Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia.

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.

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

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.

Monotherapy Versus Combination Therapy in the Treatment of Painful Diabetic Neuropathy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy. METHODS: PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool. RESULTS: A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy. CONCLUSION: In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

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.

Neurometabolite changes in response to antidepressant medication: A systematic review of 1H-MRS findings.

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 (1H-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 1H-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 1H-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 1H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

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.).

The effect of duloxetine on female sexual functions in the treatment of stress incontinence.

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.

Prediction of early improvement of major depressive disorder to antidepressant medication in adolescents with radiomics analysis after ComBat harmonization based on multiscale structural MRI.

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-T1WI)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-D17) 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.

A Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD): study protocol for a randomized clinical trial and prognosis study.

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.

Advances in Pharmacotherapy for Pediatric Anxiety Disorders.

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, 5HT1A 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 5HT1A agonist, buspirone, in pediatric anxiety disorder cases.

The current state-of-the-art in pharmacotherapy for pediatric generalized anxiety disorder.

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.

Real-world characteristics of European patients receiving SNRIs as first-line treatment for major depressive disorder.

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.

Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression.

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-HT4R) 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-HT4R density. Participants underwent both EEG and 5-HT4R neuroimaging with [11C]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-HT4R 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-HT4R 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.

Predictors of treatment response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

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 treatment­nonresponsive if the SNRI treatment resulted in a reduction in reported pain by less than 30%. All participants were examined by a physician and completed self­report questionnaires. Blood samples were drawn to assess fasting glucose and insulin levels and to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA­IR) 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 HOMA­IR 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 HOMA­IR 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, HOMA­IR) as well as the presence of psychiatric comorbidities could affect the response to treatment with SNRIs in the patients with FM.

Systematic Review and Meta-Analysis of Salt Valproate Preventing Switch Associated with Antidepressants in Chinese Patients With Depressive Episodes.

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.

Efficacy and safety of serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRI) for children and adolescents with anxiety disorders: a systematic review and meta-analysis.

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.

Anxiety Disorders: A Review.

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.

Factors related to the length of stay for major depressive disorder patients in China: A real-world retrospective study.

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.

Pharmacological Treatment for Pediatric Anxiety Disorders.

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.].