Selective Serotonin Reuptake Inhibitors Research Articles

Prefrontal cortex-nucleus reuniens-hippocampus network exhibits sex-differentiated responses to stress and antidepressant treatment in rats.

Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression. In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine. Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity. RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females. Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.

Adsorption of Nefazodone on single-wall carbon nanotube as an antidepressant drug delivery: A DFT study

Nefazodone, a derivative of triazolones, belongs to a group of heterocyclic aromatic compounds. It is used as an antidepressant for treating depression, including major depressive disorder. Unlike other antidepressant groups such as selective serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors, Nefazodone does not share chemical similarities. Recent research has focused on studying the reactivity and chemical structure influenced by Nefazodone's medicinal features in the drug's adsorption process on single-wall Carbon Nanotube (CNT) as an adsorbent in the gas phase using density functional theory (DFT), Becke, 3-parameter, Lee–Yang–Parr (B3LYP) 6-311+G(d,p) basis set (DFT/B3LYP/6-311+G(d,p)). The effect of electronegative atoms and phenyl groups on the adsorption of Nefazodone on CNT has been studied by calculating the adsorption energy for all active sites. On the other hand, thermodynamic values, such as Gibbs free energy (−4873.09 kJ), Enthalpy (−4872.83 kJ), and Entropy (903.09 J/mol.kelvin), as well as thermodynamic capacity (497.45 J/mol.kelvin), were calculated to show the reactivity of Nefazodone. The stability and reactivity were examined through the energies of the highest occupied molecular orbital (HOMO) (−5.53 eV) and lowest unoccupied molecular orbital (LUMO) (−0.58 eV) of Nefazodone, highlighting ten regions with chemical activity, all of which are thermodynamically stable. Some Electronic parameters such as chemical potential (µ), electronegativity (χ), softness (σ), hardness (η), and electrophilicity index (ω) were calculated. The comparison of chemical potential values between Nefazodone(−3.05 eV) and the more stable complex (−3.81 eV) illustrates the more reactivity for the complex. This suggests that Nefazodone can be transferred to biological systems through such an adsorption mechanism.

Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response

This study compared the power of the novel inflammatory markers systemic immune inflammation index (SII) and the system inflammation response index (SIRI) versus the classical hematological indices neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and platelet counts in distinguishing between major depressive disorder (MDD) with and without suicide attempts and distinguishing the non-response to selective serotonin reuptake inhibitor (SSRI) treatment. A total of 139 young adult MDD patients and 54 healthy controls (HC) were included. We found that, in comparison to HC, baseline NLR, PLR, SII, and SIRI were significantly higher in MDD patients, but only NLR and SII had area under the ROC curve (AUC) values greater than 0.7. MDD patients with suicide attempts (SA) showed significantly higher baseline MLR and SIRI, and a tendency to increase NLR compared to those without SA. In terms of AUC, sensitivity, and specificity, NLR was better than MLR, SIRI, SII, and PLR in distinguishing SA. Non-responders to SSRI treatment showed a significant increase in baseline platelet count and PLR compared to responders with an AUC greater than 0.7. These findings highlight the potential benefit of combining novel and classical hematological indices in predicting depression, suicide attempts and treatment response.

Current trends and hotspots of depressive disorders with colorectal cancer: A bibliometric and visual study

BACKGROUND Depression is strongly associated with colorectal cancer (CRC). Few bibliometric analyses have systematically summarized the research focus and recent progress in this field. AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression. METHODS Articles on depression in CRC patients were collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were used to visualize bibliometric networks. RESULTS From 2001 to 2022, Supportive Care in Cancer , the United States, Tilburg University, and Mols were the most productive and influential journal, country, institution, and author name. Co-occurrence cluster analysis of keywords placed quality of life, anxiety, and psychological stress in the center of the visual network diagram. Further clustering was performed for the clusters with studies of the relevant mechanism of action, which showed that: (1) Cytokines have a role essential for the occurrence and development of depressive disorders in CRC; (2) MicroRNAs have a role essential for the development of depressive disorders in CRC; (3) Some anticancer drugs have pro-depressant activity; and (4) Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity. CONCLUSION Life quality and psychological nursing of the cancer population were key topics. The roles of cytokines and microRNAs, the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.

Association Between the Inflammatory Potential of Diet and Constipation Among Adults in the United States: A Cross-sectional Study.

To investigate the potential association between Dietary Inflammatory Index (DII) scores and constipation among a sample of adults in the United States. This cross-sectional study used data from adult participants in the 2005 to 2010 National Health and Nutrition Examination Survey (ie, "NHANES"). Self-reported information was used to identify cases of constipation. The DII was used to assess inflammatory potential of the diet. Odds ratios (ORs) and corresponding 95% CIs for the association between the DII and constipation were determined using multivariate logistic regression modeling. Stratified analyses explored whether there was effect modification to influence the relationship between DII and constipation. Of 8272 subjects, 759 reported constipation, and 7513 did not, corresponding to a prevalence of 9.2%. After adjusting for age, gender, race/ethnicity, marital status, education level, smoking status, alcohol consumption, physical activity, body mass index (BMI), cardiovascular diseases (CVD), hypertension, stroke, diabetes, energy intake, carbohydrate intake, and selective serotonin reuptake inhibitor (SSRI) use. Compared with lower DII scores group T1 (-5.28 to ≤0.72), the adjusted OR values for DII scores and constipation in T2 (>0.72 to ≤2.50) and T3 (>2.50 to 5.24) were 1.27 (95% CI: 1.02-1.58, P=0.029) and 1.43(95% CI: 1.14-1.8, P=0.002). Subgroup analyses showed that there were effect modification of gender and physical activity factors on DII scores and constipation. Results of this cross-sectional study suggest that a higher dietary inflammatory index score was associated with increased risk of constipation after adjustment for confounding in a multivariable analysis. gender and physical activity were found to be an effect modifier of this relationship.

Impact of the use of a drug–drug interaction checker on pharmacist interventions involving well-known strong interactors

ObjectivesSeveral drug–drug interaction (DDI) checkers such as DDI-Predictor have been developed to detect and grade DDIs. DDI-Predictor gives an estimate of the magnitude of an interaction based on the ratio...

Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci.

Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac®) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K+ channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K+ currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K+ currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 μM fluoxetine notably reduced K+ currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K+ current and revealed a rapidly activating and inactivating K+ current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K+ currents persisted following application of 100 μM fluoxetine. Additionally, marked inhibition of transient inward Na+ currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC50 values were found to be 40 µM and 32 µM for K+ and Na+ currents, respectively. In contrast, 100 μM fluoxetine had no impact on voltage-dependent K+ currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na+ and K+ conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance.

Maternal fluoxetine impairs synaptic transmission and plasticity in the medial prefrontal cortex and alters the structure and function of dorsal raphe nucleus neurons in offspring mice

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are commonly prescribed to women during pregnancy and breastfeeding despite posing a risk of adverse cognitive outcomes and affective disorders for the child. The consequences of SSRI-induced excess of 5-HT during development for the brain neuromodulatory 5-HT system remain largely unexplored. In this study, an SSRI - fluoxetine (FLX) - was administered to C57BL/6 J mouse dams during pregnancy and lactation to assess its effects on the offspring. We found that maternal FLX decreased field potentials, impaired long-term potentiation, facilitated long-term depression and tended to increase the density of 5-HTergic fibers in the medial prefrontal cortex (mPFC) of female but not male adolescent offspring. These effects were accompanied by deteriorated performance in the temporal order memory task and reduced sucrose preference with no change in marble burying behavior in FLX-exposed female offspring. We also found that maternal FLX reduced the axodendritic tree complexity of 5-HT dorsal raphe nucleus (DRN) neurons in female but not male offspring, with no changes in the excitability of DRN neurons of either sex. While no effects of maternal FLX on inhibitory postsynaptic currents (sIPSCs) in DRN neurons were found, we observed a significant influence of FLX exposure on kinetics of spontaneous excitatory postsynaptic currents (sEPSCs) in DRN neurons. Finally, we report that no changes in field potentials and synaptic plasticity were evident in the mPFC of the offspring after maternal exposure during pregnancy and lactation to a new antidepressant, vortioxetine. These findings show that in contrast to the mPFC, long-term consequences of maternal FLX exposure on the structure and function of DRN 5-HT neurons are mild and suggest a sex-dependent, distinct sensitivity of cortical and brainstem neurons to FLX exposure in early life. Vortioxetine appears to exert fewer side effects with regards to the mPFC when compared with FLX.

Gepirone: A New Extended-Release Oral Selective Serotonin Receptor Agonist for Major Depressive Disorder

Objective: To evaluate the safety, efficacy, and tolerability of gepirone (Exxua) in the treatment of adult patients with major depressive disorder. Data Sources: A literature search was performed through PubMed, Embase, and PsycINFO using the following terms: Exxua, gepirone, depression, major depressive disorder, anxiety, and anxiety disorders. Study Selection and Data Extraction: Articles that were selected included English-language dominant studies, or studies that could be translated into English by the authors, with terms associated with the safety, efficacy, and/or tolerability of gepirone. Data Synthesis: Gepirone exhibits its antidepressant activity through agonism of 5HT1A serotonin receptors. Phase 3 clinical trials showed that gepirone at a dose of 20 to 80 mg was proven to be effective in the treatment of major depressive disorder in adult patients. Common adverse effects reported in clinical trials included dizziness, nausea, headache, fatigue, and insomnia. Conclusion: This review evaluates the pharmacokinetic, pharmacologic, efficacy, and safety profile of gepirone and includes a discussion on its place in therapy for the treatment of major depressive disorder. Most clinical guidelines recommend second-generation antidepressants consisting of selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors as first-line therapy options. Gepirone is expected to receive greater clinical relevance and recommendations when compared to other azapirone medications (buspirone) within practice guidelines. Gepirone could be considered as either an alternative option for patients failing first-line therapies or for initial use to avoid unwanted side effects of other therapy options in the treatment of adult patients with major depressive disorder.

Fibromyalgia Diagnosis and Treatment Receipt in the U.S. Military Health System.

Meta-analytic findings and clinical practice guidance recommend pharmacological (e.g., pregabalin, duloxetine, and milnacipran) and non-pharmacological (e.g., exercise and sleep hygiene) interventions to reduce symptoms and improve quality of life in people living with fibromyalgia. However, some of these therapies may lack robust evidence as to their efficacy, have side effects that may outweigh benefits, or carry risks. Although the annual prevalence of fibromyalgia in active duty service members was estimated to be 0.015% in 2018, the likelihood of receiving a fibromyalgia diagnosis was 9 times greater in patients assigned female than male and twice as common in non-Hispanic Black than White service members. Therefore, the primary goal of this retrospective study is to examine co-occurring conditions and pain-management care receipt in the 3 months before and 3 months after fibromyalgia diagnosis in active duty service members from 2015 to 2022. Medical record information from active duty service members who received a fibromyalgia diagnosis between 2015 and 2022 in the U.S. Military Health System was included in the analyses. Bivariate analyses evaluated inequities in co-occurring diagnoses (abdominal and pelvic pain, insomnia, psychiatric conditions, and migraines), health care (acupuncture and dry needling, biofeedback and other muscle relaxation, chiropractic and osteopathic treatments, exercise classes and activities, massage therapy, behavioral health care, other physical interventions, physical therapy, self-care management, and transcutaneous electrical nerve stimulation), and prescription receipt (anxiolytics, gabapentinoids, muscle relaxants, non-opioid pain medication, opioids, selective serotonin and norepinephrine inhibitors, and tramadol) across race and ethnicity and assigned sex. Pairwise comparisons were made using a false discovery rate adjusted P value. Overall, 13,663 service members received a fibromyalgia diagnosis during the study period. Approximately 52% received a follow-up visit within 3 months of index diagnosis. Most service members received a co-occurring psychiatric diagnosis (35%), followed by insomnia (24%), migraines (20%), and abdominal and pelvic pain diagnoses (19%) fibromyalgia diagnosis. At least half received exercise classes and activities (52%), behavioral health care (52%), or physical therapy (50%). Less commonly received therapies included other physical interventions (41%), chiropractic/osteopathic care (40%), massage therapy (40%), transcutaneous electrical nerve stimulation (33%), self-care education (29%), biofeedback and other muscle relaxation therapies (22%), and acupuncture or dry needling (14%). The most common prescriptions received were non-opioid pain medications (72%), followed by muscle relaxers (44%), opioids (32%), anxiolytics (31%), gabapentinoids (26%), serotonin-norepinephrine reuptake inhibitor (21%), selective serotonin reuptake inhibitors (20%), and tramadol (15%). There were many inequities identified across outcomes. Overall, service members diagnosed with fibromyalgia received variable guideline-congruent health care within the 3 months before and after fibromyalgia diagnosis. Almost 1 in 3 service members received an opioid prescription, which has been explicitly recommended against use in guidelines. Pairwise comparisons indicated unwarranted variation across assigned sex and race and ethnicity in both co-occurring health conditions and care receipt. Underlying reasons for health and health care inequities can be multisourced and modifiable. It is unclear whether the U.S. Military Health System has consolidated patient resources to support patients living with fibromyalgia and if so, the extent to which such resources are accessible and known to patients and their clinicians.

The effect of vortioxetine on faecal microbiota in high-fat diet-exposed mice-A link to weight protection.

Weight gain is a common side effect of antidepressive treatment, causing distress among patients and caretakers as it can lead to treatment discontinuation and complications such as diabetes type II and cardiovascular disease. Vortioxetine is one of the newer antidepressants and the pharmacodynamics differ from the selective serotonin reuptake inhibitors. It is marketed as being weight neutral; however, there is little evidence as to why. In recent years, there has been an increased focus on the faecal microbiota and its impact on body weight and mental and physical health. In the current work, we examine the effect of vortioxetine on weight gain and faecal microbiota composition. Forty male C57BL/6NTac mice were primed for 8 weeks with a high-fat diet (Hfd) or control diet (Cd), followed by a 4-week period on the same diet and additional +/- vortioxetine 10 mg/kg/daily. Vortioxetine reduced Hfd-induced weight gain (Hfd + V: 8.2%, Hfd - V: 12.7%; p=0.0374) but did not affect weight gain of the control group (Cd + V: 7.54%, Cd - V: 7.56%; p=0.4944). Significant differences in faecal microbiota were observed in mice who received vortioxetine. Vortioxetine caused significant changes to the faecal microbiota composition and appeared to limit Hfd-induced weight gain.

Distinct homotopic functional connectivity patterns of the amygdalar sub-regions as biomarkers in major depressive disorder

BackgroundMajor depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs). MethodSixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment. ResultsPatients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = −0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases. LimitationsThe current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined. ConclusionsUsing a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.

Direct serotonin release in humans shapes aversive learning and inhibition

The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.

Fluoxetine accelerates epileptogenesis and magnifies disease severity in a rat model of acquired epilepsy.

Many people with epilepsy experience comorbid anxiety and depression, and antidepressants remain a primary treatment for this. Emerging evidence suggests that these agents may modulate epileptogenesis to influence disease severity. Here, we assessed how treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine impacts epileptogenic, behavioral, and pathological sequelae following status epilepticus. Male Wistar rats received kainic acid to induce status epilepticus (SE) or vehicle (sham). Animals then received either fluoxetine (10 mg/kg/day) or vehicle for 8 weeks via subcutaneous osmotic pump. Video-electroencephalography was recorded continuously until behavioral testing at day 56, including assessments of anxiety- and depression-like behavior and spatial cognition. Postmortem immunocytochemistry studies examined mossy fiber sprouting. Fluoxetine treatment significantly accelerated epileptogenesis following SE, reducing the average period to the first spontaneous seizure (from 32 days [vehicle] to 6 days [fluoxetine], p < .01). Also, fluoxetine exposure magnified the severity of the resultant epilepsy, increasing seizure frequency compared to vehicle (p < .01). Exposure to fluoxetine was associated with improved anxiety- and depression-like behaviors but significantly worsened cognition. Mossy fiber sprouting was more pronounced in fluoxetine-treated rats compared to vehicle (p < .0001). Our studies demonstrate that, using a model exhibiting spontaneous seizures, epileptogenesis is accelerated and magnified by fluoxetine, an effect that may be related to more severe pathological neuroplasticity. The differential influence of fluoxetine on behavior indicates that different circuitry and mechanisms are responsible for these comorbidities. These findings suggest that caution should be exercised when prescribing SSRI antidepressants to people at risk of developing epilepsy.

Probiotic Supplements For Depression In Parkinson’s Disease (Pro-Park): A Randomized, Triple-Blind, Placebo-Controlled, Phase IIb Trial Protocol

Introduction: Parkinson’s disease (PD) is the second most prevalent degenerative neurological disorder globally. Comorbid major depressive disorder (MDD) is a common occurrence which adds considerably to disease burden. This protocol presents a study designed to investigate the effect of add-on probiotic supplementation on MDD in patients with PD. Methods: We designed a phase IIb, randomized, triple-blind, placebo-controlled study to evaluate the efficacy and safety of probiotics as an adjuvant treatment to selective serotonin reuptake inhibitors (SSRI) for patients with mild to moderate PD and MDD. Participants will be randomized to probiotics (n=62) or placebo (n=62) arms using a permuted block randomization approach. Co-primary outcomes include changes in Montgomery-Åsberg Depression Rating Scale (MADRS)scores and SSRI equivalent doses, which will be compared between groups using a bivariate joint model. Secondary outcomes will include changes in both Beck Depression Inventory-II (BDI-II) score and levodopa dose, which will be analyzed using t-tests or Mann-Whitney tests as appropriate. Concurrent validity between MADRS and BDI-II will be assessed using Pearson’s or Spearman’s correlation tests. Safety will be evaluated by comparing discontinuation rates and adverse events between groups using chi-square. Data will be analyzed using intention-to-treat and per-protocol analyses, and missing data will be addressed using multiple imputation methods. Discussion: Probiotics represent a potential new approach to managing depression in patients with PD by targeting the gut-brain axis. The results will offer crucial information about the safety and efficacy of a low-cost and readily available supplement that may alleviate depression in this vulnerable population.

Periodontitis and Depressive Disorders: The Effects of Antidepressant Drugs on the Periodontium in Clinical and Preclinical Models: A Narrative Review.

Background/Objectives: Several psychological conditions, including stress and depression, can adversely affect oral health; in fact, antidepressants, commonly used to treat depressive disorders, may have conflicting effects on the periodontal status of individuals. The aim of this review was to determine the effects of antidepressants on the periodontium. Methods: A literature search was conducted using electronic databases, Pubmed/MEDLINE, Cochrane Library, focusing on the use of antidepressants and their effects on periodontal health in animals or humans. Results: Seventeen articles have been included with the use of amitriptyline (two studies), desipramine (one study), imipramine (two studies), desvenlafaxine (one study), fluoxetine (six studies), venlafaxine (three studies) and tianeptine (two studies). One study evaluated several categories of antidepressants, such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic, atypical and monoamine oxidase inhibitors (MAO). Most trials showed improvements in periodontal health, especially with fluoxetine, but also with imipramine, desipramine, desvenlafaxine and tianeptine; on the contrary, worsening of clinical periodontal indices and increased loss of alveolar bone were reported with venlafaxine. Conclusions: This review suggests that in the presence of comorbidity between periodontitis and depression, pharmacological treatment with SNRIs, SSRIs and mixed antidepressants is associated with improvement in periodontal parameters, except for venlafaxine. Healthcare professionals (especially oral and mental health professionals) should investigate proper adherence to medication therapy in patients with a history of periodontitis and depression. Further clinical trials are needed to confirm these results.

Impact of selective serotonin reuptake inhibitors on weight loss after vertical sleeve gastrectomy

BackgroundMental health disorders, such as depression, are prominent within the bariatric population, with antidepressants ranking among the most frequently prescribed medications. ObjectivesOur surgery aimed to investigate selective serotonin reuptake inhibitor (SSRI) effects on weight loss in patients undergoing vertical sleeve gastrectomy (VSG). SettingUniversity affiliated Community Hospital, United States. MethodsWe performed a retrospective chart review at a single bariatric center, involving multiple bariatric surgeons, on adults (>18 years of age) who underwent VSG between 2011 and 2018. The patients were followed for a total of 2 years. Exclusion criteria included revisional surgery during the 2-year follow-up period, SSRI prescription initiated after the index surgery or within 2 years following surgery, and individuals who missed 3 or more postoperative visits. A total of 267 patients met the criteria and were categorized into 2 groups: those prescribed an SSRI prior to surgery and those not on an SSRI. Statistical analysis was performed using T-tests and chi-square tests, with significance set at P < .05. ResultsThe preoperative weight in the SSRI group averaged 118.57 kg (±20.59), whereas in the non-SSRI group, it averaged 129.60 kg (±24.39) (P < .0001). Similarly, the preoperative body mass index (BMI) in the SSRI group averaged 43.34 (±6.14), while in the non-SSRI group, it averaged 46.13 (±6.82) (P = .001). At the 1-month, 3-month, and 6-month follow-ups, the average BMI and weight were lower in the SSRI group compared to the non-SSRI group. However, at the 1-year and 2-year follow-ups, the weight and BMI were no longer statistically different. There was no significant difference in the percentage total weight change (%TWC) between the groups; the %TWC was 22.17 in the SSRI group and 23.35 in the non-SSRI group (P = .324). Follow-up attendance significantly decreased at each subsequent interval, with 65.41% in the SSRI group and 29.27% in the non-SSRI group at the 2-year follow-up. ConclusionsBased on our analysis, we suggest that VSG can be an effective option for weight loss in patients taking SSRIs. However, due to the limitations, particularly with follow-up of this study, further research is needed to support this conclusion.

Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder

BackgroundBrain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HT4R levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment. MethodsNinety patients with moderate to severe depression underwent molecular brain imaging to measure 5-HT4R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT4R binding was assessed for its ability to predict treatment outcome at weeks 4, 8, or 12. In 40 patients who were rescanned 8 weeks posttreatment, change in cerebral 5-HT4R binding was correlated with change in verbal memory and with change in depressive symptoms, as evaluated by the 6-item Hamilton Depression Rating Scale. ResultsAfter 8 weeks of serotonergic intervention, neostriatal 5-HT4R binding was reduced by 9%. Global change in 5-HT4R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT4R binding did not predict clinical recovery status at week 8 and was not associated with change in the 6-item Hamilton Depression Rating Scale scores. ConclusionsIn patients with moderate to severe MDD, treatment with selective serotonin reuptake inhibitors downregulated neostriatal 5-HT4R levels, which is consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT4R levels were downregulated after selective serotonin reuptake inhibitors, the more verbal memory improved, highlighting the potential importance of 5-HT4R as a treatment target in MDD. The findings offer insights into mechanisms that underlie antidepressant effects and point to new directions for precision medicine treatments for MDD.

Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis and Cell Cycle Arrest.

Drug repurposing in oncology promises benefits to many patients through its ability to provide novel, and fast-tracked treatments. Previous studies have demonstrated that depression may influence tumor progression. Anti-proliferative activity of certain antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are reported in the literature. This study was conducted to repurpose selective serotonin reuptake inhibitors (SSRIs) for the treatment of breast cancers, and it merits further validation and research. Changes in cell morphology were studied using DAPI staining, while the Annexin V/PI method was employed for apoptotic analysis. The expression of specific genes involved in cancer progression was also analyzed via RT-PCR. Caspase-3 activation was measured through fluorometric assay. We have identified that sertraline hydrochloride significantly inhibited the growth of breast cancer cell in vitro. Preliminary mechanistic studies demonstrated that the cytotoxicity of sertraline hydrochloride was possibly through the induction of apoptosis, as inferred from enhanced nuclear fragmentation, flow cytometric data, and caspase-3/7 activation. Gene expression analysis also showed an increased expression of pro-apoptotic Bax, and a slight decrease in oncogene c-myc in the presence of sertraline hydrochloride. In conclusion, our study suggest that sertraline hydrochloride, an antidepressant drug, can potentially be used for the treatment of breast cancer.

WAY-208466, a 5-HT6 receptor agonist, increases food motivation in primates: A behavioural and PET imaging study opening perspectives in eating disorders

The 5-HT6 receptor (5-HT6R) is highly expressed in the anterior striatum, a region involved in food-intake and anxiety-related behaviours that shows abnormal activity in anorexia nervosa (AN) patients. Indeed, 5-HT6R antagonists decrease food motivation across species. Rodent studies have shown the acute anxiolytic properties of WAY-208466, a selective 5-HT6R agonist. Thus, we hypothesized that this agent could increase food motivation and decrease anxiety-related behaviours by impacting cortico-striatal circuits. We administered acute (0.1 mg/kg) and subchronic (0.03 and 0.1 mg/kg) intramuscular injections to four macaques performing a food-choice task and expressing spontaneous behaviours. We used PET imaging with the [18F]2FNQ1P specific tracer to determine 5-HT6R occupancy in several regions that could be linked with the induced behavioural changes. Acute and subchronic activation of 5-HT6R transmission led to a reversible increase in food motivation. WAY-208466 also decreased anxiety-like behaviours when given acutely but not subchronically. However, in the subchronic protocol, the higher dose led to increased activity characterized by movements and object-related behaviour expression. PET imaging revealed that these behavioural changes could be sustained by cortico-striatal circuits involved in food intake. These findings demonstrate that this 5-HT6R agonist subchronic treatment successfully increases food motivation but does not fully achieve the expected anxiolytic effect in monkeys. It suggests that targeting 5-HT6Rs may be a promising approach for treating the restrictive subtype of AN, which, unlike anxiety, has not been shown to benefit from treatment with selective serotonin reuptake inhibitors.