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Search Results (179)

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Keywords = selective serotonin reuptake inhibitors (SSRI)

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18 pages, 1203 KiB  
Communication
Efficacy of a Novel Lactiplantibacillus plantarum Strain (LP815TM) in Reducing Canine Aggression and Anxiety: A Randomized Placebo-Controlled Trial with Qualitative and Quantitative Assessment
by Emmanuel M. M. Bijaoui and Noah P. Zimmerman
Animals 2025, 15(15), 2280; https://doi.org/10.3390/ani15152280 - 4 Aug 2025
Abstract
Behavioral issues in domestic dogs represent a significant welfare concern affecting both canines and their caregivers, with prevalence rates reported to range from 34 to 86% across the population. Current treatment options, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, often present limitations [...] Read more.
Behavioral issues in domestic dogs represent a significant welfare concern affecting both canines and their caregivers, with prevalence rates reported to range from 34 to 86% across the population. Current treatment options, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, often present limitations including adverse effects and delayed efficacy. This randomized, placebo-controlled (maltodextrin) study investigated the effects of a novel Lactiplantibacillus plantarum strain (LP815TM) on canine behavioral concerns through gut–brain axis modulation. Home-based dogs (n = 40) received either LP815TM (n = 28) or placebo (n = 12) daily for 4 weeks, with behavioral changes assessed using the comprehensive Canine Behavioral Assessment & Research Questionnaire (C-BARQ) and continuous activity monitoring. After the intervention period, dogs receiving LP815TM showed significant improvements in aggression (p = 0.0047) and anxiety (p = 0.0005) compared to placebo controls. These findings were corroborated by objective activity data, which demonstrated faster post-departure settling, reduced daytime sleep, and improved sleep consistency in the treatment group. Throughout >1120 administered doses, no significant adverse events were reported, contrasting favorably with pharmaceutical alternatives. The concordance between our findings and previous research using different L. plantarum strains suggests a consistent biological mechanism, potentially involving GABA production and vagal nerve stimulation. These results indicate that LP815TM represents a promising, safe alternative for addressing common canine behavioral concerns with potential implications for improving both canine welfare and the human–animal bond. Full article
(This article belongs to the Section Companion Animals)
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20 pages, 820 KiB  
Article
Prevalence and Impact of Antidepressant and Anti-Anxiety Use Among Saudi Medical Students: A National Cross-Sectional Study
by Daniyah A. Almarghalani, Kholoud M. Al-Otaibi, Samah Y. Labban, Ahmed Ibrahim Fathelrahman, Noor A. Alzahrani, Reuof Aljuhaiman and Yahya F. Jamous
Healthcare 2025, 13(15), 1854; https://doi.org/10.3390/healthcare13151854 - 30 Jul 2025
Viewed by 339
Abstract
Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it [...] Read more.
Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it is crucial to understand the extent of their usage and associated effects on students’ mental health and academic performance. This cross-sectional study explored the use of antidepressants and anti-anxiety drugs and their impact on the mental health of medical students in Saudi Arabia. Methods: A cross-sectional survey of 561 medical students from 34 universities was conducted between March and July 2024. An anonymous online questionnaire was used to collect sociodemographic, mental health, and medication usage-related information. Results: Most of the participants were female (71.5%) and aged 21–25 years (62.7%). Approximately 23.8% of them used antidepressants, 5.6% reported using anti-anxiety medications, and 14.0% used both types of medication. Among the medication users, 71.7% were using selective serotonin reuptake inhibitors (SSRIs), and 28.3% were using other medications. Adverse drug reactions were reported by 58.8% of the participants, and 39.6% changed drugs with inadequate efficacy. Notably, 49.0% of the respondents who have ever used medications discontinued their medication without consulting a healthcare professional. Despite these challenges, 62.0% of the participants felt that their medications had a positive impact on their academic performance, 73.4% believed that the benefits outweighed the drawbacks, and 76.2% expressed a willingness to continue taking their medication. In particular, 77.6% agreed that treatment with these drugs could prevent mental breakdowns. Sleep duration, physical activity, and family history of psychiatric disorders were significantly associated with medication use, with p values of 0.002, 0.014, and 0.042, respectively. Conclusions: These results shed light on the need to understand the prescribing practices of antidepressant and anti-anxiety drugs among medical students while promoting the appropriate use of these medications among the students. There is a need to incorporate mental health interventions into counseling services and awareness programs to support students. Future longitudinal studies are needed to explore long-term trends. Full article
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21 pages, 2030 KiB  
Article
Restoring Balance: Probiotic Modulation of Microbiota, Metabolism, and Inflammation in SSRI-Induced Dysbiosis Using the SHIME® Model
by Marina Toscano de Oliveira, Fellipe Lopes de Oliveira, Mateus Kawata Salgaço, Victoria Mesa, Adilson Sartoratto, Kalil Duailibi, Breno Vilas Boas Raimundo, Williams Santos Ramos and Katia Sivieri
Pharmaceuticals 2025, 18(8), 1132; https://doi.org/10.3390/ph18081132 - 29 Jul 2025
Viewed by 522
Abstract
Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus [...] Read more.
Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME® reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey’s tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Results: Probiotic supplementation increased Bifidobacterium and Lactobacillus, and decreased Klebsiella and Bacteroides. Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. Conclusions: The probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations—including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation—should be considered when interpreting the findings. Although the SHIME® model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results. Full article
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13 pages, 694 KiB  
Article
Lifestyle and SSRI Interventions in Pediatric Cyclic Vomiting Syndrome: Rethinking First-Line Management
by Cansu Altuntaş, Doğa Sevinçok, Merve Hilal Dolu and Ece Gültekin
Children 2025, 12(8), 964; https://doi.org/10.3390/children12080964 (registering DOI) - 23 Jul 2025
Viewed by 228
Abstract
Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent episodes of intense nausea and vomiting. Despite increasing awareness, a standardized treatment approach remains lacking in pediatric populations. Lifestyle factors and anxiety are common triggers, yet their systematic management [...] Read more.
Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent episodes of intense nausea and vomiting. Despite increasing awareness, a standardized treatment approach remains lacking in pediatric populations. Lifestyle factors and anxiety are common triggers, yet their systematic management has not been fully incorporated into therapeutic strategies. Objective: To evaluate the effectiveness of lifestyle modifications and selective serotonin reuptake inhibitors (SSRIs) in the management of pediatric CVS and to compare their outcomes with standard cyproheptadine prophylaxis. Methods: This retrospective study included 119 patients aged 1.2–17.5 years who were diagnosed with CVS according to Rome IV criteria between September 2021 and January 2025. Clinical, psychiatric, and lifestyle data were retrieved from the university’s digital medical records. Patients were grouped according to treatment modality: cyproheptadine, SSRI, or acute attack management alone. Treatment success at 12 weeks was defined as complete cessation of vomiting episodes or absence of hospitalization, prolonged attacks, and school/work absenteeism. Results: Anxiety symptoms were present in 78.2% of patients. SSRIs were prescribed to 34 patients with moderate to severe anxiety, all of whom achieved treatment success. Lifestyle adherence was observed in 73.9% and was found to be a predictor of treatment success. Cyproheptadine was administered to 66 patients but did not provide additional benefit over effective lifestyle modification. Six patients discontinued cyproheptadine due to drowsiness or weight gain. Conclusions: Lifestyle interventions significantly improve outcomes in pediatric CVS. SSRIs represent a safe and effective prophylactic option for patients with comorbid anxiety or poor adherence to behavioral recommendations. These findings support the integration of psychosocial and lifestyle-based strategies into standard CVS treatment protocols. Full article
(This article belongs to the Section Pediatric Mental Health)
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21 pages, 3089 KiB  
Article
Design, Synthesis, and Evaluation of 1-Benzylpiperidine and 1-Benzoylpiperidine Derivatives as Dual-Target Inhibitors of Acetylcholinesterase and Serotonin Transporter for Alzheimer′s Disease
by Juan Pablo González-Gutiérrez, Damián Castillo-Ríos, Víctor Ríos-Campos, Ignacio Alejandro González-Gutiérrez, Dánae Flores Melivilu, Emilio Hormazábal Uribe, Felipe Moraga-Nicolás, Kerim Segura, Valentina Hernández, Amaury Farías-Cea, Hernán Armando Pessoa-Mahana, Miguel Iván Reyes-Parada and Patricio Iturriaga-Vásquez
Molecules 2025, 30(14), 3047; https://doi.org/10.3390/molecules30143047 - 21 Jul 2025
Viewed by 719
Abstract
Cholinergic neuron impairment is a significant cause of cognitive decline in Alzheimer’s disease (AD), making acetylcholinesterase (AChE) a key therapeutic target. AChE inhibitors are principal drugs prescribed to alleviate symptoms in AD patients, while up to 50% of these individuals also suffer from [...] Read more.
Cholinergic neuron impairment is a significant cause of cognitive decline in Alzheimer’s disease (AD), making acetylcholinesterase (AChE) a key therapeutic target. AChE inhibitors are principal drugs prescribed to alleviate symptoms in AD patients, while up to 50% of these individuals also suffer from depression, frequently treated with selective serotonin reuptake inhibitors (SSRIs). Due to the multisymptomatic nature of AD, there is a growing interest in developing multitargeted ligands that simultaneously enhance cholinergic and serotonergic tone. This study presents the synthesis of novel ligands based on functionalized piperidines, evaluated through radioligand binding assays at the serotonin transporter (SERT) and AChE and butyrylcholinesterase (BuChE) inhibition. The pharmacological results showed that some compounds exhibited moderate inhibitory activity against AChE, with one compound 19 standing out as the most potent, also displaying a moderate BuChE inhibitory activity, while showing low affinity for SERT. On the other hand, compound 21 displayed an interesting polypharmacological profile, with good and selective activity against BuChE and SERT. The results underscore the difficulty of designing promiscuous ligands for these targets and suggest that future structural modifications could optimize their therapeutic potential in AD. Full article
(This article belongs to the Special Issue Therapeutic Agents for Neurodegenerative Disorders—2nd Edition)
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14 pages, 929 KiB  
Article
Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System
by Yi Zhang, Xiaoyu Liu, Jianru Wu, Xuening Zhang, Fenfang Wei, Limin Li, Hongqiao Li, Xinru Wang, Bei Wang, Wenyu Wu and Xiang Hong
Pharmaceuticals 2025, 18(7), 1062; https://doi.org/10.3390/ph18071062 - 18 Jul 2025
Viewed by 444
Abstract
Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or [...] Read more.
Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. Objectives: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. Methods: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. Results: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω025 = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω025 = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. Conclusions: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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16 pages, 624 KiB  
Article
Selective Serotonin Reuptake Inhibitor-Associated Intracranial Hemorrhage: Drug-Specific Risk Patterns and Patient-Level Modifiers
by Josef Yayan and Kurt Rasche
Neurol. Int. 2025, 17(7), 111; https://doi.org/10.3390/neurolint17070111 - 18 Jul 2025
Viewed by 296
Abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance [...] Read more.
Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance analysis using data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Reports up to May 2025 listing an SSRI (sertraline, fluoxetine, paroxetine, escitalopram, citalopram, or fluvoxamine) as a suspect or interacting drug and involving an ICH event were included. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals. Results: Among 226 eligible ICH cases, sertraline (30.5%), paroxetine (28.8%), and fluoxetine (27.9%) were most frequently implicated. Sertraline showed a strong signal for cerebral hemorrhage (ROR = 4.97), while fluoxetine was associated with subarachnoid hemorrhage (ROR = 4.51). Sertraline had a pronounced signal among patients aged >60 years (ROR = 7.92) and in combination with anticoagulants (ROR = 9.56). Fluoxetine was underrepresented in elderly cases. Given the very small number of fluvoxamine-related cases (n = 2), interpretation should be cautious due to limited statistical power. Gender-stratified analyses showed female predominance in sertraline-related ICH and male predominance for paroxetine. Citalopram demonstrated a potentially protective profile with inverse association with cerebral hemorrhage. Conclusions: This study highlights significant differences in ICH reporting patterns across SSRIs, modified by patient age, gender, and co-medication. These findings underscore the need for individualized SSRI prescribing, particularly in patients receiving anticoagulant therapy particularly in elderly patients and those receiving anticoagulant therapy, where sertraline and fluoxetine may pose increased risk. Full article
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17 pages, 1599 KiB  
Article
Trends in Antidepressant, Anxiolytic, and Cannabinoid Use Among Italian Elite Athletes (2011–2023): A Longitudinal Anti-Doping Analysis
by Mario Ruggiero, Leopoldo Ferrante, Domenico Tafuri, Rosaria Meccariello and Filomena Mazzeo
Sports 2025, 13(7), 233; https://doi.org/10.3390/sports13070233 - 16 Jul 2025
Viewed by 458
Abstract
Mental health disorders, particularly depression and anxiety, have become increasingly prevalent among elite athletes, exacerbated by factors such as competitive pressure and the Coronavirus Disease 19 (COVID-19) pandemic. This study analyzes trends in the use of antidepressants, anxiolytics, and cannabinoids (delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) [...] Read more.
Mental health disorders, particularly depression and anxiety, have become increasingly prevalent among elite athletes, exacerbated by factors such as competitive pressure and the Coronavirus Disease 19 (COVID-19) pandemic. This study analyzes trends in the use of antidepressants, anxiolytics, and cannabinoids (delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) among Italian athletes from 2011 to the first half of 2023 (FH2023), referring to anti-doping reports published by the Italian Ministry of Health. Data from 13,079 athletes were examined, with a focus on non-prohibited medications, banned substances, and regulatory impacts, including threshold adjustments for THC since 2013 and the legalization of CBD. The results show fluctuating use of antidepressants/anxiolytics, with peaks in 2021 and the FH2023, coinciding with post-pandemic awareness. Positive THC cases rose following regulatory changes, reflecting socio-cultural trends. Gender disparities emerged, with THC use predominantly among males (e.g., nine males vs. one female in 2013), though female athletes were underrepresented in testing. This study highlights the need for personalized, evidence-based strategies that balance therapeutic efficacy and anti-doping compliance. Clinicians should carefully consider prescribing selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines to address depression and anxiety and should monitor the risks of CBD contamination. Future research should adopt longitudinal, gender-sensitive approaches to refining guidelines and combating stigma in professional sports. Full article
(This article belongs to the Topic Recent Advances in Physical Education and Sports)
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15 pages, 575 KiB  
Review
Neuroactive Steroids as Novel Promising Drugs in Therapy of Postpartum Depression—Focus on Zuranolone
by Jolanta B. Zawilska and Ewa Zwierzyńska
Int. J. Mol. Sci. 2025, 26(13), 6545; https://doi.org/10.3390/ijms26136545 - 7 Jul 2025
Viewed by 979
Abstract
Postpartum depression (PPD) remains a significant health concern worldwide. Both non-pharmacological and pharmacological treatments are available for patients with PPD; however, the standard approach involving selective serotonin reuptake inhibitors (SSRIs) and other antidepressants fails to provide a rapid response. This narrative review presents [...] Read more.
Postpartum depression (PPD) remains a significant health concern worldwide. Both non-pharmacological and pharmacological treatments are available for patients with PPD; however, the standard approach involving selective serotonin reuptake inhibitors (SSRIs) and other antidepressants fails to provide a rapid response. This narrative review presents basic clinical and epidemiological data on PPD, summarizes currently used pharmacotherapies of PPD, highlights their limitations, and discusses new therapies based on a revised understanding of the disease’s pathogenesis. Numerous studies indicate that dysregulation of GABAergic neurotransmission, which may result from fluctuating levels of neuroactive steroids during pregnancy and the postpartum period, plays an important role in the complex pathology of PPD. Considering this, neuroactive steroids, which act as positive allosteric modulators of central GABAA receptors (GABAARs), may offer new promising avenues for treating PPD. The first rapid-acting neurosteroid approved by the FDA to treat PPD in women is brexanolone, although its use is constrained by pharmacokinetic properties. The first oral neuroactive steroid-based antidepressant approved by the FDA for PPD is zuranolone. This review discusses the molecular mechanism of zuranolone action and the results of preclinical and clinical studies regarding the effectiveness and safety of the drug in treating PPD. Full article
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31 pages, 5415 KiB  
Review
Psychopharmacological Therapy Positively Modulates Disease Activity in Inflammatory Bowel Disease: A Systematic Review
by Federica Di Vincenzo, Antonio Maria D’Onofrio, Angelo Del Gaudio, Elena Chiera, Gaspare Filippo Ferrajoli, Francesco Pesaresi, Alessio Simonetti, Marianna Mazza, Georgios Demetrios Kotzalidis, Mauro Pettorruso, Giovanni Martinotti, Loris Riccardo Lopetuso, Antonio Gasbarrini, Gabriele Sani, Gionata Fiorino, Franco Scaldaferri and Giovanni Camardese
Int. J. Mol. Sci. 2025, 26(13), 6514; https://doi.org/10.3390/ijms26136514 - 6 Jul 2025
Viewed by 871
Abstract
Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis [...] Read more.
Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis and frequent use of psychotropic medications in IBD patients, limited evidence exists regarding the effects of psychiatric treatments on gastrointestinal disease activity. Therefore, the aim of this systematic review is to evaluate the effectiveness of psychiatric therapies on gastrointestinal symptoms and disease activity in patients with IBD. The work was conducted in accordance with PRISMA guidelines. Searches were performed across PubMed, Web of Science, and Scopus up to July 2024. Eligible studies evaluated the effectiveness of psychiatric medications—including antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers, anticonvulsants, and others—on at least one gastrointestinal outcome in patients with IBD. Outcomes included changes in commonly used clinical and endoscopic scores for Crohn’s disease (CD) and ulcerative colitis (UC), number of bowel movements, stool consistency, presence of blood in stool, severity of abdominal pain, as well as in surrogate markers of disease activity following treatment. Out of 8513 initially identified articles, 22 studies involving 45,572 IBD patients met the inclusion criteria. Antidepressants, particularly bupropion, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and duloxetine, were associated with improvements in IBD activity scores, including Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD, Mayo score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for UC. Case reports highlighted potential benefits of pregabalin and lithium carbonate, respectively, showed by the reduction in clinical and endoscopic score of disease activity for pregabalin and improvement of UC symptoms for lithium carbonate, while topiramate showed limited efficacy. Clonidine and naltrexone determined the reductions in clinical and endoscopic score of disease activity, including CDAI and Crohn’s disease endoscopy index severity score (CDEIS) for CD and Disease Activity Index (DAI) for UC. Despite the limited data and study heterogeneity, antidepressants, naltrexone, and clonidine were associated with improvements in IBD activity. Larger, prospective studies are needed to confirm the therapeutic potential of psychiatric medications in modulating IBD activity and to guide integrated clinical management. Full article
(This article belongs to the Section Molecular Immunology)
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9 pages, 672 KiB  
Review
Ketamine and Esketamine in Psychiatry: A Comparative Review Emphasizing Neuroplasticity and Clinical Applications
by Georgios Mikellides
Psychoactives 2025, 4(3), 20; https://doi.org/10.3390/psychoactives4030020 - 23 Jun 2025
Viewed by 1092
Abstract
Ketamine and esketamine are two closely related compounds with fast-acting antidepressant properties that have reshaped the treatment landscape for individuals with treatment-resistant depression (TRD). Originally developed as anesthetic agents, both have since demonstrated rapid and robust antidepressant effects in patients who have not [...] Read more.
Ketamine and esketamine are two closely related compounds with fast-acting antidepressant properties that have reshaped the treatment landscape for individuals with treatment-resistant depression (TRD). Originally developed as anesthetic agents, both have since demonstrated rapid and robust antidepressant effects in patients who have not responded to conventional treatments such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy. This narrative review synthesizes evidence on their pharmacology, mechanisms of action, clinical efficacy, safety profiles, and regulatory considerations, with a particular focus on their neuroplastic effects. While ketamine is a racemic mixture composed of equal parts R- and S-enantiomers, esketamine consists solely of the S-enantiomer and has been approved for intranasal use by the FDA and EMA for TRD. These agents have been shown to produce symptom relief within hours of administration—an unprecedented effect in psychiatric pharmacology. This rapid onset is particularly valuable in managing suicidal ideation, offering potential lifesaving benefits in acute settings. Furthermore, ketamine and esketamine’s influence on synaptic plasticity, brain-derived neurotrophic factor (BDNF), and glutamate transmission provides insights into novel therapeutic targets beyond monoaminergic systems. This review incorporates recent real-world findings and peer-reviewed literature to contextualize the clinical use of these agents in modern psychiatry, bridging experimental research with practical application. Full article
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15 pages, 281 KiB  
Review
Depression and Coronary Artery Disease—Where We Stand?
by Anastasios Apostolos, Konstantinos Konstantinou, Nikolaos Ktenopoulos, Panayotis K. Vlachakis, Ioannis Skalidis, Grigorios Chrysostomidis, Vasileios Panoulas and Konstantinos Tsioufis
J. Clin. Med. 2025, 14(12), 4281; https://doi.org/10.3390/jcm14124281 - 16 Jun 2025
Viewed by 884
Abstract
Coronary artery disease (CAD) and mental health disorders, particularly depression and anxiety, exhibit a complex, bidirectional relationship that adversely influences clinical outcomes and mortality. Mental illnesses account for approximately 8 million deaths annually, while cardiovascular diseases, including CAD, contribute to about 17 million [...] Read more.
Coronary artery disease (CAD) and mental health disorders, particularly depression and anxiety, exhibit a complex, bidirectional relationship that adversely influences clinical outcomes and mortality. Mental illnesses account for approximately 8 million deaths annually, while cardiovascular diseases, including CAD, contribute to about 17 million deaths, with CAD alone responsible for one-third of deaths among individuals aged ≥35 years. This review offers a structured synthesis of current knowledge focusing on the (1) epidemiology, emphasizing the reciprocal risk between CAD and psychiatric conditions; (2) pathophysiological insights, including inflammation, neurohormonal dysregulation, platelet hyperactivation, and shared genetic determinants; and (3) therapeutic approaches, encompassing pharmacological management, psychotherapeutic interventions, and integrated care models. Selective serotonin reuptake inhibitors (SSRIs) remain the pharmacologic agents of choice in patients with CAD and depression due to their favorable cardiac profile, while cognitive behavioral therapy (CBT) offers psychological benefit. However, evidence for mortality reduction remains limited. Emerging research highlights the importance of biomarker-driven care, gut–brain–heart axis modulation, and AI-enabled clinical integration. Full article
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9 pages, 207 KiB  
Article
Passiflora Incarnata L. Herba in the Treatment of Anxiety Symptoms and Insomnia in Children and Adolescents with Feeding and Eating Disorders
by Angela La Tempa, Giulia Ferraiuolo, Beatrice Pranzetti, Jacopo Pruccoli and Antonia Parmeggiani
Adolescents 2025, 5(2), 24; https://doi.org/10.3390/adolescents5020024 - 5 Jun 2025
Viewed by 1402
Abstract
Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been [...] Read more.
Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been suggested as a potential treatment option for anxiety and insomnia in youth. Methods: this is an observational and retrospective study that includes patients assessed in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents between 1 January 2020 and 31 December 2023. Eligible patients had a confirmed diagnosis of a FED, along with either an anxiety or a sleep disorder. During follow-up, the clinical efficacy of Passiflora incarnata L. Herba was assessed using the Clinical Global Impression–Improvement scale (CGI-I). Comparative analyses were conducted by stratifying the sample based on the target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used. Results: this study includes 94 patients, with most diagnosed with anorexia nervosa (71.3%). Passiflora incarnata L. Herba was administered at a dosage of 200 mg (1–2 tablets for day). It was often combined with selective serotonin reuptake inhibitors (SSRIs) (56.5%), atypical antipsychotics (27.7%), or benzodiazepines (7.4%). Treatment was initiated for anxiety symptoms (75.5%) or insomnia (28.7%). No side effects were reported. Among patients with specific outcome data, 53.3% reported improvements in anxiety symptoms, and 45.4% reported improvements in insomnia. Conclusions: this is the first study to evaluate the use of Passiflora incarnata L. Herba for anxiety and insomnia in children and adolescents with FEDs. Our findings suggest that Passiflora incarnata L. Herba may serve as a well-tolerated adjunctive treatment, showing symptomatic improvement in up to 53% of the patients with data on treatment outcomes. Notably, 53.3% and 45.4% of participants, with specific outcome data, reported reduced anxiety and insomnia symptoms, respectively. Given its excellent safety profile and preliminary efficacy, Passiflora incarnata L. Herba may represent a promising alternative for patients with mild symptoms or for caregivers hesitant about conventional pharmacotherapy. Full article
11 pages, 239 KiB  
Review
When Standard Is Not Enough: A Narrative Review of Supratherapeutic SSRI Doses in Resistant Obsessive Compulsive Disorder
by Giacomo Gualtieri, Alessandro Cuomo, Simone Pardossi and Andrea Fagiolini
J. Clin. Med. 2025, 14(11), 3858; https://doi.org/10.3390/jcm14113858 - 30 May 2025
Viewed by 1945
Abstract
Background/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic [...] Read more.
Background/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic doses of SSRIs have been proposed as an alternative strategy. However, the evidence supporting this approach remains limited and fragmented. This review aims to evaluate the rationale, clinical efficacy, tolerability, and practical considerations associated with high-dose SSRI use in OCD. Methods: A structured narrative review was conducted using targeted literature searches in PubMed and Scopus. Studies were included if they reported on the use of high-dose SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline) in patients with OCD and provided efficacy and/or tolerability data. Clinical trials, observational studies, and case reports were all reviewed. Results: Evidence shows that higher doses of SSRIs are significantly more effective than low or medium doses in reducing OCD symptoms—especially in individuals who have only partially responded to standard treatment. Smaller clinical studies and case reports have also demonstrated that supratherapeutic dosing, beyond typical regulatory limits, can be both effective and well tolerated in treatment-resistant OCD. Conclusions: High-dose SSRI treatment may be a valuable option for selected OCD patients who do not respond to standard therapy. However, careful patient selection, regular monitoring, and further controlled studies are necessary to better define its long-term safety and effectiveness. In this context, increasingly advanced technologies—such as therapeutic drug monitoring and pharmacogenetic testing for relevant polymorphisms—may support more individualized and safer treatment strategies. Full article
20 pages, 4116 KiB  
Article
Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention
by Michail Evgeniou, Paul Perco, Fabian Eibensteiner, Markus Unterwurzacher, Andreas Vychytil, Rebecca Herzog and Klaus Kratochwill
J. Clin. Med. 2025, 14(11), 3733; https://doi.org/10.3390/jcm14113733 - 26 May 2025
Viewed by 497
Abstract
Background/Objectives: Peritoneal dialysis (PD) is a renal replacement therapy for patients with kidney failure. Managing PD patients often involves addressing a complex interplay of comorbidities and complications, necessitating the use of multiple medications. This study aimed to systematically characterize commonly co-prescribed drugs in [...] Read more.
Background/Objectives: Peritoneal dialysis (PD) is a renal replacement therapy for patients with kidney failure. Managing PD patients often involves addressing a complex interplay of comorbidities and complications, necessitating the use of multiple medications. This study aimed to systematically characterize commonly co-prescribed drugs in PD and to identify novel drug combinations that may target dysregulated molecular mechanisms associated with PD’s pathophysiology. Methods: We analyzed clinical records from 702 PD patients spanning 30 years, encompassing over 5500 prescription points. Using network-based modeling techniques, we assessed drug co-prescription patterns, clinical outcomes, and longitudinal treatment trends. To explore potential drug repurposing opportunities, we constructed a molecular network model of PD based on a consolidated transcriptomics dataset and integrated this with drug–target interaction information. Results: We found commonly prescribed drugs such as furosemide, sucroferric oxyhydroxide, calcitriol, darbepoetin alfa, and aluminum hydroxide to be integral components of PD patient management, prescribed in over 30% of PD patients. The molecular-network-based approach found combinations of drugs like theophylline, fluoxetine, celecoxib, and amitriptyline to possibly have synergistic effects and to target dysregulated molecules of PD-related pathomechanisms. Two further distinct categories of drugs emerged as particularly interesting in our study: selective serotonin reuptake inhibitors (SSRIs), which were found to modulate molecules implicated in peritoneal fibrosis, and vascular endothelial growth factor (VEGF) inhibitors, which exhibit anti-fibrotic properties that are potentially useful for PD. Conclusions: This comprehensive exploration of drug co-prescriptions in the context of PD-related pathomechanisms provides valuable insights for opening future therapeutic strategies and identifying new targets for drug repurposing. Full article
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