Selective Serotonin Reuptake Inhibitor Antidepressants Research Articles

Vilazodone,aNovel SSRI Antidepressant with 5-HT1A Partial Agonist Properties: Diminished Potentiation of Chronic Oral Methylphenidate-Induced Dynorphin Expression in the Striatum in Adolescent Male Rats.

Selective serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine are used in combination with the medical psychostimulant methylphenidate (Ritalin) in a variety of treatments in children and adults. Unintended co-exposure to these psychotropic medications also occurs in patients on SSRIs who abuse methylphenidate as a "cognitive enhancer" or recreational drug. Preclinical research shows that SSRIs such as fluoxetine when given in conjunction with methylphenidate potentiate addiction-related gene regulation by methylphenidate in the striatum, consistent with the known facilitatory role for serotonin in psychostimulant-induced neuronal and behavioral changes. Moreover, fluoxetine combined with methylphenidate also facilitated subsequent acquisition of cocaine self-administration in adolescent rats, suggesting an increased addiction liability for methylphenidate. In the present study, we investigated the impact of a novel SSRI, vilazodone, on methylphenidate-induced gene regulation in adolescent male rats. In contrast to prototypical SSRIs such as fluoxetine, vilazodone also acts as a partial 5-HT1A serotonin receptor agonist and is thus proposed to temper serotonin input to the striatum. We compared the effects of chronic treatment (4 weeks) with vilazodone (10mg/kg, twice daily) with those of fluoxetine (5mg/kg, twice daily) on striatal dynorphin expression induced by oral methylphenidate treatment (30/60mg/kg/day in drinking water, 8h access daily). Our results demonstrate that, in contrast to fluoxetine, vilazodone had minimal or no potentiating effects on methylphenidate-induced dynorphin expression. This diminished impact on gene regulation was seen throughout the striatum, including the nucleus accumbens, where increased dynorphin expression has previously been associated with various aspects of addiction. Our findings suggest that vilazodone may serve as a better adjunct SSRI with reduced addiction-facilitating properties.

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

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

Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study.

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR = 0.62, 95% CI = (0.41-0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.

Integrated physio-biochemical and transcriptomic analysis reveals the joint toxicity mechanisms of two typical antidepressants fluoxetine and sertraline on Microcystis aeruginosa

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 μg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin−leucine−arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.

Predictive modeling of antidepressant efficacy based on cognitive neuropsychological theory

BackgroundWe aimed to develop a clinical predictive model based on the cognitive neuropsychological (CNP) theory and machine-learning to examine SSRI efficacy in the treatment of MDD. MethodsBaseline assessments including clinical symptoms (HAMD, HAMA, BDI, and TEPS scores), negative biases (NEO-PI-R-N and NCPBQ scores), sociodemographic characteristics (social support and SES), and a 5-min eye-opening resting-state EEG were completed by 69 participants with first-episode major depressive disorder (MDD) and 36 healthy controls. The clinical symptoms and negative bias were again assessed after an 8-week treatment of depression with selective serotonin reuptake inhibitors (SSRIs). A multi-modality machine-learning model was developed to predict the effectiveness of SSRI antidepressants. ResultsAt baseline, we observed significant differences between MDD patients and healthy controls in terms of social support, clinical symptoms, and negative bias characteristics (p < 0.001). A negative association was found (p < 0.05) between neuroticism and alpha asymmetry in both the central and central-parietal areas, as well as between negative cognitive processing bias and alpha asymmetry in the parietal region. Compared to responders, non-responders exhibited less negative cognitive processing bias and greater alpha asymmetry in both central and central-parietal regions. Importantly, we developed a multi-modality machine-learning model with 83 % specificity using the above salient features. ConclusionsResearch results support the CNP theory of depression treatment. To some extent, the multimodal clinical model constructed based on the CNP theory effectively predicted the efficacy of this treatment in this population. LimitationsSmall sample and only focus on the mechanisms of delayed-onset SSRI treatment.

Sex-Specific Transcriptomic Changes in the Villous Tissue of Placentas of Pregnant Women Using a Selective Serotonin Reuptake Inhibitor.

About 5% of pregnant women are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants to treat their depression. SSRIs influence serotonin levels, a key factor in neural embryonic development, and their use during pregnancy has been associated with adverse effects on the developing embryo. However, the role of the placenta in transmitting these negative effects is not well understood. In this study, we aim to elucidate how disturbances in the maternal serotonergic system affect the villous tissue of the placenta by assessing whole transcriptomes in the placentas of women with healthy pregnancies and women with depression and treated with the SSRI fluoxetine during pregnancy. Twelve placentas of the Biology, Affect, Stress, Imaging and Cognition in Pregnancy and the Puerperium (BASIC) project were selected for RNA sequencing to examine differentially expressed genes: six male infants and six female infants, equally distributed over women treated with SSRI and without SSRI treatment. Our results show that more genes in the placenta of male infants show changed expression associated with fluoxetine treatment than in placentas of female infants, stressing the importance of sex-specific analyses. In addition, we identified genes related to extracellular matrix organization to be significantly enriched in placentas of male infants born to women treated with fluoxetine. It remains to be established whether the differentially expressed genes that we found to be associated with SSRI treatment are the result of the SSRI treatment itself, the underlying depression, or a combination of the two.

Prediction of treatment response in major depressive disorder using a hybrid of convolutional recurrent deep neural networks and effective connectivity based on EEG signal.

In this study, we have developed a novel method based on deep learning and brain effective connectivity to classify responders and non-responders to selective serotonin reuptake inhibitors (SSRIs) antidepressants in major depressive disorder (MDD) patients prior to the treatment using EEG signal. The effective connectivity of 30 MDD patients was determined by analyzing their pretreatment EEG signals, which were then concatenated into delta, theta, alpha, and beta bands and transformed into images. Using these images, we then fine tuned a hybrid Convolutional Neural Network that is enhanced with bidirectional Long Short-Term Memory cells based on transfer learning. The Inception-v3, ResNet18, DenseNet121, and EfficientNet-B0 models are implemented as base models. Finally, the models are followed by BiLSTM and dense layers in order to classify responders and non-responders to SSRI treatment. Results showed that the EfficiencyNet-B0 has the highest accuracy of 98.33, followed by DensNet121, ResNet18 and Inception-v3. Therefore, a new method was proposed in this study that uses deep learning models to extract both spatial and temporal features automatically, which will improve classification results. The proposed method provides accurate identification of MDD patients who are responding, thereby reducing the cost of medical facilities and patient care.

Adjuvant administration of probiotic effects on sexual function in depressant women undergoing SSRIs treatment: a double-blinded randomized controlled trial

BackgroundAccording to the Institute of Health Metrics and Evaluation’s Global Health Data Exchange (2023) it is estimated that 5% of all adults will experience depressive disorder. Amongst the general loss of pleasure and interest in everyday activities that are symptoms of low mood, reduced sexual desire and sexual dysfunction can be particularly overlooked. Human sexuality is complex, but finding solutions based on scientific evidence to limit the symptoms of depressive disorder and the iatrogenic impact of antidepressant treatment to improve this outcome is an important step in promoting psychological health and general wellbeing.ObjectiveThe present study aimed is to provide scientific evidence to assess the effect of oral probiotic on sexual function in women with depressive disorder treated with Selective Serotonin Reuptake Inhibitors (SSRIs) in an Iranian population.DesignThis study was a double-blind randomized clinical trial. Eligible women were assigned to lactofem plus SSRIs (n = 58) or SSRIs alone (n = 54). In group A, SSRI antidepressants were prescribed together with Lactofem, and in group B, SSRI antidepressants were prescribed alone. Lactofem including Lactobacillus acidophilus 2 × 109 cfu/g, Bifidobacterium bifidus 2 × 109 cfu/g, Lactobacillus rutri 2 × 109 cfu/g, Lactobacillus fermentum 2 × 109 cfu/g; capsule weight of 500 mg bio-capsule administered orally and daily. The duration of intervention in two groups was two months. All questionnaires were completed by the patients before and after the intervention. The Female Sexual Function Index (FSFI), Hamilton Depression Rating Scale and Larson's Sexual Satisfaction Questionnaire were used to evaluate sexual function, severity of depressive disorder and sexual satisfaction, respectively.ResultsBased on the results of the present study, there was a statistically significant difference in sexual satisfaction and severity of depressive disorder between the groups before and after the intervention (P < 0.05). Also, our findings showed that after eight weeks, the Lactofem plus SSRIs group showed significant improvement in FSFI domains and total scores compared to SSRIs alone group (P < 0.05).ConclusionsThe results of the present study show that taking probiotics for eight weeks may improve the severity of depressive disorder, sexual function and sexual satisfaction in depressed women treated with SSRIs.Trial registrationClinicalTrials.govidentifier: IRCT20160524028038N14 (19/12/2022)

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (β = –18.3, 95% CI (–34.3 to –2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study.

Our knowledge of the broader impacts of antidepressant withdrawal, beyond physical side effects, is limited. Further research is needed to investigate the lived experiences of withdrawal, to aid clinicians on how to guide patients through the process. To explore antidepressant users' experiences and views on the withdrawal process and how it affected their quality of life across multiple life domains. We conducted in-depth qualitative interviews with 20 individuals from the community who had attempted to withdraw from Serotonin Reuptake Inhibitor antidepressants in the past year. Semi-structured interviews were conducted online. A topic guide was used to ensure consistency across interviews. The interviews were audio-recorded and transcribed verbatim and analysed using inductive reflexive thematic analysis. Five themes were generated. The first highlighted the challenges of managing the release from emotional blunting and cognitive suppression following antidepressant discontinuation. The second related to the negative impact of withdrawal on close relationships and social interactions. The third showed that concurrent with negative physical symptoms, there was a positive impact on health (exercise was reported by some as a coping mechanism). The fourth theme focused on support from GPs and families, emphasising the importance of mental health literacy in others. The final theme underscored the importance of gradual and flexible tapering in enabling a manageable withdrawal experience,and the consideration of timing. The lived experience of withdrawal significantly impacts individuals' well-being. Participants emphasised that withdrawal is not just about physical side effects but also affects their emotional, cognitive, and social functioning. Eight people attended individual online meetings to share their experiences of antidepressant withdrawal to help inform the study design and recruitment strategy. Insights from these meetings informed the development of the topic guide. Questions about GP involvement, family relationships, and mood and thinking changes were included based on this PPI work. This ensured the inclusion of topics important to antidepressant users and facilitated the researcher's questioning during the interviews.

Cohort study finds prenatal SSRI exposure linked to reduced brain volume

A population‐based cohort study has found that prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants was associated with reduced brain volume in children aged 7 to 15. The study did not examine whether any of the observed changes in the brain predisposed these young people to any impairments.

Probable fluoxetine-induced hepatomegaly: a case report

Depressive disorder is a common behavioural, psychiatric disorder. Among various antidepressants selective serotonin reuptake inhibitors (SSRIs) are preferred drugs for the treatment of depression. When second-generation antidepressants SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat depression, 0.5–1% of patients develop mildly altered liver function without any symptoms. Various degrees of organ dysfunction are linked with drug-induced liver injury, which is unpredictable and might result from exposure to a drug. We reported suspected fluoxetine-induced hepatomegaly secondary to nine weeks of treatment with an SSRI fluoxetine. Upon cessation of the agent, the patient recovered symptomatically. The evidence is vital that the hepatomegaly in this patient was caused by fluoxetine.

Prediction of Treatment Outcome in Major Depressive Disorder Using Ensemble of Hybrid Transfer Learning and Long Short-Term Memory Based on EEG Signal

Major Depressive Disorder (MDD) is a widespread global mental disease. The Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) antidepressants prescribed for MDD patients is limited and pre-treatment assessment of treatment outcome is a vital task. In this study, a hybrid model based on Transfer Learning (TL) of powerful pre-trained deep Convolutional Neural Networks (CNNs) empowered with bidirectional Long Short-term Memory (BLSTM) cells and attention mechanism were developed to classify Responders (R) and Non-Responders (NR) to SSRI antidepressants, using raw data images of pre-treatment EEG signal obtained from 30 MDD patients. TL-LSTM-Attention models based on VGG16, Xception, and Densenet121 models were created for the classification of R/NR. Results show that the highest performance of hybrid TL-LSTM-Attention models was achieved by VGG16-LSTM-Attention with an accuracy of 98.21%, sensitivity of 96.22%, and specificity of 99.67%. An Ensemble model based on weighted majority voting among hybrid models is constructed to surpass the performance of each single hybrid model. Our proposed ensemble model gained accuracy, sensitivity, and specificity of 98.84%, 97.80%, and 99.60%, respectively. Hence, the proposed model which is an ensemble of TL-LSTM-Attention models fed by raw data images of EEG signal leads to high confidence in the prediction of antidepressants treatment outcome.

Combined Chronic Oral Methylphenidate and Fluoxetine Treatment During Adolescence: Effects on Behavior.

Attention Deficit Hyperactivity Disorder (ADHD) can be comorbid with depression, often leading to the prescription of both methylphenidate (MP) and selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (FLX). Moreover, these drugs are often misused as cognitive enhancers. This study examined the effects of chronic oral co-administration of MP and FLX on depressive- and anxiety-like behaviors. Adolescent rats received daily either water (control), MP, FLX, or the combination of MP plus FLX in their drinking water over the course of 4 weeks. Data analysis shows a decrease in food consumption and body weight for rats exposed to FLX or the combination of MP and FLX. Sucrose consumption was significantly greater in FLX or MP+FLX groups compared to controls. FLX-treated rats showed no effect in the elevated plus maze (EPM; open arm time) and forced swim test (FST; latency to immobility). However, rats treated with the combination (MP+FLX) showed significant anxiolytic-like and anti-depressive-like behaviors (as measured by EPM and FST), as well as significant increases in overall activity (distance traveled in open field test). Finally, the combined MP+FLX treatment induced a decrease in anxiety and depressive- like behaviors significantly greater than the response from either of these drugs alone. These behavioral results characterize the long-term effects of these drugs (orally administered) that are widely co-administered and co-misused and provide important insight into the potential neurobiological and neurochemical effects. Future research will determine the potential risks of the long-term use of MP and FLX together.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report

BackgroundPanic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy.Case presentationThis report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly.ConclusionsThe immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient’s clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Reduced risk of mortality among COVID-19 patients with in-hospital selective serotonin reuptake inhibitor administration

Abstract Objectives The anti-inflammatory properties of selective serotonin reuptake inhibitors (SSRI)s, particularly fluvoxamine, have been hypothesized to reduce clinical deterioration in patients with COVID-19 when administered early in the disease course. The objective of this analysis was to examine the effect of maintenance SSRI administration, including variation among different medications, on the outcomes of hospitalized patients with COVID-19. Methods Retrospective analysis of disease progression and mortality risk of over 230,000 patients hospitalized with COVID-19 at facilities associated with a large healthcare system in the United States. Key findings Receipt of SSRIs during the hospital encounter occurred in approximately 10.6% (n = 24,690) of COVID-19 patients. When matched for patient characteristics, disease severity and other treatments, receipt of any SSRI was associated with a 30% reduction in the relative risk of mortality (RR: 0.70, 95% confidence interval [CI]: 0.67–0.73; adjusted P-value &amp;lt;0.001). Similar reductions in the relative risk of mortality were seen with nearly every individual SSRI; for sertraline-treated patients, the most commonly used SSRI in the data set, there was a 29% reduction in the relative risk of mortality (RR: 0.71, 95% CI: 0.66–0.77; adjusted P-value &amp;lt;0.001). Conclusions In total, this retrospective analysis suggests that there is a significant association between SSRI antidepressants and reduced morality among patients hospitalized with COVID-19.

Repurposing selective serotonin reuptake inhibitors for severity of COVID-19: A population-based study

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

Association analysis of gut microbiota and efficacy of SSRIs antidepressants in patients with major depressive disorder

BackgroundRelevant studies have shown that gut microbiome plays an important role in the occurrence, development and treatment of major depressive disorder (MDD). Many studies have also shown that, selective serotonin reuptake inhibitors (SSRIs) antidepressants can improve the symptoms of depression by changing the distribution of gut microbiome, Here we investigated whether a distinct gut microbiome was associated with Major depressive disorder (MDD), and how it was modulated by SSRIs antidepressants. MethodIn this study, we analyzed the gut microbiome composition of 62 patients with first-episode MDD and 41 matched healthy controls, before SSRIs antidepressants treatment, using 16S rRNA gene sequencing. MDD patients characterized as treatment-resistant (TR) or responders (R) to antidepressants by score reduction rate were ≥50 % after SSRIs antidepressants treatment for eight weeks. ResultsLDA effect size (LEfSe) analysis found that there were 50 different bacterial groups among the three groups, of which 19 genera were mainly at the genus level. The relative abundance of 12 genera increased in the HCs group, 5 genera in the R group increased in relative abundance, and 2 genera in the TR group increased in relative abundance. The correlation analysis of 19 bacterial genera and the score reduction rate showed that Blautia, Bifidobacterium and Coprococcus with higher relative abundance in the treatment effective group were related to the efficacy of SSRIs antidepressants. ConclusionsPatients with MDD have a distinct gut microbiome that changes after SSRIs antidepressants treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients with MDD.

Effects of probiotic supplement Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 on sleep quality in patients with anxiety and depression comorbidity

IntroductionRecent studies have supported that Lactobacillus plantarum can reduce the severity of anxiety and depression. However, previous studies did not focus on the sleep quality. This study determines whether Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 reduce the severity of insomnia, and improves sleep quality in patients who comorbidity of depression and anxiety disorders.ObjectivesAn assessment of insomniac effects a probiotic supplement containing Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 (PLANTARUM) in patients with anxiety and depression comorbidity undergoing treatment with selective serotonin reuptake inhibitors (SSRI) antidepressants.MethodsSixty patients with mixed anxiety and depressive disorder (according to ICD-10 diagnostic criteria F41.2) were included in an 8-week open label study. Thirty participants received either SSRI antidepressants with PLANTARUM at a dose of 1.0 × 109 CFU once per day and thirty patients received SSRI antidepressants only. The severity of insomnia was assessed using Insomnia Severity Index (ISI). The severity of depressive symptoms was rated using Hamilton Depressive Rating Scale (HDRS). The severity of anxiety symptoms was assessed using Hamilton Anxiety Rating Scale (HAM-A) and General Anxiety Disorder Scale (GAD-7).ResultsAfter 8 weeks intervention, a significant reduction of ISI total score (from 22,1±2,8 to 14,1±2,1) was detected in patients with anxiety and depression who prescribed SSRI antidepressants and PLANTARUM (p˂0,05), compared with participants who didn’t receive probiotics (p&gt;0,05). Also, we detected a significant improve sleep quality of insomniac patients with comorbidity of anxiety and depressive symptoms (p˂0,05) who received SSRI antidepressants and probiotic supplement Lactobacillus Plantarum CECT7485/Lactobacillus Brevis CECT7480.ConclusionsThe present data illustrated that probiotic supplement Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 is a feasible for adjunctive to SSRI antidepressants intervention for insomniac patients with anxiety and depressive comorbidityDisclosure of InterestNone Declared

The effect psychobiotics on anxiety symptoms

IntroductionPsychobiotics are a group of probiotics that affect the central nervous system related functions and behaviors mediated by the gut-brain-axis via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal function but also the antidepressant and anxiolytic capacity.ObjectivesAn assessment of psychobiotic and anti-anxiety effects a probiotic supplement containing Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 (PLANTARUM) in patients with anxiety undergoing treatment with selective serotonin reuptake inhibitors (SSRI) antidepressants.MethodsSixty patients with mixed anxiety and depressive disorder (according to ICD-10 diagnostic criteria F41.2) were included in an 8-week open label study. Thirty participants received either SSRI antidepressants with PLANTARUM at a dose of 1.0 × 109 CFU once per day and thirty patients received SSRI antidepressants only. The severity of anxiety symptoms was assessed using Hamilton Anxiety Rating Scale (HAM-A) and General Anxiety Disorder Scale (GAD-7).ResultsAfter 8 weeks intervention, a significant reduction of HAM-A total score (from 37,8±5,3 to 23,6±4,4) was detected in patients with anxiety who prescribed SSRI antidepressants and PLANTARUM (p˂0,05), compared with participants who didn’t receive probiotics (p&gt;0,05). Also, a significant reduction of GAD-7 total score (from 21,7±3,3 to 12,5±2,4) was detected in patients with anxiety symptoms who received SSRI antidepressants and PLANTARUM (p˂0,01), compared with patients who didn’t intake probiotics (p&gt;0,05).ConclusionsThe present data illustrated that probiotic supplement PLANTARUM is a feasible for adjunctive to SSRI antidepressants intervention for anxiety treatment.Disclosure of InterestNone Declared