Uso de antipsicóticos en los pacientes con demencia en España: comparación con la prescripción de los inhibidores de la acetilcolinesterasa y de la memantina, y análisis de las asociaciones / Use of antipsychotics in patients with dementia in Spain: Comparison with prescription of acetylcholinesterase inhibitors and memantine and analysis of associations

Objetivo: Se ha analizado la prevalencia de antipsicóticos, inhibidores de la acetilcolinesterasa (IACE) y memantina en pacientes con demencia en España y la influencia de estas asociaciones en su prescripción. Método: Estudio descriptivo, retrospectivo y transversal de la base BIFAP de 2017 en los mayores de 65 años con demencia. Se recogieron las prescripciones de antipsicóticos, los IACE y la memantina. Para los antipsicóticos también se recogieron, la duración del tratamiento y el tiempo desde el diagnóstico de demencia, al de prescripción. Resultados: Se recuperaron 1.327.792 sujetos, 89.464 (6,73%) con demencia. El 31,76% tuvieron prescritos antipsicóticos; los más frecuentes: quetiapina (58,47%), risperidona (21%) y haloperidol (19,34%). Las prescripciones de IACE y memantina fueron más frecuentes en los menores de 84 años y las de antipsicóticos en los mayores de 85 años (p<0,001). Los antipsicóticos se mantuvieron una media de 1.174,5 días. En el 26,4% de los casos se prescribieron aislados, OR: 0,61 (IC 95%: 0,59-0,62), en el 35,85% asociados a IACE, OR: 1,26 (IC 95%: 1,22-1,30) y en el 42,4% a memantina, OR: 1,69 (IC 95%: 1,62-1,78); p<0,000). Desde el diagnóstico de demencia transcurrieron de 461 días (±1.576,5) cuando se prescribieron aislados; 651 días (±1.574,25) asociados a IACE y 1.224 (±1.779) a memantina. Conclusiones: Una tercera parte de los pacientes con demencia tuvieron prescritos antipsicóticos, mayoritariamente atípicos, más frecuentemente en los mayores de 85 años y durante periodos prolongados. La prescripción de IACE y memantina se asoció al incremento del riesgo de uso de antipsicóticos, pero paradójicamente, a la prolongación del tiempo hasta su prescripción.(AU)

ObjectiveWe have analyzed the prevalence of antipsychotics in patients with dementia in Spain, their age distribution and the influence of treatment with IACEs and memantine on their prescription. Method: Descriptive, retrospective and cross-sectional study of the 2017 BIFAP database in over 65 years of age with dementia. Prescriptions of antipsychotics, IACEs and memantine were collected. For antipsychotics were also collected, the duration of treatment and time from dementia diagnosis to prescription. Results: A total of 1,327,792 subjects were retrieved, 89,464 (6.73%) with dementia. Antipsychotics were prescribed in 31.76%; by frequency: quetiapine (58.47%), risperidone (21%) and haloperidol (19.34%). Prescriptions of IACEs and memantine were clustered in those younger than 84 years and antipsychotics in those older than 85 (P<.001). Antipsychotics were maintained for a mean of 1174.5 days. In 26.4% of cases they were prescribed alone, OR 0.61 (95% CI: 0.59-0.62), in 35.85% associated with IACEs, OR 1.26 (95% CI: 1.22-1.30) and in 42.4% with memantine, OR 1.69 (95% CI: 1.62-1.78) (P<.000). From the diagnosis of dementia, 461 days (±1576.5) elapsed when isolated drugs were prescribed; 651 days (±1574.25) associated with IACEs and 1224 (±1779) with memantine. Conclusions: One third of patients with dementia were prescribed antipsychotics, mostly atypical, more frequently in those older than 85 years and for prolonged periods. IACEs and memantine were associated with the risk of antipsychotic prescription, but paradoxically, with prolonged time to onset.(AU)

Antipsychotics: Past, Present, and Future (Part 2): Article 2 of 3.

The history of antipsychotics in nursing facilities is one piece of a much larger, more complex puzzle. In many ways, it reflects the virtues and limitations of the entire health care system and those who provide care. None of the issues related to the use of antipsychotics are specific to these medications or to nursing facilities. After decades of effort to reduce unwarranted antipsychotics use, the current situation is still a work in progress. Many widely held assumptions and standard narratives, such as those about behavior, the place of medications in person-centered care, and the causes of inappropriate medication use are only partially correct. This second of three articles is not intended to discuss how to diagnose and manage behavior disorders or choose medications. Instead, it addresses the diverse perspectives and key players that have been involved and the results of their efforts. Ultimately, this will set the stage for specific recommendations (part 3) about learning from past efforts surrounding antipsychotics to identify more definitive and lasting improvements in the future. Part 1 of this series covered the history of attempts to influence use of medications-especially, antipsychotics-in nursing facility care of residents with behavior, mood, and cognitive issues. These improvement efforts can be described as fragmented, often ineffectual, and politically fraught. After decades of effort, and despite a significant reduction in the indiscriminate use of antipsychotics, psychotropics are still widely used in nursing facilities.1 The extent of improvement overall in managing individuals with dementia and other diverse behavior, mood, and cognitive issues is unclear.

The Impact of Clozapine Delay on Clinical Outcomes in Schizophrenia.

Background: Clozapine is the drug of choice indicated for treatment-resistant schizophrenia (TRS), but delays in initiation and underutilization might have affected its effectiveness in practice. In this study, we sought to examine the clinical outcomes of patients on clozapine treatment and if a delay in initiation was associated with poorer outcomes.Methods: This study was conducted at a tertiary mental health institution in patients aged 21 to 80 years from January 2016 to October 2019 who were on a stable dose of clozapine for 2 weeks. All patients were assessed using the Structured Clinical Interview for DSM-IV-TR (SCID-I) to ascertain diagnoses of schizophrenia and schizoaffective disorder. Each patient was assessed on the Positive and Negative Syndrome Scale (PANSS) and Social Occupational Functioning Assessment Scale (SOFAS). Past antipsychotic treatment trials were obtained from the medical records. Symptom remission status was defined using the PANSS symptom criteria proposed by Andreasen and colleagues in 2005. Functional remission was defined as a SOFAS score ≥ 60.Results: A total of 159 individuals with schizophrenia or schizoaffective disorder were recruited. The mean age of patients was 40.01 years, and the majority of patients were male (64.2%) and Chinese (85.5%). Thirty-seven patients (23.3%) achieved symptom remission, and 101 (63.5%) achieved functional remission. The median number of antipsychotic trials before clozapine initiation was 6 (interquartile range, 5-8). Patients in either symptom or functional remission had shorter time periods and fewer numbers of antipsychotic trials before first clozapine initiation. However, the trend was statistically significant only for median number of antipsychotic trials in the functional remission (P = .027) and symptom remission (P = .011) groups.Conclusion: Our study found a significant delay in the initiation of clozapine despite current guidelines indicating it for TRS. This delay might have contributed to the poorer clinical outcomes. Further research is needed to provide a clearer understanding of clozapine delay, evaluate its impact on outcomes, and find ways to improve access to clozapine.

Uso de antipsicóticos atípicos no tratamento da esquizofrenia no Sistema Único de Saúde do Brasil: estudo de coorte, 2008-2017 / Uso de antipsicóticos atípicos en el tratamiento de la esquizofrenia en el Sistema Único de Salud de Brasil: estudio de 2008 a 2017 / Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

Prescripción de antipsicóticos de depósito en la policlínica del Hospital Vilardebó / Prescripción de antipsychotics deposito in the polyclinic of the Hospital Vilardebó

Los medicamentos en su formulación de depósito son utilizados como una intervención para la adherencia cuando se dificulta el cumplimiento vía oral. Es frecuente la baja adherencia a los tratamientos por vía oral en las personas con enfermedades crónicas. Se llevó a cabo un estudio observacional, descriptivo de corte transversal, de una muestra aleatorizada de los pacientes que reciben antipsicóticos de depósito, asistidos en la Policlínica del Hospital Vilardebó en el año 2014. El objetivo fue describir las características de la población que tiene prescripto antipsicótico de depósito en la consulta ambulatoria y conocer los hábitos prescriptivos de estos para favorecer su uso racional. La patología psiquiátrica más prevalente fue la esquizofrenia con 56,4 %, donde se usó con más frecuencia la pipotiazina, siendo este más oneroso que el tratamiento con haloperidol y con un perfil de seguridad y efectividad similar. No se encontraron diferencias entre el uso de anticolinérgicos para los efectos extrapiramidales. Más de dos tercios de los pacientes (69,7 %) estuvieron con polifarmacia antipsicótica y un cuarto de los pacientes (24,7 %) con más de 2 antipsicóticos, a pesar de que en las pautas internacionales no recomiendan tratamientos que justifiquen el uso de más de dos antipsicóticos, dado que no existe evidencia que avale esta práctica, además del riesgo aumentado de reacciones adversas. Un bajo porcentaje (20 %) recibió la medicación de depósito todos los meses del año, resultando de vital importancia evaluar en estudios posteriores las causas intervinientes.

Depot formulation drugs are used as an adherence intervention when oral adherence is difficult to achieve. Low adherence to oral drugs is commonly observed in people with chronic diseases. An observational, descriptive, cross-sectional study was carried out on a randomized sample of patients receiving depot antipsychotics, treated at Hospital Vilardebó Outpatient Clinic in 2014. The aim was to describe this population's characteristics and prescription habits at the clinic in order to promote rational use. The most prevalent disorder was Schizophrenia (56.4%); pipothiazine was the most frequently used drug. It is more expensive than haloperidol with similar safety and efficacy profiles. There was no difference in the use of anticholinergic drugs to prevent extrapyramidal side effects. More than two thirds of the patients (69.7%) received antipsychotic polypharmacy and a fourth of the patients (24.7%) received more than two antipsychotics in spite of the fact that international treatment guides do not recommend the use of more than two because of lack of benefit evidence and increased risk of adverse reactions. Only 20 % of the patients received the depot every month of the year, being of vital importance to evaluate in subsequent studies the intervening causes.

Changes of Mental State and Serum Prolactin Levels in Patients with Schizophrenia and Depression after Receiving the Combination Therapy of Amisulpride and Chloroprothixol Tablets.

OBJECTIVE: To investigate the changes in mental state and serum prolactin levels in patients with schizophrenia and depression after receiving the combination therapy of amisulpride and chloroprothixol tablets. METHODS: A total of 148 schizophrenic patients with depression were randomly divided into control group (N = 73) and study group (N = 75). The control group was treated with clopidothiol, and the study group was treated with amisulpride. Symptom scores, sleep quality, adverse reactions, therapeutic effects, prolactin, and progesterone levels, HAMD, PANSS, and PSP scores were compared between the two groups. RESULTS: The symptom scores of both groups were significantly reduced, but when compared to the control group, the symptom scores of the research group were significantly reduced more significantly (P < 0.05); serum GDNF levels of both groups were significantly increased, while serum NSE, IL-1, and MBP levels were significantly reduced (P < 0.05). However, the research group altered more substantially (P < 0.05) than the control group; the overall PSQI score of the research group was lower (P < 0.05) than the control group; and the incidence of adverse responses in the control and study groups was 12.3 percent and 4.0 percent. The research group had a lower rate of adverse responses (P < 0.05) than the control group, and the effective treatment of the control and research groups was 82.2 percent and 98.7%, respectively. The research group had a lower rate of adverse reactions (P < 0.05) than the control group, while the control and research groups' successful treatment rates were 82.2 percent and 98.7%, respectively. When compared to the control group, the research group had a greater treatment efficiency (P < 0.05); blood prolactin and progesterone levels were considerably lowered in both groups, but the reductions in the research group were more evident (P < 0.05). Both groups had considerably lower HAMD and PANSS scores, and both had significantly higher PSP scores, although the difference in the research group was more evident (P < 0.05). CONCLUSION: For people with schizophrenia and depression, a combination of amisulpride and chloroprothixol pills has a considerable effect. It can help patients with their clinical symptoms and sleep quality while also lowering their serum prolactin levels, which is favorable to their illness recovery. As a result, the combined treatment of amisulpride and chloroprothixol pills deserves to be promoted and used.

Alternative Routes of Administration of Clozapine.

Clozapine is the only antipsychotic with proven effectiveness in treatment-resistant schizophrenia. It is usually administered using commercially available oral tablets, but not all patients are willing or able to take medicines in this way. Orodispersible clozapine tablets are available from several manufacturers and may be useful where swallowing solid dosage forms is difficult, or as an aid to observe compliance. Liquid formulations of clozapine can be prepared extemporaneously or purchased commercially, but most preparations are suspensions (clozapine is poorly soluble) and patients may find them unpalatable. The administration of clozapine (suspension or crushed tablets) via enteral feeding tubes (predominantly nasogastric) has been reported both in medically unwell patients and in patients refusing clozapine. Enteral administration is likely to be superseded by intramuscular clozapine, which has recently been re-introduced and is being widely used in some countries. Successful use of this formulation in enforced treatment strategies has been described by several authors with good long-term outcomes when switched to oral treatment. Intramuscular clozapine has also been used in physically ill patients who are unable to take any form of enteral medication. Other methods of delivery (transdermal, nasal) are not yet commercially available, but offer promise of further treatment options for this group of seriously ill patients.

Traditional Chinese herbal medicine in treating amenorrhea caused by antipsychotic drugs: Meta-analysis and systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Amenorrhea caused by antipsychotic drugs is not uncommon in clinical practice, and various treatment strategies are used to treat the condition. Chinese herbal medicine has its own theory for amenorrhea caused by antipsychotic drugs and has developed its own medication methods. AIM OF THE STUDY: To review and conduct meta-analysis of the use of traditional Chinese herbal medicine in treatment of amenorrhea caused by antipsychotic drugs. MATERIALS AND METHODS: A search was conducted across seven Chinese electronic databases (the China National Knowledge Infrastructure (CNKI) database, the China Science and Technology Journal Database, the Wanfang Database, the SinoMed, the Foreign Medical Literature Retrieval Service(FMRS), the Chinese University of Hong Kong Library, the Airiti Library), and the following English databases: MEDLINE, PreMEDLINE, OLD MEDLINE、Publisher Supplied Citation in pubmed; JBI EBP Database, EBM Reviews, Embase, OVID Emcare, Ovid MEDLINE(R), Maternity & Infant Care Database(MIDIRS), APA PsycInfo in OVID, and Cochrane Database of Systematic Reviews (Cochrane Reviews), Database of Abstracts of Reviews of Effects (Other Reviews), Cochrane Central Register of Controlled Trials (Clinical Trials),The Cochrane Methodology Register (Method Studies), Health Technology Assessment Database (Technology Assessments), NHS Economic Evaluation Database (Economic Evaluations) in Cochrane Library; and four databases (Science Direct, ProQuest, Web of Science, and Scopus) in official website using common standards and inclusion/exclusion criteria. The remaining reports were used for preliminary studies. Due to inconsistencies in control groups, randomized controlled trials and articles that combined with other drugs were also excluded. This study is a META analysis of a single rate. RESULTS: Initial screening returned 912 potentially relevant publications in all databases. After subsequent filtering, a total of 18 articles were included in the analysis. The overall effectiveness for treatment amenorrhea caused by antipsychotic drugs using traditional Chinese herbal medicine was 0.91, with 95% confidence interval of 0.89-0.93. Notably in most studies, the time needed to achieve this level of effectiveness was relatively long, usually in excess of three months. Although a satisfactory verification of an improvement in menstrual cycling takes time, the long treatment duration is a downside. Our analysis revealed that the following Chinese herbal remedies were most common: Danggui (Angelica sinensis (Oliv.) Diels), Chuanxiong (Ligusticum striatum DC.), Taoren (Prunus persica (L.) Batsch), Honghua (Carthamus tinctorius L.), Gancao (Glycyrrhiza uralensis Fisch.), Fuling ((Fungus) Poria cocos (Schw.) Wolf), Baizhu (Atractylodes macrocephala Koidz.), Xiangfu (Cyperus rotundus L.), Chaihu (Bupleurum chinense DC.), Shudihuang (Rehmannia glutinosa (Gaertn.) DC.(Processed), Baishao (Cynanchum otophyllum C.K.Schneid.) CONCLUSIONS: Chinese herbal medicine can effectively treat amenorrhea caused by psychiatric drugs, although it takes a long time to achieve satisfactory effectiveness. More research is needed to better understand different aspects of Chinese herbal medicine use in treatment of this particular medical condition.

Adverse events after antipsychotic discontinuation: an individual participant data meta-analysis.

BACKGROUND: Adverse events can occur after antipsychotic discontinuation but evidence from antipsychotic drug trials is scarce. We aimed to estimate the occurrence of adverse events after discontinuing antipsychotics. METHODS: For this two-stage individual participant data meta-analysis, we searched the Yale University Open Data Access Project's database for randomised controlled trials of antipsychotics from database inception until May 6, 2021. We included placebo-controlled antipsychotic randomised controlled trials with individual participant data of participants (aged ≥ 18 years, of any sex and ethnicity) with schizophrenia, schizoaffective disorder, or bipolar disorder. Studies were excluded if treatment with antidepressants, lithium, or antiepileptic drugs was initiated as additive therapy at the start of the placebo phase. Starting from the screening or washout phase, we divided participants who were randomised to placebo into two groups: the discontinuation group (participants who discontinued prestudy antipsychotics at the start of the screening or washout phase) and control group (participants who did not take prestudy antipsychotics for at least 4 weeks before the start of the screening or washout phase). Participants were excluded from the discontinuation and control groups if they discontinued prestudy treatment with antidepressants, lithium, or antiepileptic drugs up to 4 weeks before baseline, received an antipsychotic as a tolerability test, or received a long-acting injection of an antipsychotic within 12 weeks before baseline. In the discontinuation group, individuals were excluded if they discontinued prestudy antipsychotic treatment more than 3 days before, or any day after, the start of screening or washout phase. The prespecified primary outcome was occurrence of at least one new somatic adverse event with an onset within 4 weeks after the start of the screening or washout phase. We implemented a generalised linear model that accounted for potential confounders, to estimate the effect of antipsychotic discontinuation. This study is registered with PROSPERO (CRD42021224350). FINDINGS: We identified 409 records of which 18 were eligible and included in the analysis. From these 18 studies, 692 individuals (242 [35·0%] women and 450 [65·0%] men) were eligible for the discontinuation group and 935 individuals (339 [36·3%] women and 596 [63·7%] men) were eligible for the control group (median age in both groups: 39 years [IQR 30-47]). New somatic adverse events occurred in 295 (43%) individuals in the discontinuation group and 293 (31%) individuals in the control group (OR 1·74; 95% CI 1·27-2·39; τ2=0·15; moderate strength of evidence). New psychiatric adverse events were also more frequent in the discontinuation group than the control group (OR 2·01; 95% CI 1·38-2·94). Longer duration of treatment before discontinuation (OR for doubling the duration of treatment: 1·08; 95% CI 1·01-1·14) was associated with a higher probability of new somatic adverse events after antipsychotic discontinuation, and tapered discontinuation (compared with abrupt discontinuation: 0·54; 0·32-0·91) and no history of somatic illness (compared with history of somatic illness: 0·63; 0·43-0·91) were associated with lower probabilities of new somatic adverse events after antipsychotic discontinuation. The risk of bias was moderate in 13 (72·2%) studies and serious in five (27·8%) studies. INTERPRETATION: We detected moderate evidence of emerging somatic adverse events after discontinuation of first-generation and second-generation antipsychotics, particularly after discontinuation of longer durations of treatment. Tapered discontinuation can mitigate the risk of emerging somatic adverse events after antipsychotic discontinuation. These findings have implications for the safety of treatment discontinuation and could be used for tailored treatment planning. FUNDING: German Research Foundation.

Incident infection during the first year of treatment - A comparison of clozapine and paliperidone palmitate long-acting injection.

BACKGROUND: To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI). METHOD: A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services. RESULTS: The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; p = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15-15.76, p = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related. CONCLUSION: Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.

Impact of drug-induced Parkinsonism and tardive dyskinesia on health-related quality of life in schizophrenia.

BACKGROUND: Both drug-induced Parkinsonism (DIP) and tardive dyskinesia (TD) have been shown to be associated with lower health-related quality of life (HRQOL) in schizophrenia, but few studies have examined their relative impact. AIMS: This study aimed to examine and compare the association of DIP and TD with HRQOL in schizophrenia. METHODS: In total, 903 patients with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). EuroQoL five-dimensional (EQ-5D-5L) utility scores were derived from PANSS scores via a previously validated algorithm and used as a measure of HRQOL. RESULTS: In total, 160 (17.7%) participants had only DIP, 119 (13.2%) had only TD, and 123 (13.6%) had both DIP and TD. HRQOL was lowest for participants with both DIP and TD, followed by only DIP group, only TD group, and highest in the group with neither condition. HRQOL scores differed significantly between the four groups, F(3, 892) = 13.724, p < 0.001, ηp2 = 0.044). HRQOL of participants having only DIP or both DIP and TD was significantly lower than those having neither condition. There was no significant interaction between the presence of DIP and TD on the association with HRQOL. CONCLUSIONS: DIP was the main antipsychotic-induced movement disorder associated with a poorer HRQOL in patients with schizophrenia. Therefore, clinicians should focus on prevention, detection, and effective management of DIP to optimize HRQOL in patients with schizophrenia.

Impact of schizophrenia relapse definition on the comparative effectiveness of oral versus injectable antipsychotics: A systematic review and meta-analysis of observational studies.

Although relapse is an important outcome to measure the effectiveness of schizophrenia treatment, no standard definition exists. This review aimed at identifying definitions and measurements of schizophrenia relapse in observational studies of long-acting injectables (LAIs) versus oral antipsychotics (OAPs) and at determining their impact on heterogeneity of comparative effectiveness estimates. A systematic review was conducted using MEDLINE and Embase (01 January 2010-11 November 2019 [date last searched]). Pragmatic searches of gray literature and snowballing were also conducted. Search outputs were screened independently by two assessors at first stage, and full-text of potentially eligible sources at second stage. For each retained source, definition and measurement of relapse, study methods, and comparative effectiveness estimates were extracted. Heterogeneity of estimates was assessed using I2 statistic with a threshold of 50% for substantial heterogeneity. Literature search yielded 543 sources and pragmatic searches, 21, of which 35 were eligible. Twelve definitions of relapse were found based on hospitalization/emergency department (ED) data (28 studies) or clinical assessment (5 studies). No definition was provided in five studies. According to quantitative analyses, in studies defining relapse as schizophrenia-related hospitalization and/or ED visits over 1-year follow-up, LAIs were significantly more effective than OAPs. For studies measuring relapse based on all-cause hospitalization, heterogeneity was too high for pooling; yet this definition is the most frequently found in pooled estimates published in the literature. Schizophrenia relapse definitions led to substantial heterogeneity of comparative effectiveness estimates of LAIs versus OAPs. Creating study subgroups based on relapse definition effectively reduces statistical heterogeneity.

Is There a Link between Oropharyngeal Microbiome and Schizophrenia? A Narrative Review.

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.

Pimavanserin augments the efficacy of atypical antipsychotic drugs in a mouse model of treatment-refractory negative symptoms of schizophrenia.

Negative symptoms are a core, pervasive, and often treatment-refractory phenotype of schizophrenia, one which contributes to poor functional outcome, ability to work, pursue educational goals, and quality of life, as well as caretaker burden. Improvement of negative symptoms in some patients with schizophrenia has been reported with some atypical antipsychotic drugs [AAPDs], but improvement is absent in many patients and partial in others. Therefore, more effective treatments are needed, and better preclinical models of negative symptoms are needed to identify them. Sub-chronic [sc] treatment of rodents with phencyclidine [PCP], a noncompetitive N-methyl-d-aspartate [NMDAR] antagonist, produces deficits in social interactions [SI] that have been widely studied as a model of negative symptoms in schizophrenia. Acute restraint stress [ARS] also provides a model of treatment-refractory negative symptoms [TRS] to AAPDs. By themselves, in sc-PCP mice, the AAPDs, risperidone, olanzapine, and aripiprazole, but not the selective 5-HT2AR inverse agonist, pimavanserin [PIM], rescued the SI deficit in sc-PCP mice, as did the combination of PIM with sub-effective doses of each of these AAPDs. These three AAPDs alone did not rescue SI deficit in sc-PCP+ 2 h-ARS mice, indicating these mice were treatment refractory. However, co-administration of PIM with any of the AAPDs significantly restored SI in these mice. PIM may be an effective adjunctive therapy for treating negative symptoms of schizophrenia in some patients who have failed to respond to AAPDs, but further studies are needed.

Association of Social Determinants of Health With Adherence to Second-generation Antipsychotics for People With Bipolar Disorders in a Medicaid Population.

BACKGROUND: About 7 million people, 2.8% of US adults, have bipolar disorder (BD). While second-generation antipsychotics (SGA) are indicated as acute and maintenance treatments for BD, therapeutic success requires medication adherence and reported nonadherence estimates to range as high as 60%. Identifying patient risk factors for nonadherence is important for reducing it. OBJECTIVE: The objective of this study was to quantify the associations of risk factors, including social determinants of health, with SGA nonadherence among patients with BD. METHODS: In this cross-sectional study of 2015-2017 MassHealth Medicaid data, we examined several definitions of adherence and used logistic regression to identify risk factors for nonadherence (medication possession ratio <0.8) among all adults aged 18-64 diagnosed with BD who could be followed for 12 months following SGA initiation. RESULTS: Among 5197 patients, the mean (±SD) age was 37.7 (±11.4) years, and 42.3% were men. Almost half (47.7%) of patients were nonadherent to SGAs when measured by medication possession ratio. The prevalence of nonadherence peaked at middle age for men and younger for women. Nonadherence was less common among Massachusetts' Department of Mental Health clients (odds ratio=0.60, 95% confidence limit: 0.48-0.74) and among those who used other psychotropic medications (odds ratios between 0.45 and 0.81); in contrast, increase in neighborhood socioeconomic stress was associated with increased odds of nonadherence. CONCLUSIONS/IMPLICATIONS: Adherence to SGA treatment is suboptimal among people with BD. Recognizing risk factors, including those related to social determinants of health, can help target interventions to improve adherence for people at high risk and has implications for adherence-based quality measures.

Prevalence and Appropriateness of Antipsychotic Prescribing in an Italian Prison: Is Everything Always Really Overprescribed?

PURPOSE/BACKGROUND: Although the prevalence of mental disorders in prisoners is known to be higher than in the general population, less is known about the antipsychotic (AP) prescribing rate in jail. The aim of this research was to investigate prevalence and appropriateness of AP prescription in an Italian prison to expand our understanding on this crucial area of clinical-forensic practice. METHODS/PROCEDURES: A cross-sectional (census day) design was used among male adults in the Parma Penitentiary Institutes (PPI). Sociodemographic, clinical and prescription data were collected from the PPI electronic clinical database management system. The AP prescribing appropriateness was examined in accordance with the therapeutic indications included in the Italian National Formulary. A descriptive statistical analysis was performed. FINDINGS/RESULTS: A total of 98 (14.1%) of 696 PPI prisoners were taking AP medications. Moreover, 90 (91.8%) of the 98 PPI participants were also taking other psychotropic medications concurrently. Quetiapine and olanzapine were the most common prescribed APs. Antipsychotic medications were most likely to be prescribed for off-label indications (74.4%). Less than one fifth of all AP prescriptions were for psychotic disorders. IMPLICATIONS/CONCLUSIONS: Antipsychotic medications are widely used in prison, often together with other psychotropic drugs. Considering their common adverse effects, it is crucial to longitudinally monitor their potential risk of metabolic, cardiovascular, and extrapyramidal symptoms and signs, as well as their early risk of mortality. Given the high prevalence of AP off-label prescription, the rationale for AP prescribing should be clearly documented and regularly reviewed within the prison by mental health professionals.