Hyperprolactinemia (HPRL) is a common adverse reaction induced by antipsychotic therapy in patients with schizophrenia, which greatly undermines medication adherence and impairs physiological functions of multiple body systems. In this real-world study, we analyzed retrospective prolactin testing data to compare the incidence of HPRL between schizophrenia patients and patients with other psychiatric disorders, so as to identify clinical high-risk factors. Meanwhile, hormones including thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), tetraiodothyronine (T4), Triiodothyronine (T3), and estradiol that closely correlated with prolactin metabolism were also included in the analysis. The results indicated that female patients with schizophrenia had the highest risk of HPRL (19.31%, n = 2009), and women during the prime reproductive (25-40 years) showed the highest average prolactin concentration (1,389.22 ± 50.138 mIU/L, n = 966). Distinct antipsychotics usage rates were observed among different clinical subgroups. Risperidone, paliperidone and sulpiride showed an increasing trend with elevated PRL levels, whereas quetiapine and aripiprazole were more frequently prescribed in the low-risk HPRL group. Antipsychotics showed divergent dopamine D2/D3 and 5-HT2A receptor-binding affinities (Ki values), and we constructed a weighted multi-receptor affinity index that demonstrated a strong linear correlation with the PRL risk score (R[2] = 0.878). Additionally, the average incidence of extrapyramidal symptoms (EPS) increased with rising PRL levels (P = 2.24E-10). Further analysis of EPS risk revealed distinct safety profiles across antipsychotics, with aripiprazole-characterized by low HPRL liability-demonstrating a higher EPS risk. The severe HPRL group presented a tendency of decreased thyroid function (TSH, P = 0.0027; FT4, P = 0.000031; FT3, P = 0.0076; T4, P = 0.0025) and a significant reduction in estradiol levels (P = 0.000049). Based on homogeneous clinical real-world data, this study comprehensively evaluated multiple antipsychotic medications simultaneously. It provides empirical clinical evidence for individualized medication strategies in patients with comorbid HPRL and EPS, and offers real-world evidence for the clinical early risk recognition, and long-term medication decision-making among patients with multiple adverse reactions concurrently.

The matrix effect is a prevalent interference in LC-MS/MS bioanalysis of small-molecule drugs, with lipids as a major source of such interference in plasma matrices. Leveraging the lipid-adsorbing capability of multi-walled carbon nanotubes (MWCNTs), this study synthesized TiO2@MWCNTs composites and developed a novel dispersive solid-phase extraction (d-SPE) method to reduce matrix effects in rat plasma. Lipid profiles were compared to characterize the lipid purification capacity of TiO2@MWCNTs in rat plasma samples. The matrix effects of representative small-molecule drugs, including metformin, amisulpride, and aripiprazole, were compared across TiO2@MWCNTs-based d-SPE, protein precipitation, and traditional solid-phase extraction. Method validation and sample determination were subsequently performed. The results demonstrated that TiO2 could be successfully loaded onto MWCNTs. The responses of 72 differential lipid ions were significantly reduced by at least 2-fold after TiO2@MWCNTs treatment, and the IS-normalized matrix factors for metformin (from 13.69-20.00% to 31.49-44.39%) and amisulpride (from 71.01-84.82% to 91.69-101.48%) as well as the accuracy for aripiprazole at low concentration were significantly improved compared with protein precipitation treatment. Method validation results confirmed excellent selectivity, accuracy, precision, and reproducibility. The validated method was also successfully applied to a pharmacokinetic study of metformin with pharmacokinetic parameters comparable to those reported previously. This study shows that the dispersive solid-phase extraction method based on TiO2@MWCNTs could act as a simple, rapid, low-cost and reliable pretreatment strategy to mitigate matrix effects for small-molecule analytes with low lgP in rat plasma as a proof-of-concept attempt.

BackgroundIndividuals with schizophrenia and concurrent substance use disorders (SUDs) face a high risk of rapid weight gain during residential treatment, driven by inpatient environmental factors, baseline metabolic vulnerability, and metabolically active psychotropic medications. Clozapine, commonly indicated for treatment-resistant psychosis, is frequently associated with early and substantial weight gain. This study examined whether adjunctive metformin or aripiprazole attenuated weight gain in individuals taking clozapine in a naturalistic residential setting.MethodsThis retrospective cohort study included adults prescribed clozapine during admission to a 105-bed provincial concurrent disorders facility in British Columbia, Canada (2021-2024). Adults with ≥90-day admissions and available therapeutic drug monitoring were included. Monthly weights were extracted from electronic records and linked to serum concentrations and medication exposure. Linear mixed-effects models with random intercepts and slopes assessed predictors of weight trajectories, with fixed effects including age, sex, baseline weight, norclozapine concentration, opioid agonist therapy (OAT), augmenting antipsychotic defined daily dose, and adjunctive metformin and aripiprazole. Interaction terms between time and adjunctive agents evaluated effects on weight trajectories.ResultsEighty individuals contributed 306 matched serum concentration-weight observations. The cohort was predominantly male with schizophrenia and comorbid SUDs. Higher baseline weight and greater time between admission and blood draw were associated with increased weight. In adjusted models, norclozapine concentration and OAT were associated with higher weight. Metformin was associated with attenuation of weight gain over time (time × metformin: B = -2.63, 95% CI -4.49 to -0.76), whereas aripiprazole was not (B = -0.38, 95% CI -2.58 to 1.82).ConclusionMetformin was associated with attenuation of weight gain trajectory in this population, whereas aripiprazole showed no clear effect. These findings highlight substantial metabolic vulnerability in inpatient concurrent disorders settings and support early preventive metabolic interventions during clozapine treatment.

Inadequate and poorly documented data on psychotropic drug utilization in schizophrenia in India necessitates systematic evaluation of prescribing patterns and associated adverse drug reactions. This prospective observational study assessed drug utilization, prescription rationality and adverse drug reactions among schizophrenia patients attending a tertiary care psychiatric outpatient department using WHO prescribing indicators. A total of 112 prescriptions comprising 285 drugs were analyzed, with atypical antipsychotics prescribed in 87% of first-visit cases, while combination therapies and polypharmacy were frequently observed. Significant dose variations were noted in commonly used antipsychotics such as risperidone, olanzapine and aripiprazole, as well as benzodiazepines like clonazepam and lorazepam (p<0.001). Atypical antipsychotics predominated due to better tolerability and lower extrapyramidal side effects, highlighting evolving prescribing trends. Thus, structured evidence on drug utilization patterns and variability in dosing, help in optimizing rational prescribing practices in schizophrenia management.

ObjectiveLong-acting injectable (LAI) antipsychotics may improve treatment adherence by maintaining stable plasma drug concentrations and reducing relapse risk associated with inconsistent oral medication use. Although LAIs are widely used in adults with severe psychiatric disorders, their use in pediatric populations remains off-label, and evidence is limited. Aripiprazole, a partial dopamine D2 receptor agonist, has a favorable tolerability profile in adolescents, particularly regarding metabolic adverse effects and prolactin elevation.MethodsThis retrospective case series describes the clinical use of aripiprazole monohydrate LAI (AM LAI) in six adolescents aged 13-17 years with severe psychiatric conditions and poor adherence to oral treatment.ResultsTreatment with AM LAI was associated with improved adherence and clinical stabilization in most cases. Reductions in symptom severity and improvements in functional outcomes were observed during follow-up. No serious adverse effects were reported.ConclusionAM LAI appears to be a safe and effective off-label treatment option in high-risk adolescents with poor adherence to oral antipsychotics. This case series contributes clinically relevant real-world data to the limited literature on LAI use in pediatric psychiatry.

Risperidone is a second-generation antipsychotic that is widely used in the treatment of psychotic disorders. It is generally well tolerated, although uncommon adverse effects have been reported. Nasal congestion and urinary frequency have only rarely been described in association with risperidone treatment. A 27-year-old male with delusional disorder developed nasal congestion and urinary frequency after starting risperidone. He underwent evaluation by both family medicine and otolaryngology (ENT), and no alternative cause of his symptoms was identified. Despite treatment with antihistamines, intranasal budesonide, and xylometazoline, his symptoms persisted. The symptoms resolved when he stopped taking risperidone for two days and returned when the medication was restarted. Risperidone was subsequently discontinued and replaced with aripiprazole. Following the switch, the patient's symptoms resolved completely. This case suggests a probable association between risperidone and the development of nasal congestion and urinary frequency. Awareness of these uncommon adverse effects may help clinicians identify medication-related symptoms, avoid unnecessary investigations, and improve treatment adherence.