Serotonin Reuptake Inhibitors Research Articles

Citalopram & escitalopram: Mechanisms of cardiotoxicity, toxicology predisposition and risks of use in geriatric & hemodialysis populations.

The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are extensively prescribed for various psychopathies. Despite their reputation for safety compared to older antidepressants, concerns have arisen regarding their cardiotoxic potential, notably in prolonging the QTc interval. In this comprehensive review, we investigate the intricate mechanisms of cardiotoxicity induction by citalopram/escitalopram, with a special focus on their interactions with ion channels like Kv11.1, Nav1.5, and Cav1.2 which may contribute to QTc-prolongation, increasing the risk of life-threatening arrhythmias such as Torsades de Pointes (TdP). Moreover, we explore the predisposing factors to their associated cardiotoxicity along with an investigation of the QRS/QTc ratio as a potential biomarker for identifying patients at risk of ventricular arrhythmias, taking into consideration the impact of genetic variations and drug interactions, especially those involving the liver CYP2C19 metabolism. Our review extends to the geriatric population's use of citalopram and escitalopram, emphasizing the significance of assessing a patient's medical history and cumulative drug use to evaluate their susceptibility to cardiac adverse events. Finally, we scrutinize the compound relationship between QTc-prolongation, proton pump inhibitors (PPIs) and serum-to-dialysate potassium gradients in influencing the proarrhythmic potential of citalopram/escitalopram in hemodialysis patients.

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.

MDMA Therapy for PTSD: Inching Closer to-or Farther From-Approval?

In recent years, scientists have initiated a renaissance in psychedelic research following decades of prohibition. Compounds such as ketamine, LSD, and psilocybin 'once primarily associated with recreational use' are now being investigated for their therapeutic potential, with promising results. An estimated 40-60% of people with post-traumatic stress disorder (PTSD) do not respond to selective serotonin reuptake inhibitors, which are the first-line medications for this condition. However, one standout among these psychedelics is methylenedioxy methamphetamine (MDMA), which has demonstrated exceptional efficacy in treating PTSD and medication-resistant depression. Growing results in research were so positive that, in 2017, the US Food and Drug Administration (FDA) designated MDMA-assisted psychotherapy as a breakthrough therapy. Though MDMA is not yet officially legal or approved for clinical use, Phase 3 trials are underway, and expanded access status was granted in 2020 in the United States and Israel. Preliminary clinical studies are extremely promising, and the FDA could approve MDMA-assisted psychotherapy for PTSD as early as 2024, offering a potential treatment for this crippling mental health condition that affects almost 3.5% of US adults.

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.

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.

Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice

Serotonin reuptake inhibitor antidepressants such as fluoxetine are widely used to treat mood disorders. The mechanisms of action include an increase in extracellular level of serotonin, neurogenesis, and growth of vessels in the brain. We investigated whether fluoxetine could have broader peripheral regenerative properties. Following prolonged administration of fluoxetine in male mice, we showed that fluoxetine increases the number of muscle stem cells and muscle angiogenesis, associated with positive changes in skeletal muscle function. Fluoxetine also improved skeletal muscle regeneration after single and multiples injuries with an increased muscle stem cells pool and vessel density associated with reduced fibrotic lesions and inflammation. Mice devoid of peripheral serotonin treated with fluoxetine did not exhibit beneficial effects during muscle regeneration. Specifically, pharmacological, and genetic inactivation of the 5-HT1B subtype serotonin receptor also abolished the enhanced regenerative process induced by fluoxetine. We highlight here a regenerative property of serotonin on skeletal muscle.

From Zero to Overwhelm: PANS and PANDAS as Culprits Behind Sudden OCD in Pediatrics

Pediatric autoimmune neuropsychiatric disorders (PANDAS) and patient neuropsychiatric syndrome (PANS) are psychiatric illnesses characterized by a rapid onset of symptoms, including obsessive-compulsive disorder (OCD), behavioral symptoms and poor motor functions in children. The rapid onset and severity of OCD symptoms prompted investigations to provide an evidence-based intervention. This case series investigates the causes, diagnosis and treatment of the disease among children presenting with neuropsychiatric symptoms and acute-onset OCD. The diagnostic procedures provided grounds for the indication of medication. Methods: Bacterial infections, autoimmune cases and viral infections among 12 children with PANDAS and PANS were retrospectively studied. Pre- and post-treatment symptomatology were examined to monitor the effectiveness of interventions, following laboratory diagnostic approaches, including the Cunningham panel, serology, stool sample analysis, polymerase chain reaction (PCR), and bacterial cultures to determine the cause of the disorder. Diagnostic results informed treatments like non-steroidal anti-inflammatory drugs (NSAIDs), intravenous immunoglobulin (IVIG), fluid therapy, antibiotics, antivirals, steroids, and selective serotonin reuptake inhibitors (SSRIs) in each child. Post-treatment diagnostic results revealed remarkably improved symptoms of PANDAS and PANS, like inflammation and viral or bacterial infection. A combined therapy of antibiotics and NSAIDs or steroids was used to clear bacterial infections and manage inflammation. SSRIs and antiviral or fluid therapy were indicated for OCD and viral infections, respectively. Conclusions: OCD is a common comorbid disorder among children with PANS and PANDAS. Despite the severity and prevalence, OCD in children raises health concerns. The case series demonstrated the effectiveness of antibiotic therapy, RRIs, cognitive behavioral therapy, IVIG, steroids and NSAIDs in managing OCD in PANDAS and PANS, with a unique rationale of indication to every child. Keywords: PANS, PANDAS, Sudden Onset OCD, Pediatric OCD, Autoimmune Neuropsychiatric Disorders

French adaptation and validation of the Niigata PPPD Questionnaire: measure of severity of Persistent Postural-Perceptual Dizziness and its association with psychiatric comorbidities and perceived handicap.

Persistent Postural-Perceptual Dizziness (PPPD) is a functional vestibular condition. Despite being the most common chronic neuro-otologic disorder, it remains undertreated. The Niigata PPPD Questionnaire (NPQ), developed by Yagi et al. in 2019 to assess the severity of PPPD, could be a useful tool to help in the screening and diagnosis of this condition. This study aimed to validate a French version of the NPQ and make it an available assessment tool. Moreover, we aimed to understand the characteristics of PPPD patients better. The NPQ was translated and adapted into French. 50 PPPD patients, 50 patients with vestibular disorders without PPPD, and 50 healthy controls were included. They answered the adapted NPQ and additional questionnaires assessing trait (STAI) and state anxiety (HADS-A), depression (HADS-D) and handicap related to dizziness (DHI). The NPQ's reliability was assessed by Cronbach's alpha. Intergroup comparisons and multiple linear regressions were conducted to examine the characteristics of PPPD patients compared to vestibular patients and healthy controls, to validate NPQ's reliability, and to explore the effect of clinical parameters and treatment with selective serotonin reuptake inhibitors. Receiver operating characteristic (ROC) curves were carried out to determine the diagnostic values of the NPQ total score and sub-scores. Relations between NPQ and reported handicap, depression and anxiety were evaluated by correlations between questionnaire scores. The internal consistency was high (>0.8) for all NPQ subscales and the total score. Intergroup comparisons showed a significantly higher NPQ total score and sub-scores in the PPPD group compared to the two others. The ROC curve analysis showed a significant, but poor, discrimination of NPQ (AUC = 0.664) and its subscales. DHI scores, depressive symptoms and trait anxiety were significantly higher in PPPD patients than in vestibular patients and healthy controls. State anxiety did not differ between patients with PPPD and vestibular patients without PPPD. Finally, there was a significant correlation between the NPQ and the DHI. Our study provides a better understanding of PPPD symptomatology and its assessment. It showed that the NPQ is a reliable tool that can assist in symptom assessment for a French-speaking population.

Effect of reboxetine and citalopram on anal opening pressure in healthy women: A randomized, double-blind, placebo-controlled crossover study.

In placebo-controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers. In a double-blind, three-way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8-day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs. Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5-30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2-29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo. An 8-mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40-mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone.

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.

Common Mental Health Disorders and Their Current Prescription Patterns in Saudi Arabia's Primary Healthcare Settings.

Background The mental healthcare program is widely implemented in primary healthcare settings in Saudi Arabia. It consisted of early screening and management of mental health disorders associated with chronic health conditions. Family physicians are authorized to prescribe selective serotonin reuptake inhibitors (SSRIs) for early management of mental health disorders in primary healthcare centers (PHCs).The aim of the study is exploring the prevalence of various types of mental health disorders and to assess the prescribing pattern of SSRIs in PHCs. Materials and methods A cross-sectional study based on the data from electronic health records, telephone interviews, and prescriptions of individuals administered SSRIs at PHCs. Results Among 219 patients visiting PHCs, 67.6%were female participants. Forty-four percent of the patients were 20-30 years oldand 61.2%of them received SSRImedications. The most prevalent chronic condition was diabetes (22.5%) followed by hypertension (20.5%) and asthma (6.4%). The most prevalent mental disorder was major depressive disorder (MDD; 78.1%), followed by anxiety disorder (7.3%), panic disorder (6.4%), and MDD with anxiety disorders (5.5%). Conclusion Implementing mental healthcare programs in PHCsis believed to promote population health. MDDwas the predominant mental health disorder among patients visiting PHCs, and SSRIs were the most prescribed medications in this setting. This suggests that mental healthcare programs in PHCs are effective in improving mental health outcomes.

Antidepressant class and concurrent rTMS outcomes in major depressive disorder: a systematic review and meta-analysis

Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of-0.65 [-0.98,-0.31], p=0.0002, I2=66.1%), higher response (OR=0.97 [0.50, 1.44], p<0.0001, I2=25.33%) and remission rates (OR=1.04 [0.55, 1.52], p<0.0001, I2=0.00%) than medication with sham rTMS. No additive benefit was found for SNRIs with rTMS (SMD of 0.10 [-0.14, 0.34], p=0.42, I2=0.00%; OR=0.12 [-0.39, 0.62], p=0.64, I2=0.00%; OR=-0.31 [-0.90, 0.28], p=0.86, I2=39.9%). The overall risk of bias for the included studies ranged from low to high, with 1 study having a high risk of bias. The combination of rTMS with SSRIs, but not SNRIs, significantly reduced depression severity, increasing response and remission rates. Some analyses demonstrated high heterogeneity, which was influenced by an SSRI trial with a high effect size. Overall, these results suggest that not all antidepressant combination therapies are alike, and SSRIs should be considered when initiating rTMS. Donald T. Stuss Young Investigator Research Innovation Award from the Sandra Black Centre for Brain Resilience & Recovery and the Harquail Centre for Neuromodulation through the Sunnybrook Foundation.

Eye disorders associated with selective serotonin reuptake inhibitors: a real-world disproportionality analysis of FDA adverse event reporting system

ABSTRACT Background Selective serotonin reuptake inhibitors (SSRIs) are widely used in depression and other psychiatric disorders. Despite their efficacy, there is a growing concern about the risk of eye disorders. This study aims to explore the potential correlation between eye disorders and SSRIs utilizing real-world data. Research design and methods The data were extracted from the US FDA Adverse Event Reporting System database from 2004Q1 to 2023Q3. The analysis focused on the clinical characteristics, the ranking of adverse reactions, the time-to-onset, and the severity proportion of SSRI-related eye disorders. Results Our analysis revealed that SSRIs were significantly associated with eye disorders, with a higher risk of vision blurred with escitalopram, angle closure glaucoma with citalopram, and photopsia with paroxetine. The most common eye disorders were vision blurred, visual impairment, mydriasis, etc. Most of these adverse events occurred within the first 30 days of treatment. The reported incidence of severe eye disorders was 38.6% for SSRIs, with fluoxetine exhibiting the highest rate at 45.9%. Conclusion Our study demonstrates a significant association between SSRIs and the risk of eye disorders. These findings provide crucial insights for clinicians when prescribing SSRIs and underscore the need to monitor eye health in patients receiving these medications.

Effect of bariatric surgery on nutritional and metabolic parameters: does the type of antidepressant medication matter?

PurposeDepression is prevalent in patients undergoing bariatric surgery (BSx). Long-term use of antidepressant is associated with weight gain, particularly the use of selective serotonin reuptake inhibitors (SSRIs). Little is known about whether different types of antidepressants affect the response to BSx. The purpose of this study was to determine the relationship between SSRI use and nutritional and biochemical measurements in those with obesity pre-/post-BSx.MethodsThis is a cross-sectional and prospective cohort study. Patients were enrolled pre-BSx and divided into 3 groups: SSRI, non-SSRI and no antidepressant. Nutritional, biochemical and pharmacological data were collected pre- and 6 months post-BSx.ResultsPre-BSx, 77 patients were enrolled: 89.6% female, median age 45 years and body mass index (BMI) of 45.3 kg/m2. 14.3% were taking SSRIs and had a significantly higher BMI (52.1 kg/m2) compared to 62.3% in no antidepressant (46.0 kg/m2) and 23.4% in non-SSRI antidepressants (43.1 kg/m2). At 6 months post-BSx (n = 58), the SSRI group still had significantly higher BMI in comparison to the other two groups. No other significant differences found between groups.ConclusionDespite higher BMI, patients taking SSRI and undergoing BSx had similar responses, based on nutritional and biochemical parameters, to those on non-SSRI or no antidepressants.Level of evidenceLevel III: Evidence obtained from well-designed cohort or case–control analytic studies.

DNA Sequence Variations Affecting Serotonin Transporter Transcriptional Regulation and Activity: Do They Impact Alcohol Addiction?

Genetic features of alcohol dependence have been extensively investigated in recent years. A large body of studies has underlined the important role of genetic variants not only in metabolic pathways but also in the neurobiology of alcohol dependence, mediated by the neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded by the SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted by antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) and plays a pivotal role in serotoninergic transmission; it has been associated with psychiatric diseases and alcohol dependence. Transcriptional regulation and expression of 5-HTT depend not only on epigenetic modifications, among which DNA methylation (CpG and non-CpG) is primarily involved, but also on sequence variations occurring in intron/exon regions and in untranslated regions in 5' and 3', being the first sequences important for the splicing machinery and the last for the binding of transcription factors and micro RNAs. This work intends to shed light on the role of sequence variations known to affect the expression or function of 5-HTT in alcohol-dependent individuals. We found a statistically significant difference in the allelic (p = 0.0083) and genotypic (p = 0.0151) frequencies of the tri-allelic polymorphism, with higher function alleles and genotypes more represented in the control population. Furthermore, we identified three haplotypes more frequent in subjects with AUD (p < 0.0001) and one more frequent in the control population (p < 0.0001). The results obtained for the tri-allelic polymorphism in alcohol dependence confirm what is already present in part of the literature. The role of haplotypes requires further studies to be clarified.

Antidepressant Medication Use for Treatment of Chronic Ocular Pain.

Chronic ocular pain (COP) is a leading cause of eye care visits in the US and has a substantial impact on quality of life and visual functioning. Although many conditions underlie COP, such as dry eye disease or post-herpetic neuralgia, some people experience pain without significant ocular signs on examination or known risk factors (eg, traumatic injury). Antidepressant medications that act primarily on the central nervous system, such as tricyclic antidepressants and serotonin and norepinephrine reuptake inhibitors, are often used to treat patients with COP, but a recent Cochrane review and network meta-analysis investigating 25 different antidepressants concluded that only two serotonin and norepinephrine reuptake inhibitors, have sufficient data to support their use in chronic pain. For all other medications, the evidence was of low certainty. We contend that while these medications are not a cure-all for chronic pain or COP, it is premature to conclude that these medications have no role in their treatment. We provide a rationale for continued use of antidepressant medications as part of a multimodal targeted treatment for patients with COP.

Pharmacological Treatment of Fibromyalgia Syndrome: A Practice-Based Review.

Fibromyalgia Syndrome (FMS) is a complex chronic pain condition characterized by widespread musculoskeletal pain and numerous other debilitating symptoms. The purpose of this review is to provide a comprehensive overview, based on everyday clinical practice, of the drugs presently employed in the treatment of FMS. The treatment of FMS is based on a multimodal approach, with pharmacologic treatment being an essential pillar. The drugs used include tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, other antidepressants, anticonvulsants, myorelaxants, and analgesics. The effectiveness of these medications varies, and the choice of drug often depends on the specific symptoms presented by the patient. Many drugs tend to either address only some domains of the complex FMS symptomatology or have a limited effect on pain. Each treatment option comes with potential side effects and risks that necessitate careful consideration. It may be beneficial to divide patients into clinical subpopulations, such as FMS with comorbid depression, for more effective treatment. Despite the complexities and challenges, the pharmacological treatment remains a crucial part for the management of FMS. This review aims to guide clinicians in prescribing pharmacological treatment to individuals with FMS.

Real-world treatment patterns of patients with major depressive disorder treated with Auvelity in the United States

Aims Major depressive disorder (MDD) is a prevalent, chronic disorder. Auvelity (dextromethorphan-bupropion) is a novel, oral N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist approved (August 2022) by the FDA for treating MDD in adults. This is the first analysis on real-world Auvelity usage in the United States. Methods Adult patients initiating Auvelity in the Symphony IDV databases by September 2023 were identified (index date: the first Auvelity claim). Patients had continuous eligibility over the 12-month pre-index period and ≥1 MDD diagnosis (ICD-10-CM codes: F32.*, F33.*) over the 5-year pre-index period. Demographic and clinical characteristics, comorbidities, prior MDD-related medications, and Auvelity initiation status were assessed. Results This analysis included 22,288 patients with MDD treated with Auvelity (mean age 45.1 years; 68.1% women); 40.0% lived in the South and 58.5% had commercial insurance. Comorbidities included mental health disorders (53.5%; 47.6% had anxiety disorders). Overall, 83.7% of the patients had received treatment with selective serotonin reuptake inhibitors (SSRIs; 54.9%), the norepinephrine-dopamine reuptake inhibitor (NDRI [bupropion]; 40.4%), and/or serotonin-norepinephrine reuptake inhibitors (SNRIs; 35.9%) over the 12-month pre-index period. The last MDD-related treatment prior to Auvelity comprised SSRI (22.4%), SNRI (13.2%), and NDRI (12.8%) monotherapies; 294 (1.3%) patients received esketamine. In total, 6,418 (28.8%) patients initiated Auvelity as monotherapy vs 15,870 (71.2%) as an add-on; Auvelity was most frequently added to an SSRI alone (10.7%) or SNRI alone (6.5%). A total of 2,254 (10.1%) patients initiated Auvelity without prior treatment in the 12-month pre-index period. Limitations Incomplete data due to reporting; diagnoses captured subject to coding error; and limited generalizability to other populations. Conclusions Using a large demographically distributed claims database, 22,288 patients with MDD initiated Auvelity within a year of its approval; 10.1% were treatment-naïve and 28.8% initiated Auvelity as monotherapy. Most patients had mental health-related comorbidities and attempted various MDD-related treatments prior to Auvelity.

Selective Serotonin Reuptake Inhibitor and Serotonin-Noradrenaline Reuptake Inhibitor Withdrawal Changes DSM Presentation of Mental Disorders: Results from the Diagnostic Clinical Interview for Drug Withdrawal

Introduction: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause withdrawal at dose decrease, discontinuation, or switch. Current diagnostic methods (e.g., DSM) do not take such phenomenon into account. Using a new nosographic classification of withdrawal syndromes due to SSRI/SNRI decrease or discontinuation [by Psychother Psychosom. 2015;84(2):63–71], we explored whether DSM is adequate to identify DSM disorders when withdrawal occurs. Methods: Seventy-five self-referred patients with a diagnosis of withdrawal syndrome due to discontinuation of SSRI/SNRI, diagnosed via the Diagnostic Clinical Interview for Drug Withdrawal 1 – New Symptoms of Selective Serotonin Reuptake Inhibitors or Serotonin-Norepinephrine Reuptake Inhibitors (DID-W1), and at least one DSM-5 diagnosis were analyzed. Results: In 58 cases (77.3%), the DSM-5 diagnosis of current mental disorder was not confirmed when the DID-W1 diagnosis of current withdrawal syndrome was established. In 13 cases (17.3%), the DSM-5 diagnosis of past mental disorder was not confirmed when criteria for DID-W1 diagnosis of lifetime withdrawal syndrome were met. In 3 patients (4%), the DSM-5 diagnoses of current and past mental disorders were not confirmed when the DID-W1 diagnoses of current and lifetime withdrawal syndromes were taken into account. The DSM-5 diagnoses most frequently mis-formulated were current panic disorder (50.7%, n = 38) and past major depressive episode (18.7%, n = 14). Conclusion: DSM needs to be complemented by clinimetric tools, such as the DID-W1, to detect withdrawal syndromes induced by SSRI/SNRI discontinuation, decrease, or switch, following long-term use.

The Risk of Postpartum Hemorrhage with Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors: Preliminary Results from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

Background: Previous studies suggest an association between late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and increased postpartum hemorrhage (PPH) risk. This is the first pregnancy registry study to compare PPH outcomes among women with psychiatric illness exposed or unexposed to SSRIs/SNRIs proximate to delivery. Methods: This study used data from the National Pregnancy Registry for Psychiatric Medications to evaluate the relationship between SSRI/SNRI exposure in late pregnancy and PPH risk. The sample included n = 953 participants with retrospectively collected medical record data on postpartum blood loss, n = 453 unexposed to SSRIs/SNRIs during pregnancy, and n = 500 exposed at least during the week of delivery. PPH was defined as an estimated blood loss ≥500 mL following vaginal delivery or ≥1,000 mL following cesarean section (C-section), with onset of excessive bleeding occurring within the first 24 hours postpartum. Univariate and multivariate logistic regression analyses were performed to determine odds ratios. Results: Overall PPH incidence was 13.1%. SSRI/SNRI exposure was associated with a PPH unadjusted odds ratio of 1.42 compared to no exposure (95% confidence interval [CI: 0.97, 2.08]) and an adjusted odds ratio of 1.33 (95% CI [0.90, 1.97]). When stratified by delivery type, the odds ratio following vaginal delivery among women exposed to SSRIs/SNRIs was 1.04 (95% CI [0.63, 1.70]) versus 2.31 (95% CI [1.25, 4.26]) for C-section delivery; the adjusted C-section odds ratio was 2.21 (95% CI [1.18, 4.13]). Conclusions: Although these findings align with accumulating evidence suggesting SSRI/SNRI exposure may confer a modestly increased risk of PPH, particularly after C-section, the study was underpowered to make definitive conclusions. These preliminary data highlight the need for further research with larger sample sizes. Nevertheless, the findings underscore the importance of greater clinical monitoring for PPH following C-section, especially in women who may have other known PPH risk factors and are exposed to SSRIs/SNRIs in late pregnancy.