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Objective: To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus., Study Design: Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024., Methodology: Patients with end-stage renal disease having pruritus for at least 6 weeks were included. Exclusion criteria comprised other dermatological or systemic diseases associated with pruritus, mental health issues, thrice-a-week haemodialysis schedule, and use of other treatments for uraemic pruritus. They were randomised to receive either pregabalin 75mg daily or sertraline 50mg daily for six weeks using computer-generated sequences. The Urdu version of the 5-D Itch scale was used to document the severity of pruritus at the baseline and at the end of therapy. Side effects to the treatment were also monitored., Results: There were 8 (16.67%) females and 40 (83.33%) males, with a mean age of 52.19 ± 12.19 years. The baseline 5-D Itch scale scores were equal in both groups. Mean improvement in 5-D Itch scale scores was 3.75 ± 1.26 and 2.08 ± 1.18 with pregabalin and sertraline, respectively (p <0.001). Side effects were reported by 2 (8.33%) patients on pregabalin and none using sertraline (p = 0.489)., Conclusion: Pregabalin was found to be more effective than sertraline in treating uraemic pruritus, though with a statistically insignificant trend towards a higher frequency of side effects., Key Words: Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.

Objective: To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer's disease (AD)., Methods: Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically 'AND' between different categories (e.g., 'Alzheimer's Disease' AND 'SSRIs') and 'OR' within the same category (e.g., 'citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline'), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis., Results: Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings., Conclusion: This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary., (© 2024. The Author(s).)

Background: Premenstrual syndrome (PMS) is a combination of physical, psychological and social symptoms in women of reproductive age, and premenstrual dysphoric disorder (PMDD) is a severe type of the syndrome, previously known as late luteal phase dysphoric disorder (LLPDD). Both syndromes cause symptoms during the two weeks leading up to menstruation (the luteal phase). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as a treatment for PMS and PMDD, either administered in the luteal phase or continuously. We undertook a systematic review to assess the evidence of the positive effects and the harms of SSRIs in the management of PMS and PMDD., Objectives: To evaluate the benefits and harms of SSRIs in treating women diagnosed with PMS and PMDD., Search Methods: We searched the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO for randomised controlled trials (RCTs) in November 2023. We checked reference lists of relevant studies, searched trial registers and contacted experts in the field for any additional trials. This is an update of a review last published in 2013., Selection Criteria: We considered studies in which women with a prospective diagnosis of PMS, PMDD or LLPDD were randomised to receive SSRIs or placebo., Data Collection and Analysis: We used standard Cochrane methods. We pooled data using a random-effects model. We calculated standardised mean differences (SMDs) with 95% confidence intervals (CIs) for premenstrual symptom scores, using 'post-treatment' scores for continuous data. We calculated odds ratios (ORs) with 95% CIs for dichotomous outcomes. We stratified analyses by type of administration (luteal phase or continuous). We calculated absolute risks and the number of women who would need to be taking SSRIs in order to cause one additional adverse event (i.e. the number needed to treat for an additional harmful outcome (NNTH)). We rated the overall certainty of the evidence for the main findings using GRADE., Main Results: We included 34 RCTs in the review. The studies compared SSRIs (i.e. fluoxetine, paroxetine, sertraline, escitalopram and citalopram) to placebo. SSRIs probably reduce overall self-rated premenstrual symptoms in women with PMS and PMDD (SMD -0.57, 95% CI -0.72 to -0.42; I 2 = 51%; 12 studies, 1742 participants; moderate-certainty evidence). SSRI treatment was probably more effective when administered continuously than when administered only in the luteal phase (P = 0.03 for subgroup difference; luteal phase group: SMD -0.39, 95% CI -0.58 to -0.21; 6 studies, 687 participants; moderate-certainty evidence; continuous group: SMD -0.69, 95% CI -0.88 to -0.51; 7 studies, 1055 participants; moderate-certainty evidence). The adverse effects associated with SSRIs were nausea (OR 3.30, 95% CI 2.58 to 4.21; I 2 = 0%; 18 studies, 3664 women), insomnia (OR 1.99, 95% CI 1.51 to 2.63; I 2 = 0%; 18 studies, 3722 women), sexual dysfunction or decreased libido (OR 2.32, 95% CI 1.57 to 3.42; I 2 = 0%; 14 studies, 2781 women), fatigue or sedation (OR 1.52, 95% CI 1.05 to 2.20; I 2 = 0%; 10 studies, 1230 women), dizziness or vertigo (OR 1.96, 95% CI 1.36 to 2.83; I 2 = 0%; 13 studies, 2633 women), tremor (OR 5.38, 95% CI 2.20 to 13.16; I 2 = 0%; 4 studies, 1352 women), somnolence and decreased concentration (OR 3.26, 95% CI 2.01 to 5.30; I 2 = 0%; 8 studies, 2050 women), sweating (OR 2.17, 95% CI 1.36 to 3.47; I 2 = 0%; 10 studies, 2304 women), dry mouth (OR 2.70, 95% CI 1.75 to 4.17; I 2 = 0%; 11 studies, 1753 women), asthenia or decreased energy (OR 3.28, 95% CI 2.16 to 4.98; I 2 = 0%; 7 studies, 1704 women), diarrhoea (OR 2.06, 95% CI 1.37 to 3.08; I 2 = 0%; 12 studies, 2681 women), and constipation (OR 2.39, 95% CI 1.09 to 5.26; I 2 = 0%; 7 studies, 1022 women). There was moderate-certainty evidence for all adverse effects other than somnolence/decreased concentration, which was low-certainty evidence. Overall, the certainty of the evidence was moderate. The main weakness was poor reporting of study methodology. Heterogeneity was low or absent for most outcomes, although there was moderate heterogeneity in the analysis of overall self-rated premenstrual symptoms. Based on the meta-analysis of response rate (the outcome with the most included studies), there was suspected publication bias. In total, 68% of the included studies were funded by pharmaceutical companies. This stresses the importance of interpreting the review findings with caution., Authors' Conclusions: SSRIs probably reduce premenstrual symptoms in women with PMS and PMDD and are probably more effective when taken continuously compared to luteal phase administration. SSRI treatment probably increases the risk of adverse events, with the most common being nausea, asthenia and somnolence., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The CUSP9 protocol is a polypharmaceutical strategy aiming at addressing the complexity of glioblastoma by targeting multiple pathways. Although the rationale for this 9-drug cocktail is well-supported by theoretical and in vitro data, its effectiveness compared to its 511 possible subsets has not been comprehensively evaluated. Such an analysis could reveal if fewer drugs could achieve similar or better outcomes. We conducted an exhaustive in vitro evaluation of the CUSP9 protocol using COMBImageDL, our specialized framework for testing higher-order drug combinations. This study assessed all 511 subsets of the CUSP9v3 protocol, in combination with temozolomide, on two clonal cultures of glioma-initiating cells derived from patient samples. The drugs were used at fixed, clinically relevant concentrations, and the experiment was performed in quadruplicate with endpoint cell viability and live-cell imaging readouts. Our results showed that several lower-order drug combinations produced effects equivalent to the full CUSP9 cocktail, indicating potential for simplified regimens in personalized therapy. Further validation through in vivo and precision medicine testing is required. Notably, a subset of four drugs (auranofin, disulfiram, itraconazole, sertraline) was particularly effective, reducing cell growth, altering cell morphology, increasing apoptotic-like cells within 4-28 h, and significantly decreasing cell viability after 68 h compared to untreated cells. This study underscores the importance and feasibility of comprehensive in vitro evaluations of complex drug combinations on patient-derived tumor cells, serving as a critical step toward (pre-)clinical development., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Primrose syndrome (PS) is a rare genetic disease characterized by developmental delay, intellectual disability, sensorineural hearing loss, and dysmorphic features. PS is caused by de novo pathogenic variants in the ZBTB20 gene, which encodes a transcription factor modulating neurogenesis. We describe resolution with sertraline of neurobehavioral difficulties in a 17-year-old Hispanic male with PS with de novo heterozygous c.1916G > A (p.C639Y) variant of ZBTB20. Neurobehavioral difficulties included aggression towards self and others, irritability, tearfulness, and mood liability that did not respond to behavioral interventions or aripiprazole. Treatment with sertraline, a medication indicated for psychiatric disorders including anxiety and depression, led to the resolution of neurobehavioral difficulties after 2 weeks of initiation of medication. The treatment course suggests that selective serotonin reuptake inhibitors, such as sertraline, may be a useful tool for neurobehavioral difficulties in PS over antipsychotics that are accompanied by complex side effect profiles, and suggest that anxiety is the primary cause of the neurobehavioral difficulties in this patient., (© 2024 Wiley Periodicals LLC.)

American Urological Association (AUA) guidelines recommend selective serotonin reuptake inhibitors (SSRI) as first-line pharmacotherapy for premature ejaculation (PE). While previous studies have described sexual adverse events (AE) associated with each medication, there is limited data directly comparing rates of specific sexual AEs across SSRIs. This study investigates the Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports of monotherapy use of fluoxetine 20 mg, paroxetine 20 mg, sertraline 50 mg, and sertraline 100 mg in males from January 2004-June 2021. We examined 2608 reports from patients using SSRIs for PE or other psychiatric conditions. The average number of AEs was significantly different (p < 0.01) with paroxetine 20 mg having the highest (5.1 AEs/case report). Changes in libido was the most common sexual AE for fluoxetine 20 mg (6.7% of reports), paroxetine 20 mg (4.2%), and sertraline 50 mg (7.2%) while orgasm disorder was the most reported for sertraline 100 mg (3.9%). The SSRIs had different rates of changes in libido, erection disorder, orgasm disorder, and other sexual dysfunction (outside those listed). The SSRIs also differed in the rates of fatigue, ear/hearing changes, headache, and psychological AEs. The differences in specific AEs warrant future studies to determine true differences that would affect patient counseling., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD)., Methods: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring., Results: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups., Conclusion: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use)., Methods: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use)., Results: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome., Conclusions: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years., (© 2024 Association for Child and Adolescent Mental Health.)

We report the case of a 49-year-old male treatment-resistant schizophrenia patient, whose treatment with clozapine and sertraline was supplemented with cariprazine 1.5 mg/day while regularly presenting for electroconvulsive therapy. After 3 weeks of adjunctive treatment with cariprazine, blood tests revealed pronounced signs of rhabdomyolysis, including a creatine kinase serum level of 20 386 U/L and an AST serum level of 696 U/L. Clinically, the patient did not report somatic symptoms other than mild back pain. After discontinuation of cariprazine and normal saline infusion, the above-mentioned findings resolved rapidly. Although very rare, rhabdomyolysis can be a potentially dangerous side effect of cariprazine and clinicians should be aware of its possible occurrence., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In addition to trauma-focussed psychotherapy, pharmacological treatment is often unavoidable, especially in patients with severe posttraumatic stress disorder (PTSD). As long as comorbid disorders do not dictate the pharmacotherapy approach, sertraline and paroxetine, along with other off-label prescribable substances approved in Germany, can be used for the treatment of PTSD. Venlafaxine, in particular, has shown good effectiveness in studies, whereas risperidone has shown lower effectiveness in augmentation. Overall, only a small to medium effect size is to be expected for all substances. Psychopharmacotherapy plays an important role in addressing sleep disorders, which are highly prevalent in PTSD. Treatment of trauma-related nightmares can be attempted with doxazosin or clonidine. In contrast, there are limited empirical data available for sleep disorders associated with PTSD, but the pharmacological treatment of insomnia can provide some guidance., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Rationale: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD., Aims: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers., Methods: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50 mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1β were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity., Results: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1β, nor TNF-α (p's>0.05)., Conclusion: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD., Competing Interests: Declaration of Competing Interest ALM holds a provisional patent on the anti-inflammatory effects of allopregnanolone and related neurosteroids, and has current and previous funding from Sage Therapeutics related to the anti-inflammatory actions of allopregnanolone. LH has consulted for PureTech Health and Flo Health. JLP has research funding from NIMH and Janssen Pharmaceuticals; served as a consultant to SAGE Therapeutics, Biogen, Merck, Brii Biologics, Pure Tech, Dionysus Health, and Flo Health; speaker for employees of Karuna Therapeutics; founder’s stock in Dionysus Health; two patents: “Epigenetic Biomarkers of Postpartum Depression” and “Epigenetic Biomarkers of PMDD and SSRI Response.” LMO reports no conflicts of interest, but has research funding from NIMH and NICHD and receives royalties and editorial fees from APA Publishing, Elsevier, and UpToDate., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram., Aims: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice., Method: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication., Results: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events., Conclusions: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Generalized anxiety disorder (GAD) (Chittodvega) is one among many types of mental disorders explained in Ayurveda. It can be defined as a Chitta (mind) + Udvega (anxiety)= Chittodvega - Anxious status of a mind. Celastrus paniculatus also known as Jyotishmati. stimulates and improves the digestive fire and metabolism at a cellular level ( Jatharagni and Majja dhatwagni). It can be correlated to GAD. GAD is characterized by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. It affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects. In modern medicine the first-line psychological and pharmaceutical treatments are selective serotonin reuptake inhibitors (SSRIs) like sertraline (SNRIs)., Aim and Objectives: To evaluate the comparative efficacy of Jyotishmati versus sertraline in the management of Chittodvega., Methods: In this randomized active controlled double blind equivalence trial a total of 70 patients will be enrolled and divided into two equal groups. Patients between 20-50 years age of either gender having symptoms of Chittodvega and a Hamilton anxiety rating (HAM-A) scale score less than 24 (i.e., mild to moderate) will be selected for the study. In Group A, sertraline capsules 25 mg for first 7 days and then dose increased to 50 mg at bedtime for next 53 days and in Group B Jyotishmati Capsules 500 mg will be given twice a day after food with water for 60 days., Result and Observation: The patients will be assessed on the HAM-A scale, serum cortisol and WHO Quality of Life on day 0, 30, 60 and 90 and data will be analyzed using paired and unpaired t-tests for continuous variables and chi-square tests for categorical variables to evaluate whether treatments are equivalent., Trial Registration: CTRI No. REF/2023/07/069880 Date - 15/09/2023., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Gamne R et al.)

Depression during the first year postpartum (postpartum depression) impacts millions of women and their families worldwide. In this narrative review, we provide a summary of postpartum depression, examining the etiology and consequences, pharmacological and psychological treatments, and potential mechanisms of change and current barriers to care. Psychological treatments are effective and preferred by many perinatal patients over medications, but they often remain inaccessible. Key potential mechanisms underlying their effectiveness include treatment variables (e.g., dosage and therapeutic alliance) and patient behaviors (e.g., activation and avoidance and emotional regulation). Among pharmacological treatments, the selective serotonin reuptake inhibitor (SSRI) sertraline is generally the first-line antidepressant medication recommended to women in the postpartum period due to its minimal passage into breastmilk and the corresponding decades of safety data. Importantly, most antidepressant drugs are considered compatible with breastfeeding. Neurosteroids are emerging as an effective treatment for postpartum depression, although currently this treatment is not widely available. Barriers to widespread access to treatment include those that are systematic (e.g., lack of specialist providers), provider-driven (e.g., lack of flexibility in treatment delivery), and patient-driven (e.g., stigma and lack of time for treatment engagement). We propose virtual care, task-sharing to non-specialist treatment providers, and collaborative care models as potential solutions to enhance the reach and scalability of effective treatments to address the growing burden of postpartum depression worldwide and its negative impact on families and society., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice., Methods: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ 2 ), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables., Results: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05)., Conclusion: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373., (© 2024. The Author(s).)

Purpose: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment., Methods: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated., Results: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables., Conclusion: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Archer 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.)

Objective: This study (a) examined anxious youth with and without asthma on measures of negative self-talk, parental psychopathology, worry content, physical symptoms, panic symptoms, generalized symptoms, and separation anxiety symptoms, and (b) tested if outpatient CBT or medication were differentially effective in reducing anxiety for youth with asthma and anxiety., Methods: This secondary analysis separated youth with an anxiety disorder into asthma and non-asthma groups. Youth were also compared on response to treatments (i.e. CBT, sertraline, combined, and placebo)., Results: A total of 488 participants participated in the original study, with an average age of 10 years ( SD 2.87). Youth with comorbid asthma and anxiety demonstrated higher rates of negative self-talk. Youth with comorbid asthma and anxiety did not differ from the non-asthma group on measures of physical symptoms, anxiety disorder specific symptoms, parental psychopathology, or worry content. Youth with asthma and anxiety responded similarly to the non-asthma group to treatment across treatment conditions., Conclusions: Treatment was comparably effective for youth with comorbid asthma and anxiety and youth with anxiety. Future research could examine the effects of psychopharmaceuticals on asthma and anxiety comorbidity.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms., Competing Interests: Declaration of competing interest Disclosures: This work was supported by the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command (MRMC; Randomized Controlled Trial of Sertraline, Prolonged Exposure Therapy, and Their Combination in OEF/OIF Combat Veterans with PTSD; Grant #W81XWH-11-1-0073); the National Center for Advancing Translational Sciences of the National Institutes of Health (Grant #UL1TR000433). The views expressed in this article presentation are solely those of the author(s) and do not reflect an endorsement by or the official policy of the Department of Veterans Affairs, Department of Defense, or the U.S. Government, or the official views of the National Institutes of Health. The contents do not represent the views of the US Department of Veterans Affairs (DVA), Department of Defense (DOD), or the United States Government. Dr. Rauch receives support from Wounded Warrior Project (WWP), DVA, National Institute of Health (NIH), Woodruff Foundation, and DOD and royalties from Oxford University Press and American Psychological Association Press. In the past 3 years Dr. Simon reports receiving grants from the National Institutes of Health (NIH), U.S. Department of Defense, American Foundation for Suicide Prevention, Patient-Centered Outcomes Research Institute, Ananda Scientific and support from Cohen Veterans Network and MindMed; receiving personal fees from Vanda Pharmaceuticals, Praxis Therapeutics, Genomind, Bionomics Limited, BehavR LLC, Cerevel, Engrail Therapeutics Inc; receiving fees or royalties from Wiley (Deputy Editor Depression and Anxiety), Wolters Kluwyer (UpToDate) and APA Publishing (Textbook of Anxiety, Trauma and OCD Related Disorders, 2020); and having spousal stock from G1 Therapeutics and Zentalis outside the submitted work. ClinicalTrials.gov: NCT01524133., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To examine relapse rates following remission in a 3-year follow-up study in pediatric patients with obsessive-compulsive disorder (OCD) treated with cognitive-behavioral therapy (CBT) in a first step, and either continued CBT or sertraline (randomized selection) in a second step., Method: Participants (N = 269) fulfilled DSM-IV OCD criteria with a mean severity on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) of 24.6 (SD = 5.1) and were included in analyses according to intent-to-treat principles. CBT used manualized exposure and response prevention (ERP) during both steps 1 and 2, and step 2 sertraline medication used flexible dosing. The follow-up schedules were timed to 6, 12, 24, and 36 months following step 1 CBT. Remission was defined as a CY-BOCS score ≤10 and relapse as an elevated CY-BOCS score ≥16 in those who had remitted., Results: A good third of our patients were in stable and full remission at all examinations (n = 98, 36.4%). Further, some in remission following treatment (n = 36, 13.4%) had mild OCD at some examinations. Relapses during follow-up were not uncommon (n = 28, 10.4%), but in many patients these improved again (n = 10, 3.7%) and were in remission at the final 3-year follow-up. Furthermore, a considerable proportion (n = 50, 18.6%) of the patients were initial non-remitters to the treatment but achieved remission at some point during the follow-up. In addition, 11.5% (n = 31) had persistent OCD but reached remission by the last follow-up. Finally, a smaller segment of our sample (9.7%, n = 26), did not attain remission at any point during the study., Conclusion: Our outcome paints a more promising picture of pediatric OCD long-term outcome than previous studies have done. However, both relapse rates and the presence of initial non-remitters and persistent OCD show that treatments need improvement, particularly for those who respond slowly, partially, or not at all. The lack of a general psychiatric interview at follow-up is a marked limitation., Clinical Trial Registration Information: Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study; https://www.isrctn.com; ISRCTN66385119., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking., Aims: To present systematic population-based nation-wide register data on comparative 2-year non-response within six antidepressant drug classes and 17 different antidepressants in patients with MDD., Method: The study included all 106,920 patients in Denmark with a first main index diagnosis of MDD at a psychiatric hospital inpatient or outpatient contact and who subsequently had a purchase of an antidepressant in the period from 1995 to 2018. Non-response to first antidepressant within a 2-year study period was defined as switch to or add-on of another antidepressant, antipsychotic medication, lithium, or hospitalization. Analyses emulated a targeted trial in populations standardized according to age, sex, socioeconomic status, and comorbidity with psychiatric and physical disorders., Results: Compared with sertraline, there was no difference for citalopram (RR: 1.00 [95% CI: 0.98-1.02]) but fluoxetine (1.13 [95% CI: 1.10-1.17]), paroxetine (1.06 [95% CI: 1.01-1.10]) and escitalopram (1.22 [95% CI: 1.18-1.25]) were associated with higher risk ratio of non-responses. Within selective noradrenaline reuptake inhibitors, sertraline outperformed reboxetine; within serotonin-norepinephrine reuptake inhibitors, venlafaxine outperformed duloxetine; within noradrenergic and specific serotonergic antidepressants, mirtazapine outperformed mianserin and within the class of other antidepressants, sertraline outperformed agomelatine and vortioxetine. Within tricyclic antidepressants, compared to amitriptyline, nortriptyline, dosulepin, and clomipramine had higher non-response, whereas there was no difference for imipramine., Conclusions: These analyses emulating a randomized trial of "real world" observational register-based data show that 2-year long-term non-responses to some antidepressants within six different drug classes are increased over others., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Research on long-term pharmacotherapy for trauma-affected refugees is scarce. The purpose of this follow-up study of a randomised trial was to investigate the effects of sertraline compared to venlafaxine in combination with psychotherapy, 6 and 18 months after end of trial., Method: The primary outcome was PTSD symptoms, measured by the Harvard Trauma Questionnaire (HTQ). The secondary outcomes included: Hopkins Symptom Checklist-25 (HSCL-25), somatisation items of the Symptoms Checklist-90 (SCL), pain on a visual analogue scale, well-being on the WHO-5, Sheehan Disability Scale, Hamilton Depression and Anxiety scales and Global Assessment of Functioning. Moreover, the shorter version of the Recent Life Events (IRLE) was adopted to obtain information regarding the patients' treatment and life events between the follow-up periods., Results: Out of 195 patients eligible for intention-to-treat analyses during trial, 116 participated in the 6-month follow-up and 97 participated in the 18-month follow-up. The results of our intention-to-treat analyses revealed no significant long-term differences between the groups on the primary outcome assessing PTSD symptoms (HTQ). For the secondary outcomes significant differences were found at the 18-month follow-up in favour of venlafaxine assessing symptoms of anxiety, depression and somatisation (HSCL-25 and SCL), although only in intention-to-treat and not per-protocol analyses., Conclusions: No conclusions could be drawn due to conflicting results between our intention-to-treat and per-protocol analyses.

Background: Antidepressant medications yield unsatisfactory treatment outcomes in patients with major depressive disorder (MDD) with modest advantages over the placebo, partly due to the elusive mechanisms of antidepressant responses and unexplained heterogeneity in patient's response to treatment. Here we develop a novel normative modeling framework to quantify individual deviations in psychopathological dimensions that offers a promising avenue for the personalized treatment for psychiatric disorders., Methods: We built a normative model with resting-state electroencephalography (EEG) connectivity data from healthy controls of three independent cohorts. We characterized the individual deviation of MDD patients from the healthy norms, based on which we trained sparse predictive models for treatment responses of MDD patients (102 sertraline-medicated and 119 placebo-medicated). Hamilton depression rating scale (HAMD-17) was assessed at both baseline and after the eight-week antidepressant treatment., Results: We successfully predicted treatment outcomes for patients receiving sertraline (r = 0.43, p < 0.001) and placebo (r = 0.33, p < 0.001). We also showed that the normative modeling framework successfully distinguished subclinical and diagnostic variabilities among subjects. From the predictive models, we identified key connectivity signatures in resting-state EEG for antidepressant treatment, suggesting differences in neural circuit involvement between sertraline and placebo responses., Conclusions: Our findings and highly generalizable framework advance the neurobiological understanding in the potential pathways of antidepressant responses, enabling more targeted and effective personalized MDD treatment., Trial Registration: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC), NCT#01407094., Competing Interests: Declaration of competing interest G.A.F. received monetary compensation for consulting work for SynapseBio AI and owns equity in Alto Neuroscience. W.W. and A.E. report salary and equity from Alto Neuroscience. A.E. additionally holds equity in Akili Interactive and Mindstrong Health. The remaining authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recent research revealed that several psycho-cognitive processes, such as insensitivity to positive and negative feedback, cognitive rigidity, pessimistic judgment bias, and anxiety, are involved in susceptibility to fake news. All of these processes have been previously associated with depressive disorder and are sensitive to serotoninergic manipulations. In the current study, a link between chronic treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline and susceptibility to true and fake news was examined. Herein, a sample of 1162 participants was recruited via Prolific Academic for an online study. Half of the sample reported taking sertraline (Zoloft) for at least 8 weeks (sertraline group), and the other half confirmed not taking any psychiatric medication (control group). The sertraline group was further divided according to their daily dosage (50, 100, 150, and 200 mg/day). All participants completed a susceptibility to misinformation scale, wherein they were asked to determine the veracity of the presented true and fake news and their willingness to behaviorally engage with the news. The results were compared between those of the sertraline groups and the control group. The results showed that sertraline groups did not differ significantly in the assessment of the truthfulness of information or their ability to discern the truth. However, those taking sertraline appeared to have a significantly increased likelihood of behavioral engagement with the information, and this effect was observed for both true and fake news. The research presented here represents the initial endeavor to comprehend the neurochemical foundation of the susceptibility to misinformation. The association between sertraline treatment and increased behavioral engagement with information observed in this study can be explained in light of previous studies showing positive correlations between serotonin (5-HT) system activity and the inclination to engage in social behaviors. It can also be attributed to the anxiolytic effects of sertraline treatment, which mitigate the fear of social judgment. The heightened behavioral engagement with information in people taking sertraline may, as part of a general phenomenon, also shape their interactions with fake news. Future longitudinal studies should reveal the specificity and exact causality of these interactions.

Compulsive sexual behavior disorder (CSBD) has recently been recognized as a psychiatric disorder. Pharmacological treatments for CSBD have received little study and thus have limited empirical support. The main objective of the present work is to review existing literature on the efficacy of different drugs on the symptomatology of CSBD, including the subtype of problematic pornography use (PPU). The main pharmacological approaches to treating CSBD have included opioid antagonists (naltrexone and nalmefene), selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, and sertraline), mood stabilizers (topiramate), tricyclic antidepressants (clomipramine), serotonin antagonist and reuptake inhibitors (nefazodone), and N-acetylcysteine. Since people with CSBD may experience different co-occurring disorders, these should be considered when choosing the best pharmacological treatment. Pharmacological therapy for CSBD/PPU has been suggested as an adjunct to psychological therapies, which, for the moment, have the most empirical evidence. However, to evaluate the efficacy of most of the drugs presented in this narrative review, data to date have only been available from case studies. Thus, empirical support is scant and generalizability of results is limited, highlighting the need for more research in this area., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory., Method: One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics., Results: Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model., Conclusions: Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Introduction: Premenstrual Dysphoric Disorder (PMDD) was first recognised in July 2013 in the DSM-5 after a long journey to identify its existence. It was not until 1983 that the US National Institute of Mental Health determined research criteria for the study of PMS. In 1994, the term "premenstrual dysphoric disorder" (PMDD) replaced this term in the 4th edition of the Diagnostic System Manual (DSM). It was listed in the section "Mood Disorder Not Otherwise Specified" and remained under consideration until the DSM-5, in which it appeared in the depressive disorders section. The legitimisation of the psychiatric diagnosis as well as the determination of clear symptomatology criteria in 2013 opened up possibilities for management, development of clinical, pathophysiological, therapeutic and psychotherapeutic studies. This disabling disorder can affect personal, social, family and professional life. In 2019, the ICD-11 in turn introduced the diagnosis of premenstrual dysphoric disorder, which solidifies the recognition of the disorder., Objective: (I) to review the existing treatments, both medicinal and psychotherapeutic, and (II) to review their effectiveness. At the end of this work we will formulate recommendations for the management of these patients., Methodology: A bibliographic search was carried out from 7 June 2021 to 7 July2021 on the databases (bases de données) Psychinfo APA, Scopus, PubMed, as well as the bases de données of the Cochrane organisation and the recommendation documents of the Haute Autorité de la santé. After an initial selection based on keywords, the full text of all articles were read to arrive at the final selection of 32 articles., Results: Antidepressants and Cognitive Behavioural Therapies (CBT) appear to be the most commonly recommended treatments for PMDD. Other research shows the effectiveness of oral contraceptives including drospirenone. Selective serotonin reuptake inhibitors (SSRIs) were identified as an effective treatment for PMDD. These data are consistent with the current etiological hypothesis of PMDD which has a negative impact of natural hormonal fluctuations on certain neurotransmitters. CBT showed positive results in reducing the functional impact of PMDD., Discussion: Selective serotonin reuptake inhibitor (SSRI) antidepressants were reported to be first-line treatments for PMDD (sertraline 50-150 mg/d, fluoxetine 10-20 mg/d, escitalopram 10-20 mg/d, paroxetine 12.5-25 mg/d). Drospirenone (EE 3 mg and EE 20 mg/d 24 days of hormonal pills, 4 days inactive) appears to have been a first or second line treatment depending on the articles. Current results clearly point to the effectiveness of CBT in helping to reduce: functional impairment, depressed mood, feelings of hopelessness, anxiety, mood swings, sensitivity, irritability, insomnia, conflict with others, impact of premenstrual symptoms on daily life, intensity of symptoms experienced, and symptom handicap. CBTs could also become a first-line treatment if there were to be more evidence of their effectiveness. In the future, it would seem useful to offer a psychotherapeutic treatment that can be reproduced and to multiply research with a high level of scientific comparability in order to clarify the place of CBT in the management of PMDD. Research on the etiopathology of the disorder and the optimal drug regimen is still ongoing. There is a need to develop appropriate psychotherapeutic techniques to support and accompany these patients., Conclusion: In order to better evaluate treatments for PMDD, there is a need to homogenise studies on the subject at several levels: design, treatment doses, psychotherapeutic techniques, and evaluation measures. At present, some studies include both premenstrual syndrome (PMS) and PMDD patients. PMS and PMDD do not include the same symptoms, nor the same severity and potentially the same aetiology in the patients studied. In order to propose rigorous research that evaluates the effectiveness of treatments for PMDD and to properly support people with both these disorders, it seems essential to distinguish the two conditions. The role of the health practitioner is to be able to identify PMDD by differentiating it from other clinically related disorders. The patient must then be accompanied to make a choice of treatment adapted to her symptoms, their severity, her history, her plans for procreation, contraindications and her preferences. In 2021, the French National Authority for Health did not offer any guidelines or recommendations for the management of premenstrual dysphoric disorder. There is a need to develop research in France., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Detailed data on post-stroke depression (PSD) in older adults are limited in spite of the high vulnerability of this population to stroke. In fact, PSD prevalence in older adults ranges from 16.0 to 43.9%; however, timing and instruments of evaluation often differ significantly across all available studies. The etiology, genetic and inflammatory factors, as well as structural brain alterations, are claimed as part of a multifaceted mechanism of action in PSD onset. Thus, the aim of this narrative review was to further elaborate on the prevalence, etiology, diagnosis, consequences and treatment of PSD in older adults. The consequences of PSD in older adults may be devastating, including a poor functional outcome after rehabilitation and lower medication adherence. In addition, lower quality of life and reduced social participation, higher risk of new stroke, rehospitalization, and mortality have been reported. In this scenario, treating PSD represents a crucial step to prevent these complications. Both pharmacological and non-pharmacological therapies are currently available. The pharmacological treatment utilizes antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TAs) and new multimodal antidepressants (NMAs). Non-pharmacological therapies include psychological interventions and non-invasive brain stimulation techniques, while excluding drug administration. In the general population experiencing PSD, SSRIs (sertraline in particular) are the most prescribed, whereas the combination of antidepressants and psychotherapy is underused. Furthermore, about one-third of patients do not receive treatment for PSD. In regard to older adults with PSD, the possibility of more adverse effects or contraindications to antidepressant prescription due to comorbidities may limit the therapeutic window. Although drugs such as citalopram, escitalopram, sertraline, venlafaxine, and vortioxetine are usually well tolerated by older patients with PSD, the few randomized controlled trials (RCTs) specifically considering older adults with PSD have been conducted with fluoxetine, fluvoxamine, reboxetine, citalopram and nortriptyline, often with very small patient samples. Furthermore, data regarding the results of non-pharmacological therapies are scarce. High-quality RCTs recruiting large samples of older adults are needed in order to better manage PSD in this population. In addition, adequate screening and diagnosis instruments, with reliable timing of evaluation, should be applied., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Consensus-guidelines for prescribing antidepressants recommend that clinicians should be vigilant to match antidepressants to patient's medical history but provide no specific advice on which antidepressant is best for a given medical history., Aims of the Study: For patients with major depression who are in psychotherapy, this study provides an empirically derived guideline for prescribing antidepressant medications that fit patients' medical history., Methods: This retrospective, observational, cohort study analyzed a large insurance database of 3,678,082 patients. Data was obtained from healthcare providers in the U.S. between January 1, 2001, and December 31, 2018. These patients had 10,221,145 episodes of antidepressant treatments. This study reports the remission rates for the 14 most commonly prescribed single antidepressants (amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, sertraline, trazodone, and venlafaxine) and a category named "Other" (other antidepressants/combination of antidepressants). The study used robust LASSO regressions to identify factors that affected remission rate and clinicians' selection of antidepressants. The selection bias in observational data was removed through stratification. We organized the data into 16,770 subgroups, of at least 100 cases, using the combination of the largest factors that affected remission and selection bias. This paper reports on 2,467 subgroups of patients who had received psychotherapy., Results: We found large, and statistically significant, differences in remission rates within subgroups of patients. Remission rates for sertraline ranged from 4.5% to 77.86%, for fluoxetine from 2.86% to 77.78%, for venlafaxine from 5.07% to 76.44%, for bupropion from 0.5% to 64.63%, for desvenlafaxine from 1.59% to 75%, for duloxetine from 3.77% to 75%, for paroxetine from 6.48% to 68.79%, for escitalopram from 1.85% to 65%, and for citalopram from 4.67% to 76.23%. Clearly these medications are ideal for patients in some subgroups but not others. If patients are matched to the subgroups, clinicians can prescribe the medication that works best in the subgroup. Some medications (amitriptyline, doxepin, nortriptyline, and trazodone) always had remission rates below 11% and therefore were not suitable as single antidepressant therapy for any of the subgroups., Discussions: This study provides an opportunity for clinicians to identify an optimal antidepressant for their patients, before they engage in repeated trials of antidepressants., Implications for Health Care Provision and Use: To facilitate the matching of patients to the most effective antidepressants, this study provides access to a free, non-commercial, decision aid at http://MeAgainMeds.com., Implications for Health Policies:  Policymakers should evaluate how study findings can be made available through fragmented electronic health records at point-of-care. Alternatively, policymakers can put in place an AI system that recommends antidepressants to patients online, at home, and encourages them to bring the recommendation to their clinicians at their next visit., Implications for Further Research:  Future research could investigate (i) the effectiveness of our recommendations in changing clinical practice, (ii) increasing remission of depression symptoms, and (iii) reducing cost of care. These studies need to be prospective but pragmatic. It is unlikely random clinical trials can address the large number of factors that affect remission.

Objective: Response to antidepressant treatment in major depressive disorder varies substantially between individuals, which lengthens the process of finding effective treatment. The authors sought to determine whether a multimodal machine learning approach could predict early sertraline response in patients with major depressive disorder. They assessed the predictive contribution of MR neuroimaging and clinical assessments at baseline and after 1 week of treatment., Methods: This was a preregistered secondary analysis of data from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a multisite double-blind, placebo-controlled randomized clinical trial that included 296 adult outpatients with unmedicated recurrent or chronic major depressive disorder. MR neuroimaging and clinical data were collected before and after 1 week of treatment. Performance in predicting response and remission, collected after 8 weeks, was quantified using balanced accuracy (bAcc) and area under the receiver operating characteristic curve (AUROC) scores., Results: A total of 229 patients were included in the analyses (mean age, 38 years [SD=13]; 66% female). Internal cross-validation performance in predicting response to sertraline (bAcc=68% [SD=10], AUROC=0.73 [SD=0.03]) was significantly better than chance. External cross-validation on data from placebo nonresponders (bAcc=62%, AUROC=0.66) and placebo nonresponders who were switched to sertraline (bAcc=65%, AUROC=0.68) resulted in differences that suggest specificity for sertraline treatment compared with placebo treatment. Finally, multimodal models outperformed unimodal models., Conclusions: The study results confirm that early sertraline treatment response can be predicted; that the models are sertraline specific compared with placebo; that prediction benefits from integrating multimodal MRI data with clinical data; and that perfusion imaging contributes most to these predictions. Using this approach, a lean and effective protocol could individualize sertraline treatment planning to improve psychiatric care.

Purpose: The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype., Methods: Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs)., Results: A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive., Conclusion: The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants., (© 2024. The Author(s).)

Objective: To investigate the comparative effectiveness of commonly used selective serotonin reuptake inhibitors (SSRIs) for comorbid depression in older adults with chronic somatic diseases by applying a target-trial-emulation framework., Methods: Danish target-trial-emulation study including 43,061 individuals aged ≥65 years (54.1% females, mean age 77.8 years) with a first redeemed prescription for depression with sertraline (n = 6673), escitalopram (n = 7104) or citalopram (n = 29,284) in 2006-2017. Individuals had cancer, cardiovascular diseases (CVD), chronic-obstructive-pulmonary-disease (COPD)/asthma, diabetes, neurodegenerative disorders, or osteoporosis. Outcomes were treatment switching, combination/augmentation, psychiatric hospital contact for depression, and any psychiatric in-patient care. Follow-up was one year and adjusted Cox regression analyses calculated hazard rate ratios (HRR) within each somatic disease., Results: Across all six disease groups and four outcomes, we found that citalopram use, compared with sertraline, was associated with lower risks in several analyses, with statistically significant results in cancer, CVD, COPD/asthma, and diabetes (e.g., HRRs for psychiatric hospital contacts for depression/any psychiatric in-patient care ranging between 0.47 and 0.61). For escitalopram, compared with sertraline, some analyses indicated poorer outcomes with significantly higher risks for combination/augmentation treatment (HRRs ranging between 1.15 and 1.40)., Conclusions: Although observational studies are prone to confounding, these findings indicate clinically relevant differences between the SSRIs, with better outcomes in citalopram users and poorer outcomes in escitalopram users than sertraline, urging the need for clinical studies in this vulnerable patient population., Competing Interests: Declaration of competing interest KI and CG declare no conflict of interest. CR received the 2020 Lundbeck Foundation Talent Prize. OKF reported honoraria for lectures for Lundbeck Pharma A/S and consultant fees for WCG Clinical, all unrelated to the present work. CO reported receiving personal fees from Fortbildungskolleg, Janssen Pharmaceuticals, Lundbeck, Neuraxpharm, PeakProfiling GmbH, and LIMES Klinikgruppe and grants from the German Research Foundation, German Federal Ministry of Education and Research, European Union, and Berlin Institute of Health outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Depressive disorder is a chronic mental illness characterized by persistent low mood as its primary clinical symptom. Currently, psychotherapy and drug therapy stand as the primary treatment modalities in clinical practice, offering a certain degree of relief from negative emotions for patients. Nevertheless, sole reliance on drug therapy exhibits a delayed impact on neurotransmitters, and long-term usage often results in adverse side effects such as nausea, drowsiness, and constipation, significantly impeding medication adherence. This study aims to investigate the impact of combining transcranial magnetic stimulation with sertraline on the cognitive level, inflammatory response, and neurological function in patients with depressive disorder who engage in non-suicidal self-injury (NSSI) behavior., Methods: A total of 130 depressive patients NSSI behavior, who were admitted to our hospital from December 2020 to February 2023, were selected as the subjects for this research. The single-group (65 cases) received treatment with oral sertraline hydrochloride tablets, while the combination group (65 cases) underwent repetitive transcranial magnetic stimulation (rTMS) in conjunction with sertraline. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to assess the depression status and cognitive function levels of both groups. Additionally, the enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Furthermore, serum levels of neurotransmitters (norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT)) and neuro-cytokines (brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial fibrillary acidic protein (GFAP)) were assessed. The clinical effects of the interventions on both groups were then evaluated., Results: Following the treatment, the combination group exhibited significantly higher levels of immediate memory, delayed memory, attention, visual function, and language function compared to the single group, with statistically significant differences (p < 0.05). Additionally, the serum levels of TNF-α, IL-1β, IL-6, and GFAP in the combination group were lower than those in the single group, while the levels of BDNF and NGF were higher in the combination group compared to the single group. These differences were also statistically significant (p < 0.05). Simultaneously, the total clinical effective rate in the combination group reached 95.38%, surpassing the 84.61% observed in the single group, and the disparity between the two groups was statistically significant (p < 0.05)., Conclusions: The combined use of rTMS and sertraline in treating patients with depressive disorder exhibiting NSSI behavior has proven to be effective in enhancing cognitive function, mitigating inflammatory responses, and elevating levels of neurotransmitters and nerve cytokines in the patients.

Rationale: Premenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD's pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD., Aims: The aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms., Methods: Participants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3α,5α-THP; 3α5β-THP; pregnenolone; 3α,5α-androsterone; 3α,5β-androsterone; 3α,5α-A-diol; 3α5β-A-diol; 3α,5α-THDOC; 3α5β-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50 mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment., Results: Participants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (p > 0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3α,5α-androsterone., Conclusions: This was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JLP: I have research funding from NIMH and Janssen Pharmaceuticals. I have served as a consultant to SAGE Therapeutics, Biogen, Merck, Brii Biologics, Pure Tech, Dionysus Health, and Flo Health. I have given a talk to the employees of Karuna Therapeutics. I have founders stock in Dionysus Health. I have two patents: “Epigenetic Biomarkers of Postpartum Depression” and “Epigenetic Biomarkers of PMDD and SSRI Response.”LH: Previously served as a consultant to Pure Tech Health, Flo Health. ALM: ALM holds a provisional patent on the anti-inflammatory effects of allopregnanolone and related neurosteroids, and has current and previous funding from Sage Therapeutics related to the anti-inflammatory actions of allopregnanolone., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The effectiveness of selective serotonin reuptake inhibitors (SSRIs) as a primary treatment for obsessive-compulsive disorder (OCD) remains uncertain. Even after undergoing standard SSRIs treatment, 40%-60% of individuals with OCD persistently endure symptoms. Recent studies proposed that personality traits may influence the diversity of OCD treatment results. Thus, in this retrospective study, we evaluated the Eysenck Personality Questionnaire (EPQ) scores of 51 untreated patients with OCD and 35 healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed to assess OCD symptom severity at weeks 0, 2, 4, 8, and 12 of sertraline treatment. The primary outcome focused on the reduction rate of Y-BOCS scores (response: ≥25%; marked response: ≥50%). Our findings revealed that individuals with OCD demonstrated a significantly higher neuroticism score compared to healthy controls. Correlation analyses exposed a positive link between psychoticism and the duration of the disease. Moreover, family history strongly correlated with both obsessive thoughts and the total Y-BOCS score. Subsequent univariate Cox proportional analyses indicated that both low neuroticism and high extraversion traits could forecast the response to sertraline. Furthermore, only a high extraversion trait was linked to a marked response. Our results support the idea that personality traits may contribute to OCD vulnerability and predict sertraline treatment outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Obsessive-compulsive disorder (OCD) as a consequence of severe traumatic brain injury (TBI) has been reported in a limited number of case studies. Informed by CARE guidelines, we present the case of a boy in his late adolescence who sustained a severe TBI from a motor vehicle crash. His injuries required a prolonged stay in the hospital, including 3 weeks in the intensive care unit and a craniotomy to evacuate a large subdural haematoma. Obsessive-compulsive behaviours were first observed on discharge from the hospital and became worse over time. Compulsive behaviours were considered in light of a neuropsychological examination, and a diagnosis of OCD was attained. Sertraline was prescribed and effectively reduced the severity of OCD symptoms. Given the challenges comorbid conditions can pose to neurorehabilitation, a better understanding of patterns in OCD symptoms and brain lesions among reported cases will help guide the diagnosis of OCD among individuals with severe TBI., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Existing guidelines for primary care clinicians (PCCs) on the detection and management of perinatal depression (PD) contain important gaps. This review aims to provide PCCs with a summary of clinically relevant evidence in the field., Methods: A narrative literature review was conducted by searching PubMed and PsycINFO for articles published between 2010 to 2023. Guidelines, systematic reviews, clinical trials, and/or observational studies were all examined., Results: Screening with the Edinburgh Postnatal Depression Scale or Patient Health Questionnaire-9 followed by a diagnostic evaluation for major depressive disorder in probable cases can enhance PD detection. At-risk individuals and mild to moderate PD should be referred for cognitive behavioral therapy or interpersonal psychotherapy when available. Selective serotonin reuptake inhibitors should be used for moderate to severe PD, with sertraline, escitalopram, or citalopram being preferred first. Using paroxetine or clomipramine in pregnancy, and fluoxetine or doxepin during lactation is generally not preferred. Gestational antidepressant use is associated with a small increase in risk of reduced gestational age at birth, low birth weight, and lower APGAR scores, though whether these links are causal is unclear. Sertraline and paroxetine have the lowest rate of adverse events during lactation. Consequences of untreated PD can include maternal and offspring mortality, perinatal complications, poor maternal-infant attachment, child morbidity and maltreatment, less breastfeeding, and offspring developmental problems., Conclusions: These clinically relevant data can support the delivery of high-quality care by PCCs. Risks and benefits of PD treatments and the consequences of untreated PD should be discussed with patients to support informed decision making., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare., (© Copyright by the American Board of Family Medicine.)

Objective: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes., Methods: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders., Results: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years)., Conclusions: This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment., Competing Interests: Dr. Nierenberg has served as a consultant for Alkermes, Clexio, Ginger/Headspace Health, Janssen, Merck, Neuronetics, NeuroRx, Otsuka, Protagenics, SAGE, Sunovion, and Unravel Bioscience, as a scientific advisory board member for 4M Therapeutics, Altimate, Flow, the Milken Center for Strategic Philanthropy, and Myriad Genetics, and as an adjudication committee member for Novartis; he has received honoraria from Belvoir, Eisai, Slack (Psychiatric Annals), and Wiley (Depression and Anxiety); and he has received royalties from Guilford Publications and Up-to-Date/Wolters Kluwer Health. The other authors report no financial relationships with commercial interests.

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/toxicity study to explore the therapeutic effect in mice subjected to the unpredictable chronic mild stress (UCMS) protocol. Neurotransmitters and melatonin were quantified in prefrontal cortex and plasma, respectively. A different drug biodistribution behavior was unveiled for a CNS-acting drug administered by means of the IN route. For the first time, IN administration of sertraline exhibited heightened systemic exposure (bioavailability = 166 %), and a sustained drug release into the brain, in opposition to IV and oral routes, avoiding drug fluctuation. The lower lung exposition (given by normalized area under the curve) observed after IN instillation envisions the reduction of sertraline pulmonary side effects and similarly other peripheral side effects. IN sertraline treatment displayed significant efficacy in ameliorating anhedonia after one week of administration while the 14-day IN treatment regimen translated into decreased immobility time and increased swimming time in the forced swimming test, suggesting an improvement of the depressive-like behavior displayed by the animal depressive-model. Remarkably, these effects were absent with oral sertraline, despite the higher used dose. Noteworthy neurotransmitter alterations were observed, with IN sertraline markedly reducing adrenaline in the prefrontal cortex, while serotonin and melatonin increased following both administration routes. With its sustained brain delivery and serotonin- and melatonin-enhancing potential, the innovative strategy of IN sertraline holds the potential not only to effectively address depressive symptoms but also to mitigate challenges inherent to classic treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Evidence for the efficacy of a low dose of olanzapine (OLA) in combination with antidepressants has been limited and without positive trials in first-episode (FE) patients with schizophrenia (SCH). This study aimed to compare the efficacy in treating negative and depressive symptoms between those FE patients with SCH treated with a combination of OLA plus sertraline and those treated with OLA monotherapy., Methods: One hundred and ninety-six first-episode and drug naïve patients with SCH were randomized to receive low-dose OLA (7.5-10 mg/day) combined with sertraline (50-100 mg/day) (OS group) or normal-dose OLA monotherapy (12.5-20 mg/day) (NO group). Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), and the depressive symptoms were evaluated by the Hamilton Depression Scale (HAMD). Psychosocial functioning was assessed by the Personal and Social Performance Scale (PSP)., Results: In the intent-to-treat efficacy analysis, the OS group had greater decreases in negative and depressive symptoms (pall < 0.01) and a greater increase in PSP total score compared with the NO group (p < 0.01). Moreover, reductions in HAMD total score and PANSS negative subscore and sex were associated with the improvements in psychosocial functioning from baseline to week 24, after controlling for baseline psychosocial function, age, and onset age., Conclusion: This study demonstrates that low-dose OLA in combination with sertraline had clinically meaningful improvements not only in the negative and depressive symptoms but also in psychosocial functioning in patients with FE-SCH, while not affecting positive symptoms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Changes in trauma-related beliefs and therapeutic alliance have been found to temporally precede symptom reduction; however, it is likely these processes do not act in isolation but rather in interactive ways., Methods: The present study examined the temporal relationships between negative posttraumatic cognitions (PTCI) and therapeutic alliance (WAI) in 142 patients who were part of a randomized trial comparing prolonged exposure (PE) to sertraline for chronic PTSD., Results: Using time-lagged mixed regression models, improvements in the therapeutic alliance predicted subsequent improvements in trauma-related beliefs ( d  = 0.59), an effect accounted for by between-patient variability ( d  = 0.64) compared to within-patient variability ( d  = .04) giving weaker support to the causal role of alliance on outcome. Belief change did not predict improvements in alliance and neither model was moderated by treatment type., Conclusion: Findings suggest alliance may not be an independent driver of cognition change and point to the need for additional study of the impact of patient characteristics on treatment processes.

Objective: Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications., Design: Retrospective cohort study., Setting: The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California., Participants: Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018., Main Outcome Measures: HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities., Results: Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin., Conclusions: Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Major depressive disorder (MDD) is one of the most common psychiatric issues in hemodialysis population. However, the research on proper diagnostic tools and its treatment is still insufficient. The study was performed to investigate the safety and effectiveness of sertraline and agomelatine in a group of hemodialysis patients., Patients and Methods: 78 adult patients from one dialysis centre in Poland were included into the study. The Beck Depression Inventory II (BDI-II) was used to screen for depressive symptoms and was followed by the clinical interview with the psychiatrist. Nine patients diagnosed with major depressive disorder received antidepressant treatment with sertraline or agomelatine, according to the best clinical practice. The additional treatment with vortioxetine was used if the initial one was not effective. The time of observation was 24 weeks. The psychiatric follow up as well as the laboratory data were obtained during the course of observation., Results: All patients receiving sertraline achieved remission of depressive symptoms. In patients receiving agomelatine no remission was observed despite dose augmentation. The side effects of antidepressants were mild and did not result in treatment discontinuation. No abnormalities in liver enzymes levels were observed. In five cases the significant decrease of haemoglobin level was noticed, with no cases of bleeding reported., Conclusion: In patients receiving sertraline the antidepressant effect was satisfactory. No remission of depressive symptoms was observed in patients taking agomelatine. The side effects of antidepressants were mild and transient. Further research on depression treatment in hemodialysis patients is needed, including newer medications.

Cerebral ischemia reperfusion (I/R) is one of the neurovascular diseases which leads to severe brain deterioration. Haemorrhagic transformation (HT) is the main complication of ischemic stroke. It exacerbates by reperfusion, causing a more deleterious effect on the brain and death. The current study explored the protective effect of sertraline (Sert) against cerebral I/R in rats by inhibiting HT, together with the molecular pathways involved in this effect. Forty-eight wister male rats were divided into 4 groups: Sham, Sert + Sham, I/R, and Sert + I/R. The ischemic model was induced by bilateral occlusion of the common carotid artery for 20 min, then reperfusion for 24 h. Sertraline (20 mg/kg, p.o.) was administrated for 14 days before exposure to ischemia. Pre-treatment with Sert led to a significant attenuation of oxidative stress and inflammation. In addition, Sert attenuated phosphorylation of extracellular regulated kinases and nuclear factor kappa-p65 expression, consequently modulating microglial polarisation to M2 phenotype. Moreover, Sert prevented the hemorrhagic transformation of ischemic stroke as indicated by the notable decrease in neuronal expression of CD163, activity of Heme oxygenase-2 and matrix metalloproteinase-2 and 9 levels. In the same context, Sert decreased levels of autophagy and apoptotic markers. Furthermore, histological examination, Toluidine blue, and Prussian blue stain aligned with the results. In conclusion, Sert protected against cerebral I/R damage by attenuating oxidative stress, inflammation, autophagy, and apoptotic process. It is worth mentioning that our study was the first to show that Sert inhibited hemorrhagic transformation. The protective effect of sertraline against injury induced by cerebral ischemia reperfusion via inhibiting Hemorrhagic transformation., (© 2023. The Author(s).)

Clomipramine (CIMI) is an effective treatment for obsessive-compulsive disorder in patients who have failed to respond to trials of selective serotonin transport inhibitors (eg, sertraline). The case presented here illustrates how knowledge of the pharmacodynamics and pharmacokinetics of CIMI in a specific patient can be used to personalize treatment to optimize the likelihood of efficacy (ie, maximum benefit to risk ratio). The approach described in this column considered: (1) the patient's diminished ability to clear CIMI and its major metabolite, desmethlyclomipramine due to a genetic deficiency in cytochrome P450 2D6 enzyme activity, and (2) the patient's ability to extensively convert CIMI to desmethlyclomipramine. That conversion impairs the ability to inhibit the serotonin transporter, the mechanism that is most likely responsible for the efficacy of CIMI in obsessive-compulsive disorder., Competing Interests: Over his 45-year career, S.H.P. has worked with over 145 pharmaceutical and biotech companies in the United States and throughout the world. Over the past year, he has received grants/research support from or has served as a consultant, on the advisory board, or on the speaker’s bureau for Alkermes, BioXcel, Janssen. All clinical trial and study contracts were with and payments made to the Kansas University Medical Center Research Institute, a research institute affiliated with Kansas University School of Medicine-Wichita. R.R. declares no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Escitalopram and sertraline are commonly prescribed for anxiety and depressive disorders in children and adolescents. The pharmacokinetics (PK) of these medications have been evaluated in adults and demonstrate extensive variability, but studies in pediatric patients are limited. Therefore, we performed a population PK analysis for escitalopram and sertraline in children and adolescents to characterize the effects of demographic, clinical, and pharmacogenetic factors on drug exposure., Methods: A PK dataset was generated by extracting data from the electronic health record and opportunistic sampling of escitalopram- and sertraline-treated psychiatrically hospitalized pediatric patients aged 5-18 years. A population PK analysis of escitalopram and sertraline was performed using NONMEM. Concentration-time profiles were simulated using MwPharm++ to evaluate how covariates included in the final models influence medication exposure and compared to adult therapeutic reference ranges., Results: The final escitalopram cohort consisted of 315 samples from 288 patients, and the sertraline cohort consisted of 265 samples from 255 patients. A one-compartment model with a proportional residual error model best described the data for both medications. For escitalopram, CYP2C19 phenotype and concomitant CYP2C19 inhibitors affected apparent clearance (CL/F), and normalizing CL/F and apparent volume of distribution (V/F) to body surface area (BSA) improved estimations. The final escitalopram model estimated CL/F and V/F at 14.2 L/h/1.73 m 2 and 428 L/1.73 m 2 , respectively. For sertraline, CYP2C19 phenotype and concomitant CYP2C19 inhibitors influenced CL/F, and empirical allometric scaling of patient body weight on CL/F and V/F was significant. The final sertraline model estimated CL/F and V/F at 124 L/h/70 kg and 4320 L/70 kg, respectively. Normalized trough concentrations (C trough ) for CYP2C19 poor metabolizers taking escitalopram were 3.98-fold higher compared to normal metabolizers (151.1 ng/mL vs 38.0 ng/mL, p < 0.0001), and normalized C trough for CYP2C19 poor metabolizers taking sertraline were 3.23-fold higher compared to normal, rapid, and ultrarapid metabolizers combined (121.7 ng/mL vs 37.68 ng/mL, p < 0.0001). Escitalopram- and sertraline-treated poor metabolizers may benefit from a dose reduction of 50-75% and 25-50%, respectively, to normalize exposure to other phenotypes., Conclusion: To our knowledge, this is the largest population PK analysis of escitalopram and sertraline in pediatric patients. Significant PK variability for both medications was observed and was largely explained by CYP2C19 phenotype. Slower CYP2C19 metabolizers taking escitalopram or sertraline may benefit from dose reductions given increased exposure., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50-100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety., (© 2023. Springer Nature Limited.)

Major depressive disorder is one of the most common psychiatric disorders in the world. It is essential to study and use effective, available, and affordable psychotherapy methods along with drug therapy to manage the symptoms of this disease. Therefore, the current study aimed to determine the effect of mobile phone-based logotherapy on depression, suicidal ideation, and hopelessness in patients with major depressive disorder by using a mixed-methods approach. In the first phase of this mixed-methods study, 70 patients completed the quantitative phase (control group = 35, intervention group = 35). The intervention group received an 8-week mobile-based logotherapy program via WhatsApp (one 180-min module per week) combined with sertraline, while the control group received just sertraline plus education about pharmacotherapy. Data was collected before, immediately after the intervention, and 3 months later using the Beck depression inventory short form items (BDI-13), the Beck hopelessness scale (BHS), and the Beck scale for suicide ideation (BSSI). Then, a qualitative study on the intervention group was conducted to explain the findings of the quantitative phase. The repeated measure MANOVA revealed a significant interaction effect of time and group on the set of dependent variables (F(6,63) = 25.218, P < 0.001). Qualitative analysis confirmed the efficacy of sertraline plus mobile-based logotherapy on depression, suicidal ideation, and hopelessness in the intervention group. Three key themes extracted from the participants' experiences of mobile-based logotherapy were "efficient instruction", "user-friendly intervention" and "constructive change". Mobile-based logotherapy through WhatsApp was an effective psychotherapy method for decreasing depression, hopelessness, and suicidal ideation in patients with major depressive disorder. It is suggested that educational, institutional, and technological infrastructure for providing and using mobile-based logotheapy for patients with major depressive disorder be considered in the mental health care system., (© 2023. Springer Nature Limited.)

Background: As 40-60% of the patients with obsessive-compulsive disorder (OCD) do not adequately respond to the first-line treatment, finding an effective second-line treatment is required. Our aim was to assess the efficacy and safety of agomelatine (a selective melatonin receptor agonist and a 5-hydroxytryptamine (HT)2 C antagonist) augmentation of sertraline in the treatment of patients with moderate to severe OCD., Methods: In this 12-week randomized, double-blinded, placebo-controlled, parallel-group clinical trial, 65 patients with moderate to severe OCD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5) criteria and a Yale-Brown obsessive compulsive scale (Y-BOCS) score of over 21, were included. They were assigned with sertraline (100 mg/day for the first 4 weeks and 200 mg/day for the next 8 weeks) and either agomelatine (25 mg/day) or placebo. The primary outcome was OCD symptoms measured by the Y-BOCS., Results: Fifty patients (24 in agomelatine group and 26 in placebo group) completed the trial. The Y-BOCS scores in total (MD (95% CI) = 12.25 (11.00, 13.49) (P < 0.001) vs. MD (95% CI) = 12.46 (6.65, 15.74) (P < 0.001)), the obsession subscale (MD (95% CI) = 5.04 (4.19, 5.88) (P < 0.001) vs. MD (95% CI) = 5.00 (3.84, 6.16) (P = 0.0001)), and compulsion subscale (MD (95% CI) = 7.21 (6.34, 8.07) (P < 0.001) vs. MD (95% CI) = 7.460 (6.50, 8.42) (P < 0.001)) significantly decreased in both groups. Although, at the end of the trial, no significant difference was observed between the scores of the two groups in total (MD (95% CI) = 0.480 (-1.23, 2.19) (P = 0.78)), the obsession subscale (MD (95% CI) = 1.020 (-0.15, 2.19) (P = 0.38)), and the compulsion subscale (MD (95% CI) = 0.540 (-0.34, 1.42) (P = 0.54)). No major adverse effects were recorded, and the frequency of side effects was not significantly different between the groups., Conclusion: Agomelatine in augmentation with sertraline is safe and tolerable in patients with moderate to severe OCD. However, our study does not support its efficacy in improving OCD symptoms, compared to placebo., Trial Registration: The trial was registered at the Iranian Registry of Clinical Trials on 14/07/2020 ( www.irct.ir ; IRCT ID: IRCT20170123032145N5)., (© 2023. BioMed Central Ltd., part of Springer Nature.)