OBJECTIVE: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers.
METHODS: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively.
METHODS: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang.
METHODS: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD.
METHODS: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis.
RESULTS: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone.
CONCLUSIONS: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer\'s disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs.

BACKGROUND: Schizophrenia is often a severe and disabling psychiatric disorder. Antipsychotics remain the mainstay of psychotropic treatment for people with psychosis. In limited resource and humanitarian contexts, it is key to have several options for beneficial, low-cost antipsychotics, which require minimal monitoring. We wanted to compare oral haloperidol, as one of the most available antipsychotics in these settings, with a second-generation antipsychotic, olanzapine.
OBJECTIVE: To assess the clinical benefits and harms of haloperidol compared to olanzapine for people with schizophrenia and schizophrenia-spectrum disorders.
METHODS: We searched the Cochrane Schizophrenia study-based register of trials, which is based on monthly searches of CENTRAL, CINAHL, ClinicalTrials.gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP. We screened the references of all included studies. We contacted relevant authors of trials for additional information where clarification was required or where data were incomplete. The register was last searched on 14 January 2023.
METHODS: Randomised clinical trials comparing haloperidol with olanzapine for people with schizophrenia and schizophrenia-spectrum disorders. Our main outcomes of interest were clinically important change in global state, relapse, clinically important change in mental state, extrapyramidal side effects, weight increase, clinically important change in quality of life and leaving the study early due to adverse effects.
METHODS: We independently evaluated and extracted data. For dichotomous outcomes, we calculated risk ratios (RR) and their 95% confidence intervals (CI) and the number needed to treat for an additional beneficial or harmful outcome (NNTB or NNTH) with 95% CI. For continuous data, we estimated mean differences (MD) or standardised mean differences (SMD) with 95% CIs. For all included studies, we assessed risk of bias (RoB 1) and we used the GRADE approach to create a summary of findings table.
RESULTS: We included 68 studies randomising 9132 participants. We are very uncertain whether there is a difference between haloperidol and olanzapine in clinically important change in global state (RR 0.84, 95% CI 0.69 to 1.02; 6 studies, 3078 participants; very low-certainty evidence). We are very uncertain whether there is a difference between haloperidol and olanzapine in relapse (RR 1.42, 95% CI 1.00 to 2.02; 7 studies, 1499 participants; very low-certainty evidence). Haloperidol may reduce the incidence of clinically important change in overall mental state compared to olanzapine (RR 0.70, 95% CI 0.60 to 0.81; 13 studies, 1210 participants; low-certainty evidence). For every eight people treated with haloperidol instead of olanzapine, one fewer person would experience this improvement. The evidence suggests that haloperidol may result in a large increase in extrapyramidal side effects compared to olanzapine (RR 3.38, 95% CI 2.28 to 5.02; 14 studies, 3290 participants; low-certainty evidence). For every three people treated with haloperidol instead of olanzapine, one additional person would experience extrapyramidal side effects. For weight gain, the evidence suggests that there may be a large reduction in the risk with haloperidol compared to olanzapine (RR 0.47, 95% CI 0.35 to 0.61; 18 studies, 4302 participants; low-certainty evidence). For every 10 people treated with haloperidol instead of olanzapine, one fewer person would experience weight increase. A single study suggests that haloperidol may reduce the incidence of clinically important change in quality of life compared to olanzapine (RR 0.72, 95% CI 0.57 to 0.91; 828 participants; low-certainty evidence). For every nine people treated with haloperidol instead of olanzapine, one fewer person would experience clinically important improvement in quality of life. Haloperidol may result in an increase in the incidence of leaving the study early due to adverse effects compared to olanzapine (RR 1.99, 95% CI 1.60 to 2.47; 21 studies, 5047 participants; low-certainty evidence). For every 22 people treated with haloperidol instead of olanzapine, one fewer person would experience this outcome. Thirty otherwise relevant studies and several endpoints from 14 included studies could not be evaluated due to inconsistencies and poor transparency of several parameters. Furthermore, even within studies that were included, it was often not possible to use data for the same reasons. Risk of bias differed substantially for different outcomes and the certainty of the evidence ranged from very low to low. The most common risks of bias leading to downgrading of the evidence were blinding (performance bias) and selective reporting (reporting bias).
CONCLUSIONS: Overall, the certainty of the evidence was low to very low for the main outcomes in this review, making it difficult to draw reliable conclusions. We are very uncertain whether there is a difference between haloperidol and olanzapine in terms of clinically important global state and relapse. Olanzapine may result in a slightly greater overall clinically important change in mental state and in a clinically important change in quality of life. Different side effect profiles were noted: haloperidol may result in a large increase in extrapyramidal side effects and olanzapine in a large increase in weight gain. The drug of choice needs to take into account side effect profiles and the preferences of the individual. These findings and the recent inclusion of olanzapine alongside haloperidol in the WHO Model List of Essential Medicines should increase the likelihood of it becoming more easily available in low- and middle- income countries, thereby improving choice and providing a greater ability to respond to side effects for people with lived experience of schizophrenia. There is a need for additional research using appropriate and equivalent dosages of these drugs. Some of this research needs to be done in low- and middle-income settings and should actively seek to account for factors relevant to these. Research on antipsychotics needs to be person-centred and prioritise factors that are of interest to people with lived experience of schizophrenia.

BACKGROUND: Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients.
METHODS: The QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications.
RESULTS: We recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P < 0.005). Patients who were taking activating second-generation antipsychotics (SGAs) had lower scores on total SQLS, Motivation/ Energy domain of SQLS (SQLS-ME) as well as Symptoms/ Side effects domain of SQLS (SQLS-SS) compared to those taking non-activating SGAs (all P < 0.005). Multiple regression analysis showed that depressive/ anxiety symptoms and cognitive impairment had significant negative effects on QoL (P ≤ 0.001), while activating SGAs had a positive effect (P < 0.005). Blunted affect and unemployment were inversely associated with the motivation/energy domain (P < 0.001).
CONCLUSIONS: Our findings emphasize the important role of depression/anxiety symptoms and cognitive impairment in the QoL of patients with chronic schizophrenia. Activating SGAs and employment may improve the QoL of these individuals.
BACKGROUND: This protocol was registered at chictr.org.cn (Identifier: ChiCTR2100043537).

We present a young woman with clozapine-resistant schizoaffective disorder who was treated with maintenance electroconvulsive therapy and multiple antipsychotics but continued to have auditory hallucinations. She had a haemorrhagic stroke secondary to a ruptured arteriovenous malformation at the right superior temporal gyrus, which was excised during emergency craniotomy. Despite having neurological deficits after the stroke, she reported cessation of auditory hallucinations. Magnetic resonance imaging of the brain showed Wallerian degeneration over the right temporal region. Personalised neuromodulation intervention may be a more effective treatment option for clozapine-resistant schizophrenia.

BACKGROUND: Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE.
METHODS: This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences.
RESULTS: Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05).
CONCLUSIONS: PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
CONCLUSIONS: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
BACKGROUND: PROSPERO-ID CRD42023410645.

OBJECTIVE: To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts.
METHODS: A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups.
RESULTS: 1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05).
CONCLUSIONS: Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.

Schizophrenia (SZ) is a serious, destructive neurodevelopmental disorder. Antipsychotic medications are the primary therapy approach for this illness, but it\'s important to pay attention to the adverse effects as well. Clinical studies for SZ are currently in phase ΙΙΙ for SEP-363856 (SEP-856)-a new antipsychotic that doesn\'t work on dopamine D2 receptors. However, the underlying action mechanism of SEP-856 remains unknown. This study aimed to evaluate the impact and underlying mechanisms of SEP-856 on SZ-like behavior in a perinatal MK-801 treatment combined with social isolation from the weaning to adulthood model (MK-SI). First, we created an animal model that resembles SZ that combines the perinatal MK-801 with social isolation from weaning to adulthood. Then, different classical behavioral tests were used to evaluate the antipsychotic properties of SEP-856. The levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β), apoptosis-related genes (Bax and Bcl-2), and synaptic plasticity-related genes (brain-derived neurotrophic factor [BDNF] and PSD-95) in the hippocampus were analyzed by quantitative real-time PCR. Hematoxylin and eosin staining were used to observe the morphology of neurons in the hippocampal DG subregions. Western blot was performed to detect the protein expression levels of BDNF, PSD-95, Bax, Bcl-2, PI3K, p-PI3K, AKT, p-AKT, GSK-3β, p-GSK-3β in the hippocampus. MK-SI neurodevelopmental disease model studies have shown that compared with sham group, MK-SI group exhibit higher levels of autonomic activity, stereotyped behaviors, withdrawal from social interactions, dysregulated sensorimotor gating, and impaired recognition and spatial memory. These findings imply that the MK-SI model can mimic symptoms similar to those of SZ. Compared with the MK-SI model, high doses of SEP-856 all significantly reduced increased activity, improved social interaction, reduced stereotyping behavior, reversed sensorimotor gating dysregulation, and improved recognition memory and spatial memory impairment in MK-SI mice. In addition, SEP-856 can reduce the release of proinflammatory factors in the MK-SI model, promote the expression of BDNF and PSD-95 in the hippocampus, correct the Bax/Bcl-2 imbalance, turn on the PI3K/AKT/GSK-3β signaling pathway, and ultimately help the MK-SI mice\'s behavioral abnormalities. SEP-856 may play an antipsychotic role in MK-SI \"dual-hit\" model-induced SZ-like behavior mice by promoting synaptic plasticity recovery, decreasing death of hippocampal neurons, lowering the production of pro-inflammatory substances in the hippocampal region, and subsequently initiating the PI3K/AKT/GSK-3β signaling cascade.

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia.
METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates.
RESULTS: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78]).
CONCLUSIONS: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia.
METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits.
RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05).
CONCLUSIONS: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.