1.5 years after childbirth, the aHR was 0.81 (95% CI, 0.66-1.00). Lower hazard rates for psychiatric-related outpatient visits in the discontinued vs continued use group at 90 days (aHR, 0.59; 95% CI, 0.53-0.66) and 1.5 years (aHR, 0.60; 95% CI, 0.57-0.64) after childbirth were found. No difference in sick leave absence was found; however, individuals who discontinued had fewer days of sick leave by 1.5 years after childbirth than those who continued (mean [SD], 44.6 [70.6] days vs 53.1 [82.3] days)., Conclusions and Relevance: In this study, approximately half of pregnant women discontinued SSRIs or SNRIs, and discontinuation during pregnancy was not associated with adverse psychiatric-related outcomes, including hospitalizations, outpatient visits, suicidal behavior, or sick leave absence in the 90 days or 1.5 years after childbirth.

Available data shows associations between chronotype, circadian rhythms, sleep quality and fibromyalgia (FM) presentation. However, no studies have explored links between the chronobiological variables and effectiveness of pharmacotherapy. We aimed to assess the chronotypes, circadian rhythms, sleep-wake cycle and sleep quality in FM and their links to treatment response to serotonin and noradrenalin reuptake inhibitors (SNRI). 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-]) and 30 healthy controls participated. Subjects were assessed by physician and with questionnaire tools: Composite Scale of Morningness, Biological Rhythms Interview of Assessment in Neuropsychiatry, Sleep-Wake Pattern Assessment Questionnaire, Pittsburgh Sleep Quality Index and Fibromyalgia Impact Questionnaire. ANOVA analysis and simple logistic regressions were used to examine the relationships between chronological variables and response to SNRI. FM T[-] vs. FM T[+] presented lower morning affect (11.50[95%CI 9.96-13.04] vs. 14.00[95%CI 12.42-15.57];p=0.04), anytime wakeability (2.27[95%CI 1.4-3.13] vs. 4.03[95%CI 2.99-5.08];p=0.013) worse overall (11.40[95%CI 9.92-12.88] vs. 7.97[95%CI 6.75-9.19];p=0.002) and subjective (1.70[95%CI 1.30-2.01] vs. 1.17[95%CI 0.94-1.39];p=0.008) sleep quality, higher circadian rhythm disruptions (55.47[95%CI 52.32-58.62] vs. 44.97[95%CI 41.31-48.62];p<0.001), sleep disturbances (1.63[95%CI 1.38-1.68] vs. 1.30[95%CI 1.1-1.5];p=0.04), sleeping-medication use (1.80[95%CI 1.27-2.32] vs. 0.70[95%CI 0.28-1.12];p=0.003). Levels of morningness (AIC=82.91,OR=0.93,p=0.05), morning affect (AIC=81.901,OR=0.86,p=0.03) diurnal dysrhythmia (AIC=69.566,OR=1.14,p<0.001), anytime wakeability (AIC=80.307,OR=0.76,p=0.015), overall sleep quality (AIC=74.665, OR=1.31,p=0.002) subjective sleep quality (AIC=79.353, OR=2.832,p=0.01) and disturbances (AIC=82.669,OR=2.54,p=0.043), sleep medication use (AIC=77.017, OR=1.9,p=0.003) and daytime disfunction (AIC=82.908, OR=1.971,p=0.049) were predictors of non-response to SNRI. Chronobiological variables vary between FM T[+] and FM T[-] and are predictors of non-response to SNRI., (© 2024. The Author(s).)

Background: The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI)., Methods: 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance)., Results: MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia., Conclusion: IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI., (© 2024. The Author(s).)

For more than 20 years, the mainstay of pharmacologic treatment for depression and anxiety disorders has been serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors. There are newer medications, many with novel mechanisms of action, that have come to market; however, first-line treatments remain the same. There are now more robust data on the use of various augmentation agents in the treatment of major depressive disorder providing better recommendations for use by the primary care provider. Data to support the use of psychedelic-assisted psychotherapy in the treatment of mood and anxiety disorders are not robust enough to recommend generalized use at this time., Competing Interests: Disclosure Neither Dr J. Markman nor Dr H. Combs have any financial conflicts of interest or funding sources to declare., (Published by Elsevier Inc.)

Background : Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. Objective : To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Methods : Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder). Treatment response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in symptom severity was evaluated as a function of time, and post hoc analyses were conducted to determine the sensitivity of these results across sample heterogeneity and alternative functional forms. Results : Data were included from 11 trials of youth (SSRI, κ = 7; SNRI, κ = 4) and 71 studies of adults (SSRI, κ = 46; SNRI, κ = 25). In total, 1067 youth participated in SSRI trials and 1024 in SNRI trials. In total, 10,826 adults participated in SSRI trials (placebo, n = 5367; SSRI n = 5,459) and 6232 in SNRI trials (placebo, n = 3,128; SNRI n = 3,094). A logarithmic model best described the response. Placebo response was similar in youth and adults (mean difference = -1.98 ± 6.21, 95% credible interval [CrI]: -10.2 to 14.2, p = 0.750), and statistically significant improvement from baseline emerged by week 2 in both adults (mean difference: -18.34 + 1.017, 95% CrI: -20.3 to 16.3, p < 0.001) and youth (mean difference: -23.74 + 3.736, 95% CrI: -31.1 to -16.4, p < 0.001). SSRIs produced similar improvements for youth and adults ( p = 0.129), but SNRIs produced slower improvement in youth than adults ( p = 0.018). Conclusions : Antidepressant-related improvement occurs early in youth and adults with anxiety disorders. SSRI response is similar in adults and youth; however, SNRIs produce greater responses in adults than youth, potentially representing a developmental effect.

Background: There have only been two efficacy trials reporting a head-to-head comparison of medications and psychotherapy for PTSD, and neither was conducted in primary care. Therefore, this protocol paper describes a pragmatic trial that compares outcomes of primary care patients randomized to initially receive a brief trauma-focused psychotherapy or a choice of three antidepressants. In addition, because there are few trials examining the effectiveness of subsequent treatments for patients not responding to the initial treatment, this pragmatic trial also compares the outcomes of those switching or augmenting treatments., Method: Patients screening positive for PTSD (n = 700) were recruited from the primary care clinics of 7 Federally Qualified Health Centers (FQHC) and 8 Department of Veterans Affairs (VA) Medical Centers and randomized in the ratio 1:1:2 to one of three treatment sequences: 1) selective serotonin reuptake inhibitor (SSRI) followed by augmentation with Written Exposure Therapy (WET), 2) SSRI followed by a switch to serotonin-norepinephrine reuptake inhibitor (SNRI), or 3) WET followed by a switch to SSRI. Participants complete surveys at baseline, 4 months, and 8 months. The primary outcome is PTSD symptom severity as measured by the PTSD Checklist (PCL-5)., Results: Average PCL-5 scores (M = 52.8, SD = 11.1) indicated considerable severity. The most common bothersome traumatic event for VA enrollees was combat (47.8%), and for FQHC enrollees was other (28.2%), followed by sexual assault (23.4%), and child abuse (19.8%). Only 22.4% were taking an antidepressant at baseline., Conclusion: Results will help healthcare systems and clinicians make decisions about which treatments to offer to patients., Competing Interests: Declaration of competing interest The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work., (Published by Elsevier Inc.)

Anxiety disorders are the most common psychiatric illness and include disorders such as generalized anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (SAD). Psychotherapy and pharmacotherapy are both effective treatments for anxiety disorders, with efficacy between 60% and 85%. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are first-line pharmacologic treatment for GAD, PD, and SAD. Recommendations for treating pediatric and geriatric populations vary slightly, but first-line treatments remain the same. Recent advancements in the treatment of anxiety disorders are limited although research has discovered novel pathways, which may lead to additional treatment options in the future., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This was a double-blind, randomized, phase 2 study of adults (18-64 years) with DSM-5 diagnosis of major depressive disorder (MDD), with moderate-to-severe episode severity (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥25) despite an adequate course with ongoing antidepressant for ≥6 weeks to ≤12 months. Following a double-blind placebo lead-in period (up to 3 weeks), participants were randomized to receive once daily aticaprant 10 mg or continue placebo, added to their ongoing treatment, for 6 weeks. Of 184 participants enrolled, 169 were included in safety analyses (aticaprant n = 85, placebo n = 84) and 166 in full intent-to-treat (fITT) efficacy analyses; 121 placebo lead-in non-responders (<30% reduction in MADRS total score) in fITT were included in enriched ITT (eITT) analyses. Improvement (least squares mean difference [upper limit 1-sided 80% CI] versus placebo) in MADRS total score at week 6 for aticaprant was significant versus placebo (eITT: -2.1 [-1.09], 1-sided p = 0.044; effect size (ES) 0.23; fITT -3.1 [2.21], 1-sided p = 0.002; ES 0.36). The between-group difference was larger among participants with Snaith-Hamilton Pleasure Scale (SHAPS) score greater/equal to versus less than baseline median SHAPS. The most common treatment-emergent adverse events reported for aticaprant (versus placebo) were headache (11.8% versus 7.1%), diarrhea (8.2% versus 2.4%), nasopharyngitis (5.9% versus 2.4%), and pruritus (5.9% versus 0%). One participant (1.2%) in each arm discontinued treatment due to an adverse event. In this study of participants with MDD and inadequate response to SSRI/SNRI, adjunctive treatment with aticaprant significantly reduced depressive symptoms versus placebo, without resulting in significant safety signals, supporting further investigation in larger trials., (© 2024. The Author(s).)

Psychopharmacological treatment may be an independent risk factor for increased length of stay and readmission after hip and knee replacement. Thus, temporary perioperative discontinuation may be beneficial. However, little is known regarding the treatments, and not all are feasible to discontinue. Therefore, the aim of this study was to describe the treatments in terms of type, dose, duration, indication and initiating physician to assess the feasibility of temporary perioperative discontinuation. We included 482 patients planned for hip or knee replacement in psychopharmacological treatment for psychiatric disorders from 2021 to 2023 at five orthopaedic departments in Denmark. Most patients were treated with antidepressants (89%); most frequently, either selective serotonin reuptake inhibitors (SSRIs; 48%) or serotonin-norepinephrine reuptake inhibitors (SNRIs; 21%). The majority received monotherapy (70%); most frequently, an SSRI (36%) or an SNRI (12%). Most antidepressants were initiated by general practitioners (71%), and the treatments had lasted for more than a year (87%). The doses of SSRIs/SNRIs were moderate, and the most frequent indication for antidepressants was depression (77%). These results imply that temporary perioperative SSRI/SNRI discontinuation may be feasible in hip and knee replacement patients and support a future randomized controlled trial investigating the potential benefits of temporary discontinuation., (© 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Efforts to reduce the heterogeneity of major depressive disorder (MDD) by identifying subtypes have not yet facilitated treatment personalization or investigation of biology, so novel approaches merit consideration., Methods: We utilized electronic health records drawn from 2 academic medical centers and affiliated health systems in Massachusetts to identify data-driven subtypes of MDD, characterizing sociodemographic features, comorbid diagnoses, and treatment patterns. We applied Latent Dirichlet Allocation (LDA) to summarize diagnostic codes followed by agglomerative clustering to define patient subgroups., Results: Among 136,371 patients (95,034 women [70 %]; 41,337 men [30 %]; mean [SD] age, 47.0 [14.0] years), the 15 putative MDD subtypes were characterized by comorbidities and distinct patterns in medication use. There was substantial variation in rates of selective serotonin reuptake inhibitor (SSRI) use (from a low of 62 % to a high of 78 %) and selective norepinephrine reuptake inhibitor (SNRI) use (from 4 % to 21 %)., Limitations: Electronic health records lack reliable symptom-level data, so we cannot examine the extent to which subtypes might differ in clinical presentation or symptom dimensions., Conclusion: These data-driven subtypes, drawing on representative clinical cohorts, merit further investigation for their utility in identifying more homogeneous patient populations for basic as well as clinical investigation., Competing Interests: Declaration of competing interest Dr. Perlis has received consulting fees from Burrage Capital, Genomind, RIDVentures, and Takeda. He holds equity in Outermost Therapeutics and PsyTherapeutics. The other authors report no competing interests. Dr. Finale Doshi-Velez has no competing interested to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Irritable bowel syndrome (IBS) is responsive to treatments using central neuromodulators. Central neuromodulators work by enhancing the synaptic transmission of 5-hydroxytryptamine, noradrenalin, and dopamine, achieving a slower regulation or desensitization of their postsynaptic receptors. Central neuromodulators act on receptors along the brain-gut axis, so they are useful in treating psychiatric comorbidities, modifying gut motility, improving central downregulation of visceral signals, and enhancing neurogenesis in patients with IBS. Choosing a central neuromodulator for treating IBS should be according to the pharmacological properties and predominant symptoms. The first-line treatment for pain management in IBS is using tricyclic antidepressants. An alternative for pain management is the serotonin and noradrenaline reuptake inhibitors. Selective serotonin reuptake inhibitors are useful when symptoms of anxiety and hypervigilance are dominant but are not helpful for treating abdominal pain. The predominant bowel habit is helpful when choosing a neuromodulator to treat IBS; selective serotonin reuptake inhibitors help constipation, not pain, but may cause diarrhea; tricyclic antidepressants help diarrhea but may cause constipation. A clinical response may occur in 6-8 weeks, but long-term treatment (usually 6-12 months) is required after the initial response to prevent relapse. Augmentation therapy may be beneficial when the therapeutic effect of the first agent is incomplete or associated with side effects. It is recommended to reduce the dose of the first agent and add a second complementary treatment. This may include an atypical antipsychotic or brain-gut behavioral treatment. When tapering central neuromodulators, the dose should be reduced slowly over 4 weeks but may take longer when discontinuation effects occur., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction / Objectives: Stressful events like earthquakes might worsen the symptoms of fibromyalgia, although the influence of medications on these consequences is yet uncertain. The objective of this study was to examine the influence of an earthquake on the symptoms of fibromyalgia and evaluate the impacts of medications used to treat fibromyalgia on the clinical picture., Method: Ninety-five fibromyalgia patients were enrolled in a comparative study and divided into two groups: medication and non-medication. Three subcategories of medication groups were established: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoid drugs (GDs). Before and after the earthquake, clinical evaluations were conducted using the Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Rating Scale (JSS). Statistical analyses were conducted to compare the scores before and after the earthquake and evaluate the differences between the groups., Results: Statistically significant increases were observed in FIQ, HADS-anxiety, HADS-depression, and JSS scores in the medication and non-medication groups before and after the earthquake comparisons (p < 0.05). Non-medication group reported significantly higher post-earthquake changes in FIQ, HADS-anxiety, HADS-depression, and JSS compared to the medication group (p < 0.05). While HADS-anxiety, HADS-depression, and JSS changes after the earthquake differed according to the drug subgroups (p < 0.05), no statistically significant difference was observed in FIQ values (p > 0.05). The highest scores were detected in the GD subgroup., Conclusions: This study highlights the substantial impact of earthquakes on fibromyalgia patients. Medication use may assist in reducing the detrimental effects of stresses like earthquakes on fibromyalgia symptomatology. Future research with larger sample sizes and more extended follow-up periods is needed to explain these findings and optimize treatment regimens for fibromyalgia patients experiencing significant stressors., (© 2024. The Author(s).)

Background: How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown., Methods: We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models., Results: Across 122 trials (N=15,760), SSRIs, SNRIs, and benzodiazepines produced significant improvement in anxiety compared to placebo. Benzodiazepines produced faster improvement by the first week of treatment ( p  < 0.001). By week 8, the response for benzodiazepines and SSRIs ( p  = 0.103) and SNRIs ( p  = 0.911) did not differ nor did SSRIs and SNRIs differ ( p  = 0.057), although for patients with generalized anxiety disorder (GAD), the benzodiazepines produced greater improvement than SNRIs at week 8 (difference - 12.42, CrI: -25.05 to -0.78, p  = 0.037). Medication response was similar across anxiety disorders except for benzodiazepines, which produced greater improvement over the first 4 weeks compared to SSRIs and SNRIs in panic disorder. For SSRIs and SNRIs, women improved more than men, and for benzodiazepines, older patients improved more compared to younger patients. Finally, placebo response plateaued by week 4 of treatment, and, at week 8, social anxiety disorder trials had lower placebo response compared to other anxiety disorders., Conclusions: Benzodiazepines show early improvement compared to SSRIs and SNRIs. However, by week 8, all treatments yield similar results. Patient characteristics influence the improvement trajectory and magnitude, suggesting potential for personalized medication selection.

Background: Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes., Methods: Population-based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020. The index date was the date of the first such prescription, and the exposure of interest was serum electrolyte measurement during the subsequent 7 days. The primary outcome was any emergency department or hospital admission with hyponatremia within 8-60 days of antidepressant initiation. Poisson regression models compared individuals who had versus did not have their serum electrolytes tested in the week following SSRI/SNRI initiation, weighting by propensity score-based overlap weights., Results: Among the 420,085 patients aged ≥66 years initiating treatment with an SSRI/SNRI, 26,808 (6.4%) had serum electrolytes measured in the subsequent 7 days and 6109 (1.5%) subsequently presented to hospital with hyponatremia. The time from drug initiation to hospitalization varied (median 29, interquartile range [IQR] 17-44 days), and the median sodium concentration measured in the community (136, IQR 133-138 mmol/L) was marginally higher than those at the time of hospitalization (132, IQR 130-134 mmol/L). Patients who underwent electrolyte testing in the week following SSRI/SNRI treatment were more likely to attend an emergency department (ED) or hospital with hyponatremia within 8-60 days relative to those who did not (relative risk = 2.31, 95% confidence interval: 2.16-2.46)., Conclusions: Testing serum electrolytes in the week after starting an SSRI/SNRI is not associated with a reduced risk of a hospital visit with hyponatremia. These findings do not support current guidelines recommending routine electrolyte monitoring., (© 2024 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Temporomandibular joint (TMJ) arthrocentesis is one of the most commonly used non-invasive surgical interventions in the treatment of refractory pain and dysfunction associated with internal derangement. Several adjunctive therapies have been used in combination with arthrocentesis in an attempt to increase its efficacy and long-term maintenance. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor which is used in different chronic pain conditions. This study aimed to assess the efficacy of duloxetine in combination with arthrocentesis compared with arthrocentesis alone. Twenty-eight patients with chronic TMJ pain were included and randomly allocated into 2 groups (control and study groups). The control group included patients who underwent TMJ arthrocentesis only, and the study group included patients who underwent arthrocentesis followed by giving duloxetine (30 mg) orally twice daily for 3 months. Pain, maximum mouth opening, and level of anxiety and depression were assessed preoperatively and followed at regular intervals of 1 week, 1 month, 3 months, and 6 months postoperatively. Pain was significantly reduced in both groups at all postoperative intervals and was significantly lower in the study group than the control group at 6 months. Maximum mouth opening increased significantly in both groups, but the difference between them was not significant. Level of anxiety and depression was significantly decreased in both groups, with no statistically significant difference between them. The results of this study indicate that duloxetine in combination with arthrocentesis may provide effective and long-term pain control; however, its use is associated with a higher risk of adverse events., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects., Case Presentation: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge., Discussion and Conclusions: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation., (© 2024. The Author(s).)

Background: While serotonin norepinephrine reuptake inhibitors (SNRIs) offer promise in managing Post-surgical neuropathic pain (PSNP), uncertainties remain. This study aims to evaluate the effectiveness and adverse events of SNRIs in managing PSNP., Methods: Systematic searches of PubMed, Embase, and Cochrane databases up to January 1st 2023 identified randomized controlled trials (RCTs) comparing SNRIs to placebo for PSNP. The primary outcome measures were pain at rest and adverse events post-surgery. Subgroup analyses were conducted based on surgical type and specific SNRIs., Results: A total of 19 RCTs, encompassing 1440 participants (719 in the SNRI group vs 721 in the placebo group), met the inclusion criteria and were included. The pooled results demonstrated that pain scores were significantly lower in patients treated with SNRIs at 2 hours (MD:-0.26; 95%CI: -0.47 to -0.04; p=0.02), 6 hours (MD:-0.68; 95%CI: -1.01 to -0.34; p<0.0001), 24 hours (MD:-0.54; 95%CI: -0.99 to -0.09; p=0.02), and 48 hours (MD:-0.66; 95%CI: -1.23 to -0.10; p=0.02) post-surgery. In terms of adverse events, dizziness (OR:2.53; 95%CI: 1.34-4.78; p=0.004) and dry mouth (OR:2.21; 95%CI: 1.25-3.92; p=0.007) were significantly higher in the SNRIs group. Subgroup analysis showed that SNRI was found to significantly lower the 24-hour pain score after spinal surgery (MD:-0.45; 95%CI: -0.84 to -0.05; p=0.03). Duloxetine (MD:-0.63; 95%CI: -1.15 to -0.11; p=0.02) had a significant effect in lowering the 24-hour pain score at rest compared to placebo, whereas venlafaxine did not., Conclusions: SNRIs yielded considerable pain score reductions across multiple post-surgical intervals, although accompanied by an increased incidence of dizziness and dry mouth., Competing Interests: Declaration of Competing Interest The authors declared that there is no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The widespread adoption of selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacological treatments in the management of clinical depression transformed the landscape of drug therapy for this condition. SSRIs are safer and better tolerated than the tricyclic antidepressants (TCAs) that they replaced. However, they have limitations that may have placed a ceiling on the expectations of first-line pharmacological treatment. Notable problems with SSRIs include induction of anxiety on treatment initiation, delayed onset of significant therapeutic effect, sexual dysfunction, sleep disturbance and overall modest efficacy. The latter is linked with an inability of SSRIs to effectively treat syndromes of anhedonia and cognitive impairment. Combined serotonin and noradrenaline reuptake inhibitors (SNRIs), such as venlafaxine, have produced some limited improvements over SSRIs in efficacy, at the cost of a greater side-effect burden. Attempts to supplement serotonin reuptake activity with actions at serotonin receptor sub-types have not yet yielded substantial benefits; however, vortioxetine may provide more utility in the management of cognitive impairment. Future advances might come from the development of SNRIs, which more closely mimic the actions of effective TCAs. There may also be possible benefits to be derived from combining SSRIs with 5-HT 4 receptor agonists and 5-HT 7 receptor antagonists., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: Chronic 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., Methods: This 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., Results: For 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., Conclusion: While 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., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines., Objectives: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis., Search Methods: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022., Selection Criteria: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo., Data Collection and Analysis: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses., Main Results: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low., Authors' Conclusions: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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.

Background: In 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., Methods: In 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., Results: Overall, 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., Conclusions: In 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.)., (Copyright © 2023 Massachusetts Medical Society.)

Objectives: Stress urinary incontinence (SUI) is defined as urinary incontinence that occurs with coughing, sneezing, and physical exercise. It is frequently observed in women after middle age and has a negative impact on their sexual function. Duloxetine as one of the Serotonin-noradrenaline reuptake inhibitors (SNRIs) is commonly used in the non-surgical treatment of SUI. The aim of our study is to investigate the effect of duloxetine, which is used in the treatment of SUI, on sexual functions in female patients., Methods: The study included 40 sexually active patients who received duloxetine 40 mg twice a day for the treatment of SUI. All patients had female sexual function index (FSFI), Beck's depression inventory (BDI), and incontinence quality of life score (I-QOL) applied before and 2 months after starting duloxetine treatment., Results: FSFI total score significantly increased from 19.9 to 25.7 (p < 0.001). In addition, significant improvement was observed in all sub-parameters of FSFI, including arousal, lubrication, orgasm, satisfaction, and pain/discomfort (p < 0.001, for each FSFI subtotal score). BDI significantly decreased from 4.5 to 1.5 (p < 0.001). I-QOL score significantly increased from 57.6 to 92.7 after the duloxetine treatment., Conclusions: Although SNRIs carry a high risk of sexual dysfunction, duloxetine may have an indirect positive effect on female sexual activity, both through its stress incontinence treatment and its antidepressant effect. In our study, Duloxetine, one of the treatment options for stress urinary incontinence and an SNRI, has a positive effect on stress urinary incontinence, mental health, and sexual activity in patients with SUI., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more hospitalizations are all factors that are related to dysthymia. Given the significant prevalence of dysthymia (including persistent depressive disorder) worldwide, its comorbidity with several mental disorders, and the detrimental effects of these comorbidities, it is important to conduct a systematic review to compare the effects of pharmacological acute and maintenance treatments for dysthymia with placebo and standard care in the last 10 years, based on the publication of DSM5., Areas Covered: This systematic review was performed according to PRISMA guidelines. Databases, including PubMed and Cochrane Central Register of Controlled Trials, were searched to assess the effects of pharmacological acute and maintenance treatments for dysthymia in comparison with placebo and treatment as usual., Expert Opinion: Our review shows that SSRIs and SNRIs present efficacy for dysthymia treatment, and L-Acetylcarnitine should be investigated further for this condition in elderly patients. The comparison of antidepressant medication versus placebo showed coherent results based on three studies favoring pharmacotherapy as an effective treatment for participants with dysthymia. However, the scarcity of research on continuation and maintenance therapy in people with dysthymia highlights the need for more primary research.

Introduction: Fibromyalgia (FM) is often comorbid with anxiety and depression. Serotonin and noradrenaline reuptake inhibitors (SNRIs) are used in the treatment of FM, depression, and anxiety, but they are ineffective in a substantial number of patients. Recently, it has been reported that FM is associated with impaired glucose metabolism., Objectives: The aim of the study was to explore the associations between insulin resistance, psychiatric comorbidities, and treatment response to SNRIs in patients with FM., Patients and Methods: A total of 59 patients with FM and 30 healthy controls (HCs) were recruited. The study patients were classified as treatment‑nonresponsive if the SNRI treatment resulted in a reduction in reported pain by less than 30%. All participants were examined by a physician and completed self‑report questionnaires. Blood samples were drawn to assess fasting glucose and insulin levels and to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA‑IR) values. Multivariable logistic regression models were constructed to analyze the associations between insulin resistance, psychiatric comorbidies, and the lack of response to treatment with SNRIs., Results: The SNRI nonresponders (FM [T-]) had higher body mass index (BMI), fasting insulin level, and HOMA‑IR values than the responders (FM [T+]) and HCs. The FM [T+] patients did not significantly differ from HCs in terms of BMI, levels of fasting glucose and fasting insulin, and HOMA‑IR values. Depression, anxiety, and personality disorders were significantly more prevalent in the FM [T-] than in the FM [T+] group. Insulin resistance, depression, anxiety, and personality disorders were identified as the predictors of nonresponse to SNRI treatment. The effect of BMI on the lack of response to SNRIs was fully mediated by insulin resistance., Conclusions: Increased values of certain clinical and metabolic parameters (BMI, fasting glucose, fasting insulin, HOMA‑IR) as well as the presence of psychiatric comorbidities could affect the response to treatment with SNRIs in the patients with FM.

Background: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the most frequently prescribed antidepressants (ADs) for major depressive disorder (MDD), with an increasing trend in the last decade. Given the relative dearth of information regarding rationales for their preferred use as first-line ADs in the broad clinical routine, the present study systematically investigated real-world characteristics of MDD patients prescribed either SNRIs or other AD substances across different countries and treatment settings., Methods: In the present secondary analyses based on a large European, multi-site, naturalistic and cross-sectional investigation with a retrospective assessment of treatment outcome, we firstly defined the proportion of MDD patients receiving SNRIs as first-line AD psychopharmacotherapy and secondly compared their sociodemographic and clinical characteristics to those patients prescribed alternative first-line ADs during their current major depressive episode (MDE)., Results: Within the total sample of 1410 MDD patients, 336 (23.8 %) received first-line SNRIs. Compared to other ADs, SNRIs were significantly associated with inpatient care, suicidality and treatment resistance during the current MDE, and a longer lifetime duration of psychiatric hospitalizations. Moreover, greater severity of depressive symptoms at study entry, higher daily doses of the administered ADs, as well as more frequent prescriptions of psychopharmacotherapeutic add-on strategies in general and antipsychotic augmentation in particular, were significantly related to first-line SNRIs., Conclusions: Considering the limitations of a cross-sectional and retrospective study design, our data point towards a preferred use of first-line SNRIs in a generally more severely ill MDD patients, although they did not lead to superior treatment outcomes compared to alternative ADs., Competing Interests: Conflict of interest Within the last three years, Dr. Bartova has received travel grants and consultant/speaker honoraria from Alpine Market Research, Angelini, Biogen, Diagnosia, Dialectica, Janssen, Lundbeck, Market Access Transformation, Medizin Medien Austria, Novartis, Schwabe and Universimed. Dr. Fugger has received consultant/speaker honoraria from Janssen and Angelini. Dr. Dold has received travel grants and consultant/speaker honoraria from Medizin Medien Austria, Janssen and Universimed. Dr. Rujescu has received grant/research support from Janssen and Lundbeck; he has served as a consultant or on advisory boards for Janssen and Rovi and he has served on speakers bureaus of Janssen and Pharmagenetix. Dr. Souery has received grant/research support from GlaxoSmithKline and Lundbeck; and he has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, and Lundbeck. Dr. Mendlewicz is a member of the board of the Lundbeck International Neuroscience Foundation and of the advisory board of Servier. Dr. Zohar has received grant/research support from Lundbeck, Servier, and Pfizer; he has served as a consultant or on the advisory boards for Servier, Pfizer, Solvay, and Actelion; and he has served on speakers' bureaus for Lundbeck, GlaxoSmithKline, Jazz, and Solvay. Dr. Montgomery has served as a consultant or on advisory boards for Lundbeck. Dr. Fabbri has served as speaker for Janssen. Dr. Serretti has served as a consultant or speaker for Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier and Taliaz. Dr. Kasper has received grant/research support from Lundbeck; he has served as a consultant or on advisory boards for Angelini, Biogen, Esai, Janssen, IQVIA, Lundbeck, Mylan, Recordati, Sage and Schwabe; and he has served on speakers bureaus for Abbott, Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Lundbeck, Recordati, Sage, Sanofi, Schwabe, Servier, Sun Pharma and Vifor., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The evidence base for psychopharmacologic interventions in children and adolescents with anxiety disorders has significantly increased, and our understanding of the relative efficacy and tolerability of interventions has expanded contemporaneously. Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for pediatric anxiety due to their robust efficacy although other agents may have efficacy. This review summarizes the data concerning the use of SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, atypical anxiolytics (eg, 5HT 1A agonists, alpha agonists), and benzodiazepines in pediatric anxiety disorder cases (ie, generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, and panic disorder). The extant data suggest that SSRIs and SNRIs are effective and well tolerated. SSRIs as monotherapy and SSRIs + cognitive behavioral therapy reduce symptoms in youth with anxiety disorders. However, randomized controlled trials do not suggest efficacy for benzodiazepines or the 5HT 1A agonist, buspirone, in pediatric anxiety disorder cases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Due to individual differences and lack of objective biomarkers, only 30-40% patients with major depressive disorder (MDD) achieve remission after initial antidepressant medication (ADM). We aimed to employ radiomics analysis after ComBat harmonization to predict early improvement to ADM in adolescents with MDD by using brain multiscale structural MRI (sMRI) and identify the radiomics features with high prediction power for selection of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)., Methods: 121 MDD patients were recruited for brain sMRI, including three-dimensional T1 weighted imaging (3D-T 1 WI)and diffusion tensor imaging (DTI). After receiving SSRIs or SNRIs for 2 weeks, the subjects were divided into ADM improvers (SSRIs improvers and SNRIs improvers) and non-improvers according to reduction rate of the Hamilton Depression Rating Scale, 17 item (HAM-D 17 ) score. Then, sMRI data were preprocessed, and conventional imaging indicators and radiomics features of gray matter (GM) based on surface-based morphology (SBM) and voxel-based morphology (VBM) and diffusion properties of white matter (WM) were extracted and harmonized with ComBat harmonization. Two-level reduction strategy with analysis of variance (ANOVA) and recursive feature elimination (RFE) was utilized sequentially to decrease high-dimensional features. Support vector machine with radial basis function kernel (RBF-SVM) was used to integrate multiscale sMRI features to construct models for early improvement prediction. Area under the curve (AUC), accuracy, sensitivity, and specificity based on the leave-one-out cross-validation (LOO-CV) and receiver operating characteristic (ROC) curve analysis were calculated to evaluate the model performance. Permutation tests were used for assessing the generalization rate., Results: After 2-week ADM, 121 patients were divided into 67 ADM improvers (31 SSRIs improvers and 36 SNRIs improvers) and 54 ADM non-improvers. After two-level dimensionality reduction, 8 conventional indicators (2 VBM-based features and 6 diffusion features) and 49 radiomics features (16 VBM-based features and 33 diffusion features) were selected. The overall accuracy of RBF-SVM models based on conventional indicators and radiomics features was 74.80% and 88.19%. The radiomics model achieved the AUC, sensitivity, specificity, and accuracy of 0.889, 91.2%, 80.1% and 85.1%, 0.954, 89.2%, 87.4% and 88.5%, 0.942, 91.9%, 82.5% and 86.8% for predicting ADM improvers, SSRIs improvers and SNRIs improvers, respectively. P value of permutation tests were less than 0.001. The radiomics features predicting ADM improver were mainly located in the hippocampus, medial orbitofrontal gyrus, anterior cingulate gyrus, cerebellum (lobule vii-b), body of corpus callosum, etc. The radiomics features predicting SSRIs improver were primarily distributed in hippocampus, amygdala, inferior temporal gyrus, thalamus, cerebellum (lobule vi), fornix, cerebellar peduncle, etc. The radiomics features predicting SNRIs improver were primarily located in the medial orbitofrontal cortex, anterior cingulate gyrus, ventral striatum, corpus callosum, etc. CONCLUSIONS: These findings suggest the radiomics analysis based on brain multiscale sMRI after ComBat harmonization could effectively predict the early improvement of ADM in adolescent MDD patients with a high accuracy, which was superior to the model based on the conventional indicators. The radiomics features with high prediction power may help for the individual selection of SSRIs and SNRIs., (© 2023. The Author(s).)

Background: Major depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, closely associated with bipolar disorder (BD). However, there is still a lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about how to identify AFD, what is the appropriate individualized treatment for AFD, and what are the predictive biomarkers of conversion to BD., Methods: The Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective, open-label study consisting of a 12-week randomized controlled trial (RCT) and a continued follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. Firstly, multivariate informatics analyses are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD, and patients with HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including "single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)", "SSRI/SNRI combined with mood stabilizer," "SSRI/SNRI combined with quetiapine (≥ 150 mg/day)," or "treatment as usual (TAU)" and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up until 4 years or switching to BD, to explore the risk factors of conversion from atypical depression to BD and eventually build the risk warning model of conversion to BD., Discussion: The first enrolment was in August 2019. The iDoT-AFD study explores the clinical and biological markers for the diagnosis, treatment, and prognosis of AFD and further provides evidence for clinical guidelines of AFD., Trial Registration: ClinicalTrials.gov NCT04209166. Registered on December 19, 2019., (© 2023. The Author(s).)

Previous studies have suggested that the loudness dependence of auditory evoked potential (LDAEP) is associated with the effectiveness of antidepressant treatment in patients with major depressive disorders (MDD). Furthermore, both LDAEP and the cerebral serotonin 4 receptor (5-HT 4 R) density is inversely related to brain serotonin levels. We included 84 patients with MDD and 22 healthy controls to examined the association between LDAEP and treatment response and its association with cerebral 5-HT 4 R density. Participants underwent both EEG and 5-HT 4 R neuroimaging with [ 11 C]SB207145 PET. Thirty-nine patients with MDD were re-examined after 8 weeks of treatment with selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitor (SSRI/SNRI). We found that the cortical source of LDAEP was higher in untreated patients with MDD compared to healthy controls (p=0.03). Prior to SSRI/SNRI treatment, subsequent treatment responders had a negative association between LDAEP and depressive symptoms and a positive association between scalp LDAEP and symptom improvement at week 8. This was not found in source LDAEP. In healthy controls, we found a positive correlation between both scalp and source LDAEP and cerebral 5-HT 4 R binding but that was not observed in patients with MDD. We did not see any changes in scalp and source LDAEP in response to SSRI/SNRI treatment. These results support a theoretical framework where both LDAEP and cerebral 5-HT 4 R are indices of cerebral 5-HT levels in healthy individuals while this association seems to be disrupted in MDD. The combination of the two biomarkers may be useful for stratifying patients with MDD. Clinical Trials Registration:https://clinicaltrials.gov/ct2/show/NCT02869035?draw=1Registration number: NCT0286903., Competing Interests: Declaration of Competing Interest All authors declare no potential conflicts of interest, (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)

Introduction: Anxiety disorders are the most prevalent psychiatric disorders among youth. Among the various anxiety disorders, generalized anxiety disorder is particularly prevalent. Youth with GAD appear at elevated risk of developing other anxiety disorders, mood disorder, and substance use disorders. Functional outcomes of youth with GAD can be improved through early recognition and treatment, thus promoting better longer-term outcomes., Areas Covered: The current article summarizes evidence-based state-of-the-art pharmacotherapy for pediatric GAD based on open-label, randomized, and controlled trials. Two electronic databases (PubMed and Scopus) were systematically searched in April 2022 for relevant publications., Expert Opinion: The literature supports a combination of psychotherapy and pharmacotherapy as being associated with better outcomes when compared to mono-therapies. While longer-term follow-ups are limited, one such study does challenge this notion. Both selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have been found across studies to have moderate effect sizes in the treatment of pediatric anxiety disorders. SSRIs continue to be a first-line intervention, whereas SNRIs may be considered a second-line treatment. While more evidence is needed, there are emerging data indicating that SSRIs are associated with a more rapid and greater reduction in anxiety symptoms when compared to SNRIs.

Objective: This overview of systematic reviews (SRs) and meta-analyses aims to critically appraise the methodology and reporting quality of relevant SRs and meta-analyses with the aim of identifying whether or not the use of valproate can prevent the switch to mania associated with antidepressant treatment in Chinese patients with depressive episodes., Methods: Electronic databases China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database) and Wanfang Database were searched for related SRs and meta-analyses from inception to the search date within Chinese restrictions. A total of 2 reviewers independently selected SRs and meta-analyses and collected related data, and a third reviewer was introduced if any disagreement occurred during the assessment. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and the US Agency for Healthcare Research and Quality (AHRQ) were employed to evaluate quality of the reporting and methodology., Results: The switch rate in the sodium valproate group by 99% and was significantly lower than in the antidepressant-only group (0% vs 5.7%; OR = 0.18; 95% CI, 0.04-0.84; Z = 2.18; P = .03). The magnesium valproate group was similar to the sodium valproate group in switch rate; the switch rate in the antidepressant group was (2.2% vs 16.92%; OR = 0.11; 95% CI, 0.03-0.39; Z = 3.47; P = .0005). The switch rate in the salt valproate combined with a selective serotonin reuptake inhibitor (SSRI) group was lower than in the SSRI group (0.51% vs 8.4%; OR = 0.15; 95% CI, 0.04-0.51; Z = 3.01; P = .003). The switch rate in the valproate combined with serotonin noradrenaline reuptake inhibitor (SNRI) group was similar to the valproate combined with SNRI group (2.3% vs 17.5%; OR = 0.12; 95% CI, 0.03-0.53; Z = 2.79; P = .05)., Conclusion: Salt valproate can reduce the switch rate related to antidepressant treatment in patients with depression.

Purpose: To assess the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs) in comparison with various control contingencies (e.g. pill placebo and cognitive behavioral treatment) for pediatric anxiety disorders. Additionally, we wanted to investigate whether serious adverse events or adverse events are more common with medication treatment compared with pill placebo., Materials and Methods: Studies were selected if they were randomized controlled trials evaluating SSRIs or SNRIs. Eligible studies included participants aged 17 years or younger. Eleven studies were included, with 2122 participants. Primary outcomes were (1) remission, (2) a continuous scale such as the Social Phobia and Anxiety Inventory for Children and (3) serious adverse events. We also calculated number needed to treat and number needed to harm., Results: SSRIs and SNRIs are an effective treatment of childhood anxiety disorders and are superior to pill placebo. While the risk of serious adverse events was low with SSRI/SNRI treatment, there was an increased risk of experiencing behavioral activation with SSRI/SNRI treatment., Conclusion: SSRI and SNRI treatment is effective for childhood anxiety disorders, with positive effect of treatment outweighing the negative effects.

Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es)ketamine are used to treat major depressive disorder (MDD). These different types of medication may involve common neural pathways related to glutamatergic and GABAergic neurotransmitter systems, both of which have been implicated in MDD pathology. We conducted a systematic review of pharmacological proton Magnetic Resonance Spectroscopy ( 1 H-MRS) studies in healthy volunteers and individuals with MDD to explore the potential impact of these medications on glutamatergic and GABAergic systems. We searched PubMed, Web of Science and Embase and included randomized controlled trials or cohort studies, which assessed the effects of SSRIs, SNRIs, or (es)ketamine on glutamate, glutamine, Glx or GABA using single-voxel 1 H-MRS or Magnetic Resonance Spectroscopic Imaging (MRSI). Additionally, studies were included when they used a field strength > 1.5 T, and when a comparison of metabolite levels between antidepressant treatment and placebo or baseline with post-medication metabolite levels was done. We excluded animal studies, duplicate publications, or articles with 1 H-MRS data already described in another included article. Twenty-nine studies were included in this review. Fifteen studies investigated the effect of administration or treatment with SSRIs or SNRIs, and fourteen studies investigated the effect of (es)ketamine on glutamatergic and GABAergic metabolite levels. Studies on SSRIs and SNRIs were highly variable, generally underpowered, and yielded no consistent findings across brain regions or specific populations. Although studies on (es)ketamine were also highly variable, some demonstrated an increase in glutamate levels in the anterior cingulate cortex in a time-dependent manner after administration. Our findings highlight the need for standardized study and acquisition protocols. Additionally, measuring metabolites dynamically over time or combining 1 H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Anxiety disorders have a lifetime prevalence of approximately 34% in the US, are often chronic, and significantly impair quality of life and functioning., Observations: Anxiety disorders are characterized by symptoms that include worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Generalized anxiety disorder (6.2% lifetime prevalence), social anxiety disorder (13% lifetime prevalence), and panic disorder (5.2% lifetime prevalence) with or without agoraphobia are common anxiety disorders seen in primary care. Anxiety disorders are associated with physical symptoms, such as palpitations, shortness of breath, and dizziness. Brief screening measures applied in primary care, such as the Generalized Anxiety Disorder-7, can aid in diagnosis of anxiety disorders (sensitivity, 57.6% to 93.9%; specificity, 61% to 97%). Providing information about symptoms, diagnosis, and evidence-based treatments is a first step in helping patients with anxiety. First-line treatments include pharmacotherapy and psychotherapy. Selective serotonin reuptake inhibitors (SSRIs, eg, sertraline) and serotonin-norepinephrine reuptake inhibitors (SNRIs, eg, venlafaxine extended release) remain first-line pharmacotherapy for generalized anxiety disorder, social anxiety disorder, and panic disorder. Meta-analyses suggest that SSRIs and SNRIs are associated with small to medium effect sizes compared with placebo (eg, generalized anxiety disorder: standardized mean difference [SMD], -0.55 [95% CI, -0.64 to -0.46]; social anxiety disorder: SMD, -0.67 [95% CI, -0.76 to -0.58]; panic disorder: SMD, -0.30 [95% CI, -0.37 to -0.23]). Cognitive behavioral therapy is the psychotherapy with the most evidence of efficacy for anxiety disorders compared with psychological or pill placebo (eg, generalized anxiety disorder: Hedges g = 1.01 [large effect size] [95% CI, 0.44 to 1.57]; social anxiety disorder: Hedges g = 0.41 [small to medium effect] [95% CI, 0.25 to 0.57]; panic disorder: Hedges g = 0.39 [small to medium effect[ [95% CI, 0.12 to 0.65]), including in primary care. When selecting treatment, clinicians should consider patient preference, current and prior treatments, medical and psychiatric comorbid illnesses, age, sex, and reproductive planning, as well as cost and access to care., Conclusions and Relevance: Anxiety disorders affect approximately 34% of adults during their lifetime in the US and are associated with significant distress and impairment. First-line treatments for anxiety disorders include cognitive behavioral therapy, SSRIs such as sertraline, and SNRIs such as venlafaxine extended release.

Background: Women service members of the past 20 years experienced high rates of traumatizing events resulting in pharmacological treatment. Post-military lives may include having children. Typically, Veterans Health Administration (VHA) patients' pregnancies are managed outside the VHA. This study examined medication exposures during pregnancy. Materials and Methods: The Center for Maternal and Infant Outcomes Research in Translation (COMFORT) study collected primary survey data and linked secondary health care data from the VHA from 2015 to 2021. Medication fills and covariates were extracted for three 9-month periods: preconception, pregnancy, and postpartum. Multiple regression assessed factors associated with use during pregnancy of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) or of non-recommended, potentially risky drugs, and of discontinuation of those medications from prepregnancy to pregnancy. Results: The cohort comprised 501 women-29% Black, 65% White, and 6% other races, of whom 63% had 50%-100% service-connected disability. During pregnancy, 36% had a pain-related disorder, 19% major depression, and 18% post-traumatic stress disorder. The median number of drug classes prescribed during pregnancy was 5. The use of SSRI/SNRI antidepressants dropped from 36% preconception to 26% during pregnancy including new starts; 15% discontinued SSRI/SNRI. Comorbidity predicted medication use. Depression predicted discontinuing SSRI/SNRI during pregnancy; no predictors of discontinuing potentially risky drugs were identified. Conclusions: Based on prescriptions filled within the VHA only-ignoring potential community-based fills-women veterans were prescribed numerous medications during pregnancy and discontinued antidepressants alarmingly. Veterans of childbearing potential should receive counseling about medication use before pregnancy occurs. Their non-VHA obstetricians and VHA providers should share information to optimize outcomes, reviewing medications as soon as pregnancy is detected as well as after pregnancy concludes.

Pediatric anxiety disorders (PADs) occur in up to 20% of youth and can cause impairment across the lifespan. Coronavirus disease 2019 (COVID-19) added unique pressures on those with PADs, as children and adolescents endured the longest pandemic restrictions, stymieing their ability to develop socially, emotionally, and cognitively. Although first-line treatment for PADs is psychotherapy, those with severe anxiety symptoms will require pharmacological interventions. Selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor (SNRI) medications are effective in treating PADs, yet only duloxetine (a SNRI) is approved by the U.S. Food and Drug Administration for children aged >7 years with generalized anxiety disorder. Treatment of children and adolescents with benzodiazepines for PADs presents unique challenges with potential paradoxical reactions. Caution must be observed as well due to risk for misuse related to long-term use of benzodiazepines with PADs. [ Journal of Psychosocial Nursing and Mental Health Services, 60 (9), 6-9.].

Objective: Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment., Method: A systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: "depressed" [All Fields] OR "depression" [MeSH Terms] OR "depression" [All Fields] OR "depressions" [All Fields] OR "depression s" [All Fields] OR "depressive disorder"[MeSH Terms] OR ("depressive"[All Fields] AND"disorder"[All Fields]) OR"depressive disorder"[All Fields] OR"depressivity"[All Fields] OR"depressive"[All Fields] OR "depressively" [All Fields] OR "depressiveness" [All Fields] OR "depressives" [All Fields]) AND ("esketamine" [Supplementary Concept] OR "esketamine" [All Fields] OR "esketamine" [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French., Results: Four randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence., Conclusions: Intranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine., (Copyright © 2022 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: As numerous patients with depression have to be hospitalized because of various reasons, the demand far exceeds the limited bed count in the psychiatry department. Controlling the length of stay (LOS) of the patient is gradually being considered an effective method to alleviate this problem. Given the lack of statistical evidence of the LOS of patients with major depressive disorder (MDD) in China and the strain on the limited psychiatric resources, the purpose of our study was to investigate the LOS of patients with MDD among in-patient samples and to analyze related factors of the LOS in China by building a regression model., Method: The data were exported from the electronic medical record system. A total of three categories of independent variables were enrolled in our study, namely, demographic, clinical, and biochemical. Univariate analysis and binominal regression analysis were applied comprehensively to find the factors related to the LOS among MDD samples. The discrimination accuracy of the model was evaluated by the receiver operating characteristic (ROC) analysis. ROC analysis indicated that the discrimination accuracy of our model was acceptable (AUC = 0.790, 95% CI = 0.714-0.865, P < 0.001)., Result: A total of 254 patients were finally brought into analysis after filtering. Regression analysis indicated that abnormal LDL was the only risk factor of long LOS (OR = 3.352, 95% CI = 1.087-10.337, P = 0.035) among all the kinds of variables. Notably, in the statistically irrelevant factors of the LOS, the category of anti-depressant drugs [serotonin-norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI)] prescribed to patients with MDD was not associated statistically with the LOS, which was against our initial hypothesis that the LOS of patients with MDD treated with SNRI would vary from that of the patients treated with SSRI., Conclusion: Up to our knowledge, our research is the first study to show the potential factors related to the LOS from various domains, especially biochemical indexes, and the effect of drugs, among clinical patients with MDD in China. Our results could provide a theoretical reference for efficient psychiatry hospitalization management and prioritization of allocating medical resources. Future studies are required for updating independent variables which are potentially related to the LOS and verifying existing results in a larger sample., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cheng, Wang, Xu, Zhou, Zhao, Zhang and Li.)

As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Depression in Parkinson's Disorder (DPD) has been estimated to appear in up to 40% of people with PD and negatively impacts quality of life, motor and cognitive deficits and functional disability. Knowledge of the pathophysiology of DPD is unclear, DPD may be related to dysfunction in subcortical nuclei and the prefrontal cortex, striatal-thalamic-prefrontal and basotemporal limbic circuits, brainstem monoamine, and indolamine (i.e. dopamine, serotonin, and norepinephrine) systems. DPD is characterized by sadness, loss of interest, increased exhaustibility, feelings of helplessness, reduced drive, dysphoria, irritability, and pessimism about future. The diagnosis is complicated by overlap with PD symptoms, Detection of depression in PD should be made by psychometric depression scales. DPD is underrecognized and undertreated in clinical practice. Treatment mainly includes antidepressive medications and behavioral interventions as psychotherapy. Dopamine agonists showed some antidepressant effects, there are no sufficient numbers of RCTs. Important randomized clinical trials (RCTs) are summarized. SSRIs and SNRIs have a satisfying efficacy in DPD. TCAs are also good for improving depression. Side effects of different antidepressants (e.g. TCAs, SSRIs, SNRIs, bupropion, MAOIs) and potential interactions should be considered. In existing guidelines so far no statements, algorithms and recommendations are given for diagnosis and treatment of DPD. Methodologically adequate designed RCTs and comparative studies (NIS) which offer evidence-based results are urgently needed having the impact of DPD in mind., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Opinion Statement: Preventing depression in cancer patients on long-term opioid therapy should begin with depression screening before opioid initiation and repeated screening during treatment. In weighing the high morbidity of depression and opioid use disorder in patients with chronic cancer pain against a dearth of evidence-based therapies studied in this population, patients and clinicians are left to choose among imperfect but necessary treatment options. When possible, we advise engaging psychiatric and pain/palliative specialists through collaborative care models and recommending mindfulness and psychotherapy to all patients with significant depression alongside cancer pain. Medications for depression should be reserved for moderate to severe symptoms. We recommend escitalopram/citalopram or sertraline among selective serotonin reuptake inhibitors (SSRIs), or the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine, venlafaxine, or desvenlafaxine if patients have a significant component of neuropathic pain or fibromyalgia. Tricyclic antidepressants (TCAs) (consider nortriptyline or desipramine, which have better anticholinergic profiles) should be considered for patients who do not respond to or tolerate SSRI/SNRIs. Existing evidence is inadequate to definitively recommend methylphenidate or novel agents, such as ketamine or psilocybin, as adjunctive treatments for cancer-related depression and pain. Physicians who treat patients with cancer pain should utilize universal precautions to limit the risk of non-medical opioid use (non-medical opioid use). Patients should be screened for non-medical opioid use behaviors at initial consultation and at regular intervals during treatment using a non-judgmental approach that reduces stigma. Co-management with an addiction specialist may be indicated for patients at high risk of non-medical opioid use and opioid use disorder. Buprenorphine and methadone are indicated for the treatment of opioid use disorder, and while they have not been systematically studied for treatment of opioid use disorder in patients with cancer pain, they do provide analgesia for cancer pain. While an interdisciplinary team approach to manage psychological stress may be beneficial, this may not be possible for patients treated outside of comprehensive cancer centers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)