RESUMEN
BACKGROUND: Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25]. METHODS: We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively. RESULTS: We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87-3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33-2.31) in the period following the APP prescribing. CONCLUSIONS: Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.
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Antipsicóticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hiperprolactinemia , Servicios de Salud Mental , Humanos , Adulto , Antipsicóticos/efectos adversos , Polifarmacia , Londres , Hiperprolactinemia/inducido químicamente , Hiperprolactinemia/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiologíaRESUMEN
Antipsychotic medications are used to treat many psychiatric conditions and are paramount for relapse prevention in patients with mental illnesses. Antipsychotic monotherapy (APM) is a commonly recommended approach, however there is no clear consensus on the use of antipsychotic polypharmacy (APP). A single-center retrospective review was conducted comparing readmission rates of behavioral health patients discharged on APP or APM between August 1st 2019 and July 31st 2021. The primary outcome was the one-year psychiatric readmission rate. Secondary outcomes included further readmission time frame stratification, olanzapine equivalent doses, and use of anticholinergic medications. The total readmission rate was 24.5% (24/98) in the APP group compared to 19.1% (107/560) in the APM group (p = 0.22). Patients discharged on APM were not found to have a statistically significant increase in readmission rate compared to patients discharged on APP. Further research is needed to assess the risks and benefits of APP.
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Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Polifarmacia , Esquizofrenia/tratamiento farmacológico , Alta del Paciente , Readmisión del PacienteRESUMEN
Antipsychotic polypharmacy (APP) lacks evidence of effectiveness in the care of schizophrenia or other disorders for which antipsychotic drugs are indicated, also exposing patients to more risks. Authors assessed APP prevalence and APP association with beneficiary race/ethnicity and payer among publicly-insured adults regardless of diagnosis. Retrospective repeated panel study of fee-for-service (FFS) Medicare, Medicaid, and dually-eligible white, black, and Latino adults residing in California, Georgia, Iowa, Mississippi, Oklahoma, South Dakota, or West Virginia, filling antipsychotic prescriptions between July 2008 and June 2013. Primary outcome was any monthly APP utilization. Across states and payers, 11% to 21% of 397,533 antipsychotic users and 12% to 19% of 9,396,741 person-months had some APP utilization. Less than 50% of person-months had a schizophrenia diagnosis and up to 19% had no diagnosed mental illness. Payer modified race/ethnicity effects on APP utilization only in CA; however, the odds of APP utilization remained lower for minorities than for whites. Elsewhere, the odds varied by race/ethnicity only in OK, with Latinos having lower odds than whites (odds ratio 0.76; 95% confidence interval 0.60-0.96). The odds of APP utilization varied by payer in several study states, with odds generally higher for Dual eligibles, although the differences were generally small; the odds also varied by year (lower at study end). APP was frequently utilized but mostly declined over time. APP utilization patterns varied across states, with no consistent association with race/ethnicity and small payer effects. Greater use of APP-reducing strategies are needed, particularly among non-schizophrenia populations.
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Antipsicóticos , Adulto , Anciano , Antipsicóticos/uso terapéutico , Humanos , Medicaid , Medicare , Polifarmacia , Estudios Retrospectivos , Estados UnidosRESUMEN
Antipsychotic polypharmacy (APP), as one maintenance treatment strategy in patients with schizophrenia, has gained popularity in real-world clinical settings. Risperidone (RIS) and clozapine (CLZ) are the most commonly prescribed second-generation antipsychotics, and they are often used in combination as APP. In this study, the pharmacokinetics of RIS and CLZ in rats were examined after co-administration to explore the reliability and rationality of co-medication with RIS and CLZ. In addition, the effects of CLZ on RIS metabolism and transport in vitro were investigated. The results illustrated that in the 7-day continuous administration test in rats, when co-administered with CLZ, the area under curve and peak concentrations of RIS were increased by 2.2- and 3.1-fold at the first dose, respectively, increased by 3.4- and 6.2-fold at the last dose, respectively. The metabolite-to-parent ratio of RIS was approximately 22% and 33% lower than those of RIS alone group at the first and last doses, respectively. Moreover, CLZ significantly increased RIS concentrations in the brain (3.0-4.8 folds) and cerebrospinal fluid (2.1-3.5 folds) in rats, which was slightly lower than the impact of verapamil on RIS after co-medication. Experiments in vitro indicated that CLZ competitively inhibited the conversion of RIS to 9-hydroxy-RIS with the inhibition constants of 1.36 and 3.0 µM in rat and human liver microsomes, respectively. Furthermore, the efflux ratio of RIS in Caco-2 monolayers was significantly reduced by CLZ at 1 µM. Hence, CLZ may affect the exposure of RIS by inhibiting its metabolism and P-glycoprotein-mediated transport. These findings highlighted that APP with RIS and CLZ might increase the plasma concentrations of RIS and 9-hydroxy-RIS beyond the safety ranges and cause toxic side effects.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Antipsicóticos/farmacocinética , Clozapina/farmacocinética , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Risperidona/farmacocinética , Animales , Antipsicóticos/toxicidad , Biotransformación , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Células CACO-2 , Clozapina/toxicidad , Interacciones Farmacológicas , Humanos , Mucosa Intestinal/metabolismo , Masculino , Microsomas Hepáticos/metabolismo , Ratas Sprague-Dawley , Medición de Riesgo , Risperidona/toxicidad , Distribución TisularRESUMEN
OBJECTIVES: In Africa, antipsychotic polypharmacy (APP) is increasing due to a high antipsychotic dose prescribing, repeated psychiatric hospitalization, uncontrolled psychotic symptoms, and greater side effect burden. Therefore, the aim of this review and meta-analysis is to assess the prevalence and correlates of APP among patients with schizophrenia in Africa. METHODS: A systematic search was performed from August 1 to 31, 2020, on PubMed, MEDLINE, Google Scholar, and Science Direct databases to select articles based on the inclusion criteria. Meta-Analysis of Observational studies in Epidemiology guidelines were employed. Cross-sectional observational studies that reported APP and/or its correlates in schizophrenia patients in English language published in peer-reviewed journals without time limits were included in the review. The quality of included articles was assessed using Newcastle-Ottawa quality assessment tool. Prevalence and correlates of APP were the outcome measures of this review and meta-analysis. Open Meta Analyst and RevMan version 5.3 software were used for meta-analysis. A random effect model was used to synthesize data based on the heterogeneity test. RESULTS: Six studies that involved 2154 schizophrenia patients met the inclusion criteria in this review and meta-analysis. The quality of included studies ranges from 6.5 to 10 based on the Newcastle-Ottawa quality assessment tool. The pooled prevalence of APP among patients with schizophrenia was 40.6% with 95% confidence interval: 27.6% to 53.7%. Depot first-generation antipsychotics and oral first-generation antipsychotics were the most commonly prescribed APP combinations. Socio-demographic, clinical, and antipsychotic treatment characteristics were significantly associated with APP. There was a wide variation in the correlates of APP assessed by studies and the way that association/correlations was determined and reported. CONCLUSIONS: APP is common and highly prevalent. Advanced age, male gender, longer duration of schizophrenia, hospital admission, and longer antipsychotic treatment were correlates of APP in Africa.
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Antipsicóticos/uso terapéutico , Polifarmacia/estadística & datos numéricos , Esquizofrenia/tratamiento farmacológico , Adulto , África/epidemiología , Estudios Transversales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Prevalencia , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors. METHODS: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form. RESULTS: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses (P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness (P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics (P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics (P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics (P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP. CONCLUSION: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.
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Antipsicóticos/uso terapéutico , Polifarmacia , Esquizofrenia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Envejecimiento , Antipsicóticos/farmacología , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Although antipsychotic monotherapy is recommended as the main treatment for schizophrenia, antipsychotic polypharmacy is not rare in practice. However, longitudinal data on antipsychotic polypharmacy in schizophrenia treatment are limited. METHODS: This longitudinal database study described antipsychotic polypharmacy in the treatment of schizophrenia in real-world settings in China and Japan. We retrieved information about antipsychotic treatment for schizophrenia from January 2010 to December 2014 from two hospital Electronic Medical Records databases in China and one claims database, Japan Medical Data Centre in Japan. Eligible patients had a diagnosis of schizophrenia (International Classification of Diseases, Tenth Revision F20.x) and at least one prescription for first or second generation antipsychotics. Antipsychotic polypharmacy was defined as having more than one antipsychotic medication overlapping for ⩾60 days. The Japan Medical Data Centre study cohort was further stratified by employees (insurance beneficiaries) and their dependents. RESULTS: The study cohorts comprised 11,961 patients from China and 25,034 (10,661 employee sub-cohort and 14,373 dependent sub-cohort) from 14 days Japan Medical Data Centre in Japan. Most patients were prescribed monotherapy (87.3% in China and 80.1% in Japan), of which oral second-generation antipsychotics were the majority (78.9% in China and 65.8% in Japan). The prevalence rate of antipsychotic polypharmacy was 12.7% in China and 19.9% in Japan (13.7% in employees vs 24.5% in dependents). The most common combinations were two oral antipsychotics. Combinations of more than two drugs were uncommon in China (0.3%) but were prescribed for 5.3% of patients in Japan. Among patients treated with monotherapy, 12.6/100 person-years (11.8%) in China and 9.6/100 person-years (11.0%) in Japan switched to antipsychotic polypharmacy during follow-up. Younger patients were more likely to switch to antipsychotic polypharmacy than older patents in all study cohorts. CONCLUSION: The observed rates of antipsychotic polypharmacy ranged from 12.7% in China to 19.9% in Japan. Switching from monotherapy to antipsychotic polypharmacy was most likely to occur in younger patients with schizophrenia.
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Antipsicóticos/uso terapéutico , Quimioterapia Combinada , Esquizofrenia , Adolescente , Adulto , Factores de Edad , Anciano , Antipsicóticos/clasificación , China/epidemiología , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Japón/epidemiología , Estudios Longitudinales , Masculino , Administración del Tratamiento Farmacológico/estadística & datos numéricos , Polifarmacia , Medición de Riesgo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiologíaRESUMEN
Antipsychotic polypharmacy (APP) is a common strategy despite guidelines advising against this practice. This article seeks to quantify the prevalence and correlates of APP using Medicaid Analytic eXtract files from 2003 to 2004. Nineteen percent of Medicaid recipients who received an antipsychotic were treated with APP. Individuals who received APP were more likely to be white, male, disabled, between the ages of 18-29, diagnosed with a psychotic disorder, and diagnosed with a higher number of psychiatric conditions. Geographic variation in APP rates was also observed. Quality improvement initiatives may help reduce APP for medically vulnerable patients.
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Antipsicóticos/uso terapéutico , Utilización de Medicamentos/estadística & datos numéricos , Trastornos Mentales/tratamiento farmacológico , Polifarmacia , Adolescente , Adulto , Antipsicóticos/economía , Bases de Datos Factuales , Quimioterapia Combinada , Femenino , Geografía , Humanos , Masculino , Medicaid , Trastornos Mentales/economía , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Although clinically widespread, scientific evidence for antipsychotic polypharmacy is still limited. Combining different drugs increases the potential for drug-drug interactions, enhancing the risk of adverse drug reactions. We aimed to unravel the potential pharmacokinetic interactions between risperidone (RIS) and perazine. METHODS: Using a therapeutic drug monitoring database containing plasma concentrations of RIS and its active metabolite [9-hydroxyrisperidone (9-OH-RIS)], we considered two groups: a group of patients under antipsychotic monotherapy with RIS (n = 40) and a group of patients that was comedicated with perazine (n = 16). Groups were matched for demographic characteristics and daily dosage of RIS. Plasma concentrations, concentrations corrected for the dose (C/D) of RIS, 9-OH-RIS and the active moiety (RIS + 9-OH-RIS), as well as the metabolic ratios of concentrations of 9-OH-RIS/RIS, were compared using nonparametric tests. RESULTS: All parameters other than plasma concentrations and the C/D ratio of 9-OH-RIS differed between groups. Median values for plasma concentrations of the active moiety and C/D of the active moiety were higher in the perazine group (P < 0.001 and P < 0.001, respectively). Differences were driven by variations in the plasma concentrations and C/D of RIS, which were higher in the perazine group (P < 0.001 and P < 0.001, respectively). Metabolic ratios were lower in the perazine group (P = 0.003). DISCUSSION: The coadministration of perazine in RIS-medicated patients leads to significantly higher plasma concentrations and C/D values of RIS and its active moiety, and a lower metabolic ratio, reflecting the cytochrome P450 (CYP) 2D6 phenotype. We suggest that the mechanism underlying the effect of perazine on RIS metabolism is based on an inhibition of CYP2D6 and CYP3A4 activity.
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Antipsicóticos/farmacología , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Trastornos Mentales/tratamiento farmacológico , Polifarmacia , Adulto , Antipsicóticos/sangre , Inhibidores del Citocromo P-450 CYP2D6/farmacología , Inhibidores del Citocromo P-450 CYP3A/farmacología , Interacciones Farmacológicas , Monitoreo de Drogas/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Palmitato de Paliperidona/sangre , Palmitato de Paliperidona/farmacología , Perazina/farmacología , Estudios Retrospectivos , Risperidona/sangre , Risperidona/farmacologíaRESUMEN
BACKGROUND: While antipsychotic medications are the mainstay of therapy for individuals with schizophrenia and psychotic disorders, their use is associated with adverse effects on physical health that require the attention and care of prescribers. METHODS: We used the ADAPTE process to adapt existing guideline recommendations from the National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the dosing of antipsychotics and antipsychotic polypharmacy, screening for adverse effects of antipsychotics, and management of metabolic and extrapyramidal side effects to the Canadian context. RESULTS: Prescribers are encouraged to use the lowest effective dose and to avoid the routine use of multiple antipsychotics. Scheduled monitoring of body mass index, waist circumference, blood pressure, glucose, lipids, prolactin, electrocardiograms, and extrapyramidal symptoms is recommended. Lifestyle interventions are recommended to mitigate antipsychotic-induced weight gain. Prescribers should follow Canadian guidelines on the treatment of obesity, dyslipidemia, and diabetes. Recommendations on antipsychotic drug choice are made for users particularly concerned about extrapyramidal symptoms. CONCLUSION: Careful monitoring and attention by prescribers may mitigate adverse effects associated with antipsychotic medications.
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Antipsicóticos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Síndrome Metabólico/inducido químicamente , Trastornos del Movimiento/etiología , Polifarmacia , Guías de Práctica Clínica como Asunto/normas , Esquizofrenia/tratamiento farmacológico , Canadá , Enfermedades Cardiovasculares/diagnóstico , Humanos , Síndrome Metabólico/diagnóstico , Trastornos del Movimiento/diagnósticoRESUMEN
OBJECTIVE: This study examined the use, demographic and clinical correlates of antipsychotic polypharmacy (APP) and its associations with treatment satisfaction and quality of life (QOL) in schizophrenia patients in China. METHOD: A total of 4239 patients in 45 nationwide Chinese psychiatric hospitals/centers were interviewed in 2012 in the third cross-sectional study, with the first two having been conducted in 2002 and 2006. Patients' socio-demographic and clinical characteristics, including psychopathology, side effects, satisfaction with treatment and QOL, were recorded using a standardized protocol and data collection procedure. RESULTS: The proportion of APP prescriptions in 2012 was 34.2%, which was significantly higher than the frequency of APP in 2002 (26.1%) and 2006 (26.4%) (p<0.001). Of patients on APP, 91.1% received two antipsychotics, 8.6% received three and 0.3% received four or more antipsychotics. Multiple logistic regression analyses revealed that compared to those on antipsychotic monotherapy, patients on APP and their families had lower satisfaction with treatment, had higher QOL in the mental domain, younger age of onset, more side effects, higher doses of antipsychotics and were more likely to receive first-generation antipsychotics and less likely to receive benzodiazepines (total R (2)=0.31, p<0.001). CONCLUSIONS: APP was found in about one in three schizophrenia patients. The prevalence of APP seems to have been increasing since 2002. Considering the increased frequency of drug-induced side effects and the patients' and their relatives' dissatisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of APP and its alternatives is warranted.
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Antipsicóticos/uso terapéutico , Satisfacción del Paciente/estadística & datos numéricos , Polifarmacia , Calidad de Vida/psicología , Esquizofrenia/tratamiento farmacológico , Adulto , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/epidemiologíaRESUMEN
BACKGROUND: This study was to investigate the prescribing patterns for antipsychotic drugs in elderly hospitalized patients with a diagnosis of schizophrenia or dementia at a psychiatric hospital in Taiwan from 2007 to 2012. This study also explored the predictors of antipsychotic polypharmacy (APP). METHODS: We collected patients' demographic data, including year of admission, age, gender, and length of hospital stay, and drug-related information. RESULTS: Second-generation antipsychotic (SGA) monotherapy was the most common type of therapy in both those with dementia and with schizophrenia, and quetiapine and risperidone were the most commonly prescribed drugs for these conditions, respectively. In late-life schizophrenia, 33.8% of the patients used first-generation antipsychotics (FGA) alone. Regarding APP, a combination of FGA and SGA and combinations of SGA were most commonly noted in schizophrenia patients and dementia patients, respectively. Overall, APP increased from 2007 to 2012. It was significantly more common in patients with dementia (odds ratio: 3.49, 95% confidence interval: 1.29-9.39, P = 0.014), less concurrent use of hypnotics and sedatives (odds ratio: 0.41, 95% confidence interval: 0.17-0.99, P = 0.046), and a higher-than-recommended dose of antipsychotic drugs (odds ratio: 4.98, 95% confidence interval: 2.75-9.02, P < 0.001). CONCLUSIONS: FGA are still commonly used for the late-life schizophrenia at our hospital. Given their potentially hazardous side effects, FGA must be employed with caution. The use of APP involving SGA increased over the 6 years of the study period, especially among patients with dementia. However, the use of SGA in dementia began to decline after the US Food and Drug Administration's 2005 warning about SGA being associated with increased mortality in dementia patients, which contrasts with the trends examined in this study. Further controlled trials exploring the efficacy, safety, and tolerability of APP in this population are warranted to gain an additional insight into this practice.
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Antipsicóticos/uso terapéutico , Demencia/tratamiento farmacológico , Hospitalización , Hospitales Psiquiátricos , Esquizofrenia/tratamiento farmacológico , Psicología del Esquizofrénico , Anciano , Anciano de 80 o más Años , Antipsicóticos/efectos adversos , Demencia/diagnóstico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fumarato de Quetiapina/efectos adversos , Fumarato de Quetiapina/uso terapéutico , Risperidona/efectos adversos , Risperidona/uso terapéutico , Esquizofrenia/diagnóstico , TaiwánAsunto(s)
Antipsicóticos/uso terapéutico , Polifarmacia , Ensayos Clínicos Controlados Aleatorios como Asunto , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Purpose Given the metabolic and neurologic side effects of antipsychotics and concerns about the increased risks associated with concomitant use, antipsychotic polypharmacy is a quality concern. This study assessed the operating characteristics of a Medicaid claims-based measure of antipsychotic polypharmacy. Methods A random sample from 10 public mental health clinics and 312 patients met criteria for this study. Medical record extractors were blind to measure status. We examined the prevalence, sensitivity, specificity, and positive predictive value (PPV) in Medicaid claims, testing nine different definitions of antipsychotic polypharmacy, including >14, >60, or >90 days concurrent use of ≥2 antipsychotic agents, each with allowable gaps of up to 0, 14, or 32 days in days' supply of antipsychotic medications. Results All Medicaid claims measure definitions tested had excellent specificity and PPV (>91%). Good to excellent sensitivity was dependent upon use of a 32-day gap allowance, particularly as duration of concurrent antipsychotic use increased. The proposed claims-based measure (90-day concurrent use of ≥2 or more antipsychotics, allowing for a 32-day gap) had excellent specificity (99.1%, 95%CI: 98.2-99.6) and PPV (90.9%, 95%CI: 83.1-95.7) with good sensitivity (79.4%, 95%CI: 70.4-86.6). The overall level of concordance between claims and medical record-based categorization of antipsychotic polypharmacy was high (96.4%, n = 301/312 clients, Cohen's K = 84.7, 95%CI: 75.9-93.5). Discrepant cases were reviewed, and implications are discussed. Conclusions Administrative claims data can be used to construct valid measures of antipsychotic polypharmacy.
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Antipsicóticos/uso terapéutico , Utilización de Medicamentos/normas , Revisión de Utilización de Seguros/normas , Medicaid/normas , Polifarmacia , Adolescente , Adulto , Antipsicóticos/efectos adversos , Niño , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.
RESUMEN
BACKGROUND: Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically review clinical interventions randomizing patients to reducing APP to APM versus continuing APP. METHODS: Systematic literature review searching Medline and Embase (latest search January 10, 2024) for randomized clinical trials (RCTs) studying interventions comparing individuals randomized to reduction of APP to APM with individuals continuing on APP. Two independent reviewers performed the literature screening, data extraction, and risk of bias assessment (RoB2). We performed random effects meta-analyses on the main outcome all-cause discontinuation/"acceptability" of the treatment strategy and secondary outcomes change in psychopathology, functional level, and side effects. RESULTS: The search identified 4672 hits, whereof 8 trials (N = 1204, 6 patient-level RCTs and 2 cluster-RCTs) were included, primarily in patients with schizophrenia. All trials were associated with high risk of bias. Compared to APP continuation, reduction to APM was associated with no significant change in all-cause discontinuation (studies = 6, n = 455, RR = 1.48, 95%CI = 0.74-2.95, I2 = 78 %) or inefficacy-related discontinuation (studies = 5, n = 351, RR = 1.60, 95%CI = 0.46-5.55, I2 = 70 %). Patients randomized to APM showed a trend towards greater reduction in psychopathology (studies = 5, n = 244, SMD = -0.24, 95%CI = -0.49, 0.02, I2 = 0 %) but no difference in functional level nor side effects. The cluster-RCTs found that interventions at the departmental level can result in lower rates of APP. CONCLUSION: Although switching patients from APP to APM can be a viable approach, too few RCTs exist on this important topic. Clinicians need to evaluate potential benefits and risks of APP and APM on an individual basis. PROSPERO REGISTRATION: CRD42022329955.
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Antipsicóticos , Polifarmacia , Ensayos Clínicos Controlados Aleatorios como Asunto , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Aceptación de la Atención de Salud , Evaluación de Resultado en la Atención de SaludRESUMEN
Objective Patients challenging refractory and residual psychotic symptoms have led to the concomitant use of combined antipsychotics, which was later introduced and labelled 'antipsychotic polypharmacy' (APP). Many clinicians have become somewhat hesitant to adjust psychotropic medication dosages, resulting in a higher dose and combination prescription of antipsychotics and only achieving modest success. This study examines and investigates clinician perspectives and the rationale for the prescription of antipsychotic polypharmacy. Methods A structured questionnaire designed to reflect 15 target-directed questions evaluating clinicians' attitudes and rationale on antipsychotic polypharmacy prescription was administered from November to December 2022. Information was obtained from inpatient and outpatient prescribers (psychiatric consultants) in two government-funded psychiatric facilities and outpatient clinics in the East Perth Metropolitan Area in Western Australia. Results After exclusion, a total of 45 participants' responses were analysed. These results suggest a higher frequency of questions relating to the prescription of APP based on previous prescribers' consultation and recommendation from a prior treating team; senior nurses' pressure impacting clinicians' decisions on APP perception; and the patient's risk of aggression impacting the clinician's rationale for the prescription of APP. Conclusions Clinicians' rationale and attitude towards the prescription of APP are mostly influenced by recommendations from prior treatment teams or consultations and patients' risk for aggression without compromising practice guidelines. Our findings also highlight the need to evaluate prescribers' attitudes and how it presents an opportunity to enhance patients' holistic outcomes.
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The aim of this study was to identify the factors associated with antipsychotic polypharmacy (APP), investigate whether APP could affect the risk of rehospitalization, and explore temporal trends in APP use. Schizophrenia patients discharged from the study hospital between 2006 and 2021 (n = 16,722) were included in the analysis. The logistic regression model was employed to determine the predictors significantly associated with APP use. Survival analysis was used to compare time to rehospitalization between APP and antipsychotic monotherapy (AMT). The temporal trend of APP use was analyzed using the Cochran-Armitage Trend test. In comparison with the patients (n = 10,909) who were discharged on AMT, those (n = 5,813) on APP were significantly more likely to be male gender, to receive LAIs, to take clozapine, to take anticholinergic agents, to have a greater number of previous hospitalizations, and to have a higher CPZ equivalent dose of antipsychotic prescription. The prescription rate of APP significantly increased from 18.4 % in 2006 to 44.9 % in 2021. Compared with AMT, APP was associated with more clozapine use, more LAI use, higher doses of antipsychotics, and an increased risk of rehospitalization. In addition, the prescription of APP continued to increase during the study period.
Asunto(s)
Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Masculino , Femenino , Antipsicóticos/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Clozapina/uso terapéutico , Polifarmacia , Alta del Paciente , Hospitales Psiquiátricos , TaiwánRESUMEN
Purpose: There is little evidence regarding the effects of dental status on body mass index (BMI) in inpatients with schizophrenia. Thus, we performed a cross-sectional study to explore the associations between the number of remaining teeth and BMI in Japanese inpatients with schizophrenia. Patients and Methods: We performed multiple regression analysis to assess the effects of potential predictors (age, sex, number of remaining teeth, number of antipsychotics prescribed, chlorpromazine equivalent dose, and antipsychotic type) on BMI in 212 inpatients with schizophrenia. We then compared the number of remaining teeth between inpatients with schizophrenia and the Japanese general population (3283 individuals) from the Japan Dental Diseases Survey 2016, using an analysis of covariance with age and sex as covariates. Results: Multiple regression analysis showed that the number of remaining teeth and the number of antipsychotics prescribed were significantly correlated with BMI (standardized regression coefficient = 0.201 and 0.235, respectively). In the analysis of covariance, inpatients with schizophrenia had significantly fewer remaining teeth compared with the Japanese general population (mean 14.8 [standard deviation: 10.9] vs mean 23.0 [standard deviation: 8.1]). Conclusion: These results suggested that tooth loss and antipsychotic polypharmacy affect BMI in inpatients with schizophrenia, and that inpatients with schizophrenia lose more teeth compared with the general population.
RESUMEN
Background: Nonesterified, total docosahexaenoic acid (DHA) and eicosapenaenoic acid (EPA) plasma levels were evaluated in patients with schizophrenia on different medications compared with healthy individuals using validated LC-MS/MS methods. Methods: Samples for nonesterified DHA and EPA assay were extracted in n-hexane-dichloromethane-isopropyl alcohol (2:1:0.1, V/V/V) and hydrolyzed at 90°C for 2 h before total DHA and EPA determination. Methods were validated in surrogate matrix and plasma. Results: These methods generated similar recovery for plasma (>89%) and surrogate matrix (>87%) and negligible matrix effects. Linearity, lower limit of quantification, accuracy, precision and stability were also validated. Conclusions: This study successfully determined DHA and EPA plasma levels in patients with schizophrenia and healthy individuals using validated LC-MS/MS methods. Therefore, nonesterified DHA and total EPA levels could be used as schizophrenia biomarkers.