Nationwide trends in antipsychotic and co-medication prescribing for schizophrenia: analysis of National Health Insurance data (2011-2023).

Schizophrenia is a chronic mental health condition that most commonly develops in the third decade of life, but may emerge during adolescence, although in rare cases it can also present in childhood. Pre-adult onset is associated with substantial morbidity, functional impairment, and long-term disability. Accurately diagnosing schizophrenia in youth is particularly challenging, as its symptoms frequently overlap with or are misattributed to other psychiatric or developmental conditions. Conversely, misdiagnosis can also occur when psychotic symptoms are present in patients suffering from other conditions. Establishing an accurate and timely diagnosis is therefore critical to prevent errors in treatment and to optimize prognosis and functional outcomes. Antipsychotic medications are first-line interventions for schizophrenia in youth, with second-generation antipsychotics (SGAs) having the strongest evidence base in this population. Randomized controlled trials and open-label studies support the efficacy of risperidone, aripiprazole, olanzapine, quetiapine, paliperidone, lurasidone, and brexpiprazole in reducing psychotic symptoms in adolescents. In contrast, ziprasidone and asenapine have not demonstrated clear benefit in treatment of schizophrenia in youth. Similar to studies in adults, evidence from pediatric clinical trials suggests that clozapine remains the most effective option for treatment-resistant adolescent schizophrenia, although its use requires close monitoring for hematologic and other adverse effects. While SGAs are generally favored over first-generation antipsychotics (FGAs) in youth because of their reduced propensity for causing extrapyramidal side effects as well as a stronger evidence base to support their use, their safety profiles require careful consideration. Weight gain, metabolic syndrome, sedation, extrapyramidal symptoms, and endocrine effects have been reported in youth with schizophrenia. Such side effects can significantly impact adherence and long-term physical health, necessitating the need for ongoing monitoring and thoughtful agent selection tailored to each patient's individual clinical profile and risk factors. Overall, current evidence supports SGAs as the foundation of psychopharmacologic treatment for schizophrenia in pediatric-aged patients, with clozapine reserved for refractory cases. However, the relative paucity of pediatric-specific data compared with adult populations underscores the importance of continued research to guide clinical practice. In the meantime, accurate diagnosis, early intervention, and vigilant monitoring of both therapeutic response and side effects remain essential to optimizing outcomes for youth with schizophrenia.

Objective: This study investigated current clinical practices, organizational barriers, and resource availability in managing dual diagnosis (co-occurring psychiatric and substance use disorders) among Italian psychiatrists in a healthcare system characterized by service fragmentation between mental health and addiction care. Methods: A structured, self-administered online questionnaire was distributed nationwide to Italian psychiatrists. The survey covered demographic characteristics; organizational aspects and service collaboration; pharmacological and nonpharmacological approaches; and perceived clinical challenges. Data were analyzed descriptively to identify practice patterns and priority intervention areas. Results: Seventy-nine psychiatrists participated from diverse settings (38% addiction services, 25% community mental health services, 14% hospitals, 15% other facilities). While 78% regularly treated dual diagnosis patients, only 38% reported structured protocols between mental health and addiction services. Collaboration was rated as only partially effective by 44%. Integrated treatment was preferred by 61%. The most commonly prescribed medications included mood stabilizers (94%), atypical antipsychotics (68%), anticraving agents (54%), and antidepressants (37%). For depression, trazodone (32%) and serotonergic antidepressants (25%) were used most. For psychosis, aripiprazole (47%) was predominant. Most clinicians (81%) combined pharmacotherapy with psychosocial interventions. Key barriers included insufficient training (67% highlighted need for specialized clinicians), poor service integration, and diagnostic uncertainty. Conclusions: Significant gaps persist in Italian dual diagnosis care despite clinical awareness. Urgent priorities include routine screening, clinician training, national guideline development, organizational reforms promoting service collaboration, and increased availability of structural resources, which was reported as insufficient by 61% of respondents. These improvements are essential for delivering timely, evidence-based, integrated care to this vulnerable population.

Antipsychotic polypharmacy (APP), defined as the concurrent use of two or more antipsychotic agents, remains common in clinical practice despite antipsychotic monotherapy being the recommended standard for schizophrenia treatment. This nationwide cross-sectional survey examined the prevalence and determinants of APP among outpatients with schizophrenia in Japan. Data were collected from 3657 patients across 36 medical institutions between 21 and 25 October 2024. Patients were categorized into antipsychotic monotherapy and APP groups, and demographic and clinical characteristics, including age, sex, medication administration frequency, use of long-acting injectables, clozapine, and concomitant psychotropic medications, were compared. Antipsychotic doses were standardized to chlorpromazine equivalents and analyzed by sex and age group. APP was observed in 40.8% of patients. Multivariable analyses showed that APP was significantly associated with male sex, older age, long-acting injectable use, and concomitant use of antiparkinsonian agents, anxiolytics/hypnotics, and mood stabilizers, whereas clozapine use was inversely associated with APP. Chlorpromazine equivalent doses increased with the number of antipsychotics prescribed, peaking in patients aged 40-59 years and declining thereafter. Second-generation antipsychotics predominated overall, although first-generation antipsychotic use increased with polypharmacy. These findings underscore the importance of careful management of APP, taking sex- and age-related prescribing patterns into consideration.

Mania and psychosis following chimeric antigen receptor T-cell therapy: A report of two cases and mechanistic discussion.

Anticholinergic exposure is common in nursing homes; however, the true burden may be underestimated, particularly due to over-the-counter agents such as first-generation antihistamines that are not consistently captured in prior claims-based studies. This gap limits accurate characterization of anticholinergic use and its clinical implications in older adults. Veterans aged ≥ 65 years with stays ≥ 90 days (N = 45,183) residing in US Department of Veterans Affairs (VA) Community Living Centers (CLC). This study is a secondary data analysis of residents identified during fiscal years 2007-2019. True anticholinergic exposure through barcode-based medication administration dispensing records allowed daily measurement of anticholinergic exposure, with follow-up extending from admission to discharge, death, or April 1, 2025. Anticholinergic medication use was defined as use ≥ 4 days per week during the CLC stay. Drugs were identified using VA classifications aligned with the 2023 American Geriatrics Society Beers Criteria and grouped into nine anticholinergic classes. Outcomes included prevalence, duration, and number of anticholinergic drug classes used; patterns by dementia status; and temporal trends over time. Among 45,183 CLC residents, 33.4% (n = 15,074) used anticholinergic medications. Residents with dementia (n = 20,254) showed substantial exposure to neuropsychiatric anticholinergics, including second-generation antipsychotics (30.6%) and antiparkinsonian agents (10.1%). First-generation antihistamine use remained high in this group (29.5%). Residents without dementia (n = 24,929) more frequently received antihistamines (34.4%), bladder antimuscarinics (23.7%), and skeletal muscle relaxants (11.1%). From FY2007-2019, anticholinergic use declined modestly, with decreases in antihistamines (12.1%-8.8%), antidepressants (6.8%-3.5%), and antiemetic/antivertigo agents (5.2%-1.2%). Most residents used a single anticholinergic class, increasing from 75.5% to 82.2% over time. Although some anticholinergic classes may be clinically necessary, our findings highlight potentially underrecognized and modifiable sources of exposure, particularly first-generation antihistamines, underscoring the need for deprescribing efforts.

Research objective: The aim of this study was to present the current state of knowledge about bipolar affective disorder (BD) — its classification, clinical picture, pharmacological treatment and alternative methods, with particular emphasis on bipolar depression. Methodology: The study is based on a narrative review of recent scientific literature concerning bipolar affective disorder, conducted using the PubMed database with the following keywords: bipolar disorder; bipolar depression; lithium; atypical neuroleptics; ketamine; psilocybin; neuromodulation; electroconvulsive therapy; rTMS; phototherapy. Main conclusions: Bipolar affective disorder is a chronic and recurrent mood disorder characterized by alternating episodes of mania, hypomania and depression, leading to significant functional decline, increased risk of suicide and shortened life expectancy. Lithium remains the drug of first choice for the treatment and prevention of mania, while valproate and carbamazepine are effective but carry a higher risk of side effects, and atypical neuroleptics are active in both mania and depression. For treatment-resistant cases, especially refractory bipolar depression, neuromodulatory techniques (ECT, rTMS, tDCS, VNS) and the use of ketamine and psychedelics such as psilocybin show promising results. Electroconvulsive therapy is currently the best studied of these methods, rTMS and tDCS show moderate efficacy with good tolerance, ketamine provides rapid antidepressant and anti-suicidal effects despite limited long-term data, and phototherapy demonstrates beneficial effects in seasonal and non-seasonal depression with a good safety profile. Application of the study: The findings may support clinicians in improving diagnostic accuracy and optimizing treatment strategies for patients with bipolar affective disorder, particularly through a more individualized approach to the management of bipolar depression. Originality/Novelty of the study: The review integrates recent findings on emerging therapeutic perspectives in bipolar affective disorder, highlighting advances in neuromodulation, ketamine and psychedelic-assisted treatment, and their potential role in addressing treatment-resistant bipolar depression.

Clinical and quality of life predictors in patients with schizophrenia with and without substance use disorder.

Individuals diagnosed with schizophrenia have been shown to have a significantly different lifespan, often dying 15 years to 20 years earlier than the general population. This excess mortality is primarily attributable to atherosclerotic cardiovascular disease, rather than the psychiatric symptoms themselves. Second-generation antipsychotics represent the prevailing standard of treatment in modern medicine; however, their efficacy is accompanied by significant drawbacks. While these medications are imperative in the prevention of suicide and relapse, they can concomitantly induce metabolic dysfunction. A rigorous examination of the molecular underpinnings of the endoplasmic reticulum stress response is imperative to elucidate its role as a mediator of antipsychotic-induced insulin dysregulation. Additionally, we examine the “clinical paradox” that the pursuit of psychiatric stabilization through pharmacotherapy may inadvertently expedite cardiovascular aging. Moving forward, clinical models must shift from an emphasis on individual variable analyses (e.g. , body mass index or positive/negative symptom scale scores) to an integrated framework. This framework should consider the control of psychiatric symptoms as a prerequisite for metabolic health. In order to address the disparity in survival rates within this vulnerable population, there is a necessity to evolve research methodologies in order to facilitate clinical evaluation of a trinity of pharmacology, psychopathology, and lifestyle.

BackgroundPatients in forensic psychiatric care (FPC) are often treated with various psychotropic medications. However, evidence regarding their effectiveness in this setting is lacking.ObjectiveThe study aimed to estimate how different psychotropic medications are associated with the use of coercive measures and recidivism during FPC.MethodsIn this observational national register-based study, we included all patients newly registered as admitted to FPC in Sweden between January 2009 and August 2024. Exposures included major classes of psychotropic medication (typical antipsychotics, atypical antipsychotics, antidepressants, hypnotics and sedatives, antiepileptic medications, opioids, medications for addictive disorders and mood stabilisers), antipsychotic treatment strategies (no use, monotherapy, polypharmacy, long-acting injectables or clozapine) and specific antipsychotic agents. Outcomes were the use of coercive measures and recidivism into criminal behaviour. We performed a within-individual analysis using conditional generalised estimating equation models, where the risk of outcomes was compared between exposed and non-exposed time periods.FindingsIn total, 2690 patients were included, of which 25.1% experienced at least one occasion of coercion and 27.1% at least one event of recidivism during FPC. Atypical antipsychotics were associated with a reduced risk of subsequent use of coercive measures (OR 0.70, 95% CI 0.55 to 0.89) and recidivism (OR 0.79, 95% CI 0.63 to 0.99). Medication for addictive disorders was associated with a reduced risk of coercive measures by 34% (OR 0.66, 95% CI 0.47 to 0.93). Among antipsychotic agents, clozapine was associated with the largest risk reduction in the use of coercive measures (OR 0.48, 95% CI 0.33 to 0.69) and recidivism (OR 0.49, 95% CI 0.33 to 0.74). There was no significant difference between long-acting injectable, oral monotherapy or polypharmacy.ConclusionsWe observed that atypical antipsychotics, especially clozapine, were associated with a risk reduction for coercive measures and recidivism during FPC. Additionally, medications for addictive disorders were associated with a reduced risk of coercive measures.Clinical implicationsOur results can help inform decision-making processes in this clinical setting regarding pharmacotherapy but should be interpreted as one of many aspects influencing treatment success in FPC.

ABSTRACTObjectiveBipolar disorder (BD) often emerges during mid‐adolescence and young adulthood, and leads to functional and social impairment, with a prevalence of 0.87% among Dutch youth. Lithium, the first‐line BD maintenance treatment, stabilizes mood, prevents suicide, and is well tolerated, yet its use has declined as long‐term second‐generation antipsychotics (SGAs) prescriptions increased. This study explores the prevalence, incidence, duration, prior and concurrent use of psychotropic medications, and dosage patterns of lithium dispensing in Dutch youth.MethodA retrospective cohort study using the Dutch community pharmacy‐based IADB.nl database included 567 youths (6–25 years), who were dispensed lithium between 2011 and 2022.ResultsThe yearly prevalence of lithium dispensing per 100,000 fluctuated between 30.3 in 2011 and 34.8 in 2022 (p = 0.40), with the lowest prevalence in 6–12‐year‐olds and highest in 20–25‐year‐olds. Females had overall higher prevalence rates than males (p = 0.03). Overall incidence rose from 7.9 to 9.3 (p = 0.68). In 2011, incidence was 10.7 for both the 13–19 and 20–25 age groups. By 2022, this decreased to 4.2 in 13–19‐year‐olds and increased to 19.0 in 20–25‐year‐olds. Approximately 55% of individuals received other psychotropics before lithium, and 52% concurrently, with SGAs and antidepressants being most commonly dispensed.ConclusionDespite lithium's efficacy and status as first‐line BD maintenance treatment, its dispensing in Dutch youth remains low compared to the BD prevalence. This may be due to misdiagnosis of BD and/or clinicians' reluctance to prescribe lithium, highlighting the need for improved diagnostics, clinician education, and further research into lithium's safety in youths.

Long-term antipsychotic use and cardiometabolic adverse effects in adults with non-psychotic disorders: A systematic review.

BackgroundAlzheimer's disease (AD) is commonly treated with memantine alone or in combination with cholinesterase inhibitors (ChEIs) or second-generation antipsychotics (SGAs), but the safety of these combinations remains unclear.ObjectiveTo characterize FDA Adverse Event Reporting System (FAERS)-based signals of disproportionate reporting associated with memantine-based combination therapies in patients with AD.MethodsA disproportionality analysis was conducted using data from FAERS from 2014Q1 to 2025Q2 via the MY FAERS platform. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated to identify safety signals. Sensitivity analyses were conducted using ChEIs or SGAs monotherapy as reference groups to assess the robustness.Results2531 patients prescribed memantine were identified, comprising memantine monotherapy (n = 1965), memantine-ChEIs combination (n = 482), and memantine-SGAs combination (n = 84). Compared to memantine monotherapy, the memantine- ChEIs combination showed disproportionate reporting signals for skin (ROR, 3.46; 95% CI, 2.05-5.85), gastrointestinal (ROR, 2.53; 95% CI, 1.92-3.33), musculoskeletal (ROR, 2.13; 95% CI, 1.29-3.50), psychiatric (ROR, 1.60; 95% CI, 1.27-2.00), general (ROR, 1.53; 95% CI, 1.18-1.97), and nervous system disorders (ROR, 1.48; 95% CI, 1.19-1.84). The memantine-SGAs combination was strongly associated with the signals of general (ROR, 3.97; 95% CI, 1.74-9.05), psychiatric (ROR, 2.14; 95% CI, 1.32-3.49), nervous system disorders (ROR, 2.03; 95% CI, 1.20-3.43), and hip fracture (ROR, 15.84; 95% CI, 3.72-67.41). Sensitivity analyses confirmed robustness across subgroups.ConclusionsMemantine-based combination therapies were associated with distinct safety signals of disproportionate reporting compared with monotherapies. These findings should be interpreted as pharmacovigilance signals that warrant cautious interpretation and further validation in well-designed observational or prospective studies.

Atypical antipsychotics are common adjunctive therapies for major depressive disorder (MDD) with inadequate antidepressant (ADT) response. In 2025, lumateperone was approved in the US as adjunctive treatment for adults with MDD, and comparative evidence is lacking. This network meta-analysis compared the efficacy and safety of lumateperone with those of other approved atypical antipsychotics for MDD. Registrational randomized clinical trials as documented in US product labeling (RCTs; N = 10; aripiprazole, brexpiprazole, cariprazine, lumateperone, and quetiapine XR) were used to build a star-shaped, 11-treatment-dose node network anchored on placebo + ADT. Outcomes available for ≥ 9 RCTs were considered. Efficacy outcomes comprised change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), MADRS response and remission, and change from baseline in Clinical Global Impression-Severity (CGI-S) scale. Safety outcomes included weight change from baseline, akathisia, and somnolence. A fixed-effect Bayesian approach was applied. Pairwise treatment effects were compared; a probability of superiority > 85% (< 15%) indicated favored (unfavored) treatment. Network-wide treatment ranking was estimated using Surface Under the Cumulative Ranking (SUCRA) curves. Based on MADRS change from baseline, all atypical antipsychotics were favored versus placebo + ADT, with mean difference from placebo highest for lumateperone 42mg/day (- 4.70). Other efficacy endpoints showed a consistent pattern, with active treatments favored over placebo + ADT across most nodes for response (10/11), remission (6/11), and CGI-S change (10/11). SUCRA ranking placed lumateperone as the treatment with the highest likelihood of being most efficacious across endpoints. Treatments differed in their safety profiles. Lumateperone was the only node with no weight gain relative to placebo and ranked first for weight-related safety outcomes. Lumateperone also ranked better than average for akathisia risk but below average for somnolence risk. Lumateperone represents an effective adjunctive therapy for adult MDD, with no weight change.

Second-generation antipsychotics, a cornerstone of psychiatric disorder management, render treated patients highly prone to metabolic abnormalities. To address this unmet clinical need, this post-hoc analysis drew on data from a previous trial to examine the correlations between plasma short-chain fatty acid (SCFA) level alterations and metabolic changes in the context of probiotic-fiber intervention. In this trial, individuals diagnosed with schizophrenia or bipolar disorder, who were undergoing stable atypical antipsychotic therapy, were recruited for this study. They were subsequently randomized in a 1:1:1:1 ratio to four treatment groups: combined probiotics (1680mg/d) and dietary fiber (60g/d); probiotics (1680mg/d) with dietary fiber placebo; dietary fiber (60g/d) with probiotics placebo; and double placebo (probiotics placebo plus dietary fiber placebo). Assessments were conducted at screening/baseline, week 4, and week 12, and the measurement of circulating SCFAs was performed via liquid chromatography-mass spectrometry. The analysis, employing the last-observation-carried-forward method, encompassed 79 participants who provided at least one follow-up plasma sample for the quantification of SCFAs. The 12-week combined administration of probiotics and dietary fiber was associated with changes in circulating levels of SCFAs and improvements in metabolic indices. More importantly, the higher levels of propionate were associated with decreased weight (adjusted odds ratio [OR]: 0.61 per quartile increase, 95% confidence interval [CI]: 0.38-0.96) and homeostatic model assessment of insulin resistance (HOMA-IR) (adjusted OR:0.58, 95% CI: 0.36-0.94). Also, the higher levels of butyrate were associated with a 42% lower odds (adjusted OR: 0.58, 95%CI:0.36-0.93) of elevated body mass index (BMI) and a 49% lower odds (adjusted OR: 0.51, 95%CI:0.31-0.86) of elevated insulin levels. The findings of this study suggested that elevated circulating levels of butyrate and propionate might be associated with reduced weight gain and improved insulin resistance in individuals receiving antipsychotic medications. ClinicalTrials.gov NCT03379597, trial registration date: 11/29/2017. Overall Recruitment Status: completed.

Major depressive disorder (MDD) in adolescents remains a significant public health challenge. Treatment-resistant depression (TRD) affects a substantial proportion of cases and is associated with chronic symptoms, comorbidities, and elevated suicide risk. Standard treatments frequently show limited success, leading to off-label consideration of atypical antipsychotics as augmentation agents. Risperidone has shown promise in adults, but data in adolescents are limited. This retrospective study evaluates clinical outcomes of risperidone augmentation in adolescent TRD, complemented by in silico modeling of potential molecular interactions. Retrospective data from 50 adolescents (aged 12-18) with DSM-5 MDD and TRD (non-response to ≥2 antidepressants) were analyzed. Risperidone (0.25-2mg/day) was added to ongoing antidepressants for ≥8weeks. Efficacy was assessed via changes in CDRS-R and HAM-D scores, response (≥50% reduction), and remission rates. Adverse events were documented. In silico molecular docking and 200 ns MD simulations explored risperidone's interactions with selected targets (DRD2, 5-HT2AR, SERT, and NMDA) using available PDB structures. Mean age was 15.4years; 56% female. Depression scores improved: CDRS-R decreased from 64.3 to 38.9 (mean change -25.4 points), HAM-D from 23.6 to 12.1 (mean change -11.5 points). Response rates were 64% (CDRS-R) and 60% (HAM-D); remission rates were 40% and 36%, respectively. Baseline severity was associated with response (OR 1.22, p = 0.01). Common adverse events (mostly mild-moderate) included weight gain (24%), sedation (16%), and EPS (12%). Docking and MD simulations suggested favorable binding, particularly to DRD2 and 5-HT2AR. In this retrospective cohort, risperidone augmentation was associated with symptom improvement in adolescents with TRD and showed an acceptable short-term safety profile. In silico analyses suggest potential interactions with monoaminergic receptors that may contribute to its effects. These findings are hypothesis-generating and require confirmation in prospective randomized controlled trials.

Are psychotropic medications equivalent in fall risk among nursing home residents? A meta-analysis of pharmacologic subtypes and polypharmacy effects.

The association between long-term use of benzodiazepines (BDZs) and cognitive function in patients with schizophrenia has not been fully characterized. This study aimed to investigate the relationship between long-term BDZs use and cognitive function in schizophrenia. Data were derived from an observational study of treatment with atypical antipsychotics in Chinese patients with schizophrenia (SALT-C). Fifty-seven patients with long-term use of BDZs (≥60 days) were included, and 57 BDZs non-users were matched using propensity scores for age, sex, disease duration, and atypical antipsychotics received. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA); psychotic symptoms, illness severity, and psychosocial functioning were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Between-group comparisons were performed using independent-samples t-tests or Mann-Whitney U tests. Spearman correlation analysis was performed to assess the association between benzodiazepine dose and MoCA total scores among BDZ users.Factors associated with MoCA total scores were examined using multiple linear regression models. The long-term BDZs user group showed a significantly lower total MoCA score [16.02 (6.69)] than the BDZs non-user group [19.33 (7.11)] (FDR-adjust p = 0.048). No significant between-group differences were observed in total scores on the PANSS, CGI-S, or PSP (all p > 0.05). No significant association was observed between benzodiazepines dose and MoCA scores (r = -0.098, p = 0.466). Multiple linear regression revealed that long-term BDZs use (β = -0.182, p = 0.008), PANSS total score (β = -0.217, p = 0.003) and anticholinergic burden (β = -0.199, p = 0.008) were independently associated with poorer cognitive performance, whereas years of education showed a positive association with cognitive performance (β = 0.460, p < 0.001). Long-term BDZs use is associated with poorer cognitive performance in patients with schizophrenia, suggesting that cognitive function should be monitored and prolonged treatment avoided.

Cytokine changes during a 12-month pragmatic randomized trial in schizophrenia spectrum disorders comparing amisulpride, aripiprazole and olanzapine.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits. To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD. Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I 2 to quantify heterogeneity. Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I 2 approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies. The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.