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1.
Acta Med Okayama ; 76(2): 195-202, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503448

RESUMO

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference -4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference -3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event.


Assuntos
Antipsicóticos , Delírio , Neoplasias , Idoso , Antipsicóticos/efeitos adversos , Delírio/induzido quimicamente , Delírio/etiologia , Humanos , Isoindóis , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Psico-Oncologia , Risperidona/efeitos adversos , Tiazóis
2.
J Clin Psychopharmacol ; 42(3): 238-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35489029

RESUMO

PURPOSE/BACKGROUND: Acute hyperkinetic movement disorders have been reported with the concomitant use of attention-deficit/hyperactivity disorder (ADHD) stimulants and antipsychotics in children and adolescents. We analyzed postmarketing reports of suspected acute hyperkinetic movement disorder associated with concomitant use of ADHD stimulants and antipsychotics. METHODS/PROCEDURES: We searched for postmarketing reports of acute hyperkinetic movement disorders associated with concomitant use of ADHD stimulants-antipsychotics in the US Food and Drug Administration Adverse Event Reporting System through December 6, 2019. PubMed and EMBASE were also searched for acute hyperkinetic movement reports with the concomitant use of ADHD stimulants-antipsychotics through January 13, 2020. FINDINGS/RESULTS: We identified 36 cases resulting in acute hyperkinetic movement disorder associated with the concomitant use of ADHD stimulants-antipsychotics, 19 of which were also identified in the medical literature. From an ADHD stimulant perspective, methylphenidate products accounted for the largest number of cases (n = 23 [64%]), followed by amphetamine products (n = 9 [25%]) and atomoxetine (n = 4 [11%]). From an antipsychotic perspective, all 36 cases were reported with second-generation antipsychotics, particularly risperidone (n = 20 [56%]). Most of the cases were reported in boys (n = 31 [86%]) aged 6 to 12 years (n = 27 [75%]). Approximately 53% of the cases reported a time to onset within 24 hours of the drug change. Acute dystonic reactions (n = 27 [75%]) were the most frequently reported movement disorder. IMPLICATIONS/CONCLUSIONS: As outlined in changes to the US prescribing information for all methylphenidate and risperidone products, health care professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.


Assuntos
Antipsicóticos , Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Adolescente , Anfetamina/uso terapêutico , Antipsicóticos/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Interações Medicamentosas , Humanos , Hipercinese/induzido quimicamente , Hipercinese/tratamento farmacológico , Masculino , Metilfenidato/efeitos adversos , Risperidona/efeitos adversos
3.
Psychopharmacol Bull ; 52(1): 53-56, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35342201

RESUMO

Stuttering, a disturbance in the normal fluency and time patterning of speech is usually developmental. In some cases, it is acquired, and causes include stroke, brain tumor, and trauma. Implicated in the causation of stuttering are overactive presynaptic dopamine systems in the region of the brain that modulate verbalization. It is a rare side effect of antipsychotic medications and has been reported with phenothiazines, clozapine, and risperidone. This is a report of a patient who developed stuttering when treated first with chlorpromazine and later with risperidone. Patient had a diagnosis of schizoaffective disorder and had been treated with antipsychotic medications including haloperidol, olanzapine, and paliperidone. He developed stuttering for the first time upon receiving intramuscular injections of chlorpromazine for treatment of agitation. The stutter improved and eventually resolved. He subsequently presented with a severe stutter when he was treated with risperidone. The stutter improved after risperidone was discontinued. It is speculated that drug-induced stuttering may be a manifestation of akathisia leading to noradrenergic and serotonergic mechanisms being implicated. It could be that either the cholinergic, dopaminergic or serotonergic systems are involved or that there is an imbalance of these systems that may be relevant.


Assuntos
Antipsicóticos , Gagueira , Antipsicóticos/farmacologia , Benzodiazepinas/uso terapêutico , Clorpromazina/efeitos adversos , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Humanos , Masculino , Risperidona/efeitos adversos , Gagueira/induzido quimicamente , Gagueira/tratamento farmacológico
4.
Adv Ther ; 39(5): 1993-2008, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35247186

RESUMO

INTRODUCTION: Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP. METHODS: We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs). RESULTS: Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94). CONCLUSIONS: Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.


Assuntos
Antipsicóticos , Demência , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Benzodiazepinas/uso terapêutico , Demência/complicações , Demência/tratamento farmacológico , Humanos , Metanálise em Rede , Uso Off-Label , Olanzapina/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etiologia , Fumarato de Quetiapina/uso terapêutico , Risperidona/efeitos adversos , Resultado do Tratamento
6.
Clin Perinatol ; 49(1): 1-14, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35209993

RESUMO

Delirium is likely present in the neonatal intensive care unit and has been largely unrecognized. There are several risk factors for delirium including illness severity, neurosedative exposure, and environmental disruptions that put infants at risk for delirium. Regular use of scoring systems should be considered to improve delirium detection. When identified, initial steps in management should include resolving underlying causes and implementation of standard nonpharmacologic measures. Mounting pediatric evidence suggests that the atypical antipsychotics, as well as the α-2 agonists, may be additionally beneficial in treating delirium as well as improving the ability to wean off other neurosedative medications.


Assuntos
Antipsicóticos , Delírio , Antipsicóticos/uso terapêutico , Benzodiazepinas/efeitos adversos , Criança , Delírio/induzido quimicamente , Delírio/diagnóstico , Delírio/terapia , Humanos , Lactente , Recém-Nascido , Olanzapina/uso terapêutico , Risperidona/efeitos adversos
7.
J Clin Psychopharmacol ; 42(2): 198-208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35020712

RESUMO

BACKGROUND: Psychotic disorders produce important morbidity and disability in children and adolescents. There have been few relevant treatment trials, encouraging assessment of research aimed at testing efficacy and safety of antipsychotics for juveniles. We aimed to compare the short- and long-term efficacy and safety of antipsychotics to treat psychotic disorders among children and adolescents. METHODS: Four major bibliographic databases (PubMed, MEDLINE, PsycINFO, and EMBASE) were searched for clinical trials of antipsychotics in children or adolescents, from database inception to May 2021. We searched for clinical trials comparing antipsychotics with control conditions for juvenile psychosis based on blinded review by 2 independent investigators (C.S.Y. and M.L.). We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and applied the Cochrane risk-of-bias tool to appraise study quality. One reviewer (A.B.) performed data abstraction which was confirmed by 2 independent, blinded reviewers (C.S.Y. and M.L.). Primary outcomes were scores rating psychosis symptoms and dichotomized retention in treatment protocols versus dropouts because of adverse events. Effect sizes were pooled using frequentist random-effects network meta-analysis modeling to generate summary rate ratios (RRs) and Cohen d standardized mean differences. RESULTS: Systematic searching generated 1330 unique records. Of these, short-term (n = 15, for 6 [3-12] weeks) and long-term (n = 10, for 12 [6-60] months) treatment trials involved 2208 (39.2% females; median age, 15.3 years), and 1366 subjects (35.0% females; median age, 15.6 years), respectively. Short-term reduction of psychosis scores ranked clozapine (d = -1.35; 95% confidence interval [CI], -1.97 to -0.73]), molindone (-1.22; 95% CI, -1.68 to -0.75), olanzapine (-1.12; 95% CI, -1.44 to -0.81), and risperidone (-0.93; 95% CI, -1.22 to -0.63) as the most effective agents. In longer-term treatment, only lurasidone was effective. Clozapine (RR, 12.8) and haloperidol (RR, 5.15) led to more all-cause and adverse event-related dropouts. There were few trials/drug (1 each for aripiprazole, asenapine, lurasidone, molindone, paliperidone, and ziprasidone, short term; aripiprazole, clozapine, haloperidol, lurasidone, and molindone, long-term). Heterogeneity and inconsistency were high, especially in long-term trials, without evidence of publication bias. CONCLUSIONS: Some antipsychotics were effective and tolerated short term, but longer-term evidence was very limited. The overall paucity of trials and of adequate controls indicates that more well-designed randomized controlled trials are required for adequate assessment of antipsychotic drug treatment for juveniles. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021232937.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Adolescente , Antipsicóticos/efeitos adversos , Criança , Feminino , Humanos , Masculino , Metanálise em Rede , Transtornos Psicóticos/tratamento farmacológico , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico
8.
J Clin Psychopharmacol ; 42(2): 133-139, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35001060

RESUMO

PURPOSE: This retrospective cohort study aimed at determining whether the daily administration pattern of risperidone influences time to rehospitalization in patients with schizophrenia. Previous studies have related more frequent dosing to poor medication adherence. This causes suboptimal disease control, which entails shorter times between hospital admissions. METHODS: We investigated admission records from 1 tertiary psychiatric hospital in Taiwan. Patients were included if they had a main diagnosis of schizophrenia or schizoaffective disorder and were receiving oral risperidone. The enrollment period was July 2001 to December 2016; we observed whether rehospitalization would occur in subsequent periods of 3-month, 6-month, and 1-year follow-ups. RESULTS: There were 1504 patients grouped by daily dosing frequency of oral risperidone. Most patients (95.9%) received 6 mg or less of risperidone per day. After adjustment for covariates, including daily total dosages of risperidone, it showed an independent association that more frequent dosing frequency of risperidone had higher hazard ratios (HRs) of rehospitalizations (in 1-year follow-up: 2 vs 1 dosing a day: HR, 1.566; 3 vs 1 dosing a day: HR, 3.010; 4 vs 1 dosing a day: HR, 4.305) and a significant trend of more possible rehospitalizations (Cochran-Armitage test for trend: P < 0.001) in 3-month, 6-month, and 1-year follow-up. CONCLUSIONS: Patients receiving more doses of risperidone per day are more likely to be readmitted within 1 year following last discharge, indicating poorer treatment outcomes for patients who receive more frequent doses.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Hospitalização , Humanos , Estudos Retrospectivos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico
11.
Asia Pac Psychiatry ; 14(1): e12469, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754473

RESUMO

OBJECTIVE: To investigate macroprolactinemia caused by antipsychotics and its clinical significance. METHODS: A total of 133 patients with schizophrenia were selected, all of whom were treated with either risperidone or amisulpride alone. The levels of total prolactin (T-PRL) and macroprolactin (MPRL) were measured before treatment as well as the second, fourth, and sixth weeks of treatment. RESULTS: After 2 weeks of treatment, 75.09% (100/133) of the patients met the diagnostic criteria for hyperprolactinemia, the incidence of macroprolactinemia was 43% (43/100), and MPRL levels were positively correlated T-PRL levels. CONCLUSION: Risperidone and amisulpride caused hyperprolactinemia and macroprolactinemia; thus, detection of MPRL in the clinical setting should be performed as this phenomenon appears early in treatment (the second week) and continues, that can avoid unnecessary examination and treatment for asymptomatic patients with macroprolactinemia.


Assuntos
Antipsicóticos , Hiperprolactinemia , Esquizofrenia , Amissulprida , Antipsicóticos/efeitos adversos , Humanos , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/epidemiologia , Prolactina , Risperidona/efeitos adversos , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico
12.
J Child Adolesc Psychopharmacol ; 32(1): 52-60, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34283934

RESUMO

Objectives: The study investigates the risk of obesity for young children prescribed an atypical antipsychotic (AAP) for 6 months or more. AAPs are associated with risk of obesity. They are used in children for a variety of psychiatric conditions and are often prescribed off-label. Long-term risk of obesity in this age group is unknown as most studies are short-term investigations and generally combine younger children with adolescents and adults. Methods: A retrospective cohort of children, 10 years old or younger, prescribed either an AAP or selective serotonin reuptake inhibitor (SSRI) for 6 months or more were followed for up to 9.5 years. The primary endpoint was the body-mass index (BMI) reaching the 95th percentile. Results: One thousand six hundred fifty-five patients met inclusion criteria. One thousand one hundred eighteen patients were prescribed an AAP and 537 were prescribed an SSRI: 1152 (74.5%) patients were male and mean (standard deviation) age was 7.9 [1.90] years at study entry. Median follow-up was 3.58 years for the AAP cohort and 3.28 years for the SSRI cohort (p = 0.02). After adjusting for baseline demographic variables, BMI, and other concomitantly prescribed medications, children prescribed AAPs for 6 months or longer were twice as likely to become obese compared with children prescribed SSRIs (adjusted hazard ratio [HR] 2.06 [95% confidence interval; CI 1.60-2.66], p < 0.0001). Further stratification by AAP revealed that the obesity risk for patients prescribed aripiprazole was 34% greater than for those prescribed risperidone (adjusted HR 1.34 [95% CI 1.01-1.78], p = 0.0033). Conclusions: The risk of obesity for young children prescribed an AAP for 6 months or more is approximately double that of children prescribed an SSRI. The risk of obesity is greater with aripiprazole than risperidone in the first year. Prescribers should consider the risk of obesity when prescribing AAPs and consider alternative treatment modalities in this vulnerable patient population.


Assuntos
Antipsicóticos , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Estudos Retrospectivos , Risperidona/efeitos adversos
13.
Int Clin Psychopharmacol ; 37(3): 92-101, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35258035

RESUMO

This study aimed to investigate the efficacy and safety of antitumor necrosis factor-alpha (TNF-α) therapy using adalimumab in patients with chronic schizophrenia. This is a randomized, double-blind, placebo-controlled clinical trial carried out at Roozbeh Hospital (Tehran, Iran) from June 2020 to October 2021. The patients were randomly divided into two parallel adalimumab + risperidone and placebo + risperidone groups. Participants in the intervention group received adalimumab subcutaneous injection (40 mg) by pen-injector at weeks 0 and 4. Using the Positive and Negative Symptoms Scale (PANSS), patients' positive and negative symptoms were assessed at weeks 0, 4, and 8. Forty patients (20 in each group) were included. PANSS total (t = 4.43, df = 38, P < 0.001), negative (t = 2.88, df = 38, P = 0.006), and general psychopathology (t = 4.06, df = 38, P < 0.001) scores demonstrated a significantly greater decline in adalimumab compared with the placebo group from baseline study endpoint. However, improvement of PANSS positive subscale scores showed no significant difference from the baseline study endpoint. There was no significant between-group difference regarding levels of C-reactive protein, interleukin (IL)-1ß, TNF-α, IL-6, and IL-8 at baseline and also at the week 8 visit (P > 0.05 for all). The current study found adalimumab adjunctive therapy effective in treating schizophrenia, particularly its negative and general psychopathology symptoms, with no side effects.


Assuntos
Antipsicóticos , Esquizofrenia , Adalimumab/efeitos adversos , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Irã (Geográfico) , Escalas de Graduação Psiquiátrica , Risperidona/efeitos adversos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Resultado do Tratamento
14.
Pak J Pharm Sci ; 34(5(Special)): 2053-2057, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34862873

RESUMO

To investigate the efficacy and safety of olanzapine, aripiprazole, and risperidone in the treatment of mental and behavioral symptoms of Alzheimer's Disease. A retrospective analysis was performed on the clinical data of 126 patients with Alzheimer's Disease from February 2018 to February 2020. The patients were divided into group A (aripiprazole, n=44), group B (olanzapine, n=42) and group C (risperidone, n=40) based on the treatment method. Remarkably differences at different time points among the three groups were observed (P<0.05). Significant differences in the Positive and Negative Syndrome Scale scores of different time points and cross-group comparison among the three groups were detected (P<0.05). The time-point comparison of BEHAVE-AD scores among the three groups indicated a remarkable difference (P<0.05). After 4 weeks of treatment, the Positive and Negative Syndrome Scale and BEHAVE-AD scores of group A were lower than those of groups B and C (P<0.05). The total incidence of adverse reactions in group A was remarkably lower than in groups B and C (P<0.05). Olanzapine, aripiprazole and risperidone are effective in treating Alzheimer's disease and aripiprazole, with a better safety profile and fewer adverse reactions, is more suitable for elderly patients.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Feminino , Humanos , Masculino , Olanzapina/efeitos adversos , Estudos Retrospectivos , Risperidona/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
Cochrane Database Syst Rev ; 12: CD013304, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918337

RESUMO

BACKGROUND: Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials have yielded negative results and effectiveness may be outweighed by harms. OBJECTIVES: To assess the efficacy and safety of antipsychotics for the treatment of agitation and psychosis in people with Alzheimer's disease and vascular dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid Sp), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register, and the International Clinical Trials Registry Portal on 7 January 2021. Two review authors independently screened the title and abstract of the hits, and two review authors assessed the full text of studies that got through this screening. SELECTION CRITERIA: We included randomised, placebo-controlled, parallel-arm trials comparing the effects of antipsychotics and placebo for the treatment of agitation or psychosis in people with dementia due to Alzheimer's disease or vascular dementia, or both, irrespective of age, severity of cognitive impairment, and setting. (The majority of) participants had to have clinically significant agitation (including aggression) or psychosis or both at baseline. We excluded studies about antipsychotics that are no longer available in the USA or EU, or that are used for emergency short-term sedation. We also excluded head-to-head trials and antipsychotic withdrawal trials. DATA COLLECTION AND ANALYSIS: The primary outcomes were (1) reduction in agitation or psychosis in participants with agitation or psychosis, respectively at baseline, and (2) the number of participants with adverse events: somnolence, extrapyramidal symptoms, any adverse event, any serious adverse event (SAE), and death. Two review authors independently extracted the necessary data and assessed risk of bias with the Cochrane risk of bias tool. We calculated the pooled effect on agitation and psychosis for typical and atypical antipsychotics separately, and the pooled risk of adverse effects independent of the target symptom (agitation or psychosis). We used RevMan Web for the analyses. MAIN RESULTS: The search yielded 8233 separate hits. After assessing the full-text of 35 studies, we included 24 trials that met the eligibility criteria. Six trials tested a typical antipsychotic, four for agitation and two for psychosis. Twenty trials tested an atypical antipsychotic, eight for agitation and 12 for psychosis. Two trials tested both drug types. Seventeen of 26 comparisons were performed in patients with Alzheimer's disease specifically. The other nine comparisons also included patients with vascular dementia or mixed dementia. Together, the studies included 6090 participants (12 to 652 per study). The trials were performed in institutionalised, hospitalised and community-dwelling patients, or a combination of those. For typical antipsychotics (e.g. haloperidol, thiothixene), we are uncertain whether these drugs improve agitation compared with placebo (standardised mean difference (SMD) -0.36, 95% confidence interval (CI) -0.57 to -0.15, 4 studies, n = 361); very low-certainty evidence, but typical antipsychotics may improve psychosis slightly (SMD -0.29, 95% CI -0.55 to -0.03, 2studies, n= 240; low-certainty evidence) compared with placebo. These drugs probably increase the risk of somnolence (risk ratio (RR) 2.62, 95% CI 1.51 to 4.56, 3 studies, n = 466; moderate-certainty evidence) and increase extrapyramidal symptoms (RR 2.26, 95% CI 1.58 to 3.23, 3 studies, n = 467; high-certainty) evidence. There was no evidence regarding the risk of any adverse event. The risks of SAEs (RR 1.32, 95% CI 0.65 to 2.66, 1 study, n = 193) and death (RR 1.46, 95% CI 0.54 to 4.00, 6 studies, n = 578) may be increased slightly, but these estimates were very imprecise, and the certainty was low. The effect estimates for haloperidol from five trials were in line with those of the drug class. Atypical antipsychotics (e.g. risperidone, olanzapine, aripiprazole, quetiapine) probably reduce agitation slightly (SMD -0.21, 95% CI -0.30 to -0.12, 7 studies, n = 1971; moderate-certainty evidence), but probably have a negligible effect on psychosis (SMD -0.11, 95% CI -0.18 to -0.03, 12 studies, n = 3364; moderate-certainty evidence). These drugs increase the risk of somnolence (RR 1.93, 95% CI 1.57 to 2.39, 13 studies, n - 3878; high-certainty evidence) and are probably also associated with slightly increased risk of extrapyramidal symptoms (RR 1.39, 95% CI 1.14 to 1.68, 15 studies, n = 4180; moderate-certainty evidence), serious adverse events (RR 1.32, 95% CI 1.09 to 1.61, 15 studies, n= 4316; moderate-certainty evidence) and death (RR 1.36, 95% CI 0.90 to 2.05, 17 studies, n= 5032; moderate-certainty evidence), although the latter estimate was imprecise. The drugs probably have a negligible effect on the risk of any adverse event (RR 1.05, 95% CI 1.02 to 1.09, 11 studies, n = 2785; moderate-certainty evidence). The findings from seven trials for risperidone were in line with those for the drug class. AUTHORS' CONCLUSIONS: There is some evidence that typical antipsychotics might decrease agitation and psychosis slightly in patients with dementia. Atypical antipsychotics reduce agitation in dementia slightly, but their effect on psychosis in dementia is negligible. The apparent effectiveness of the drugs seen in daily practice may be explained by a favourable natural course of the symptoms, as observed in the placebo groups. Both drug classes increase the risk of somnolence and other adverse events. If antipsychotics are considered for sedation in patients with severe and dangerous symptoms, this should be discussed openly with the patient and legal representative.


Assuntos
Doença de Alzheimer , Antipsicóticos , Demência Vascular , Transtornos Psicóticos , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/efeitos adversos , Demência Vascular/tratamento farmacológico , Humanos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risperidona/efeitos adversos
16.
Drug Des Devel Ther ; 15: 4371-4382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703212

RESUMO

INTRODUCTION: This open-label, one-sequence study evaluated the steady-state comparative bioavailability of risperidone in situ microimplants (ISM®) and oral risperidone in patients stabilized on oral risperidone treatment. METHODS: Repeat oral administration of once daily 4 mg risperidone for 7 days was followed by 4 monthly (once every four weeks) intramuscular (IM) doses of risperidone ISM 100 mg. Mean steady-state concentration versus time profiles for risperidone, 9-OH risperidone, and risperidone active moiety was characterized. RESULTS: A total of 104 subjects were enrolled, 81 were included in the safety population and 58 completed the study. Intersubject variability for the steady-state concentrations versus time profiles for risperidone active moiety presented a greater variability range for oral risperidone versus risperidone ISM (% coefficient of variation [CV] range: 40-65% and 38-52%, respectively). Minimum plasma concentration at steady-state (Cmin, ss) and fluctuation in plasma concentrations (Fluc) of risperidone active moiety after risperidone ISM administration met bioequivalence criteria compared to the reference oral risperidone (geometric mean ratio [GMR] = 1.09 and 0.96, respectively; both 90% CIs were within 0.80-1.25). Area under the curve during the dosing interval (AUCtau), maximum plasma concentration at steady-state (Cmax, ss) and average plasma concentration (Cave) were only slightly higher (GMR [90% CI] = 1.25 [1.16-1.34], 1.17 [1.08-1.27], and 1.25 [1.16-1.34], respectively). Overall, once daily oral risperidone 4 mg and once monthly IM risperidone ISM 100 mg were generally safe and well tolerated in the participating subjects with schizophrenia previously stabilized with oral risperidone. CONCLUSION: The rapid release of risperidone ISM allows the achievement of the desired levels similar to those observed at the steady-state after oral risperidone treatment. Therefore, direct switch after 24 hours from the last oral risperidone dose to risperidone ISM treatment can be done in schizophrenia patients with no time lag, maintaining steady-state levels of the active moiety throughout treatment and without the need for oral risperidone supplementation or loading doses.


Assuntos
Antipsicóticos/administração & dosagem , Risperidona/administração & dosagem , Esquizofrenia/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Preparações de Ação Retardada , Implantes de Medicamento , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Risperidona/efeitos adversos , Risperidona/farmacocinética , Equivalência Terapêutica , Adulto Jovem
17.
Psychiatry Res ; 305: 114246, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34717208

RESUMO

Fentanyl, a highly potent synthetic opioid, is a major cause of overdose deaths in the United States and worldwide. Urine drug immunoassay tests that include fentanyl in their drug panel are the common screening tool. However, false positive results may compromise test accuracy and cause grave clinical outcomes. In this preliminary report we describe 3 cases of patients with schizophrenia, who are treated with long-term injectable risperidone (Risperdal Consta) and were false positively screened for fentanyl by a rapid commercial screening kit. This finding warrants clinical attention to the possibility of inaccurate results regarding fentanyl misuse in multiple clinical settings.


Assuntos
Overdose de Drogas , Esquizofrenia , Analgésicos Opioides/uso terapêutico , Fentanila/farmacologia , Fentanila/uso terapêutico , Humanos , Risperidona/efeitos adversos , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Estados Unidos
18.
J Prev Alzheimers Dis ; 8(4): 520-533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34585228

RESUMO

OBJECTIVES: To evaluate the comparative efficacy, safety, tolerability, and effectiveness of atypical antipsychotics (AAPs) for the treatment of dementia related psychosis (DRP) in older adults. METHODS: In this systematic literature review (SLR), we qualitatively synthesized evidence on the comparative efficacy (based on neuropsychiatric inventory), tolerability (weight gain), and safety (cerebrovascular adverse events [CVAE], cardiovascular events, mortality, somnolence, extrapyramidal symptoms [EPS]) of AAPs used to treat DRP. We also assessed effectiveness based on all-cause discontinuations and discontinuations due to lack of efficacy or adverse events (AE). Published articles from through March 2021 from PubMed, EMBASE, PsycINFO, and Cochrane databases evaluated. We included double-blind, active-comparator/placebo-controlled randomized trials, open-label trials, and observational studies. RESULTS: This qualitative synthesis included 51 eligible studies with sample size of 13,334 and mean age of 79.36 years. Risperidone, olanzapine, quetiapine, and aripiprazole demonstrated numerically small improvement in psychotic symptoms among patients with DRP. Somnolence was the most reported AE for all the AAPs, with weight gain and tardive dyskinesia more common with olanzapine and risperidone, respectively. These AAPs are associated with falls, EPS, cognitive declines, CVAE, and mortality. Aripiprazole and olanzapine had lower odds of discontinuation due to lack of efficacy, with olanzapine having greater discontinuation odds due to AEs. CONCLUSION: This SLR demonstrated that AAPs used off-label to treat DRP are associated with small numerical symptom improvement but with a high risk of AEs, including cognitive decline and potentially higher mortality. These results underscore the need for new treatments with a favorable benefit-risk profile for treating DRP.


Assuntos
Antipsicóticos , Aripiprazol , Demência/complicações , Olanzapina , Transtornos Psicóticos/tratamento farmacológico , Risperidona , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Aripiprazol/efeitos adversos , Aripiprazol/uso terapêutico , Humanos , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Risperidona/efeitos adversos , Risperidona/uso terapêutico
19.
Transl Psychiatry ; 11(1): 458, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482368

RESUMO

A growing number of studies have shown that brain-derived neurotrophic factor (BDNF) is associated with weight gain during antipsychotic treatment in schizophrenia patients. However, there is still a lack of research results in the initial stage of antipsychotic treatment. This study aimed to evaluate the relationship between weight gain caused by risperidone monotherapy for 12 weeks and BDNF level in antipsychotic-naive and first-episode (ANFE) patients with schizophrenia, and we hypothesize that this may depend on BDNF Val66Met gene polymorphism. In a 12-week longitudinal trial, 225 ANFE patients were enrolled and treated with risperidone. Body weight was measured at baseline and during the 12-week follow-up. After treatment, the average weight of ANFE patients increased by 2.6 kg. Furthermore, we found that in patients with Val/Val genotype, the increase in serum BDNF levels was negatively correlated with risperidone-induced weight gain (r = -0.44, p = 0.008). Regression analysis showed that the baseline BDNF level was a predictor of weight gain after treatment (ß = -0.45, t = -3.0, p = 0.005). Our results suggest that the BDNF signaling may be involved in weight gain caused by risperidone treatment. Furthermore, the negative association between weight gain and increased BDNF levels during risperidone treatment in ANFE schizophrenia depends on the BDNF Val66Met polymorphism.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Fator Neurotrófico Derivado do Encéfalo/genética , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Ganho de Peso/genética
20.
BMC Med ; 19(1): 195, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34429113

RESUMO

BACKGROUND: Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). METHODS: We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. RESULTS: Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference - 5.83, 95% CI - 10.79 to - 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (- 6.01, 95% CI - 8.7 to - 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (- 7.89, 95% CI - 12.1 to - 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. CONCLUSION: IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.


Assuntos
Antipsicóticos , Transtorno Bipolar , Esquizofrenia , Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Humanos , Masculino , Palmitato de Paliperidona/efeitos adversos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico
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