People with coronavirus disease (COVID-19) might have several risk factors for delirium, which could in turn notably worsen the prognosis. Although pharmacological approaches for delirium are debated, haloperidol and other first-generation antipsychotics are frequently employed, particularly for hyperactive presentations. However, the use of these conventional treatments could be limited in people with COVID-19, due to the underlying medical condition and the risk of drug–drug interactions with anti-COVID treatments. On these premises, we carried out a rapid review in order to identify possible alternative medications for this particular population. By searching PubMed and the Cochrane Library, we selected the most updated systematic reviews of randomised trials on the pharmacological treatment of delirium in both intensive and non-intensive care settings, and on the treatment of agitation related to acute psychosis or dementia. We identified medications performing significantly better than placebo or haloperidol as the reference treatment in each population considered, and assessed the strength of association according to validated criteria. In addition, we collected data on other relevant clinical elements (i.e. common adverse events, drug-drug interactions with COVID-19 medications, daily doses) and regulatory elements (i.e. therapeutic indications, contra-indications, available formulations). A total of 10 systematic reviews were included. Overall, relatively few medications showed benefits over placebo in the four selected populations. As compared with placebo, significant benefits emerged for quetiapine and dexmedetomidine in intensive care unit (ICU) settings, and for none of the medications in non-ICU settings. Considering also data from indirect populations (agitation related to acute psychosis or dementia), aripiprazole, quetiapine and risperidone showed a potential benefit in two or three different populations. Despite limitations related to the rapid review methodology and the use of data from indirect populations, the evidence retrieved can pragmatically support treatment choices of frontline practitioners involved in the COVID-19 outbreak, and indicate future research directions for the treatment of delirium in particularly vulnerable populations.
BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues.
METHODS: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences.
RESULTS: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation.
CONCLUSIONS: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
INTRODUCCIÓN: Los meta-análisis son una manera conveniente para los clínicos y los investigadores para revisar los datos con respecto a las diferentes intervenciones. Los meta-análisis puede superar muchas de las limitaciones de los estudios individuales, a saber, el poder para detectar diferencias, y ayudar a resolver los resultados de los estudios inconsistentes. Áreas cubiertas: Este artículo es una revisión de los meta-análisis de los antipsicóticos atípicos orales para el tratamiento de la esquizofrenia, que se encuentra a través de PubMed y Cochrane Database of Systematic Reviews. Un total de 91 meta-análisis fueron identificados que incluían datos sobre la eficacia de resultado para los 10 antipsicóticos atípicos disponibles en los EE.UU. (11 centrado en la clozapina, 17 para la risperidona, la olanzapina 8, 5 para quetiapina, ziprasidona para 3, 10 para el aripiprazol, 5 para paliperidona, 1 para iloperidone, 0 para asenapina o lurasidone, y otros 31 que fueron clasificados de manera más amplia). Esto incluye revisiones Cochrane y otros informes del mismo modo ejecutadas, así como los análisis agrupados etiquetados meta-en PubMed como un meta-análisis. OPINIÓN DE LOS EXPERTOS: En general, existe una gran heterogeneidad entre los antipsicóticos atípicos en términos de eficacia, con clozapina que evidencia consistente superioridad sobre los antipsicóticos típicos, seguido por detrás de la olanzapina y la risperidona. Los metanálisis general no son compatibles con las diferencias de eficacia entre los antipsicóticos atípicos en comparación con los agentes más antiguos típicos. Aunque esta revisión se centra en la eficacia, otras consideraciones son también importantes, incluyendo las grandes diferencias de tolerabilidad entre todos los agentes y la necesidad de individualizar la elección medicina basada en la historia pasada de la respuesta terapéutica, antecedentes de problemas de tolerancia y los valores personales del individuo y sus preferencias .
People with coronavirus disease (COVID-19) might have several risk factors for delirium, which could in turn notably worsen the prognosis. Although pharmacological approaches for delirium are debated, haloperidol and other first-generation antipsychotics are frequently employed, particularly for hyperactive presentations. However, the use of these conventional treatments could be limited in people with COVID-19, due to the underlying medical condition and the risk of drug–drug interactions with anti-COVID treatments. On these premises, we carried out a rapid review in order to identify possible alternative medications for this particular population. By searching PubMed and the Cochrane Library, we selected the most updated systematic reviews of randomised trials on the pharmacological treatment of delirium in both intensive and non-intensive care settings, and on the treatment of agitation related to acute psychosis or dementia. We identified medications performing significantly better than placebo or haloperidol as the reference treatment in each population considered, and assessed the strength of association according to validated criteria. In addition, we collected data on other relevant clinical elements (i.e. common adverse events, drug-drug interactions with COVID-19 medications, daily doses) and regulatory elements (i.e. therapeutic indications, contra-indications, available formulations). A total of 10 systematic reviews were included. Overall, relatively few medications showed benefits over placebo in the four selected populations. As compared with placebo, significant benefits emerged for quetiapine and dexmedetomidine in intensive care unit (ICU) settings, and for none of the medications in non-ICU settings. Considering also data from indirect populations (agitation related to acute psychosis or dementia), aripiprazole, quetiapine and risperidone showed a potential benefit in two or three different populations. Despite limitations related to the rapid review methodology and the use of data from indirect populations, the evidence retrieved can pragmatically support treatment choices of frontline practitioners involved in the COVID-19 outbreak, and indicate future research directions for the treatment of delirium in particularly vulnerable populations.
