Responsiveness to mood-stabilizing pharmacotherapy varies in bipolar disorder (BD). We investigated clinical correlates of second-generation antipsychotic (SGA) treatment response and conducted the first genome-wide association study (GWAS), including exploratory polygenic scores (PGS), of SGA pharmacogenomic treatment response in BD. Treatment response was quantified using the Alda scale, and GWAS was performed using Alda-A score, controlling for sex, genotyping batch, and the genomic principal components. The cohort included 2,159 adults with BD (1,416 BD-I, 691 BD-II, 51 schizoaffective BD), mean age 41.8 years, 62% female, 84% white, and 14% Hispanic. Nearly half (48%) were treated with SGAs. Current SGA users were younger (41.2 ± 14.7 vs. 42.5 ± 15.3 years, p = 0.040), more likely to be Hispanic (14% vs. 11%, p = 0.047), had a higher body mass index (BMI; 30.4 ± 7.6 vs. 29.5 ± 7.1kg/m2, p = 0.005). Lifetime comorbidity patterns for current SGA users include higher rates of manic psychosis (29% vs. 17%, p < 0.001) and eating disorders - Anorexia Nervosa (7% vs. 4%, p = 0.003), Bulimia Nervosa (7% vs. 4%, p = 0.003), and Binge Eating Disorder (14% vs. 11%, p = 0.030). We detected a genome-wide significant association between SGA Alda-A scores and GAS7 variants (top variant: rs202127418, β=-2.998, p = 4.96E-08). However, SGA response was not significantly associated with PGS for schizophrenia, BD, and major depression (FDR > 0.05). SGAs are frequently utilized as mood stabilizers in patients with BD and are associated with manic psychosis and eating disorders. GAS7 variants may predict SGA response, but larger, more diverse cohorts are needed for validation.

Backgroud Second-generation antipsychotics (SGAs) are widely used in the treatment of schizophrenia, however, growing concerns have emerged regarding their adverse effects on glucose and lipid metabolism. This study aimed to investigate the potential mechanisms underlying SGA-induced disturbances in glucose and lipid metabolism by integrating gut microbiota profiling with metabolomic analysis, thereby providing a scientific basis for future clinical interventions. Methods A self-controlled before-after study was conducted on subjects who were initially medication-free (pre-medication group) and subsequently initiated on second-generation antipsychotics for 3 months (post-medication group). Anthropometric measurements—including waist circumference, hip circumference, body weight—as well as fasting blood samples (for assessment of glucose, insulin, C peptide, blood lipid) and stool samples were collected at baseline and after three months of treatment. Gut microbiota composition and fecal metabolomic profiles were analyzed using high-throughput sequencing and mass spectrometry–based approaches, respectively. Results Firstly, Gut microbial diversity differed significantly between groups. At genus level, the abundances of Escherichia and Bifidobacterium were increased significantly in the post-medication patients, while the abundances of Faecalibacterium and Blautia were decreased. Metabolomic analysis revealed decreased levels of oleamide and stearamide in the post-medication group, which exhibited a negative correlation with the abundance of Faecalibacterium . Additionally, the arginine and proline metabolic pathway, D-amino acid metabolic pathway, and arginine biosynthesis pathway were also altered in this group. Ornithine was identified as a key player in these three differential metabolic pathways. Conclusion In summary, first-time exposure to second-generation antipsychotics in patients with schizophrenia is associated with disturbances in glucose and lipid metabolism, which appear to be closely linked to SGA-induced perturbations in gut microbiota composition and their associated metabolic profiles.

Dopamine is a monoamine neurotransmitter that regulates neuronal activity and synaptic transmission. While dopaminergic activity is known to suppress action potential-dependent glutamate release in certain brain regions, the modulatory effect of dopaminergic tone on spontaneous glutamate release is unclear. Here, we used primary rat ventral tegmental area-cortex co-cultures to assess how decreased dopaminergic tone affects spontaneous synaptic glutamate release using whole-cell patch-clamp electrophysiology. We found that an acute decrease in dopaminergic tone increases the frequency of spontaneous glutamate release, driven by a surge in basal presynaptic calcium. This presynaptic calcium surge results from disinhibition of voltage-gated calcium channels (VGCCs) due to reduced Gβγ subunit activity downstream of D2 receptor signaling. While acute reduction in dopaminergic tone has robust presynaptic effects, chronic reduction results in homeostatic synaptic plasticity, characterized by postsynaptic insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, a process known as synaptic upscaling. Notably, chronic antagonism of both D1 and D2 receptors using selective antagonists, as well as long-term treatment with first- and second-generation antipsychotics haloperidol, chlorpromazine, olanzapine, clozapine, and aripiprazole, promoted robust synaptic upscaling. These findings reveal a novel mechanism of action for antipsychotic medications and suggest that antipsychotics do not solely act on counteracting hyperdopaminergia, but also tune glutamatergic neurotransmission by activating homeostatic plasticity mechanisms.

Lithium was the first discovered mood stabilizer for bipolar disorder. However, several antiepileptics such as valproate and carbamazepine have also proven to be mood stabilizers in all phases of bipolar disorder with profiles barely distinguishable from lithium. Second-generation antipsychotics were slowly recognized in almost all cases to be useful in all phases of bipolar disorder. These different treatments have not been found to have any common mechanism of action. Indeed, lithium itself has numerous biochemical effects that are often not replicable. The newest biochemical effects described for lithium are exciting but are still merely promising and should not be taught to medical students as facts, especially since they do not explain the fact that several antiepileptic and second-generation antipsychotics also work well in all phases of bipolar disorder. Lithium is not specific to bipolar disorder but has uses in several other psychiatric and nonpsychiatric conditions. Lithium, like most treatments in medicine, is nonspecific; it is still useful in many cases, but is not in any sense a “gold standard”.

Antipsychotic-induced weight gain (AIWG) exhibits marked heterogeneity. We conducted a secondary analysis of the Chinese First-Episode Schizophrenia Trial, leveraging frequent body mass index (BMI) measurements over 12 months. Our aims were to identify latent BMI trajectories in first-episode schizophrenia (FES) patients treated with second-generation antipsychotics (SGAs) and to explore predictors of trajectory membership. Subjects in this study were from the Chinese First-Episode Schizophrenia Trial (CNFEST). After quality control, a total of 361 drug-naïve FES patients treated with olanzapine, risperidone, or aripiprazole were included. BMI was measured at 7 timepoints over 12 months. Latent class trajectory modeling (LCTM) was used to identify distinct BMI trajectories. Multinomial logistic regression was applied to detect predictors of trajectory membership. Four BMI trajectories were emerged, including Low Baseline BMI with Rapid Increase (LBRI) (6.1%, +3.5kg/m² within the first 3 months), Moderate Baseline BMI with Gradual Increase (MBGI) (33.8%, steady rising during 9 months), and Low/High Baseline BMI with Slight Increase (LBSI/HBSI) (46%/14.1%, Minimal change (<1.5 kg/m²)). Baseline BMI (χ² = 144.5, p < 0.001) was the strongest predictor of the LBRI trajectory. A numerically higher, though not statistically stable, odds were observed for olanzapine vs. aripiprazole (OR = 20.4, 95% CI = 2.48-166.67). Shorter duration of untreated psychosis (DUP < 1 year) (OR = 4.12, 95% CI = 1.31-12.93) and lower education (OR = 5.40, 95% CI = 1.19-24.52) further increased LBRI risk. A high-risk subgroup (LBRI) with rapid early weight gain was identified, driven by olanzapine use, shorter DUP, and lower educational attainment. These findings advocate for dynamic risk stratification and early preventive interventions in vulnerable FES patients (Trial Registration: This trial was registered at ClinicalTrials.gov (Identifier: NCT01057849) on January 26, 2010).

Individuals with schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs) are at heightened risk for obesity, prediabetes, and type 2 diabetes, contributing to increased cardiovascular morbidity and premature mortality. Early intervention with glucagon-like peptide-1 receptor agonists (GLP-1RAs) may help mitigate long-term cardiometabolic risk. To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities. This was a multicenter, double-blind, placebo-controlled, randomized clinical trial. Participants were enrolled from 3 clinical sites in Denmark between September 2021 and August 2024. Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years. Participants had early-stage glycemic dysregulation (hemoglobin A1c [HbA1c], 5.4%-7.4%) and were not receiving antidiabetic therapy. Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks. The prespecified primary outcome was change in HbA1c level from baseline to week 26. The primary analysis adhered to the intention-to-treat principle. Of 104 individuals screened, 73 were randomized and 57 (78%) completed the trial. Baseline characteristics were comparable between groups. Mean (SD) age was 35 (12) years, 48 were female (65%), and mean (SD) body mass index was 36.1 (7.9). At week 26, semaglutide significantly reduced HbA1c level compared with placebo (mean difference, -0.25%; 95% CI, -0.33 to -0.16; P < .001); 43% of participants (12 of 28) treated with semaglutide achieved low-risk HbA1c levels (<5.4%) vs 3% with placebo. Greater reductions in body weight (-9.2 kg; 95% CI, -13.3 to -5.1 kg; P < .001), waist circumference (-7.0 cm; 95% CI, -10.6 to -3.3 cm; P < .001), and fat mass (-6.1 kg; 95% CI, -10.2 to -1.9 kg; P = .006) were observed with semaglutide. No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed. Gastrointestinal adverse events were common but mild and transient; psychiatric adverse events were similar across groups. Results of this randomized clinical trial show that adjunctive semaglutide significantly improved glycemic control and weight outcomes in individuals with schizophrenia spectrum disorders. Secondary outcomes were exploratory. These findings support the use of GLP-1RAs as a potential early intervention strategy to reduce cardiometabolic risk in this vulnerable population. ClinicalTrials.gov Identifier: NCT04892199.

To investigate the prevalence and associated factors of fecal incontinence among hospitalized patients with bipolar disorder, examining demographic, clinical, and pharmacological determinants to inform evidence-based clinical management strategies. This retrospective cross-sectional study analyzed 200 hospitalized bipolar disorder patients (50% male, 50% female; mean age 37.63 ± 9.67 years) recruited from educational treatment centers affiliated with Shiraz University of Medical Sciences. Fecal incontinence severity was assessed using standardized Vaizey and Wexner scoring systems. Comprehensive data collection included demographic characteristics, psychiatric medication use across four therapeutic classes (antidepressants, mood stabilizers, first- and second-generation antipsychotics), illness duration, bipolar disorder subtypes, and relevant medical history. Statistical analyses employed non-parametric tests, risk calculations, and chi-square associations to identify significant predictors of incontinence outcomes. The overall fecal incontinence prevalence was 48.5% (97/200 patients), substantially exceeding community rates of 2-8%. Female gender emerged as the strongest predictor (OR = 7.71, 95% CI: 4.11-14.47, p < 0.001), with 72% of women experiencing symptoms compared to 25% of men. Educational attainment showed significant association with incontinence severity (p = 0.008). Age-stratified analysis revealed consistently high prevalence across all age groups (42-52%), challenging typical age-related patterns. Medication-specific analysis demonstrated heterogeneous effects within drug classes: haloperidol (RR = 1.56) and quetiapine (RR = 1.54) increased risk, while olanzapine appeared protective (RR = 0.46). Valproate among mood stabilizers showed increased risk (RR = 1.32), whereas lamotrigine demonstrated complete protection. This study reveals an exceptionally high prevalence of fecal incontinence in hospitalized bipolar disorder patients, with demographic factors proving more predictive than broad medication classes. The profound gender disparity and medication-specific risk profiles necessitate systematic continence screening protocols and individualized pharmacological selection strategies. These findings highlight the critical need for multidisciplinary care approaches integrating psychiatric treatment with specialized continence management to address this previously underrecognized complication affecting nearly half of hospitalized bipolar patients. Not applicable.

Metformin for overweight and obese children and adolescents with bipolar spectrum and related mood disorders treated with second-generation antipsychotics: a randomised, pragmatic trial.

Patients prescribed second-generation antipsychotics (SGA) are at risk of antipsychotic induced weight gain (AIWG). The objective was to estimate weight changes after prescription of incretin-based weight loss medications by category of expected AIWG: high (olanzapine, clozapine), intermediate (risperidone, quetiapine, paliperidone) and low (e.g., asenapine, aripiprazole). We conducted a retrospective cohort study using electronic health records (June 2021-December 2023) from Epic Cosmos for adults (≥18 years) without diabetes, prescribed SGA, and eligible for incretin-based weight loss medications. We studied changes in weight (kg) and the probability of at least 5% weight loss after 6 months of prescription of incretin-based medications by categories of AIWG. The analytic sample (n = 66,574) were aged 51.9 years (SD: 17.7), with average BMI of 39.5 kg/m2 (SD: 7.7). Those prescribed incretin-based medications lost -2.17 kg (95% CI: -2.49, -1.84), and were 1.71 (95% CI: 1.63, 1.80) times more likely to achieve 5% weight loss, relative to those who didn't receive prescriptions. Weight loss was greater among those prescribed SGAs of low AIWG (-3.02 kg, 95% CI: -3.29, -2.74), relative to those prescribed high AIWG (-1.33 kg, 95% CI: -2.04, -0.62). Semaglutide and tirzepatide induce weight loss among those prescribed SGAs, with lower effectiveness in those prescribed higher AIWG SGAs.

Demographic and clinical characteristics of patients with borderline personality disorder: Real-world insights from a retrospective observational study.

Comparative efficacy of antidepressant augmentation with amantadine vs pramipexole in treatment-resistant unipolar depression: A randomised controlled trial.

ObjectiveSince its development in 2002 by the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders, the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) has undergone five revisions.MethodsTo improve survey efficiency, reflect general clinical practice, and facilitate comparisons with previous KMAP-DD revisions, the overall structure of the questionnaire was retained. The six sections of the questionnaire were as follows 1) pharmacological treatment strategies for major depressive disorder with and without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus on treatment-resistant depression; 4) selection of an antidepressant in consideration of safety, adverse effects, and comorbid physical conditions; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. First-, second-, and third-line treatment recommendations were statistically derived.ResultsCompared to KMAP-DD 2021, only minor changes were noted, due to the limited introduction of new medications or treatment modalities. Nonetheless, notable shifts included an increased preference for atypical antipsychotics (AAPs), and higher preference of combination strategies involving AAPs and mood stabilizers, indicating a more proactive and intensive treatment trend in Korea.ConclusionKMAP-DD is expected to serve as a valuable clinical resource by providing expert consensus-based recommendations on specific treatment strategies and pharmacological options for major depressive disorders, thereby supporting the integration of real-world clinical practice with evidence-based medicine.

While studies have shown a possible link between antipsychotic medication and the development of breast cancer, results remain inconclusive. The aim of the study was to assess the relationship between antipsychotic therapy and breast cancer risk, providing relevant determinative insights. A systematic database search was conducted in PubMed, ScienceDirect, and Cochrane Library databases, along with a manual search of references, until October 13th, 2025, for literature on studies investigating the association between antipsychotic therapy and breast cancer in women. Primary analysis involved an overall hazard ratio meta-analysis, with secondary odds ratio analysis for complementary evidence. Further subgroup and meta-regression analyses were conducted. Subgroup and meta-regression analyses aimed to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies with 3,347,235 patients were included. Results support that exposure to antipsychotics leads to an overall 21% increased risk for breast cancer (HR = 1.21, 95% CI 1.03-1.42) compared to no exposure, which was more pronounced among retrospective studies. Furthermore, prolactin (PRL)-increasing antipsychotics pose an elevated risk (HR: 1.23, 95% CI 1.08-1.40) compared to PRL-sparing or none. Additionally, prolonged duration of therapy overall was associated with increased breast cancer risk (> 5years: HR: 1.47, 95% CI 1.22-1.76), when compared to therapy for less than 1year. Furthermore, first generation antipsychotics (FGAs) showed a significant association with duration (OR: 1.46, 95%CI 1.32-1.62), although second generation antipsychotics (SGAs) had no statistically significant results (OR: 1.09, 95% CI 0.94-1.25). There is a statistically significant association between breast cancer risk in women and the use of antipsychotics. PRL-increasing medications seem to have a higher correlation with breast cancer risk compared to PRL-sparing drugs. Longer duration of exposure to FGAs results in a higher risk of breast cancer. While these findings are hypothesis-generating, they underline the need for definitive prospective studies accounting for confounding factors. Careful consideration of medical history is required when choosing antipsychotic therapy to optimize both effectiveness and safety.

What Is the Issue? Quetiapine is a second-generation antipsychotic (SGA) or atypical antipsychotic drug primarily used for treating schizophrenia and bipolar disorder. Quetiapine extended-release is also indicated by Health Canada for the symptomatic relief of major depressive disorder (MDD) when currently available approved antidepressant drugs have failed. Decision-makers are interested in understanding the evidence regarding quetiapine’s clinical effectiveness, safety, and place in therapy relative to other medications for the treatment of MDD. What Did We Do? We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2020. What Did We Find? The evidence suggests that quetiapine and other SGAs (particularly aripiprazole, brexpiprazole, cariprazine, olanzapine, risperidone, and ziprasidone) have similar efficacy but have unique safety profiles when used for the treatment of adults with treatment-resistant MDD. The evidence also suggests that treatment with quetiapine reduced symptoms of treatment-resistant depression compared to treatment with lithium. Evidence-based guidelines recommend using quetiapine as a second-line augmentation treatment option for MDD in patients whose disease had partial or no response to an adequate dose of initial pharmacotherapy. The Canadian Network for Mood and Anxiety Treatments (CANMAT) guideline recommends atypical antipsychotics such as quetiapine in combination with an antidepressant as the first-line treatment for MDD with psychotic features. The Royal Australian and New Zealand College of Psychiatrists (RANZCP) guideline suggests using quetiapine as monotherapy or adjunct therapy for patients with major depression. What Does It Mean? Quetiapine could be used as second-line augmentation treatment for MDD in patients whose disease had partial or no response to an adequate dose and duration of 2 or more antidepressants (i.e., those with treatment-resistant depression or difficult to treat depression). SGAs such as quetiapine, in combination with an antidepressant, may be used as a first-line treatment for MDD that is very severe or has associated psychotic features. Quetiapine may reduce symptoms of depression and improve social functioning compared with lithium. However, patients reported more side effects with quetiapine than lithium and viewed the side effects of lithium as more manageable. Factors such as patient characteristics, patient tolerability, patient values, side effect profiles of different treatment options, and clinician expertise may also be important to guide choice of treatment for MDD.

What Is the Issue? Pharmacological treatments used for bipolar disorder include mood stabilizers (e.g., lithium, valproate), atypical (second generation) antipsychotics (e.g., quetiapine, lurasidone, cariprazine, olanzapine, aripiprazole, ziprasidone), either alone or in combination, as well as the occasional addition of antidepressants or benzodiazepines. Decision-makers are interested in understanding quetiapine’s place in therapy compared with other medications for the treatment of bipolar disorder in adults. What Did We Do? We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2020. What Did We Find? Clinical evidence suggests that quetiapine and lithium have similar efficacy and safety for the treatment of bipolar depression in adults. Quetiapine appears to be efficacious for the treatment of bipolar depression in adults despite its adverse effects, such as somnolence and weight gain. Evidence-based guidelines recommend the use of antipsychotics (including quetiapine), either as monotherapy or in combination with a mood stabilizer, for both the treatment and maintenance of mania (or hypomania) and bipolar depression. The choice of antipsychotic should be guided by patient preference and past response to therapy. What Does This Mean? Quetiapine, among other antipsychotics, could be used as first-line treatment option for the management of bipolar disorder in adults. The prescribing of antipsychotics (either alone or in combination with a mood stabilizer) for the management of bipolar disorder should be guided by patient characteristics, patient tolerability, patient values, side effect profiles of individual antipsychotic medications, and clinician expertise.

Objectives: To evaluate reports of diabetic ketoacidosis (DKA) associated with antipsychotic drug (APD) use submitted to the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from January 2000 to December 2022. DKA cases were identified using the MedDRA preferred term “diabetic ketoacidosis” in reports listing antipsychotic drugs as suspect medications. Disproportionality analyses, including the proportional reporting ratio (PRR) and empirical Bayes geometric mean (EBGM), were used to assess reporting patterns. Multiple analyses were performed, including those restricted to primary suspect listed drugs only, expanded to incorporate secondary suspect drugs, and sensitivity analyses excluding reports submitted by legal professionals. Results: Among 19,961 DKA reports in FAERS, 2489 (12.5%) listed atypical antipsychotics as the primary suspect drug, whereas reports involving typical APDs were rare. The majority of reports were submitted by healthcare professionals (74.1%), and nearly half originated from the United States (45.4%). Hospitalization was a frequent outcome, reported in 74.3% of cases. Quetiapine and olanzapine were the most frequently reported atypical APDs, with disproportionality analyses demonstrating strong safety signals when compared to all other drugs in FAERS: olanzapine PRR 13.2 (95% CI: 12.4–14.2) and quetiapine PRR 11.8 (95% CI: 11.1–12.5). The findings remained consistent across multiple sensitivity analyses, including incorporating secondary suspect drugs, when the comparator group was restricted to only psychotropic drugs, and excluding reports submitted by lawyers. Conclusions: This pharmacovigilance analysis highlights a potential safety signal for DKA with atypical antipsychotic drugs, notably quetiapine and olanzapine. While these findings do not establish causality, they underscore the need for further investigation using clinical and epidemiological data.

Introduction: Othello syndrome, also known as delusional jealousy, is a rare subtype of delusional disorder characterized by a persistent, unfounded belief in a partner's infidelity. Although classically associated with psychiatric disorders, OS is increasingly recognized in the context of neurological diseases, particularly Parkinson’s disease. This review explores the epidemiology, pathogenesis, symptomatology, and treatment of OS, with emphasis on its manifestation in PD patients.Materials and Methods: This narrative review examines recent research on OS, focusing on its presentation in PD and current treatment approaches. Sources include studies from 2021-2024 identified via PubMed database, along with DSM-5 and ICD-10 guidelines.Results: The prevalence of OS ranges from 0.5-1.4% in psychiatric populations and up to 15.8% in individuals with major neurocognitive disorders, including PD. In PD, delusional jealousy is the second most common type of delusion after persecutory delusions and is most commonly linked to dopamine agonist therapy rather than PD dementia. Neuroimaging studies suggest dysfunction in the frontal-limbic circuitry, especially in the right prefrontal cortex, contributes to the development of OS. Symptoms include fixed delusions of infidelity, compulsive behaviours, emotional dysregulation, and occasionally, visual hallucinations. These often result in interpersonal conflict, aggression, and increased risk of suicide and homicide.Conclusions: Management of OS in PD is complex and often requires modification of dopaminergic treatment. Reducing or discontinuing dopamine agonists may alleviate symptoms but can exacerbate motor dysfunction. Atypical antipsychotics, mood stabilizers, and SSRIs have shown benefit. Recognition of OS is crucial, as its impact on patient quality of life and interpersonal relationships can be profound. Early diagnosis and individualized treatment are essential to prevent escalation to violence or psychiatric crises.

Background and Objectives: Schizophrenia is associated with a 15–20-year reduction in life expectancy, with cardiovascular disease as the leading cause. Sudden unexpected death is common in this population, often linked to structural heart disease, antipsychotic use, and overlapping cardiometabolic, autonomic, and drug-related factors. This study aimed to determine the incidence and causes of sudden unexpected death among schizophrenia inpatients between 2014 and 2024 and compare these findings with historical data from the same institution. Materials and Methods: We conducted a retrospective cohort study of schizophrenia inpatients admitted from January 2014 to December 2024. Hospital records were reviewed to identify sudden and unexpected deaths, verified by the Forensic Medicine Service Brașov. Sudden death was defined as death in an asymptomatic patient or within one hour of new symptom onset, excluding suicide, homicide, or accidental overdose. In accordance with Romanian legislation, an autopsy was performed in every case. Results: Over the 10-year period, six schizophrenia inpatients (mean age 53.2 ± 17.8 years) died suddenly. All had long-standing schizophrenia (mean illness duration 28.7 ± 17.7 years) and were receiving second-generation antipsychotics. Cardiovascular comorbidity was present in three cases. All patients received antipsychotic treatment within 24 h before death. No deaths occurred within the first 24 h of admission; one occurred within 48 h. Compared with the 1989–2013 cohort, which included 57 sudden deaths, the incidence during 2014–2024 declined substantially (0.27% vs. 0.79%). Conclusions: The incidence of sudden unexpected death among schizophrenia inpatients declined significantly over the past decade compared with the 1989–2013 cohort, reflecting improved multidisciplinary care, prompt transfer to general hospitals, and wider use of second-generation antipsychotics. Autopsy findings emphasize the continuing importance of cardiovascular disease and airway obstruction as preventable causes of sudden death in this population.

Schizophrenia is a chronic and complex mental illness that substantially impacts a person’s thoughts, emotions, and daily life. It is characterized by a combination of positive symptoms such as hallucinations and delusions, and negative symptoms such as emotional withdrawal, lack of motivation, and cognitive difficulties. Historically, the dopamine system has been the forefront of research on schizophrenia, but serotonin’s role has recently come into sharper focus. While serotonin is necessary for regulating emotions and mental processes, dopamine imbalances are known to result in psychotic symptoms and cognitive impairments. Interactions between these neurotransmitters affect brain functions. Many patients have seen better results due to advancements in treatment, especially second-generation antipsychotics that target both the dopamine and serotonin systems. However, challenges still exist, especially in effectively managing negative and cognitive symptoms. This review highlights key findings that support a more integrative model involving serotonin-dopamine interactions, emphasizing the role of receptors such as dopamine receptor D1, dopamine receptor D2, 5-hydroxytryptamine 1A (5-HT1A), and 5-hydroxytryptamine 2A (5-HT2A). It also explores the therapeutic potential of newer agents like brexpiprazole, cariprazine, and pimavanserin, which offer more targeted symptoms control with fewer adverse effects. Additionally, emerging research on the gut-brain axis and glutamatergic modulation presents promising directions for future treatment strategies. In this review, we looked at the research on the roles of dopamine and serotonin in schizophrenia and discussed the therapeutic approaches that could lead to more comprehensive and effective treatment plans.

Schizophrenia, defined by the presence of delusions, hallucinations, and flat affect, is more commonly seen alongside depression, anxiety, and substance misuse in patients. Antipsychotics, including second-generation antipsychotics olanzapine, clozapine, and risperidone, are prescribed to control symptoms of schizophrenia, and function through the antagonism and agonism of various receptors including D2, 5-HT2C, 5-HT2A, and 5-HT1A. The effects of antipsychotics are widespread and often include varying impacts to multiple cerebral areas and functions such as measured cortical thickness, regional homogeneity, and volume of numerous brain components like the caudate, putamen, and gray matter. This study aimed to analyze the widespread effects of antipsychotic use on various brain structures based on a review of current scientific literature. Our review revealed that impacts to brain function were widely varied, showing a need for more robust clinical research. A comprehensive understanding of the effects on brain structures of antipsychotics will help to guide medical professionals in the treatment and management of psychosis-related syndromes.