BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study.
METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension).
RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation.
CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment.
BACKGROUND: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

BACKGROUND: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study.
METHODS: The qualitative study will use semi-structured interviews to explore pilot trial participants\' and clinicians\' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations.
CONCLUSIONS: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations.
UNASSIGNED: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.

OBJECTIVE: To collect evidence on the possibility that patients with depression experience self-stigmatization based on label information for medications.
METHODS: We developed a discrete-choice experiment (DCE) survey instrument that asked respondents to make choices between hypothetical treatments for major depressive disorder (MDD). We also included treatment type (antidepressants versus antipsychotics) and approved indications for the medication. The choice questions mimicked the information presented in product inserts and required systematic tradeoffs between treatment efficacy, treatment type, and indication. We calculated how many patients were willing to forgo efficacy to avoid treatments with information associated with self-stigmatization, and how much efficacy they were willing to forgo. We also evaluated the impact of contextualizing the treatment information to reduce self-stigmatization by randomizing respondents who received additional context.
RESULTS: A total of 501 patients with MDD were recruited to complete the DCE survey. Respondents had well-defined preferences for treatment outcomes. Over 60% (63.4%) of respondents were found to be significantly affected by treatment indication. These respondents were willing to forgo about 2.5 percentage points in the chance of treatment efficacy to avoid treatments indicated for schizophrenia. We also find that some level of contextualization of the treatment details could help reduce the negative impact of treatment type and indications.
CONCLUSIONS: Product-label treatment indication can potentially lead to patient self-stigmatization as shown by patients\' avoidance of treatments that are also used to treat schizophrenia. While the effect appears to be relatively small, results suggests that the issue is likely pervasive.

BACKGROUND: Recent studies have shown that liver enzyme abnormalities were not only seen with typical antipsychotics (APs) but also with atypical antipsychotics (AAPs). During the last 20 years, the hepatotoxicity of various antipsychotics received much attention. However, systematic evaluations of hepatotoxicity associated with APs are limited.
METHODS: All drug related hepatic disorders cases were retrieved from the FDA Adverse Event Reporting System (FAERS) database using standardized MedDRA queries (SMQ) from the first quarter of 2017 to the first quarter of 2022. Patient characteristics and prognosis were assessed. In this study, a case/non-case approach was used to calculate reporting odds ratio (RORs) and 95% confidence intervals (CIs). We calculated the drug-induced liver injury (DILI) RORs for each AAPs.
RESULTS: A total of 408 DILI cases were attributed to AAPs during the study period. 18.6% of these were designated as serious adverse event (SAE), which include death (19.74%), hospitalization (68.42%), disability (2.63%), and life-threatening (9.21%) outcomes. The RORs values in descending order were: quetiapine (ROR = 0.782), clozapine (ROR = 0.665), aripiprazole (ROR = 0.507), amisulpride (ROR = 0.308), paliperidone (ROR = 0.212), risperidone (ROR = 0.198), ziprasidone (0.131).
CONCLUSIONS: The result found in our study was that all AAPs didn\'t have a significant correlation with increased hepatotoxicity. Future analysis of the FAERS database in conjunction with other data sources will be essential for continuous monitoring of DILI.

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Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as \"rabbit\" syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical-epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among adults in psychiatric hospitals was 1.2% (range 0-4.4%). The mean age of affected patients was 49.2 (SD: 17.5), and 63.6% were females. Schizophrenia was the most frequent comorbidity found in 47.6%, followed by bipolar disorder (17.8%), major depressive disorder (10.3%), and obsessive-compulsive disorder (3.7%). Five cases were idiopathic. The most common medications associated with RS were haloperidol (17%), risperidone (14%), aripiprazole (7%), trifluoperazine (5%), and sulpiride (5%). The mean duration of pharmacotherapy before RS was 21.4 weeks (SD: 20.6). RS occurred in association with drug-induced parkinsonism (DIP) in 27.4% and with tardive dyskinesia (TD) in 8.2% of cases. Antipsychotic modification and/or anticholinergic drugs resulted in full or partial recovery in nearly all reported cases in which they were prescribed. Conclusions: RS occurs as a distinct drug-induced syndrome associated primarily but not exclusively with antipsychotics. Distinguishing RS from TD is important because the treatment options for the two disorders are quite different. By contrast, RS may be part of a spectrum of symptoms of DIP with similar course, treatment outcomes, and pathophysiology.

Schizophrenia poses significant challenges for individuals and caregivers, often leading to recurrent hospitalizations. Limited information on patients with schizophrenia and multiple hospitalizations in Romania is available in the scientific literature. Our study aimed to evaluate the characteristics of patients with schizophrenia with multiple hospitalizations in a single center in Cluj-Napoca, analyzing if specific patterns exist between patients with two or more hospitalizations or between men and women. We conducted a retrospective study on patients diagnosed with schizophrenia according to the 10th revision of the International Classification of Diseases (ICD 10), hospitalized at the County Emergency Hospital of Cluj-Napoca, Romania, between 2018 and 2022. Data on demographics, somatic comorbidities, symptom severity using the positive and negative syndrome scale (PANSS) or the brief psychiatric rating scale (BPRS), antipsychotic medication, and adverse effects were collected. We evaluated 62 patients, aged from 23 to 57 years, with 157 hospitalizations (ranging from two to seven per patient). No familial history of schizophrenia (56.5%) or bipolar disorder (71%) was reported by most patients. Forty-eight patients were male, and 45 had two hospitalizations. Age, sex, living place and conditions, season of birth, and marital status were similar in patients with two or more than two hospitalizations (p-values > 0.10). Significant differences were observed between patients with two or more than two hospitalizations regarding smoking (63.3% vs. 79.1%, p-value = 0.0029) and symptoms of fear at admission (40.0% vs. 65.7%, p-value = 0.0015). We observed lower scores in the overall PANSS and BPRS scores at discharge compared to admission (p-values < 0.001), regardless of the group (two or more than two hospitalizations, men vs. women). Men and women showed differences in hospitalization stays (median 17.25 vs. 15 days, p-value < 0.001) and BPRS scores at admission (p-value = 0.012) and discharge (p-value = 0.016). Fewer First-Generation Antipsychotics were prescribed for those with two admissions, and nearly half reported adverse effects, notably tachycardia (29%), with similar occurrence within groups. Our results showed that the candidate for multiple hospitalizations is a male, with a mean age of 37 years, unmarried, and living with someone in urban settings, more likely a smoker who exhibits fear symptoms.

Schizophrenia is a frequently debilitating and complex mental disorder affecting approximately 1% of the global population, characterized by symptoms such as hallucinations, delusions, disorganized thoughts and behaviors, cognitive dysfunction, and negative symptoms. Traditional treatment has centered on postsynaptic dopamine antagonists, commonly known as antipsychotic drugs, which aim to alleviate symptoms and improve functioning and the quality of life. Despite the availability of these medications, significant challenges remain in schizophrenia therapeutics, including incomplete symptom relief, treatment resistance, and medication side effects. This opinion article explores advancements in schizophrenia treatment, emphasizing molecular mechanisms, novel drug targets, and innovative delivery methods. One promising approach is novel strategies that target neural networks and circuits rather than single neurotransmitters, acknowledging the complexity of brain region interconnections involved in schizophrenia. Another promising approach is the development of biased agonists, which selectively activate specific signaling pathways downstream of receptors, offering potential for more precise pharmacological interventions with fewer side effects. The concept of molecular polypharmacy, where a single drug targets multiple molecular pathways, is exemplified by KarXT, a novel drug combining xanomeline and trospium to address both psychosis and cognitive dysfunction. This approach represents a comprehensive strategy for schizophrenia treatment, potentially improving outcomes for patients. In conclusion, advancing the molecular understanding of schizophrenia and exploring innovative therapeutic strategies hold promise for addressing the unmet needs in schizophrenia treatment, aiming for more effective and tailored interventions. Future research should focus on these novel approaches to achieve better clinical outcomes and improve the functional level and quality of life for individuals with schizophrenia.

BACKGROUND: Clozapine is the only recommended antipsychotic medication for individuals diagnosed with treatment-resistant schizophrenia. Unfortunately, its wider use is hindered by several possible adverse effects, some of which are rare but potentially life threatening. As such, there is a growing interest in studying clozapine use and safety in routinely collected healthcare data. However, previous attempts to characterise clozapine treatment have had low accuracy.
OBJECTIVE: To develop a methodology for identifying clozapine treatment dates by combining several data sources and implement this on a large clinical database.
METHODS: Non-identifiable electronic health records from a large mental health provider in London and a linked database from a national clozapine blood monitoring service were used to obtain information regarding patients\' clozapine treatment status, blood tests and pharmacy dispensing records. A rule-based algorithm was developed to determine the dates of starting and stopping treatment based on these data, and more than 10% of the outcomes were validated by manual review of de-identified case note text.
RESULTS: A total of 3,212 possible clozapine treatment periods were identified, of which 425 (13.2%) were excluded due to insufficient data to verify clozapine administration. Of the 2,787 treatments remaining, 1,902 (68.2%) had an identified start-date. On evaluation, the algorithm identified treatments with 96.4% accuracy; start dates were 96.2% accurate within 15 days, and end dates were 85.1% accurate within 30 days.
CONCLUSIONS: The algorithm produced a reliable database of clozapine treatment periods. Beyond underpinning future observational clozapine studies, we envisage it will facilitate similar implementations on additional large clinical databases worldwide.

BACKGROUND: Schizophrenia is a pervasive and severe mental disorder characterized by significant disability and high rates of recurrence. The persistently high rates of readmission after discharge present a serious challenge and source of stress in treating this population. Early identification of this risk is critical for implementing targeted interventions. The present study aimed to develop an easy-to-use predictive instrument for identifying the risk of readmission within 1-year post-discharge among schizophrenia patients in China.
METHODS: A prediction model, based on static factors, was developed using data from 247 schizophrenia inpatients admitted to the Mental Health Center in Wuxi, China, from July 1 to December 31, 2020. For internal validation, an additional 106 patients were included. Multivariate Cox regression was applied to identify independent predictors and to create a nomogram for predicting the likelihood of readmission within 1-year post-discharge. The model\'s performance in terms of discrimination and calibration was evaluated using bootstrapping with 1000 resamples.
RESULTS: Multivariate cox regression demonstrated that involuntary admission (adjusted hazard ratio [aHR] 4.35, 95% confidence interval [CI] 2.13-8.86), repeat admissions (aHR 3.49, 95% CI 2.08-5.85), the prescription of antipsychotic polypharmacy (aHR 2.16, 95% CI 1.34-3.48), and a course of disease ≥ 20 years (aHR 1.80, 95% CI 1.04-3.12) were independent predictors for the readmission of schizophrenia patients within 1-year post-discharge. The area under the curve (AUC) and concordance index (C-index) of the nomogram constructed from these four factors were 0.820 and 0.780 in the training set, and 0.846 and 0.796 for the validation set, respectively. Furthermore, the calibration curves of the nomogram for both the training and validation sets closely approximated the ideal diagonal line. Additionally, decision curve analyses (DCAs) demonstrated a significantly better net benefit with this model.
CONCLUSIONS: A nomogram, developed using pre-discharge static factors, was designed to predict the likelihood of readmission within 1-year post-discharge for patients with schizophrenia. This tool may offer clinicians an accurate and effective way for the timely prediction and early management of psychiatric readmissions.