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1.
BMC Complement Altern Med ; 19(1): 352, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805998

RESUMO

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta and clinically manifested mainly with motor dysfunctions. Plants are rich source of medicinally important bioactive compounds and inhabitants of underdeveloped countries used plants for treatment of various ailments. Albizia lebbeck has been reported to possess antioxidant and neuroprotective properties that suggest the evaluation of its traditional therapeutic potential in neurodegenerative diseases. The aim of present study was to validate the traditional use of Albizia lebbeck (L.) and delineate its mechanism of action in PD. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD. METHODS: The haloperidol-induced catalepsy was adopted as experimental model of PD for in-vivo studies in wistar albino rats. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD. RESULTS: In-vivo studies revealed that Albizia lebbeck improved the motor functions and endurance as demonstrated in behavioral studies which were further supported by the rescue of endogenous antioxidant defense and reversal of ultrastructural damages in histological studies. System pharmacology approach identified 25 drug like compounds interacting with 132 targets in a bipartite graph that revealed the synergistic mechanism of action at system level. Kaemferol, phytosterol and okanin were found to be the important compounds nodes with prominent target nodes of TDP1 and MAPT. CONCLUSION: The therapeutic efficiency of Albizia lebbeck in PD was effectively delineated in our experimental and systems pharmacology approach. Moreover, this approach further facilitates the drug discovery from Albizia lebbeck for PD.


Assuntos
Albizzia/química , Doença de Parkinson Secundária , Extratos Vegetais , Animais , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Modelos Animais de Doenças , Haloperidol/efeitos adversos , Destreza Motora/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson Secundária/fisiopatologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
2.
Medicine (Baltimore) ; 98(45): e17863, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702651

RESUMO

RATIONALE: In the past decade, only a few studies have focused on simultaneous bilateral ulnar neuropathy. PATIENT CONCERNS: A 54-year-old Asian male who has suffered from paranoid schizophrenia for 2 years. He reported that flexion contracture occurring over his fourth and fifth fingers on both hands appeared since six months after he started taking the antipsychotic drug. The electromyogram revealed bilateral ulnar neuropathy with chronic axonal degeneration at the elbow level. McGowan classification was performed to evaluate the severity of the ulnar nerve injury, and the patient was diagnosed with a grade 3 injury on his left hand and a grade 2 injury on his right hand. DIAGNOSIS: Simultaneous bilateral ulnar neuropathy at the elbow, a complication caused by tardive dyskinesia in a patient under the high-dose, first-generation, antipsychotic drug. INTERVENTIONS: We consulted a psychiatrist to assist in adjusting the patient's kind of the antipsychotic drug and performed the anterior transposition of ulnar nerve to avoid nerve entrapment caused by tardive dyskinesia. OUTCOMES: Numbness of the palms continued to regress over the following 6 months after the anterior transposition of the ulnar nerve. Regression of the involuntary movements, including repeated bending of the elbows, and shaking of both feet, was noted from the patient but was incomplete. LESSONS: Two literatures concluded that parkinsonian rigidity is the main cause of simultaneous bilateral ulnar neuropathy by Sampath et al and Kurlan et al. Unlike the cases of stereotyped posture-caused neural compression reported previously, we inferred that repeated involuntary motion caused by first-generation antipsychotic drug might have been one of the causes of the patient's nerve compression.


Assuntos
Antipsicóticos/efeitos adversos , Haloperidol/efeitos adversos , Discinesia Tardia/induzido quimicamente , Neuropatias Ulnares/induzido quimicamente , Antipsicóticos/administração & dosagem , Relação Dose-Resposta a Droga , Haloperidol/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia Paranoide/tratamento farmacológico
3.
BMC Res Notes ; 12(1): 376, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262359

RESUMO

OBJECTIVE: Drugs for managing mental disorders can cause adverse drug reactions (ADRs) that have negative impacts on patients yet, in Malawi, epidemiological data on the drug-related problems are limited. This study assessed the prevalence and severity of ADRs in out-patients at Zomba Mental Hospital. RESULTS: Twenty-six of forty patients (65.0%) were taking haloperidol and 14 (35.0%) chlorpromazine. The commonest diagnosis was schizophrenia (n = 23, 57.5%) followed by epileptic psychosis (n = 4, 10.0%) and general psychosis (n = 4, 10.0%) with one of psychotic depression and one psychosis secondary to general medical condition. Comorbidities were also found with epilepsy being the commonest (n = 4, 10.0%). All patients reported at least one ADR of varying severity (mild, moderate and severe). Polydipsia was the most prevalent (24, 60.0%) followed by weight gain (20, 50.0%), spasm (15, 37.5%) and xerostomia (15, 37.5%). Some ADRs were gender specific and these included impotence (6/27, 29.6%) for males and menstrual changes (3/14, 21.4%) for females. Severe ADRs were more common in the older aged group (> 35 years 8.3% vs 7.1%), in males (11.1% vs 0.0%) and on chlorpromazine (14.3% vs 3.8%). Patients taking chlorpromazine and haloperidol are at risk of experiencing a wide range of ADRs with varying degrees of severity.


Assuntos
Antipsicóticos/efeitos adversos , Clorpromazina/efeitos adversos , Disfunção Erétil/diagnóstico , Haloperidol/efeitos adversos , Distúrbios Menstruais/diagnóstico , Polidipsia/diagnóstico , Espasmo/diagnóstico , Xerostomia/diagnóstico , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Clorpromazina/administração & dosagem , Estudos Transversais , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Feminino , Haloperidol/administração & dosagem , Hospitais Psiquiátricos , Humanos , Malaui , Masculino , Distúrbios Menstruais/etiologia , Distúrbios Menstruais/fisiopatologia , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Polidipsia/etiologia , Polidipsia/fisiopatologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Espasmo/etiologia , Espasmo/fisiopatologia , Ganho de Peso/efeitos dos fármacos , Xerostomia/etiologia , Xerostomia/fisiopatologia
5.
Cochrane Database Syst Rev ; 4: CD011408, 2019 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-31006114

RESUMO

BACKGROUND: Schizophrenia is a disabling serious mental illness that can be chronic. Haloperidol, one of the first generation of antipsychotic drugs, is effective in the treatment of schizophrenia but can have adverse side effects. The effects of stopping haloperidol in people with schizophrenia who are stable on their prescription are not well researched in the context of systematic reviews. OBJECTIVES: To review the effects of haloperidol discontinuation in people with schizophrenia who are stable on haloperidol. SEARCH METHODS: On 20 February 2015, 24 May 2017, and 12 January 2019, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers. SELECTION CRITERIA: We included clinical trials randomising adults with schizophrenia or related disorders who were receiving haloperidol, and were stable. We included trials that randomised such participants to either continue their current treatment with haloperidol or discontinue their haloperidol treatment. We included trials that met our selection criteria and reported usable data. DATA COLLECTION AND ANALYSIS: We independently checked all records retrieved from the search and obtained full reports of relevant records for closer inspection. We extracted data from included studies independently. All usable data were dichotomous, and we calculated relative risks (RR) and their 95% confidence intervals (95% CI) using a fixed-effect model. We assessed risk of bias within the included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: We included five randomised controlled trials (RCTs) with 232 participants comparing haloperidol discontinuation with haloperidol continuation. Discontinuation was achieved in all five studies by replacing haloperidol with placebo. The trials' size ranged between 23 and 87 participants. The methods of randomisation, allocation concealment and blinding were poorly reported.Participants allocated to discontinuing haloperidol treatment were more likely to show no improvement in global state compared with those in the haloperidol continuation group (n = 49; 1 RCT; RR 2.06, 95% CI 1.33 to 3.20; very low quality evidence: our confidence in the effect estimate is limited due to relevant methodological shortcomings of included trials). Those who continued haloperidol treatment were less likely to experience a relapse compared to people who discontinued taking haloperidol (n = 165; 4 RCTs; RR 1.80, 95% CI 1.18 to 2.74; very low quality evidence). Satisfaction with treatment (measured as numbers leaving the study early) was similar between groups (n = 43; 1 RCT; RR 0.13, 95% CI 0.01 to 2.28; very low quality evidence).No usable mental state, general functioning, general behaviour or adverse effect data were reported by any of the trials. AUTHORS' CONCLUSIONS: This review provides limited evidence derived from small, short-term studies. The longest study was for one year, making it difficult to generalise the results to a life-long disorder. Very low quality evidence shows that discontinuation of haloperidol is associated with an increased risk of relapse and a reduction in the risk of 'global state improvement'. However, participant satisfaction with haloperidol treatment was not different from participant satisfaction with haloperidol discontinuation as measured by leaving the studies early. Due to the very low quality of these results, firm conclusions cannot be made. In addition, the available studies did not report usable data regarding the adverse effects of haloperidol treatment.Considering that haloperidol is one of the most widely used antipsychotic drugs, it was surprising that only a small number of studies into the benefit and harm of haloperidol discontinuation were available. Moreover, the available studies did not report on outcomes that are important to clinicians and to people with schizophrenia, particularly adverse effects and social outcomes. Better designed trials are warranted.


Assuntos
Antipsicóticos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Haloperidol/efeitos adversos , Adulto , Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico
6.
Int J Med Mushrooms ; 21(4): 323-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002628

RESUMO

Haloperidol-induced catalepsy is an animal model of a psychotic disorder that may be associated with neurodegeneration and free radical damage. Auricularia polytricha is effective in both prevention and treatment of numerous types of neurological disorders. In the present study, anticataleptic activity of aqueous extract of A polytricha (AEAP) at different doses (400 and 600 mg/kg, respectively, p.o.) was studied using haloperidol-induced (1 mg/ kg, i.p.) catalepsy in rats. Repeated treatment with haloperidol (1 mg/kg, i.p.) on each other day for 15 days (days 5, 10, and 15) significantly induced catalepsy in rats. The effect of AEAP at different doses (400 and 600 mg/kg, p.o.) on levels of superoxide dismutase, catalase, and glutathione reductase as well as inhibition of lipid peroxidation in the forebrain region was assessed. After 15 days of treatment, AEAP (400 and 600 mg/kg) significantly inhibited haloperidol-induced catalepsy. Treatment with AEAP (400 and 600 mg/kg) exhibited significant elevation in the levels of superoxide dismutase, catalase, and glutathione reductase as well as lipid peroxidation in the forebrain region compared to the haloperidol-treated group. The study concludes that AEAP (400 and 600 mg/kg) significantly protects animals against haloperidol-induced catalepsy.


Assuntos
Basidiomycota/química , Catalepsia/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antipsicóticos/efeitos adversos , Catalepsia/induzido quimicamente , Modelos Animais de Doenças , Carpóforos/química , Haloperidol/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Água
8.
J Emerg Med ; 56(5): 484-490, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30745194

RESUMO

BACKGROUND: Rapid treatment of agitation in the emergency department (ED) is critical to avoid injury to patients and providers. Treatment with intramuscular antipsychotics is often utilized, but there is a paucity of comparative effectiveness evidence available. OBJECTIVE: The purpose of this investigation was to compare the effectiveness of droperidol, olanzapine, and haloperidol for treating agitation in the ED. METHODS: This was a retrospective observational study of adult patients who received intramuscular medication to treat agitation. Patients were classified based on the initial antipsychotic they received. The primary effectiveness outcome was the rate of additional sedation administered (rescue medication) within 1 h. Secondary outcomes included rescue sedation for the entire encounter and adverse events. RESULTS: There were 15,918 patients included (median age 37 years, 75% male). Rescue rates at 1 h were: 547/4947 for droperidol (11%, 95% confidence interval [CI] 10-12%), 988/8825 olanzapine (11%, 95% CI 10-12%), and 390/2146 for haloperidol (18%, 95% CI 17-20%). Rescue rates for the entire ED encounter were: 832/4947 for droperidol (17%, 95% CI 16-18%), 1665/8825 for olanzapine (19%, 95% CI 18-20%), and 560/2146 for haloperidol (26%, 95% CI 24-28%). Adverse events were uncommon: intubation (49, 0.3%), akathisia (7, 0.04%), dystonia (5, 0.03%), respiratory arrest (1, 0.006%), and torsades de pointes (0), with no significant differences between drugs. CONCLUSIONS: Olanzapine and droperidol lead to lower rates of rescue sedation at 1 h and overall, compared with haloperidol. There were no significant differences in major adverse events.


Assuntos
Antipsicóticos/efeitos adversos , Hipnóticos e Sedativos/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Droperidol/efeitos adversos , Droperidol/uso terapêutico , Serviço Hospitalar de Emergência/organização & administração , Feminino , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares , Masculino , Midazolam/uso terapêutico , Pessoa de Meia-Idade , Minnesota , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Estudos Retrospectivos
9.
Early Interv Psychiatry ; 13(3): 589-597, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29498481

RESUMO

AIM: Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy. METHODS: We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge. RESULTS: Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge. CONCLUSIONS: The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.


Assuntos
Algoritmos , Antipsicóticos/uso terapêutico , Internação Compulsória de Doente Mental , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Administração Oral , Adulto , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Clozapina/uso terapêutico , Quimioterapia Combinada , Feminino , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Injeções Intramusculares , Masculino , Metotrimeprazina/efeitos adversos , Metotrimeprazina/uso terapêutico , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/uso terapêutico , Estudos Retrospectivos , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Esquizofrenia/diagnóstico , Falha de Tratamento , Resultado do Tratamento
10.
Int J Neuropsychopharmacol ; 22(1): 71-82, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169628

RESUMO

Background: With the growing use of second-generation antipsychotics for the treatment of a spectrum of psychiatric illnesses in pregnancy, concerns have been raised about the long-term impact of these medications on offspring neurodevelopment. However, preclinical and clinical evidence on the lasting effects of prenatal antipsychotic exposure is still sparse. Methods: Risperidone, a widely used second-generation antipsychotic, and haloperidol, a representative first-generation antipsychotic, were administered to pregnant C57BL/6N mice from embryonic day 6 to 16. Behavioral tests, immunohistochemical staining, Golgi-Cox technique, and western blot were used to determine the effects of prenatal antipsychotic exposure on the plasticity of the dentate gyrus and related behavior in adult male mice. Results: Both prenatal haloperidol- and risperidone-exposed mice showed recognition memory deficits but had no anxiety-related behavior. In addition, both prenatal haloperidol and risperidone exposure impaired the proliferation and maturation of adult-born dentate granule cells. We found that haloperidol exposure decreased dendritic length of dentate granule cells, while risperidone had no effect. However, both drugs inhibited dendrite branching in granule cells. Haloperidol exposure also significantly reduced total spine density in the middle dendritic segment of dentate gyrus. Prenatally risperidone-exposed mice only displayed a loss in thin and mushroom spines of infrapyramidal blade of dentate gyrus. Collectively, prenatal haloperidol exposure exerted more robust negative effects than risperidone. Conclusion: These data provide evidence for the long-term programming effects of early-life exposure to antipsychotics on hippocampal plasticity and behavior.


Assuntos
Antipsicóticos/efeitos adversos , Giro Denteado/efeitos dos fármacos , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Giro Denteado/crescimento & desenvolvimento , Giro Denteado/patologia , Giro Denteado/fisiopatologia , Feminino , Haloperidol/efeitos adversos , Masculino , Memória/fisiologia , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/patologia , Neurônios/fisiologia , Gravidez , Distribuição Aleatória , Receptores de N-Metil-D-Aspartato/metabolismo , Risperidona/efeitos adversos
11.
Int Clin Psychopharmacol ; 34(2): 89-92, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30531551

RESUMO

One of the possible long-term consequences of antipsychotic-induced hyperprolactinemia is the development of pituitary tumors - prolactinomas. So far, two pharmacovigilance studies of spontaneous adverse event report databases have suggested an increased risk, whereas a longitudinal study carried out with risperidone showed no evidence of increased risk of tumors with mass effect. Besides, information on amisulpride and paliperidone is lacking. Thus, in this study, we aimed to analyze the European pharmacovigilance database (EudraVigilance) to shed light on this issue. We searched for all suspected spontaneous cases of pituitary tumors associated with antipsychotics in EudraVigilance up to 23 March 2017. To assess the association between pituitary tumor cases and each antipsychotic, we calculated the proportional reporting ratios. Among 4 964 866 events of all types recorded in EudraVigilance, we found 292 cases of pituitary tumors associated with antipsychotics. All atypical antipsychotics except clozapine fulfilled the criteria to generate a safety signal. The highest proportional reporting ratio values were found for amisulpride 51.57 (36.3-73.2), risperidone 21.83 (18.4-25.8), and paliperidone 19.95 (14.7-27.1). Sulpiride and haloperidol showed a higher risk among typical antipsychotics 12.4 (5.89-26.1) and 7.0 (4.35-11.3). Notably, we found that a mass effect was present in 16% of the cases. Besides, 18 cases occurred in patients aged below 18 years. Our analysis of the data in EudraVigilance confirms the safety signal detected by previous studies. Interestingly, for the first time, we show that the association seems to be the strongest for amisulpride and that a mass effect was present in around 16% of the cases.


Assuntos
Antipsicóticos/efeitos adversos , Neoplasias Hipofisárias/induzido quimicamente , Adolescente , Adulto , Idoso , Amissulprida/efeitos adversos , Criança , Bases de Dados Factuais , Feminino , Haloperidol/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Palmitato de Paliperidona/efeitos adversos , Farmacovigilância , Gravidez , Fumarato de Quetiapina/efeitos adversos , Estudos Retrospectivos , Risperidona/efeitos adversos , Sulpirida/efeitos adversos , Adulto Jovem
12.
Am J Emerg Med ; 37(8): 1422-1427, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30366744

RESUMO

BACKGROUND: Given the increasing number of patients with acute renal colic, the present study examined the analgesic effects of haloperidol with or without morphine in order to find an effective method with fewer side effects for pain reduction in these patients. METHOD: In the present randomized double-blind clinical trial study, patients with a pain severity score of above 3 were randomly divided into 2 equal groups: Group A received intravenous morphine and haloperidol, and Group B received intravenous morphine with normal saline. Pain severity was recorded at Times 0, 20, 40, and 60 min following the injections based on a visual pain analog scale (VPAS) from 0 to 10. RESULTS: A total of 140 patients were included in this study. A comparison of the recorded pain severity scores did not show a significant difference between the 2 study groups (P = 0.38). The mean heart rate, the mean systolic and diastolic blood pressures, and the mean incidence rate of nausea and vomiting were not significantly different between Group A and Group B. The frequency of extrapyramidal side effects was 4.3% in the haloperidol group, which was not significantly different from that of the other group. The frequency of extra analgesic requirement was not significantly different between the 2 groups (P = 0.05). CONCLUSION: In our patients with acute renal colic, haloperidol failed to reduce pain and the incidence of nausea or vomiting, while it caused extrapyramidal side effects. Therefore, the prescription of this medication for acute pains, especially in renal colic, is not recommended.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Haloperidol/administração & dosagem , Haloperidol/efeitos adversos , Cólica Renal/tratamento farmacológico , Dor Aguda/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Medição da Dor , Falha de Tratamento
13.
J Clin Psychiatry ; 80(1)2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30549494

RESUMO

OBJECTIVE: To investigate subgroup responses to long-acting injectable (LAI) medications haloperidol decanoate (HD) and paliperidone palmitate (PP) in a randomized controlled trial that found no difference between the treatments on the primary outcome of efficacy failure. METHODS: A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) enrolled 311 participants from March 2011 to July 2013 meeting DSM-IV-TR criteria for diagnoses of schizophrenia or schizoaffective disorder at risk of relapse due to medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for up to 2 years. A committee blinded to treatment assignment adjudicated efficacy failure on the basis of participants' meeting at least 1 of these criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, could not discontinue oral antipsychotic, discontinued assigned LAI due to inadequate therapeutic benefit, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses examined modification of treatment effects on efficacy failure by age, sex, race, substance abuse, baseline symptom severity, and baseline adherence. Mixed-effect linear models and analysis of covariance examined this modification on safety outcomes. RESULTS: An interaction between age and treatment (P = .009) revealed younger participants assigned HD had longer time to efficacy failure than those assigned PP. Interactions were not significant between treatment group and sex, race, substance use disorder, baseline symptom severity, or baseline adherence. An interaction of treatment and age on akathisia (P = .047) found an advantage for PP that was larger among younger persons. An advantage for HD on serum prolactin levels was larger among younger women (P = .033). CONCLUSIONS: Among younger persons, HD was associated with lower rates of efficacy failure than PP. Age effects on adverse effects were mixed. Age-related heterogeneity of antipsychotic treatment effects warrants further investigation and consideration in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01136772.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antipsicóticos/administração & dosagem , Haloperidol/análogos & derivados , Palmitato de Paliperidona/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Antipsicóticos/efeitos adversos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Feminino , Haloperidol/administração & dosagem , Haloperidol/efeitos adversos , Humanos , Injeções Intramusculares , Estimativa de Kaplan-Meier , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Palmitato de Paliperidona/efeitos adversos , Intervalo Livre de Progressão , Falha de Tratamento , Adulto Jovem
14.
N Engl J Med ; 379(26): 2506-2516, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30346242

RESUMO

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).


Assuntos
Antipsicóticos/uso terapêutico , Estado Terminal/psicologia , Delírio/tratamento farmacológico , Antagonistas de Dopamina/uso terapêutico , Haloperidol/uso terapêutico , Piperazinas/uso terapêutico , Tiazóis/uso terapêutico , Idoso , Antipsicóticos/efeitos adversos , Estado Terminal/mortalidade , Estado Terminal/terapia , Método Duplo-Cego , Feminino , Haloperidol/administração & dosagem , Haloperidol/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Insuficiência Respiratória/psicologia , Choque/psicologia , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Falha de Tratamento
15.
Cochrane Database Syst Rev ; 6: CD005594, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29920656

RESUMO

BACKGROUND: Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence. OBJECTIVES: Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects. SEARCH METHODS: We searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature. SELECTION CRITERIA: We included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients. DATA COLLECTION AND ANALYSIS: We examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes. MAIN RESULTS: We included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.No trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).No trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence). AUTHORS' CONCLUSIONS: There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Delírio/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Delírio/mortalidade , Feminino , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Hospitalização , Humanos , Masculino , Olanzapina , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto , Risperidona/efeitos adversos , Risperidona/uso terapêutico
16.
PLoS One ; 13(6): e0199028, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29898002

RESUMO

PURPOSE: To investigate the prevalence and risk factors of acquired long QT syndrome (LQTS) on admission to a general Intensive Care Unit (ICU), and to assess the risk of LQTS associated with prescribed medications. METHODS: Prospective observational, cross-sectional study approved by the Institutional Review Board. Between May 2014 and July 2016, 412 patients >18 years-old consecutively admitted to the ICU of a university hospital were included. LQTS was defined as a QT interval on the admission electrocardiogram corrected using Bazett's formula (QTc) >460 ms for men and >470 ms for women. All medications administered within 24 hours before admission were recorded. Logistic regression was used. RESULTS: LQTS prevalence was 27.9%. In LQTS patients, 70.4% had ≥ 1 LQTS-inducing drug prescribed in the 24 hours prior to ICU admission versus 70.4% in non-LQTS patients (p = 0.99). Bradycardia and Charlson morbidity index score are independent risk factors for LQTS. Haloperidol (OR 4.416), amiodarone (OR 2.509) and furosemide (OR 1.895) were associated with LQTS, as well as another drug not yet described, namely clopidogrel (OR 2.241). CONCLUSIONS: The LQTS is highly prevalent in critically ill patients, ICU patients are often admitted with LQTS-inducing medications, and patients with slow heart rate or with high Charlson comorbidity index should be evaluated for LQTS.


Assuntos
Amiodarona/efeitos adversos , Clopidogrel/efeitos adversos , Furosemida/efeitos adversos , Haloperidol/efeitos adversos , Síndrome do QT Longo/etiologia , Adulto , Idoso , Amiodarona/uso terapêutico , Clopidogrel/uso terapêutico , Estado Terminal , Estudos Transversais , Eletrocardiografia , Feminino , Furosemida/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Fatores de Risco
17.
Biomed Pharmacother ; 103: 879-888, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29710504

RESUMO

Due to the high prevalence of psychiatric disorders and the prevalent side effects produced by the antipsychotic drugs available, it is necessary to search for new therapeutic options. Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases. From this plant, some compounds, denominated galphimines, have been discovered and have shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the Ventral tegmental area. The objective of the present work was to evaluate the effect produced by the G. glauca extract, a Galphimine rich fraction (GRF), as well as the pure galphimines (G-A, G-B, and G-E) on behavioral models in mice. Products obtained from G. glauca were evaluated in the Haloperidol-induced catalepsy test and in the acute schizophrenia-like symptoms-induced with Ketamine (KET) in mice. Catalepsy was evaluated through the bar test, and schizophrenia-like symptoms, by means of the Open Field Test (OFT), Passive Avoidance Test (PAT), and the Forced Swimming Test (FST). The methanolic extract from G. glauca, GRF, and the pure galphimines were able to interact with the dopaminergic pathway and modify the behavioral response such as to potentiate the cataleptic effect induced with Haloperidol and to inhibit the behavior induced by KET in mice exposed to OFT, and FST. Moreover, the G. glauca extract and GRF were capable of blocking the cognitive decline that was induced with KET in mice (evaluated by PAT). Based on these results, it is possible to assume that part of the effect of G. glauca is due to the interaction of Galphimines with the dopaminergic and glutamatergic systems in vivo. It can be concluded that the products obtained from G. glauca potentiate the cataleptic effect induced with Haloperidol and show a protector effect on some of the symptoms generated by KET in mice (KET is capable of provoking halucinations in humans and psychosis-like behaviour in mice). With this basis, the metanolic extract from G. glauca, and the GRF are capable of blocking positive and cognitive symptoms associated with psychosis induced by KET. In addition, it could be suggested that the galphimines are responsible for the inhibition of the positive symptoms observed.


Assuntos
Antipsicóticos/efeitos adversos , Catalepsia/induzido quimicamente , Galphimia/efeitos adversos , Haloperidol/efeitos adversos , Ketamina/efeitos adversos , Extratos Vegetais/efeitos adversos , Triterpenos/efeitos adversos , Animais , Antipsicóticos/administração & dosagem , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Catalepsia/psicologia , Relação Dose-Resposta a Droga , Haloperidol/administração & dosagem , Interações Ervas-Drogas , Ketamina/administração & dosagem , Masculino , Camundongos Endogâmicos ICR , Extratos Vegetais/administração & dosagem , Natação , Triterpenos/administração & dosagem
18.
Toxicol Appl Pharmacol ; 352: 1-8, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29778398

RESUMO

Antipsychotic drugs are known to induce neuromuscular effects. In this study, we review 13 years (2002-2014) of antipsychotic intoxications reported by the anti-poisoning center of Algiers (APCA). The most recorded symptoms were neuromuscular/muscular disorders, of which haloperidol was the most inducer among all antipsychotics. A prospective study was conducted between December 2012 and January 2017 to evaluate muscle effects generated after intentional or accidental ingestion of haloperidol. Fifty-one patients admitted in different emergency departments in Algiers were included in this study. Urine and blood samples were collected from each patient for biological and toxicological monitoring and a group of healthy volunteers was assessed for comparison purpose. There was no significant difference in plasma lactate dehydrogenase (LDH) activity between healthy volunteers and exposed patients even when high levels of haloperidol were recorded. In contrast, selenium concentration and creatine kinase (CK) activity in plasma samples were significantly higher in patients exposed to high levels of haloperidol compared to healthy volunteers. Large percentage of patients exposed to high levels of haloperidol presented a significant elevated CK activity and high selenium concentration regarding the physiological thresholds. Additionally, CK activity and selenium concentration correlated positively with plasma content of haloperidol suggesting a dose-dependent relationship. In conclusion, some biomarkers (CK and selenium) may reflect muscle adverse effects of high haloperidol exposure that result possibly from muscle rigidity.


Assuntos
Antipsicóticos/efeitos adversos , Creatina Quinase Forma MM/sangue , Haloperidol/efeitos adversos , Músculo Esquelético/efeitos dos fármacos , Doenças Musculares/induzido quimicamente , Selênio/sangue , Adolescente , Adulto , Argélia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Doenças Musculares/sangue , Doenças Musculares/diagnóstico , Centros de Controle de Intoxicações , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Regulação para Cima , Adulto Jovem
19.
Intensive Care Med ; 44(7): 1081-1089, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29767323

RESUMO

PURPOSE: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality. METHODS: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use. RESULTS: We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively. CONCLUSIONS: In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.


Assuntos
Antipsicóticos , Delírio , Haloperidol , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Brasil , Canadá , Cuidados Críticos , Delírio/tratamento farmacológico , Europa (Continente) , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Prevalência , Estudos Prospectivos , Fatores de Risco
20.
Med Princ Pract ; 27(3): 250-259, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29518791

RESUMO

OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate whether or not the use of haloperidol could reduce the incidence of delirium in adult patients. SUBJECTS AND METHODS: PubMed, Embase, the Cochrane Library, Elsevier, Wiley, and Ovid were searched for randomized controlled trials and prospective interventional cohort studies that compared haloperidol with placebo for delirium prophylaxis or with second generation antipsychotics for delirium treatment. The primary end point was the incidence and severity of delirium. After reviewing 272 relevant articles, 10 studies with 1,861 patients were finally included (haloperidol vs. placebo in 8 studies [n = 1,734], and haloperidol vs. second-generation antipsychotics in 2 studies [n = 127]). Revman 5.3 was used for the data analysis. RESULTS: Compared with placebo, a high dose of prophylactic haloperidol (≥5 mg/day) may help reduce the incidence of delirium in surgical patients (risk ratio 0.50, 95% CI 0.32, 0.79). There were no differences in the duration of delirium, QTc interval prolongation, extrapyramidal symptoms, intensive care unit stay, hospital stay, or mortality between the haloperidol and placebo groups. For delirium treatment, haloperidol exhibited similar effects as the second-generation antipsychotics. CONCLUSIONS: In this study, the limited available data revealed that prophylaxis haloperidol at a dose of ≥5 mg/day might help reduce delirium in adult surgical patients. Further outcome studies with larger sample sizes are required to confirm these findings.


Assuntos
Antipsicóticos/uso terapêutico , Delírio/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Adulto , Antipsicóticos/efeitos adversos , Delírio/etiologia , Feminino , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Masculino
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