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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.

Aims Methods Results Conclusions In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years).Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0–100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool.Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0–2 weeks), (−5.6, 95% confidence interval [CI]: −11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6 weeks and <12 months), (−9.1, 95% CI: −11.8 to −6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events.For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias. [ABSTRACT FROM AUTHOR]

Frontal alpha asymmetry (FAA) is an electroencephalography (EEG) measure that quantifies trait-like left versus right hemisphere lateralization in alpha power. Increased FAA indicates relatively greater left than right frontal cortex activation and is associated with enhanced reward-related approach behaviors rather than avoidance or withdrawal. Studies dating back several decades have often suggested that having greater FAA supports enhanced positive affect and protection against major depressive disorder (MDD), whereas having greater right frontal activation (i.e., reduced FAA) is associated with negative affect and risk for MDD. While this hypothesis is widely known, a number of other studies instead have found increased FAA in MDD, or evidence that either leftward or rightward bias in FAA is associated with depression. Here we briefly review the literature on leftward or rightward lateralization in FAA in MDD, and find much evidence that MDD is not always characterized by reduced FAA. We also review the limited literature on FAA and monoaminergic neurotransmitter systems, including pharmacologic agents that act on them. Studies of serotonin in particular provide genetic and pharmacologic evidence for modulation of FAA, where some of these data may suggest that serotonin reduces FAA. In a synthesis of the collective literature on FAA and the monoamines, we suggest that serotonin and norepinephrine may differentially affect FAA, with serotonin tending to promote right frontal activation and norepinephrine biased toward left frontal activation. These putative differences in frontal lateralization may influence MDD phenotypes or potential subtypes of the disorder, and suggest pharmacologic treatment strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Data comprehensively examining trends in central nervous system (CNS)-active polypharmacy are limited. The objective of this cross-sectional study was to characterize the composition of and trends in CNS-active medication use in US adults. METHODS: We included all participants ≥ 18 years old in the National Health and Nutrition Examination Study (NHANES), 2009-2020. The primary outcome was the percent of adults with CNS-active polypharmacy. This was defined as ≥ 3 medications among antidepressants [tricyclic, selective and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs), opioids, antiepileptics, antipsychotics, benzodiazepines, and nonbenzodiazepine receptor agonists (Z-drugs)]. Secondary outcomes included prevalence of any CNS-active medication and specific medications and classes over time, and their indications. Percentages were weighted according to NHANESs nationally representative sampling frame. log binomial regressions evaluated the relative risk (RR) for each outcome, comparing the last (2017-2020) versus the first (2010-2011) survey cycle. RESULTS: We included 34,189 adults (18.8% at least 65 years old) from five serial cross-sections (survey cycles). The prevalence of CNS-active polypharmacy was 2.1% in 2009-2010 and 2.6% in 2017-2020 [RR 1.18, 95% confidence interval (CI) 0.94-1.47]. The prevalence of CNS-active polypharmacy did not significantly change within any specific age group (e.g., age at least 65 years: RR 1.29, CI 0.74-2.24). The prevalence of any CNS-active medication was 21.0% in 2009 and 24.6% in 2017-2020 (RR] 1.12, 95% CI 1.02-1.25). A substantial increase occurred for antiepileptics (5.1-8.3%), specifically among participants aged 65 years and older (8.3-13.7%). This was largely driven by increasing gabapentin prevalence (1.4-3.6% overall; 3.3-7.9% age 65 years and older). Anticholinergic, SSRIs/SNRIs, antiepileptics, and benzodiazepines were elevated in most cycles for participants at least 65 years old compared with participants less than 65 years, and opioid use was increased in several cycles for older participants as well. Alprazolam was the most common benzodiazepine and third most common medication for anxiety/depression. Gabapentin was the most common CNS-active medication (3.6% of all participants in 2017-2020), followed by sertraline, citalopram, and acetaminophen-hydrocodone (each ~2%). The most common categories were antidepressants (13.7% in 2017-2020), followed by opioids (5.1% in 2017-2020). CONCLUSIONS: CNS-active medications are increasingly common, particularly gabapentin, and use of any CNS-active medication increased by 12%. Numerous CNS-active classes also increased in older adults throughout the years. Increasing suboptimal medication use highlight the need for further investigation into causes for potentially inappropriate prescribing, particularly for older adults.

Restless legs syndrome (RLS) is a chronic progressive movement disorder characterized by abnormal sensations, especially at rest and at night, as the need and urge to move the lower extremity. It has been reported that RLS severity and frequency increase in patients with anxiety and depression. It has been reported that serotonin-noradrenaline reuptake inhibitors such as venlafaxine and selective serotonin reuptake inhibitors such as citalopram, fluoxetine, paroxetine, and sertraline can cause RLS symptoms. No adverse effects of vortioxetine on RLS have been reported in the literature. In this case series, we report the effect of vortioxetine in patients with RLS with symptoms of depression and anxiety. In this case series, the effect of adding vortioxetine to treatment on RLS symptoms is reported in 7 patients (5 female). After the use of vortioxetine, 5 of 7 patients’ symptoms regressed without the need to start a separate drug for primary movement disorder. In conclusion, we believe that studies should be conducted to investigate the efficacy of vortioxetine in the treatment of RLS. Therefore, randomized controlled studies are needed to determine the effect and safety of vortioxetine on RLS symptoms. [ABSTRACT FROM AUTHOR]

• Our real-world study assessed the effect of SSRI on COVID-19 outcomes to consider their repurposing. • No class effect was observed for SSRIs overall. • The low prevalence of fluvoxamine prevented us from obtaining conclusive results. • Citalopram was associated with lower risk of severe COVID-19 and hospitalization. • We consider that citalopram could be repurposed as a preventive treatment in patients with COVID-19. The World Health Organization has proposed that a search be made for alternatives to vaccines for the prevention and treatment of COVID-19, with one such alternative being selective serotonin reuptake inhibitors (SSRIs). This study thus sought to assess: the impact of previous treatment with SSRI antidepressants on the severity of COVID-19 (risk of hospitalisation, admission to an intensive care unit [ICU], and mortality), its influence on susceptibility to SARS-CoV-2 and progression to severe COVID-19. We conducted a population-based multiple case-control study in a region in the north-west of Spain. Data were sourced from electronic health records. Adjusted odds ratios (aORs) and 95%CIs were calculated using multilevel logistic regression. We collected data from a total of 86,602 subjects: 3060 cases PCR+, 26,757 non-hospitalised cases PCR+ and 56,785 controls (without PCR+). Citalopram displayed a statistically significant decrease in the risk of hospitalisation (aOR=0.70; 95% CI 0.49–0.99, p = 0.049) and progression to severe COVID-19 (aOR=0.64; 95% CI 0.43–0.96, p = 0.032). Paroxetine was associated with a statistically significant decrease in risk of mortality (aOR=0.34; 95% CI 0.12 – 0.94, p = 0.039). No class effect was observed for SSRIs overall, nor was any other effect found for the remaining SSRIs. The results of this large-scale, real-world data study indicate that, citalopram, could be a candidate drug for being repurposed as preventive treatment aimed at reducing COVID-19 patients' risk of progressing to severe stages of the disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: One of the key mechanisms underlying OSA is reduced pharyngeal muscle tone during sleep. Data suggest that pharmacologic augmentation of central serotonergic/adrenergic tone increases pharyngeal muscle tone. RESEARCH QUESTION: We hypothesized that venlafaxine, a serotonin-norepinephrine reuptake inhibitor, would improve OSA severity. STUDY DESIGN AND METHODS: In this mechanistic, randomized, double-blind, placebo-controlled crossover trial, 20 patients with OSA underwent two overnight polysomnograms ≥ 4 days apart, receiving either 50 mg of immediate-release venlafaxine or placebo before bedtime. Primary outcomes were the apnea-hypopnea index (AHI) and peripheral oxygen saturation (Spo2) nadir, and secondary outcomes included sleep parameters and pathophysiologic traits with a view toward understanding the impact of venlafaxine on mechanisms underlying OSA. RESULTS: Overall, there was no significant difference between venlafaxine and placebo regarding AHI (mean reduction, -5.6 events/h [95% CI, -12.0 to 0.9]; P = .09) or Spo2 nadir (median increase, +1.0% [-0.5 to 5]; P = .11). Venlafaxine reduced total sleep time, sleep efficiency, and rapid eye movement (REM) sleep, while increasing non-REM stage 1 sleep (Pall < .05). On the basis of exploratory post hoc analyses venlafaxine decreased (improved) the ventilatory response to arousal (-30%; P = .049) and lowered (worsened) the predicted arousal threshold (-13%; [P = .02]; ie, more arousable), with no effects on other pathophysiologic traits (Pall ≥ .3). Post hoc analyses further suggested effect modification by arousal threshold (P = .002): AHI improved by 19% in patients with a high arousal threshold (-10.9 events/h [-3.9 to -17.9]) but tended to increase in patients with a low arousal threshold (+7 events/h [-2.0 to 16]). Other predictors of response were elevated AHI and less collapsible upper airway anatomy at baseline (|r| > 0.5, P ≤ .02). INTERPRETATION: In unselected patients, venlafaxine simultaneously worsened and improved various pathophysiologic traits, resulting in a zero net effect. Careful patient selection based on pathophysiologic traits, or combination therapy with drugs countering its alerting effects, may produce a more robust response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02714400; URL: www.clinicaltrials.gov.

Purpose: Selective serotonin re-uptake inhibitors (SSRIs) are frequently used to treat premature ejaculation (PE) in men. We performed a Cochrane review to assess the efficacy of SSRI treatment for PE. Materials and Methods: We extensively searched a range of databases up to May 2020 and only included randomized controlled trials. Results: A total of 31 studies with 8,254 men were included in this analysis. We found that SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of ‘better’ or ‘much better’; risk ratio [RR], 1.92; 95% confidence interval [CI], 1.66–2.23; moderate-certainty evidence) and satisfaction with intercourse (defined as a rating of ‘good’ or ‘very good’; RR, 1.63; 95% CI, 1.42–1.87; moderate-certainty evidence) compared to placebo. Furthermore, SSRI treatment likely improve participants’ self-perceived control over ejaculation (defined as rating of ‘good’ or ‘very good’; RR, 2.29; 95% CI, 1.72–3.05; moderate-certainty evidence) and probably lessens distress (defined as rating of ‘a little bit’ or ‘not at all’) about PE (RR, 1.54; 95% CI, 1.26–1.88; moderate-certainty evidence). SSRI treatment may increase IELT compared to placebo (mean difference, 3.09 minutes higher; 95% CI, 1.94 higher to 4.25 higher; low-certainty evidence). However, SSRIs may increase treatment cessations due to adverse events compared to placebo (RR, 3.80; 95% CI, 2.61–5.51; low-certainty evidence). Conclusions: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo.

On the background of a restricted armamentarium of drugs available for the management of fibromyalgia (FM), we aimed to compare the real-world effectiveness of two serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine (MTZ) and duloxetine (DLX) in FM. A medical records review was done to identify patients diagnosed with FM and prescribed a stable dose of either MTZ or DLX for more than 6 months. Their present status was determined by a telephonic interview which included a subjective assessment of improvement (Likert scale), FIQR (Revised Fibromyalgia Impact Questionnaire), adverse drug effects and compliance. One-fifty-eight patients were screened to include 81 patients [mean age 46.7 (± 13.0) years, 64 (79%) females]. Sixty (79%) had primary fibromyalgia and 66 (81.5%) were on DLX (20–40 mg) while 15(18.5%) were on MTZ (7.5 mg). In addition to the drugs, lifestyle modification was followed by 57 (70.3%). A moderate-to-good improvement was seen in 66 (81.5%), while 15 (18.5%) reported poor to no improvement overall. In the DLX group, a majority (59, 89.4%) showed moderate-to-good improvement compared to 7(46.7%) on MTZ [p = 0.001, 9.6(2.6–34)]. However, FIQR was similar for those on DLX (3.6 ± 0.9) and MTZ (3.8 ± 0.7). Adverse effects were reported for 51 (77%) of patients on DLX and all (100%) on MTZ with a poorer compliance with MTZ 5 (33.3%) compared to DLX 47 (71.2%) [p = 0.008, OR 0.1(0.03–0.4)]. On multivariate analysis, DLX use [OR 16.7 (95% CI 2.7–100); p = 0.008] and lifestyle modification [p = 0.002; OR 11.2(1.5–83.3)] were associated with better subjective outcomes. Low-dose MTZ appears to be inferior to DLX in the management of FM in this real-world cohort. [ABSTRACT FROM AUTHOR]

Purpose: Selective serotonin re-uptake inhibitors (SSRIs) are frequently used to treat premature ejaculation (PE) in men. We performed a Cochrane review to assess the efficacy of SSRI treatment for PE. Materials and Methods: We extensively searched a range of databases up to May 2020 and only included randomized controlled trials. Results: A total of 31 studies with 8,254 men were included in this analysis. We found that SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of ‘better’ or ‘much better’; risk ratio [RR], 1.92; 95% confidence interval [CI], 1.66–2.23; moderate-certainty evidence) and satisfaction with intercourse (defined as a rating of ‘good’ or ‘very good’; RR, 1.63; 95% CI, 1.42–1.87; moderate-certainty evidence) compared to placebo. Furthermore, SSRI treatment likely improve participants’ self-perceived control over ejaculation (defined as rating of ‘good’ or ‘very good’; RR, 2.29; 95% CI, 1.72–3.05; moderate-certainty evidence) and probably lessens distress (defined as rating of ‘a little bit’ or ‘not at all’) about PE (RR, 1.54; 95% CI, 1.26–1.88; moderate-certainty evidence). SSRI treatment may increase IELT compared to placebo (mean difference, 3.09 minutes higher; 95% CI, 1.94 higher to 4.25 higher; low-certainty evidence). However, SSRIs may increase treatment cessations due to adverse events compared to placebo (RR, 3.80; 95% CI, 2.61–5.51; low-certainty evidence). Conclusions: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. [ABSTRACT FROM AUTHOR]

Objective: Our study aimed to determine the relationship of antidepressant medicine use with periodontal diseases, exploring the association of different pharmacological classes of antidepressant with observations of clinical attachment loss (CAL) and alveolar bone level (BL) in patients with periodontitis. Background: Existing evidence on the impact of antidepressant medication on periodontal tissues has focused on some classes only and is still unclear. Therefore, this retrospective study evaluated the association of different antidepressant classes with clinical attachment loss (CAL) and alveolar bone level (BL). Methods: This study was carried out in a population of patients aged ≥ 30 years old with periodontitis who sought treatment at the University of Florida from 2014 to 2018. The following variables were obtained from patients' records; usage of antidepressant medications and their pharmacological classes (selective serotonin reuptake inhibitors [SSRI], serotonin‐norepinephrine reuptake inhibitors [SNRI], tricyclic, atypical, and monoamine oxidase inhibitors [MAO]), age, gender, smoking habit, mild systemic diseases, CAL, and cement‐enamel junction (CEJ) and alveolar bone crest (BC) distance, defined as BL, in the Ramfjord index teeth. Results: Five hundred and eighty‐two periodontitis patients were evaluated, of which 113 (19.4%) were antidepressant users. Antidepressant users exhibited significantly lower BL and fewer sites with severe CAL (≥5 mm), than non‐users (p <.05). Among all single‐class antidepressant users, the SSRI users showed significantly less CAL and lower BL than non‐users (p <.05). Patients taking combinations of the different classes of antidepressants also showed better CAL and BL than non‐users. Generalized linear models, including variables such as gender, age, systemic diseases, and smoking, demonstrated that antidepressant users were more likely to have lower mean BL and fewer sites with severe bone loss (i.e. BL > 3 and >5 mm) than non‐users (p <.05). Conclusions: Antidepressant medications were associated with higher alveolar bone level and less clinical attachment loss in patients with periodontitis. When the different classes of antidepressants were analyzed individually, only the SSRI class users and the multiple‐class users showed significantly less periodontal breakdown than non‐users. [ABSTRACT FROM AUTHOR]

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

ObjectiveExamine therapeutic potential of a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor (NERI) in an animal model of comorbidity between epilepsy, depression-like, and impulsive-like impairments.MethodsEpilepsy was induced in male Wistar rats by LiCl and pilocarpine. An SSRI fluoxetine (FLX), and an NERI reboxetine (RBX) were administered either alone or as a combination over 1 week. Depressive-like and impulsive-like behaviors were examined using the forced swim test. Fast scan cyclic voltammetry was used to analyze serotonergic transmission in the raphe nucleus (RN)-prefrontal cortex (PFC) pathway, and noradrenergic transmission in locus coeruleus (LC)-PFC, and LC-RN projections. Monoamine levels in PFC were measured using high-performance liquid chromatography (HPLC). Functional capacities of 5-HT1A receptors and α2A adrenoreceptors in PFC were analyzed by autoradiography.ResultsEpileptic rats showed behavioral signs of depression and hyperimpulsivity, suppressed serotonergic and noradrenergic tones, decreased levels of serotonin (5-HT), and norepinephrine (NE); 5-HT1A receptor and α2A adrenoreceptors functions remained intact. FLX failed to improve behavioral deficits, but effectively raised 5-HT level and marginally improved RN-PFC serotonergic transmission. RBX reversed impulsive-like behavior, normalized content of NE and noradrenergic tone in LC-PFC and LC-RN. FLX-RBX combination fully reversed depressive-like behavior, and normalized RN-PFC serotonergic transmission. None of the treatment modified the function of 5-HT and NE receptors.SignificanceDepressive- and impulsive-like behaviors in the pilocarpine model of epilepsy stem respectively from dysfunctions of serotonergic and noradrenergic ascending pathways. At the same time, epilepsy-associated depression is SSRI resistant. The finding that an SSRI-NERI combination exerts antidepressant effect, along with RBX-induced improvement of LC-RN noradrenergic transmission point toward the involvement of LC-RN noradrenergic input in enabling therapeutic potential of FLX. Medications that improve serotonergic and noradrenergic transmission, such as serotonin-norepinephrine reuptake inhibitors may be effective in treating epilepsy-associated SSRI-resistant depression, as well as concurrent depression and attention-deficit/hyperactivity disorder (ADHD).

Background: Previous studies have suggested an association between taking antidepressants and dental implant failure. This study aimed to investigate the association of different antidepressant classes with dental implant failure.Methods: This retrospective study included patients that received dental implants at the University of Florida from 2011 to 2016. The variables of implant failure, antidepressant use and classes (selective serotonin reuptake inhibitors [SSRI], serotonin-norepinephrine reuptake inhibitors [SNRI], tricyclic antidepressants [TCA], atypical antidepressants [AA], and monoamine oxidase inhibitors [MAOI]), age, sex, smoking, mild systemic diseases, and implant location were obtained from patients' records. Odds ratio (OR) and confidence interval (CI) of implant failure in patients taking different antidepressant classes, in relationship to non-antidepressant users, were estimated, and the influence of multiple variables on implant failure were investigated.Results: A total of 771 patients and 1,820 implants were evaluated. The statistically significant predictors for implant failure included smoking (OR = 5.221), use of antidepressants (OR = 4.285), posterior maxilla location (OR = 2.911), mild systemic disease (OR = 2.648), and age (OR = 1.037) (P <0.05). The frequency of implant failure was 33.3% in TCA users, 31.3% in SNRI users, 6.3% in SSRI users, 5.2% in Atypical antidepressant users, and 3.9% in non-users. Significant associations were observed between the use of SNRI (OR: 11.07; 95% CI: 3.265 to 33.82) and TCA (OR: 12.16; 95% CI: 1.503 to 71.58) and implant failure (P <0.05).Conclusions: Users of antidepressants were at higher risk of implant failure than non-users. Patients taking SNRI and TCA were at the highest risk of implant loss, when compared with non-users. Conclusions about TCA, however, are based on a limited number of cases. [ABSTRACT FROM AUTHOR]

Objective: To carry out an exploratory assessment of the efficacy and safety of TAS‐303, a noradrenaline reuptake inhibitor, in women with stress urinary incontinence. Methods: In a double‐blind, placebo‐controlled, early phase II study, women with stress urinary incontinence and stress urinary incontinence‐predominant mixed urinary incontinence were randomized to a placebo or TAS‐303 (3 or 6 mg) once daily for 8 weeks. The main efficacy end‐points were mean percentage change in incontinence episode frequency per 24 h from baseline to week 8 (the primary end‐point) and week 4. Results: At week 8, the mean percentage change in incontinence episode frequency per 24 h was −34.73% in the TAS‐303 3 mg group, −35.41% in the TAS‐303 6 mg group and −28.07% in the placebo group (differences vs placebo, not significant). In patients with stress urinary incontinence, or incontinence episode frequency less than two episodes per 24 h at baseline, TAS‐303 significantly reduced incontinence episode frequency versus placebo after 4 weeks; some secondary end‐points also showed a tendency to improve in the same subgroups. No serious adverse events (e.g. central nervous system or cardiovascular effects) were observed; TAS‐303 was well tolerated and had a favorable safety profile. Conclusion: These findings suggest that TAS‐303 is effective for improving stress urinary incontinence symptoms in some subgroups of patients with stress urinary incontinence. Therefore, further research is warranted. [ABSTRACT FROM AUTHOR]

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

Various antidepressants have introduced in clinical practice for pain management, but it is important to understand how to properly use them. We therefore performed a systematic review and network meta-analysis to compare and rank the efficacy and safety of antidepressants for patients with chronic back pain. We identified eligible randomized controlled trials (RCTs) that investigated the efficacy and safety of antidepressants for chronic back pain from PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov, searching from inception to May 2023. Six categories of antidepressants for the treatment of chronic back pain were included, and the surface under the cumulative ranking probabilities was applied to rank the treatment strategies. Overall, we selected 19 RCTs recruiting 2903 patients for the meta-analysis. Tricyclic antidepressants presented the best relative effects for relief in pain score (surface under the cumulative ranking, 84.4%). The results of pairwise comparison analyses found the use of serotonin-noradrenaline reuptake inhibitors (SNRIs) significantly reduced pain score and low disability score compared with placebo, irrespective of treatment duration. Noradrenaline-dopamine reuptake inhibitors (relative risk [RR], 2.80; 95% confidence interval [CI], 1.30-6.03; P = .008) and SNRIs (RR, 1.17; 95% CI, 1.07-1.27; P < .001) significantly increased the risk of adverse events. SNRIs were associated with an increased risk of withdrawal due to adverse events (RR, 2.37; 95% CI, 1.64-3.43; P < .001). This study found that antidepressants are more efficacious than placebos for treating chronic back pain, and tricyclic antidepressants are the most likely medications that lead to pain relief., (© 2023, The American College of Clinical Pharmacology.)

Zhuoyuan Zhong,1,* Limin Wang,2,* Xiaojun Wen,3 Yunyun Liu,4 Yafei Fan,5 Zhonglin Liu5 1Department of Neurology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; 2Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, China; 3Department of Neurology, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou-Birmingham University Brain and Cognition Center, Guangzhou, China; 4Department of Neurology, the Sixth Affiliated Hospital Sun Yat-sen University, Guangzhou, China; 5Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) have been commonly prescribed for depression treatment. However, their effects on blood pressure are unclear.Materials and methods: Effects on blood pressure of depressive patients in two groups (SSRIs versus placebo and SSRIs versus SNRIs) were evaluated. A search was conducted for double-blind, randomized controlled trials (RCTs) in PubMed, EMBASE, ISI Web of Science, PsycNET, CCRCT, and DARE (up to March 2017). The outcomes were systolic blood pressure (SBP) changes and diastolic blood pressure (DBP) changes from baseline to endpoint or to a certain period of treatment duration. Weighted mean differences (WMDs) and 95% CIs were calculated and pooled using random effects models. The χ2 test and I2 statistics were used to assess heterogeneity. Funnel plots, Begg’s test, and Egger’s test were used to estimate publication bias.Results: A total of 23 RCTs involving 13,285 participants were included. Patients on SSRIs showed no significant differences in blood pressure changes compared with placebo. In the group of SSRIs versus SNRIs, overall SBP changes and DBP changes revealed statistical significances (WMD 1.5 mmHg, 95% CI -2.15, -0.84, Z=4.46, P

Background: Antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed for depression treatment. Animal studies have shown that antidepressants can influence gut microbiota composition and specific bacterial taxa. We aimed to investigate the association between antidepressant use and human gut microbiota composition and functional pathway., Methods: We collected information on antidepressant use, demographic, food patterns, and clinical characteristics through questionnaires and medical records. The gut microbiota profiles of 271 depressive patients were carried out through 16S rRNA gene sequencing. Patients were categorized based on different types of antidepressant use groups for gut microbiota comparisons. MaAsLin2 was performed to evaluate microbiota composition across groups. PICRUSt2 was used to predict microbiota functional pathways., Results: Patients taking SSRIs or SNRIs had a lower microbiota diversity. We found seven taxa abundances (Turicibacter, Barnesiella, Lachnospiraceae&#95;ND3007&#95;group, Romboutia, Akkermansia, Dialister, Romboutia and Fusicatenibacter) differed in patients with various types of antidepressants compared with those without antidepressant treatments (p < 0.05). Turicibacter inversely correlated with depression severity in SSRIs or SNRI users (r = -0.43, p < 0.05). Top identified pathways were related to compound fermentation and biosynthesis in microbiota function., Conclusion: Antidepressant usage, especially SSRIs and SNRIs, associates with changes in gut microbiota composition and specific taxa. Given our study's preliminary cross-sectional nature, further research is warranted to comprehend the relationship between antidepressant use, treatment response, and gut microbiota, aiming to enhance therapeutic interventions in the future., Competing Interests: Declaration of competing interest No conflicts of interest exist, according to the authors, with the publishing of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

Background: The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors., Methods: A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study., Results: Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56)., Conclusions: SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The comparative safety of serotonin and norepinephrine reuptake inhibitors (SNRIs) as adjuvants to short-acting opioids in older adults is unknown even though SNRIs are commonly used. We compared the effects of SNRIs versus nonsteroidal anti-Inflammatory drugs (NSAIDs) on delirium among nursing home residents when SNRIs or NSAIDs were added to stable regimens of short-acting opioids., Methods: Using 2011-2016 national Minimum Data Set (MDS) 3.0 and Medicare claims data to implement a new-user design, we identified a cohort of nursing home residents receiving short-acting opioids who initiated either an SNRI or an NSAID. Delirium was defined from the Confusion Assessment Method in MDS 3.0 assessments and ICD9/10 codes using Medicare hospitalization claims. Propensity score matching balanced underlying differences for initiating treatments on 39 demographic and clinical characteristics (n SNRIs  = 5350; n NSAIDs  = 5350). Fine and Gray models provided hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for the competing risk of death., Results: Hydrocodone was the most commonly used short-acting opioid (48%). Residents received ~23 mg daily oral morphine equivalent at the time of SNRIs/NSAIDs initiation. The majority were women, non-Hispanic White, and aged ≥75 years. There were no differences in any of the confounders after propensity matching. Over 1 year, 10.8% of SNRIs initiators and 8.9% of NSAIDs initiators developed delirium. The rate of delirium onset was similar in SNRIs and NSAID initiators (HR(delirium in nursing home or hospitalization for delirium):1.10; 95% CI: 0.97-1.24; HR(hospitalization for delirium): 1.06; 95% CI: 0.89-1.25), and were similar regardless of baseline opioid daily dosage., Conclusions: Among nursing home residents, adding SNRIs to short-acting opioids does not appear to increase risk of delirium relative to initiating NSAIDs. Understanding the comparative safety of pain regimens is needed to inform clinical decisions in a medically complex population often excluded from clinical research., (© 2023 The American Geriatrics Society.)

Objective: To examine the impact of medication and medical conditions on the fall risk in older hospitalized patients. Design: Matched case-control study. Setting: Large regional hospital in a mid-sized German city. Subjects: Four hundred eighty-one inpatients aged ≥ 65 years who fell during hospitalization ("cases") and a control group of 481 controls, matched for age, gender, and hospital department. Methods: Diagnosis, medication, vital parameters, and injuries were compared between cases and controls. Univariate and multivariable odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated. Main results: Several drugs were significantly associated with falls in multivariate analyses: long-acting benzodiazepines (adjusted OR = 3.49; 95%-CI = 1.16–10.52), serotonin-noradrenalin reuptake inhibitors (SNRI) (2.57; 1.23–5.12), Z-drugs (2.29; 1.38–3.59), low-potency neuroleptics (1.87; 1.08–3.23), ACE inhibitors/sartans (1.42; 1.07–1.89). Digoxin (0.32; 0.11–0.99) and aldosterone receptor antagonists (0.54; 0.33–0.88) were negatively associated with falls. No significant association in multivariate analyses was found for short- and intermediate-acting benzodiazepines, mirtazapine, and opioids. Hyponatremia (1.52; 1.15–2.03) and leukocytosis (1.39; 1.05–1.87) in blood examination on admission showed significant association with falls. As secondary diagnoses, Parkinson syndrome (2.38; 1.27–4.46) and delirium (3.74; 2.26–6.21) were strongly associated with falls. The use of more than one psychoactive drug was a separate risk factor for falls (p < 0.0001). Conclusion: Several drugs including SNRI, neuroleptics, and Z-drugs showed a significant association with inpatient falls. The frequently prescribed tetracyclic antidepressant mirtazapine did not appear to increase the risk of falls. Psychoactive polypharmacy should be avoided. [ABSTRACT FROM AUTHOR]

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Initiating opioid use disorder treatment with buprenorphine conventionally requires the cessation of other opioid medications, including tramadol. Tramadol's spectrum of activity differs from most opioids, acting through serotonin and norepinephrine reuptake inhibition. Here, we report a case of 45-year-old man who experienced a complicated transition from tramadol to buprenorphine. We believe there were similarities to antidepressant discontinuation syndrome, which could be explained by tramadol's serotoninergic activity. Clinicians should be aware of these effects when discontinuing tramadol, even if replacing with another opioid. [ABSTRACT FROM AUTHOR]

Background: Stress, individual characteristics of each patient, visceral hypersensitivity and intestinal motility have the key importance in the pathogenesis of irritable bowel syndrome (IBS). In recent years, there has been growing interest in the use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the complex therapy of IBS patients with somatoform disorders., Aim: To examine the effectiveness of the SNRIs antidepressant therapy in the treatment of patients with IBS and diarrhea (IBS-D) with extraintestinal manifestations., Materials and Methods: 42 patients with severe IBS and diarrhea (IBS-D) were examined, among them 22 female with a median age of 32 years old (22; 38), and 20 male with a median age of 31 years old (25; 35). Treatment with duloxetine 60 mg/day was prescribed. The effectiveness of the therapy was assessed after eight weeks. The IBS clinical symptoms dynamics were assessed by the intensity of pain syndrome and bloating, which were determined using Visual Analogue Pain Scale (VAS), stool frequency and shape based on the Bristol stool scale; Visceral sensitivity threshold was assessed according to the Balloon dilatation test. There was studied the effect of the duloxetine on the extraintestinal manifestations of IBS. The psycho-emotional state was assessed using the Beck scale of anxiety and depression and the Spielberger-Khanin scale by psychiatrist, neurologist-vegetol., Results: All patients showed positive dynamics after eight weeks duloxetine treatment: the decrease of pain syndrome from 9 (9; 10) to 2 (2; 3) points, bloating from 8 (8; 9) points to 2,5 (1; 3) points according to VAS, and defecation frequency from 10 (9; 12) to 2 (1; 2) times a day; the change of stool consistency from 6th (6; 7) to 3rd (3; 4) type. The visceral sensitivity threshold increased: the time of appearance of the first urge to defecate increased from 56 (34; 74) ml to 95 (80; 98) ml. Significantly decreased extraintestinal manifestations of IBS. In reassessing each patient's individual characteristics there were the decrease of the depression level according to the Beck scale from 26 (23; 32) to 11.5 (10; 13) points and personal personal anxiety level according to the Spielberger-Khanin scale from 42.5 (35; 53) to 22 (20; 24) points, as well as the decrease of situational anxiety from 40 (37; 49) to 22 (21; 36) points., Conclusion: The severe course of IBS-D is mainly associated with the patients' individual characteristics and anxiety or anxiety-depressive syndromes. The positive impact of duloxetine therapy in severe IBS-D with extraintestinal manifestations is associated with the regulation of serotonergic and noradrenergic activity of the central.