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Revisión sistemática

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Autores Kim MS , Rhim HC , Park A , Kim H , Han KM , Patkar AA , Pae CU , Han C
Revista Journal of psychiatric research
Año 2020
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We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Revisión sistemática

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Revista Acta anaesthesiologica Scandinavica
Año 2020
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BACKGROUND: Haloperidol is the most frequently used drug to treat delirium in the critically ill patients. Yet, no systematic review has focussed on the effects of haloperidol in critically ill patients with delirium. METHODS: We conducted a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials (RCTs) assessing the effects of haloperidol versus any intervention on all-cause mortality, serious adverse reactions/events, days alive without delirium, health-related quality of life (HRQoL), cognitive function and delirium severity in critically ill patients with delirium. We also report on QTc prolongation, delirium resolution and extrapyramidal symptoms. RESULTS: We included 8 RCTs with 11 comparisons (n=951). We adjudicated one trial as having overall low risk of bias. Three trials used rescue haloperidol; excluding these, we did not find an effect of haloperidol versus control on all-cause mortality (RR 1.01; 95% CI 0.33-3.06; I2 =0%; 112 participants; 3 trials; 4 comparisons; very low certainty) or delirium severity (SMD -0.15; 95% CI -0.61-0.30; I2 =27%; 134 participants; 3 trials; 4 comparisons; very low certainty). No trials reported adequately on serious adverse reactions/events. Only one trial reported on days alive without delirium, cognitive function and QTc prolongation, and no trials reported on HRQoL. Sensitivity analyses, including trials using rescue haloperidol, did not change the results. CONCLUSIONS: The evidence for the use of haloperidol to treat critically ill patients with delirium is sparse, of low quality, and inconclusive. We therefore have no certainty regarding any beneficial, harmful or neutral effects of haloperidol in these patients.

Revisión sistemática

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Libro AHRQ Comparative Effectiveness Reviews
Año 2019
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OBJECTIVES: To assess benefits and harms of antipsychotics for the prevention and treatment of delirium in adult patient populations. DATA SOURCES: We searched PubMed®, Embase®, the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL®), and PsycINFO® through March 2019. We also hand-searched the reference lists of included articles, relevant reviews, and delirium-specific bibliographic repositories. REVIEW METHODS: We included randomized controlled trials (RCTs) of antipsychotics that evaluated benefits or harms, and also observational studies that reported harms. Two reviewers independently screened search results for eligibility, serially abstracted data, and independently assessed the risk of bias of the studies and graded the strength of evidence (SOE) for prespecified critical outcomes: delirium severity, cognitive functioning, length of stay in hospital, inappropriate continuation of antipsychotic drugs, falls, sedation, and caregiver burden/strain. RESULTS: We identified 14 RCTs and 1 observational study evaluating the use of antipsychotics in prevention of delirium. For the treatment of delirium, we identified 19 RCTs and 25 observational studies. Two RCTs were classified as both a prevention and treatment trial. In trials of the prevention of delirium across all populations, there was no difference in delirium incidence for haloperidol versus placebo (relative risk [RR], 0.94; 95% confidence interval [CI], 0.77 to 1.16). Second-generation antipsychotics, compared with placebo, may decrease delirium incidence in postoperative patients at risk for delirium (RR, 0.36; 95% CI, 0.26 to 0.50). Antipsychotics (both haloperidol and second-generation), compared to placebo, demonstrated no differences for length of stay in hospital (low SOE for second-generation antipsychotics and high SOE for haloperidol). We were unable to draw conclusions regarding the effect of antipsychotics on sedation, falls, and delirium severity (insufficient SOE). We found no studies evaluating cognitive functioning, inappropriate continuation of antipsychotic drugs, or caregiver burden/strain. For treatment of delirium, there was little to no difference in effect of haloperidol and second-generation antipsychotics compared with placebo for length of stay in hospital (moderate SOE) and sedation (low and moderate SOE, respectively) with insufficient or no evidence for cognitive functioning or delirium severity. Also, effects of second-generation antipsychotics were not significantly different compared with haloperidol for delirium severity (moderate SOE), cognitive functioning (low SOE), length of stay in hospital (moderate SOE), and sedation (moderate SOE). We found no studies reporting inappropriate continuation of antipsychotic drugs, falls, or caregiver burden/strain. We did not find statistically significant differences for haloperidol or second-generation antipsychotics in neurological harms, including extrapyramidal side effects and neuroleptic malignant syndrome. However, cardiac harms tended to occur more frequently with antipsychotics, specifically prolongation of QT interval with second-generation antipsychotics. CONCLUSIONS: Haloperidol or second-generation antipsychotics, compared to placebo, used for the prevention or treatment of delirium did not improve length of stay in hospital. We found little or no evidence to determine the effect of antipsychotics on cognitive function, delirium severity, or caregiver burden. Second-generation antipsychotics may decrease delirium incidence in postoperative patients, but this evidence is limited and requires more study. We did not detect neurological harms associated with haloperidol or second-generation antipsychotics used for the prevention or treatment of delirium. However, cardiac effects tended to occur more frequently in those receiving antipsychotics. Future studies should include standardized, clinically meaningful measures of patient distress, subsequent memories of delirium, caregiver burden and distress, inappropriate continuation of antipsychotic therapy, and long-term cognitive and functional outcomes.

Revisión sistemática

No clasificado

Revista Annals of internal medicine
Año 2019
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BACKGROUND: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear. PURPOSE: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults. DATA SOURCES: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions. STUDY SELECTION: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms. DATA EXTRACTION: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers. DATA SYNTHESIS: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently. LIMITATIONS: Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes. CONCLUSION: Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Revisión sistemática

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Revista JAMA psychiatry
Año 2019
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Importance: Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear. OBJECTIVE: To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention. Data Soures: PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018. STUDY SELECTION: Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention. Data Extraction and Synthesis: To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model. Main Outcomes and Measures: The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium. RESULTS: A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1%male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4%male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95%CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95%CI, 0.01-0.66 for ramelteon; OR, 0.25; 95%CI, 0.09-0.69 for olanzapine; OR, 0.27; 95%CI, 0.07-0.99 for risperidone; and OR, 0.50; 95%CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control. Conclusions and Relevance: This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Revisión sistemática

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Revista Psychosomatics
Año 2019
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BACKGROUND: Although haloperidol is the most widely used drug in the treatment of delirium, evidence on the relevance of atypical antipsychotics (AAPs) is growing. OBJECTIVE: To review the literature on the efficacy and tolerability of AAPs in the treatment of delirium. METHODS: A systematic search of the literature published before April 2018 was performed on PubMed using the following search strings: “Delirium” and “Atypical antipsychotics”, “Novel antipsychotics”, “New antipsychotics”, “Quetiapine”, “Olanzapine”, “Aripiprazole”, “Risperidone”, “Paliperidone”, “Clozapine”, “Asenapine”, “Iloperidone”, “Amisulpiride”, “Ziprasidone”, “Zotepine”, “Sertindole”, “Lurasidone” or “Perospirone”. RESULTS: Twelve randomized controlled trials (RCTs) and 22 open trials were considered. Despite an overall lack of large-scale RCTs, there is some evidence supporting the efficacy of olanzapine and quetiapine in placebo controlled trials. In a recent and large RCT in elderly patients, risperidone and/or haloperidol were associated with a significantly worse outcome than placebo. While preliminary, the current comparative studies suggest that haloperidol and the AAPs olanzapine, quetiapine and risperidone are similarly effective, although treatment with AAPs is associated with a reduced incidence of extrapyramidal symptoms. Ziprasidone was not shown to be effective. No RCTs are available for other AAPs. CONCLUSIONS: Although the current evidence of the efficacy and tolerability of AAPs in the treatment of delirium is limited and the heterogeneity of the data precluded a meta-analysis, olanzapine and quetiapine seem to be adequate alternatives to haloperidol, especially in patients who are vulnerable for extrapyramidal symptoms, who require sedation or who have a history of haloperidol intolerance. Evidently, larger-scale RCTs are urgently required. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Revisión sistemática

No clasificado

Revista Cochrane Database of Systematic Reviews
Año 2018
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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.

Revisión sistemática

No clasificado

Autores Kishi T , Hirota T , Matsunaga S , Iwata N
Revista Journal of neurology, neurosurgery, and psychiatry
Año 2016
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OBJETIVOS: Se realizó un meta-análisis actualizado del tratamiento antipsicótico en pacientes con delirio, basado en un metanálisis anterior publicado en 2007. Métodos: Se incluyeron en este estudio fueron aleatorizados, controlados con placebo-controlado o la atención habitual (UC) de los antipsicóticos en pacientes adultos con delirio. La medida de resultado primaria fue la tasa de respuesta en el punto final del estudio. Las medidas de resultado secundarias incluyeron la mejora de la gravedad del delirio, de Impresión Clínica Global-Severity Scale (CGI-S), el tiempo de respuesta (TTR), tasa de interrupción y los efectos adversos individuales. El riesgo relativo (RR), el número necesario a tratar número / dañar (NNT / NND), IC del 95% y la diferencia de medias estandarizada (DME), se calcularon. RESULTADOS: Se identificaron 15 estudios (duración media: 9,8 días) para la revisión sistemática (n total = 949, amisulprida = 20, el aripiprazol = 8, clorpromazina = 13, haloperidol = 316, olanzapina o haloperidol inyección intramuscular = 62, olanzapina = 144 , placebo = 75, quetiapina = 125, risperidona = 124, UC = 30 y ziprasidona = 32), de las cuales 4 fueron resúmenes de conferencias y publicado. Cuando se agruparon como grupo, los antipsicóticos fueron superiores al placebo / UC en términos de tasa de respuesta (RR = 0,22; NNT = 2), la gravedad del delirio escalas de puntajes (DME = -1,27), las puntuaciones CGI-S (DME = -1,57) y TTR (DME = -1,22). El grupo de antipsicóticos agrupado se asocia con una mayor incidencia de sequedad en la boca (RR = 13,0; NND = 5) y sedación (RR = 4,59; NND = 5) en comparación con placebo / UC. Agrupados antipsicóticos de segunda generación (ASG) se asociaron con TTR más corto (DME = -0,27) y una menor incidencia de síntomas extrapiramidales (RR = 0,31; NND = 7) en comparación con el haloperidol. Conclusiones: Nuestros resultados sugieren que los ASG tienen un beneficio para el tratamiento del delirio con respecto a la eficacia y seguridad en comparación con el haloperidol. Sin embargo, se necesitan más estudios con muestras de mayor tamaño.

Revisión sistemática

No clasificado

Revista Journal of the American Geriatrics Society
Año 2016
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OBJETIVOS: Evaluar la eficacia de los medicamentos antipsicóticos para prevenir y tratar el delirio. DISEÑO: Revisión sistemática y meta-análisis. ESCENARIO: las bases de datos PubMed, EMBASE, CINAHL, y se realizaron búsquedas en ClinicalTrials.gov a partir del 1 de enero de 1988 al 26 de noviembre de 2013. PARTICIPANTES: pacientes quirúrgicos y médicos para adultos. Intervención: administración de antipsicóticos para la prevención o el tratamiento del delirio en los ensayos controlados aleatorios o estudios de cohortes. MEDIDAS: Dos autores examinaron de forma independiente todas las citas, extrajeron los datos pertinentes, y se evaluaron los estudios de sesgo potencial. La heterogeneidad se considera como chi-cuadrado p <0,1 o I (2)> 50%. Utilizando un modelo de efectos aleatorios (I (2)> 50%) o un modelo de efectos fijos (I (2) <50%), odds ratio (OR) se calcularon para los resultados dicotómicos (incidencia delirio y mortalidad), y la media o la diferencia de medias estandarizada para los resultados continuos (duración del delirio, la gravedad, el hospital y la longitud de la unidad de cuidados intensivos (UCI) de la estancia (LOS)). Los análisis de sensibilidad estudios incluidos prevención postoperatoria sólo, la exclusión de los estudios con alto riesgo de sesgo, y típica frente a los antipsicóticos atípicos. RESULTADOS: Proyección de 10.877 registros elegibles identificaron 19 estudios. En siete estudios que comparan antipsicóticos con placebo o ningún tratamiento para la prevención del delirio después de la cirugía, no hubo un efecto significativo sobre la incidencia de delirio (OR = 0,56, 95% intervalo de confianza (IC) = 0,23 a 1,34, I (2) = 93%). El uso de los datos correspondientes a los 19 estudios, el uso de antipsicóticos no se asoció con el cambio en la duración del delirio, la gravedad, o un hospital o LOS UCI, con una alta heterogeneidad entre los estudios. No se detectó ninguna asociación con la mortalidad (OR = 0,90; IC del 95% = 0,62 a 1,29, I (2) = 0%). Conclusión: La evidencia actual no es compatible con el uso de antipsicóticos para la prevención o tratamiento del delirio. Se necesitan estudios adicionales metodológicamente rigurosos utilizando medidas de resultado estandarizadas.

Revisión sistemática

No clasificado

Revista European journal of internal medicine
Año 2016
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OBJETIVO: El haloperidol generalmente se considera el fármaco de elección para el manejo del delirio intrahospitalario. Realizamos una revisión sistemática para evaluar la evidencia de la eficacia y seguridad del haloperidol para la prevención y el tratamiento del delirio en pacientes hospitalizados. MÉTODOS: Se realizó una búsqueda sistemática de PubMed, Embase, Índice acumulativo de enfermería y salud afines (CINAHL), PsycINFO y la Biblioteca Cochrane hasta el 21 de abril de 2015. Se incluyeron ensayos controlados aleatorios de texto completo en inglés que utilizaron haloperidol para la prevención o el tratamiento de Delirio en pacientes adultos hospitalizados que informan sobre la incidencia, duración o gravedad del delirio como resultado primario. Se evaluó la calidad de la evidencia. El metanálisis no se realizó debido a la heterogeneidad entre estudios. RESULTADOS: Doce estudios cumplieron con los criterios de inclusión, cuatro de prevención y ocho de tratamiento. Las limitaciones metodológicas disminuyeron la calidad de los estudios incluidos. Los resultados de los estudios de prevención controlados con placebo sugieren un efecto protector inducido por haloperidol para el delirio en pacientes mayores programados para cirugía: dos estudios informaron una reducción significativa en la incidencia de delirio en la UCI y un estudio encontró una reducción significativa en la severidad y duración del delirio. Aunque faltan ensayos controlados con placebo, el tratamiento farmacológico del delirio establecido redujo la gravedad de los síntomas. La administración de haloperidol no se asoció con efectos secundarios limitantes del tratamiento, pero pocos estudios utilizaron un enfoque sistemático para identificar eventos adversos. CONCLUSIÓN: Aunque los resultados sobre el haloperidol para el tratamiento del delirio parecen prometedores, los ensayos de prevención actuales carecen de validez externa y los ensayos de tratamiento no incluyeron un brazo placebo por encima de la atención no farmacológica estándar. Por lo tanto, concluimos que el uso actual de haloperidol para el delirio intrahospitalario no se basa en evidencia robusta y generalizable.