Serotonin Reuptake Inhibitors Research Articles

Investigating Neuroplasticity Changes Reflected by BDNF Levels in Astrocyte-Derived Extracellular Vesicles in Patients with Depression.

To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels. Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs. After false discovery rate correction, patients with MDD exhibited higher CD81 levels (P FDR = 0.040) and lower BDNF levels (P FDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 (P FDR = 0.002) and Alix (P FDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased (P FDR = 0.046), while BDNF levels normalized to CD81 increased (P FDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (ρ=0.117, P = 0.334). This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.

Mental health landscape in Kosova from 2017 to 2022: A retrospective study of antidepressant and anxiolytic market trends and the impact of COVID-19

ObjectivesThis study explores the mental health situation in Kosova and the impact of the COVID-19 pandemic. MethodsMarketed quantities of antidepressants (N06A) and anxiolytics (N05B) from 2017 to 2022 were analyzed using the Anatomical Therapeutic Chemical/Defined Daily Doses (ATC/DDD) methodology. Caution is advised as these quantities may not directly reflect patient usage and could include uses for conditions outside their primary indications. ResultsPrior to the pandemic, antidepressant quantities remained relatively stable, but rose from 6.8 DDD/1000 inhabitants/day in 2019 to 9.7 in 2020 and 12.4 in 2021, before returning to pre-pandemic levels of 6.8 DDD in 2022. Over 80 % of these were selective serotonin reuptake inhibitors. Meanwhile, anxiolytic quantities initially decreased from 17.4 DDD in 2017 to 9.9 in 2019, then rebounded to 17.9 DDD in 2020. Notably, alprazolam usage surged from 2.9 in 2017 to 6.9 in 2021, subsequently dropping to 2.0 in 2022. ConclusionsThe volatile trends in medication quantities during the pandemic suggest a fragile mental health landscape in Kosova—a developing, post-conflict country with a youthful population—underscoring the need for proactive interventions in similar contexts globally.

Effect of Selective Serotonin Reuptake Inhibitors on iron transport and metabolism in the placenta: Exploratory study using a choriocarcinoma cell line

Effect of Selective Serotonin Reuptake Inhibitors on iron transport and metabolism in the placenta: Exploratory study using a choriocarcinoma cell line

Interventional approaches to treatment resistant depression (DTR) in children and adolescents: A systematic review and meta-analysis

BackgroundMajor depressive disorder (MDD) is highly prevalent in youth. Conventional treatment paradigms primarily involve selective serotonin reuptake inhibitors (SSRIs) and psychotherapy, yet a significant proportion of this population exhibits treatment-resistant depression (TRD). In adults, interventional therapies like Electroconvulsive Therapy (ECT), repetitive Transcranial Magnetic Stimulation (rTMS), and ketamine have shown promise for TRD, but their comparative efficacy remains underexplored in Adolescent and pediatric population. This systematic review and meta-analysis aims to assess the relative effectiveness of ECT, rTMS, and ketamine in treating TRD among adolescents. MethodsFollowing PRISMA guidelines, we systematically searched databases for studies of ECT, rTMS, or ketamine for treatment-resistant depression in youth ages 10–24. Three reviewers independently screened for inclusion based on predefined criteria. Included observational and randomized controlled trials reported depression symptoms with measures like HDRS and MADRS in youth treated with ECT, rTMS, or ketamine. Two reviewers extracted data on interventions, patients, and depression symptom outcomes. Chance-adjusted inter-reviewer agreement was calculated. For meta-analysis, we pooled standardized mean differences (SMDs) in depression scores using random effects models and assessed heterogeneity with I2 statistics. ResultsMeta-analysis of 10 observational studies examined SMD in depression scores for treatment resistant depression patients treated with ECT, ketamine, or rTMS. Patients treated with ECT had a significantly lower SMD of 1.99 (95 % CI 0.92–3.05, p < 0.001) compared to baseline. Patients treated with ketamine also had a significantly lower SMD of 1.58 (95 % CI 1.04–2.12, p < 0.001). Patients treated with rTMS had the lowest SMD of 2.79 (95 % CI 0.79–4.80, p = 0.006). There was no significant difference between the three groups overall (p > 0.05). Comparative analysis between ECT and ketamine found no significant difference in SMD (p = 0.387). Comparison of ECT versus rTMS found a significant difference in SMD favoring rTMS (p = 0.004). Comparison of ketamine versus rTMS suggested a potential difference in SMD favoring rTMS (p = 0.058). In summary, rTMS resulted in significantly larger reductions in depression scores than ECT, and potentially larger reductions than ketamine. ConclusionsThis meta-analysis illustrates the ability of rTMS, ECT, and ketamine to improve depression in youth. rTMS resulted in the largest improvements, highlighting its potential as a first-line treatment for pediatric treatment-resistant depression given its favorable side effect profile compared to ECT. Further research directly comparing these modalities is needed.

Predictors of abstinence maintenance after cocaine inpatient detoxification: A prospective study.

Cocaine is a highly addictive substance, and with no approved medication for cocaine use disorder (CUD), leading to a heavy burden. Despite validated psychosocial treatments, relapse rates after detoxification are very high in CUD. Few consistent factors can predict abstinence after detoxification. Our study, therefore, aimed at identifying factors predicting abstinence among CUD patients after inpatient detoxification. Eighty-one CUD inpatients were included during detoxification and characterized for clinical and sociodemographic data at baseline and at a follow-up of 3 months after discharge, including a standard measure of their abstinence duration from cocaine. We performed Cox univariate analyzes to determine the factors associated with abstinence maintenance, followed by a multivariate Cox regression to identify independent predictors. Abstinence maintenance was shorter in patients injecting cocaine (hazard ratio [HR] = 5.16, 95% confidence interval [CI]: 2.01-13.27, p < .001) and using cocaine heavily in the month before inclusion (HR = 1.03, 95% CI: 1.00-1.06, p = .046). Conversely, abstinence maintenance was longer in patients with longer inpatient detoxification stays (HR = 0.96, 95% CI: 0.94-0.99, p = .015) and prescribed with selective serotonin reuptake inhibitors (SSRIs) (HR = 0.30, 95% CI: 0.16-0.56, p < .001). Patients with severe CUD may require longer inpatient stays to achieve abstinence. Regarding SSRI prescription, more specific studies are needed to provide stronger recommendations about their use in clinical practice. Our findings suggest several modifiable factors to improve inpatient treatment response in CUD. As there are no specific recommendations about the optimal duration of inpatient stay, our results could pave the way for evidence-based guidelines.

Management of Psychiatric Diagnoses in Reversible Cerebral Vasoconstriction Syndrome: The Dangers of Worsening Pathology with Serotonergic Medications: A Case Report and Literature Review.

Reversible cerebral vasoconstriction syndrome (RCVS) represents a group of conditions that show reversible multifocal narrowing or constriction of the cerebral arteries that supply blood to the brain. The initial manifestation of RCVS often includes a "thunderclap" headache that is sudden, severe, and often disabling. Stimulants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and antipsychotics with serotonergic activity can alter the cerebral arterial tone, trigger vasoconstriction, and place patients at risk of a cerebrovascular accident. Thus, psychiatric medications are commonly discontinued on admission for RCVS, and psychiatry is often consulted for input on acute medication management and longitudinal treatment options. Currently, there is a dearth of literature on managing psychiatric medications in RCVS, resulting in variable practice patterns that place patients at risk of withdrawal, decompensation, and relapse. In this article, we provide a case example and aim to consolidate the limited data surrounding the management of psychiatric illness with comorbid RCVS in our discussion. There is a clear concern about worsening and even potentially lethal consequences due to serotonin or stimulant-induced vasospasm both during an acute episode and in long-term management of RCVS. We discuss the underlying pathophysiologic mechanisms proposed for serotonergic-, noradrenergic-, and dopaminergic-induced cerebral vasospasm and how this correlates with the clinical management of patients on psychiatric medications. These data will then be organized to create a risks versus benefits outline to equip psychiatrists to make decisions about when to stop and when to restart psychiatric medications in the setting of RCVS.

Neural activation changes following attention bias modification treatment or a selective serotonin reuptake inhibitor for social anxiety disorder.

Delineation of changes in neural function associated with novel and established treatments for social anxiety disorder (SAD) can advance treatment development. We examined such changes following selective serotonin reuptake inhibitor (SSRI) and attention bias modification (ABM) variant - gaze-contingent music reward therapy (GC-MRT), a first-line and an emerging treatments for SAD. Eighty-one patients with SAD were allocated to 12-week treatments of either SSRI or GC-MRT, or waitlist (ns = 22, 29, and 30, respectively). Baseline and post-treatment functional magnetic resonance imaging (fMRI) data were collected during a social-threat processing task, in which attention was directed toward and away from threat/neutral faces. Patients who received GC-MRT or SSRI showed greater clinical improvement relative to patients in waitlist. Compared to waitlist patients, treated patients showed greater activation increase in the right inferior frontal gyrus and anterior cingulate cortex when instructed to attend toward social threats and away from neutral stimuli. An additional anterior cingulate cortex cluster differentiated between the two active groups. Activation in this region increased in ABM and decreased in SSRI. In the ABM group, symptom change was positively correlated with neural activation change in the dorsolateral prefrontal cortex. Brain function measures show both shared and treatment-specific changes following ABM and SSRI treatments for SAD, highlighting the multiple pathways through which the two treatments might work. Treatment-specific neural responses suggest that patients with SAD who do not fully benefit from SSRI or ABM may potentially benefit from the alternative treatment, or from a combination of the two. ClinicalTrials.gov, Identifier: NCT03346239. https://clinicaltrials.gov/ct2/show/NCT03346239.

Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age.

There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.

Comparison Between Pregabalin and Sertraline for Treatment of Uraemic Pruritus in Patients on Maintenance Haemodialysis: A Single-Centric Study.

To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus. Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024. 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. 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). 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. Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.

Reciprocal relationships between posttraumatic stress disorder symptoms and positive and negative affect in evidence-based treatments for posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with elevated negative affect (NA; e.g., Badour et al., 2017) and diminished positive affect (PA; Nawijn et al., 2015). PTSD treatments reduce NA (e.g., Jerud et al., 2014), but changes in PA and relationships between changes in affect and PTSD symptoms remain unclear. This study examined changes in PA and NA in adults (N = 130) with PTSD receiving prolonged exposure (PE) or PE plus sertraline as part of a randomized controlled trial (NCT01600456). Participants completed measures of affect (PANAS; Watson et al., 1988) and PTSD symptoms at 10 weekly treatment sessions. Cross-lagged dynamic structural equation models examined associations between session-to-session fluctuations in affect and PTSD. PA increased moderately (d = 0.51) and NA decreased strongly (d = 0.78) across treatment sessions. Within-person fluctuations in PA and NA were generally reciprocal, PAt → NAt+1: effect size (ES) = -0.09, 95% CI [-0.15, -0.02]; NAt → PAt+1: ES = -0.20, 95% CI [-0.28, -0.13]. However, fluctuations in PTSD more strongly predicted next session NA (PTSDt → NAt+1: ES = 0.50, 95% CI [0.38, 0.60]) and PA (PTSDt → PAt+1: ES = -0.26, 95% CI [-0.34, -0.17]) than the reverse. PE augmentation with a selective serotonin reuptake inhibitor did not moderate temporal associations. Prolonged exposure produced substantial improvements in PA and NA. General affective changes may be more a consequence than a driver of PTSD improvement during PE, with improvements in NA and PA potentially linked to the extinction of negative emotional responses to trauma cues and increased engagement with rewarding activities, respectively. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Timing of Antidepressant Use in Pregnancy and Preterm Birth

OBJECTIVE: To evaluate the implication of timing of antidepressant exposure on preterm birth to better guide clinical counseling. DATA SOURCES: A systematic review and meta-analysis was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using PubMed, MEDLINE Complete, EBSCO, CINAHL Plus, and ClinicalTrials.gov along with a manual search of references in relevant publications. The databases were searched between January 2000 and December 2022 with the following keywords: antidepressants, antidepressant medication, SSRI, selective serotonin reuptake inhibitors, TCA, or SNRI AND pregnancy, pregnant, prenatal, antenatal, perinatal, maternal AND trimester or timing AND preterm or premature. METHODS OF STUDY SELECTION: The database search resulted in 162 studies. The 13 studies that met inclusion criteria compared preterm birth rates in pregnant patients exposed to antidepressants at a specified time in pregnancy (early, late, or throughout pregnancy) and a control group. Covidence was used for screening and data extraction. Excel and R were used for tabulation and statistical analysis, respectively. TABULATION, INTEGRATION, AND RESULTS: Of the 13 studies, nine measured preterm birth rates with antidepressant use in early pregnancy, 10 in late pregnancy, and four throughout pregnancy. Separate random effects models were used to synthesize the effect sizes from studies that did not adjust for presence of maternal depression in the study sample and those that did. In each model, subgroup analysis was conducted to assess the effect of timing of antidepressant exposure on the odds of preterm birth. In the model unadjusted for depression, pooled odds ratios (ORs) for the association between use of antidepressants and preterm birth were 1.41 (95% CI, 1.10–1.81) in early pregnancy, 1.51 (95% CI, 1.26–1.82) in late pregnancy, and 2.79 (95% CI, 1.27–6.12) throughout pregnancy. After adjusting for depression, the pooled ORs were 1.04 (95% CI, 0.83–1.31) in early pregnancy, 1.26 (95% CI, 0.95–1.66) in late pregnancy, and 1.79 (95% CI, 0.54–5.91) throughout pregnancy. No significant effect of timing was found in either model. CONCLUSION: Antidepressant use in pregnancy was not associated with preterm birth, regardless of timing of use. Pregnant patients with an established diagnosis of depression should receive individualized counseling regarding antidepressant use while taking into consideration their risk factors for preterm birth and the implications of untreated depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023390136.

Fluoxetine, but not paroxetine, alters the jaw-closing muscle activity during non-rapid eye movement sleep in mice

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24 h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6 h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00–08:00 and 08:00–14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

Evaluation of Anxiolytic Activity of Angiotensin Receptor Blockers Using Actophotometer Test in Wistar Rats.

Introduction Anxiety disorders are common mental illnesses impacting quality of life, with current treatments like benzodiazepines andselective serotonin reuptake inhibitors (SSRIs)facing limitations due to side effects. Angiotensin receptor blockers (ARBs), used primarily for hypertension, have shown potential neuropsychiatric benefits, including anxiolytic effects. This study explores the anxiolytic effects of two ARBs, telmisartan and losartan, by evaluating locomotor activity in Wistar rats, aiming to identify new treatment options for anxiety through modulation of the renin-angiotensin system. Aim To evaluate the anxiolytic activity of telmisartan and losartan in experimental Wistar rats. Materials and methods The study was carried out afterconsent was obtained from the Institutional Animal Ethics Committee (IAEC). The rats were divided into four groups: group 1 (control group) received distilled water (2 ml/kg), group 2 (diazepam 2 mg/kg group) received diazepam (2 mg/kg), group 3 (telmisartan 5 mg/kg group) received telmisartan (5 mg/kg), and group 4 (losartan 5 mg/kg group) received losartan (5 mg/kg). The actophotometer test, which measures the locomotor activity levels of rats, was utilized to evaluate their anxiolytic activity. The percent decrease in locomotor activity was calculated for statistical evaluation. Results Our investigation found that the telmisartan 5 mg/kg and losartan 5 mg/kg groups had considerable anxiolytic activity (p<0.05) compared to the control group, and it was comparableto the diazepam 2 mg/kg (p>0.05) group. Conclusion The findings of our study indicate that ARBs, specifically telmisartan 5 mg/kg and losartan 5 mg/kg, exhibit potential anxiolytic effects, evidenced by a significant reduction in locomotor activity in the actophotometer test. These results imply that ARBs could be considered as possible therapeutic agents for anxiety, providing a new perspective on their use beyond traditional cardiovascular applications.

Interventions to Enhance Neurocognition for Common Mental Disorders: A Brief Review

Neurocognition, particularly executive functioning (EF), is crucial in psychiatric treatments due to its complex relationship with psychopathology. Cognitive-behavioral therapies (CBTs) show potential in enhancing neurocognitive functions (eg, inhibition, set-shifting, and working memory). Post-CBT changes in brain activation have been observed in regions such as the anterior cingulate cortex and middle frontal gyrus. Although CBTs improve attention and EF in various populations, they are less effective for traumatic brain injury patients. Mindfulness-based psychotherapies also enhance neurocognitive domains, especially in psychiatric populations. Tailored delivery methods, such as face-to-face sessions, may optimize therapeutic outcomes. EF and cognitive training are beneficial for those with attention-deficit/hyperactivity disorder. Integrating CBT with physical exercise can produce synergistic effects on neurocognition. Pharmacotherapies, particularly selective serotonin reuptake inhibitors, offer modest neurocognitive improvements by optimizing neurotransmitter pathways. Clear communication of intervention strengths and limitations is vital for managing patient expectations and enhancing care by targeting clinical, functional, and neurocognitive outcomes. [ Psychiatr Ann . 2024;54(9):e263–e267.]

Psychological and pharmacological treatments of intermittent explosive disorder: a meta-analysis protocol

IntroductionIntermittent explosive disorder (IED) is characterised by recurrent, sudden episodes of impulsive aggression that are disproportionate to the provocation. The condition’s management remains challenging due to the variability in treatment...

Comparing the efficacy of saffron with fluoxetine for the effective management of premenstrual dysphoric disorder: A review

Premenstrual syndrome (PMS) significantly impacts the emotional and physical well-being of women of reproductive age. Various theories have been proposed about its etiology but still, it is unknown. The PMS starts from the luteal stage of women’s menstrual cycle and affects 20% to 40% of women in their reproductive phase. The severe form of PMS is PMDD which typically affects 3% - 5% of women in their reproductive phase. Standard treatments for these conditions include selective serotonin reuptake inhibitors such as fluoxetine, paroxetine, and sertraline. Fluoxetine is mainly used for the treatment of Premenstrual syndrome and Premenstrual dysphoric disorder. Fluoxetine appears to be more effective and better tolerated for treating physical and psychological symptoms associated with severe Premenstrual syndrome and Premenstrual dysphoric disorder. Herbal remedies like saffron (crocus sativus) consist of three bioactive compounds: procrocin, safranal, and crocin. Saffron exhibits SSRIs-like actions and is also used in the management of PMS and PMDD. This review critically evaluates the comparative effectiveness of saffron and fluoxetine in the management of PMDD, aiming to provide valuable insights for treatment decisions.

Efficacy of selective serotonin reuptake inhibitors-related antidepressants in Alzheimer’s disease: a meta-analysis

ObjectiveTo study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer’s disease (AD).MethodsRegistered 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.ResultsFourteen 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.ConclusionThis 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.

Pharmacotherapy and electroconvulsive therapy prescription for women with depressive and anxiety disorders in a psychiatric mother-baby unit.

The purpose of this study was to understand the pharmacotherapy and electroconvulsive therapy (ECT) prescription of women with depression and anxiety admitted to an Australian inpatient psychiatric mother-baby unit (MBU) and compare prescription to national clinical practice guidelines. A retrospective audit was conducted on women diagnosed with depression or anxiety admitted to a public psychiatric inpatient MBU from March 2017 to July 2019. Data was captured at three time points to assess demographic, clinical and pharmacotherapy treatment characteristics. Descriptive statistics were completed. Of the 74 women, 57 women had depression, with 73% prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) and 14% provided ECT during admission. For women with anxiety (n = 17), 23% were prescribed a benzodiazepine with concurrent antidepressant prescription. SSRI prescription increased, with other antidepressant prescription up trending through admission. Atypical antipsychotic prescription was increased initially and trended downwards at discharge. This study explored the therapeutic armamentarium employed for the treatment of mothers admitted to an inpatient psychiatric MBU with depression and anxiety. The results point to the intricate prescribing practices in a naturalistic setting and highlight that prescribing practices were in line with national guidelines.

Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis.

Animal models are critical tools in the study of psychiatric disorders; however, none of the current models fully reflect human stress-related disorders, even though most of the knowledge about the mechanisms of depression comes from animal studies. Animal studies are useful in pharmacological research, whereby we can obtain results that translate into patient treatment by controlling environmental factors, especially in behavioural research. The authors systematically reviewed this issue since medical databases provide access to many primary studies. A systematic review and meta-analysis were conducted based on 25 primary studies. The studies were identified in databases such as PubMed, Embase, and Web of Science (December 2022) according to the inclusion and exclusion criteria established at the beginning of the research and published in the form of a protocol, following the PRISMA and Cochrane Collaboration methodology for secondary studies and CAMARADES (CAMARADES Berlin, QUEST-BIH Charité) for secondary studies on animals. Forest plot analyses were performed (data presented as Mean Difference, Random Model, Inverse Variance), Risk of Bias assessment (Systematic Review Center for Laboratory animal Experimentation (SYRCLE) evaluation), quality assessment of included studies (Animal research: Reporting of In Vivo Experiments (ARRIVE)), and a range of data from source publications were compiled in tabular form. The study analysed the popularity of both animal depression models (ADM) and rat strains used in pharmacological research to test the efficacy of antidepressant drugs based on the immobility time (IT) factor (Forced Swimming Test). The study examined selective serotonin reuptake inhibitors, namely fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Additionally, the study addressed issues concerning the "data availability statement" because precise IT data analysis was impossible in the case of 212 papers. Our data confirm that the Chronic Unpredictable Mild Stress (CUMS) model is the most popular and versatile model used in preclinical depression research, while the two most popular rat strains were Wistar and Sprague-Dawley. The quality of included papers based on the ARRIVE assessment showed a ratio value equal to 0.63, meaning that studies were of intermediate overall quality. The Risk of Bias assessment based on the SYRCLE tool revealed a high risk related to the blinding and the random outcome assessment. In the meta-analysis, the results indicate that all analysed drugs demonstrated efficacy in reducing IT, and the most analysed drug was fluoxetine (confirmed based on 17 studies (19 models)). The analysis of the efficacy of ADMs showed that the most effective models were CUMS, Flinders Sensitive Line (genetic model), Social Isolation, Restraint Stress, and Low-dose Lipopolysaccharide (pharmacological model). Only 2.35% (5 out of 212) of corresponding authors responded to our data request. The study highlights the dominance of the CUMS model and the Wistar and Sprague-Dawley rat strains in preclinical depression research, affirming the efficacy of SSRIs, particularly fluoxetine, in reducing IT. The findings underscore the need for better data availability and methodological improvements despite intermediate overall study quality and notable bias risks. Enhanced transparency and rigorous assessment standards are essential for advancing the reliability of animal models in depression research.

Rapid reorganization of serotonin projections and antidepressant response to 5-HT1A-biased agonist NLX-101 in fluoxetine-resistant cF1ko mice

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) like fluoxetine remain a first-line treatment for major depression, but are effective in less than half of patients and can take 4–8 weeks to show results. In this study, we examined cF1ko mice with genetically induced upregulation of 5-HT1A autoreceptors that reduces 5-HT neuronal activity. These mice display anxiety- and depression-related behaviors that did not respond to chronic fluoxetine treatment. We examined treatment with NLX-101, a biased agonist that preferentially targets 5-HT1A heteroreceptors. By testing different doses of NLX-101, we found that a dose of 0.2 mg/kg was effective in reducing depression-related behavior in cF1ko mice without causing hypothermia, a 5-HT1A autoreceptor-mediated response. After 1 h, this dose activated dorsal raphe 5-HT neurons and cells in the medial prefrontal cortex (mPFC), increasing nuclear c-fos labelling in cF1ko mice. In cF1ko mice but not wild-type littermates, 0.2 mg/kg NLX-101 administered 1 h prior to each behavioral test for two weeks reduced depressive behavior in the forced swim test, but increased anxiety-related behaviors in the open field, elevated plus maze, and novelty suppressed feeding tests. During this treatment, NLX-101 induced widespread increases in the density of 5-HT axons, varicosities, and especially synaptic and triadic structures, particularly in depression-related brain regions including mPFC, hippocampal CA1 and CA2/3, amygdala and nucleus accumbens of cF1ko mice. Overall, NLX-101 was rapid and effective in reducing depressive behavior in SSRI-resistant mice, but also induced anxiety-related behaviors. The increase in serotonin innervation induced by intermittent NLX-101 may contribute to its behavioral actions.