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.).

Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When.

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.

Concurrent administration of serotonergic antidepressants and ozanimod in participants with relapsing multiple sclerosis from the open-label extension DAYBREAK trial.

BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.

Trajectory and magnitude of response in adults with anxiety disorders: a Bayesian hierarchical modeling meta-analysis of selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and benzodiazepines.

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.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

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.

Chronobiological variables predict non-response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia: a cross-sectional study.

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.

The effect of earthquake on fibromyalgia: a comparison of patients on medication and without medication.

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.

Efficacy of Duloxetine With Arthrocentesis in the Management of TMJ Internal Derangement.

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.

Administration of serotonin and norepinephrine reuptake inhibitors tends to have less ocular surface damage in a chronic stress-induced rat model of depression than selective serotonin reuptake inhibitors.

Depressed patients who medicate with selective serotonin reuptake inhibitors (SSRIs) often report ocular dryness. Epidemiological studies have found that serotonin and norepinephrine reuptake inhibitors (SNRIs) are not risk factors for dry eye in depressed patients. However, the effect of SNRIs on the ocular surface is unknown. A depression rat model was induced by chronic unpredictable mild stress (CUMS), and SNRIs or SSRIs were administered to the rats for 3 or 6 weeks. The levels of norepinephrine (NE) and serotonin in tear fluid were tested by ELISA. The corneal fluorescence and lissamine green staining were used to evaluate ocular surface damage. NE and/or serotonin were administered to human corneal epithelial cells in vitro. RNA sequencing (RNA-seq) analysis was performed to investigate the mRNA expression profiles. Tear NE levels were higher in the SNRIs group, and ocular surface inflammation and apoptosis were significantly reduced compared to the SSRIs group. RNA-Seq indicated that NE significantly activate MAPK signaling pathway. NE can inhibit serotonin-induced activation of the NF-κB signaling pathway through α-1 adrenergic receptors and promotes the proliferation of corneal epithelial cells through activation of the MAPK signaling pathway. SNRIs administration have less ocular surface damage than SSRIs. NE protects human corneal epithelial cells from damage, and reduce inflammation on the ocular surface via activating the MAPK signaling pathway. SNRIs might be used as an appropriate treatment for depression-related DED.

Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

Co-prescribing of Central Nervous System-Active Medications for COPD Patients: Impact on Emergency Room Visits and Hospitalization.

BACKGROUND: Anxiety and chronic pain are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which are frequently managed with benzodiazepines (BZDs) and opioids, respectively. OBJECTIVE: The purpose of this study was to determine whether different combinations of opioids, BZD, and their substitutes-gabapentinoids (GABA) and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs)-are associated with lower risk of acute respiratory events in COPD patients with co-occurring chronic pain and anxiety. METHODS: This retrospective cohort study used a nationally representative sample of Medicare beneficiaries with COPD, chronic pain, and anxiety. Patients were grouped based on drug combination (opioid + BZD/Z-hypnotics, opioid + GABA, opioid + SSRI/SNRI, BZD/Z-hypnotics + GABA, BZD/Z-hypnotics + SSRI/SNRI, GABA + SSRI/SNRI, or ≥3 drugs). The primary outcome was emergency room (ER) visit or hospitalization due to acute respiratory events assessed up to 180 days following initiation of drug combination. Overdose secondary to central nervous system (CNS)-related drugs was also assessed up to 180 days following initiation of drug combination. RESULTS: The drug combination opioid + GABA was associated with decreased risk for ER visit (hazard ratio [HR] = 0.73; 95% CI = 0.61-0.87) and hospitalization (HR = 0.69; 95% CI = 0.55-0.85). Opioid + SSRI/SNRI also showed decreased risk for ER visit (HR = 0.84; 95% CI = 0.71-0.99). There was no significant difference in risk for CNS-related drug overdose among different drug combinations compared with opioid + BZD/Z-hypnotics. CONCLUSION AND RELEVANCE: Opioids in combination with GABA and SSRI/SNRI demonstrate relatively lower risk for acute respiratory events among patients with COPD and comorbid chronic pain and anxiety. The findings emphasize the need for multimodal management in this vulnerable population.

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.

Pharmacological interventions for persistent postural-perceptual dizziness (PPPD).

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing and with visual stimulation. The condition was only recently defined and therefore the prevalence is currently unknown. However, it is likely to include a considerable number of people with chronic balance problems. The symptoms can be debilitating and have a profound impact on quality of life. At present, little is known about the optimal way to treat this condition. A variety of medications may be used, as well as other treatments, such as vestibular rehabilitation.  OBJECTIVES: To evaluate the benefits and harms of pharmacological interventions for persistent postural-perceptual dizziness (PPPD).  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with PPPD, which compared selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with either placebo or no treatment. We excluded studies that did not use the Bárány Society criteria to diagnose PPPD and studies that followed up participants for less than three months.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vestibular symptoms (assessed as a dichotomous outcome - improved or not improved), 2) change in vestibular symptoms (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) generic health-related quality of life and 6) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We planned to use GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We identified no studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: At present, there is no evidence from placebo-controlled randomised trials regarding pharmacological treatments - specifically SSRIs and SNRIs - for PPPD. Consequently, there is great uncertainty over the use of these treatments for this condition. Further work is needed to establish whether any treatments are effective at improving the symptoms of PPPD, and whether their use is associated with any adverse effects.

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.

Switching pattern and dose adjustment of antidepressants before and during pregnancy.

The purpose of the study is to examine the switching pattern and dose adjustment of antidepressants (ADs) prescribed to women from six months before to six months during pregnancy in the Netherlands. The recorded dispenses or refills were collected from the University of Groningen IADB.nl pregnancy subset for all singleton pregnancies in which the mother received ≥ 1 prescription of an AD dispensed before pregnancy and was present in the database at least six months after conception. The rates of continuation, discontinuation, and switching between 2001 and 2020 were assessed for the ADs studied. The mean number of Defined Daily Doses (DDDs) of the most frequently continued ADs used was calculated both before and during pregnancy, and a paired t-test was used to test for significant changes. The continuation rates for AD users, especially for SSRI and SNRI continued users, increased over time from 27% and 19% (2001-2005) to 65% and 65% (2016-2020). The switching rate between ADs remained consistently low from the start of the study (2001-2005) at 2.0% to the end of the study (2016-2020) at 2.3%. Most women who switched between antidepressants during pregnancy received a different SSRI monotherapy (85%), followed by an SNRI (6%), a TCA (4%), and an "other AD" (4%). In most cases observed, the dose adjustment for the mean DDDs during pregnancy compared to the mean DDDs before pregnancy only changed little (less than 10%). Continued use of SSRIs among singleton pregnancies doubled over the study period. The low rate of AD switching and little changes in the DDD adjustment for most AD continuers indicate that pregnant women prefer to continue their prepregnancy medication rather than switch it. Most observed findings cohere with the Dutch national guidelines for antidepressant use during pregnancy.

Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study.

BACKGROUND: Prior studies suggested that antidepressant use is associated with an increased risk of dementia compared to no use, which is subject to confounding by indication. We aimed to compare the dementia risk among older adults with depression receiving first-line antidepressants (i.e., SSRI/SNRI) versus psychotherapy, which is also considered the first-line therapy for depression. METHODS: This retrospective cohort study was conducted using the US Medical Expenditure Panel Survey from 2010 to 2019. We included adults aged ≥ 50 years diagnosed with depression who initiated SSRI/SNRI or psychotherapy. We excluded patients with a dementia diagnosis before the first record of SSRI/SNRI use or psychotherapy. The exposure was the patient's receipt of SSRI/SNRI (identified from self-report questionnaires) or psychotherapy (identified from the Outpatient Visits or Office-Based Medical Provider Visits files). The outcome was a new diagnosis of dementia within 2 years (i.e., survey panel period) identified using ICD-9/ICD-10 codes from the Medical Conditions file. Using a multivariable logistic regression model, we reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We also conducted subgroup analyses by patient sex, age group, race/ethnicity, severity of depression, combined use of other non-SSRI/SNRI antidepressants, and presence of underlying cognitive impairment. RESULTS: Among 2,710 eligible patients (mean age = 61 ± 8, female = 69%, White = 84%), 89% used SSRIs/SNRIs, and 11% received psychotherapy. The SSRI/SNRI users had a higher crude incidence of dementia than the psychotherapy group (16.4% vs. 11.8%), with an aOR of 1.36 (95% CI = 1.06-1.74). Subgroup analyses yielded similar findings as the main analyses, except no significant association for patients who were aged < 65 years (1.23, 95% CI = 0.93-1.62), male (1.34, 95% CI = 0.95-1.90), Black (0.76, 95% CI = 0.48-1.19), had a higher PHQ-2 (1.39, 95% CI = 0.90-2.15), and had underlying cognitive impairment (1.06, 95% CI = 0.80-1.42). CONCLUSIONS: Our findings suggested that older adults with depression receiving SSRIs/SNRIs were associated with an increased dementia risk compared to those receiving psychotherapy.

Depression and antidepressant treatment in the development of hypertensive disorders of pregnancy: Results from a prospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy are associated with longer term cardiovascular risk. Understanding if depression or antidepressant use in pregnancy is associated with HDP is important in identifying those potentially vulnerable to poorer health in later life. This study examines if depression and antidepressants are associated with HDP. METHODS: In all, 815 pregnant women were recruited within an Australian pregnancy cohort study at less than 20 weeks of pregnancy, all undertook the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and were assigned to four groups for this paper: those with unmedicated depression meeting criteria for current depression (n = 97), those taking selective serotonin reuptake inhibitors in early pregnancy (n = 101), those taking serotonin and noradrenaline reuptake inhibitors in early pregnancy (n = 31), and those without depression or taking antidepressant medication (control; n = 586). Women were then assessed again following birth. Hypertensive disorders of pregnancy were diagnosed according to the Society of Obstetric Medicine in Australia and New Zealand Guidelines. RESULTS: Use of serotonin and noradrenaline reuptake inhibitors (SNRIs) (adjusted risk ratio = 9.10, 95% confidence interval = [3.82, 21.67]) and unmedicated depression (adjusted risk ratio = 3.11, 95% confidence interval = [1.32, 7.35]) were independently associated with significantly higher risk for developing hypertensive disorders of pregnancy compared to controls. Selective serotonin reuptake inhibitors (SSRIs) use did not confer any increased risk. Higher doses of SNRIs, but not selective serotonin reuptake inhibitors, were associated with significantly higher risk for developing HDP (adjusted risk ratio = 4.83, 95% confidence interval = [1.50, 15.58]). CONCLUSIONS: Our findings suggest that those with depression in pregnancy and/or on an serotonin and noradrenaline reuptake inhibitor should have closer surveillance for the development of hypertensive disorders of pregnancy. These findings support treatment of depression in pregnancy, however, also the consideration of class of antidepressant.

Association of serotonin reuptake inhibitors with asthma control.

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

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.

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.