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Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
Critical Care (London, England) Aug 2023Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium.
METHODS
This is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life.
RESULTS
We included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo.
CONCLUSIONS
Haloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients.
TRIAL REGISTRATION
CRD42017081133, date of registration 28 November 2017.
Topics: Humans; Haloperidol; Coma; Critical Illness; Quality of Life; Delirium; Randomized Controlled Trials as Topic
PubMed: 37633991
DOI: 10.1186/s13054-023-04621-4 -
BMC Anesthesiology Feb 2024To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients.
METHODS
PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure were used to find concerned studies for meta-analysis. The main outcome was the incidence of postoperative delirium, and the secondary outcomes were side effects of haloperidol and the length of hospital stay. The meta-analyses were conducted using the Review Manager Version 5.1. This study was conducted based on the PRISMA statement.
RESULTS
Eight RCTs (1569 patients) were included in the meta-analysis. There was a significant difference in the incidence of postoperative delirium between haloperidol and control groups (OR = 0.62, 95%CI 0.48-0.80, P = 0.0002, I = 20%). In addition, side effects of haloperidol and the duration of hospitalization were comparable (OR = 0.58, 95%CI 0.25-1.35, P = 0.21, I = 0%; MD =-0.01, 95%CI -0.16-0.15, P = 0.92, I = 28%). Subgroup analysis implied the effect of haloperidol on postoperative delirium might vary with the dose (5 mg daily: OR = 0.40, 95%CI 0.22-0.71, P = 0.002, I = 0%; <5 mg daily: OR = 0.72, 95%CI 0.42-1.23, P = 0.23, I = 0%).
CONCLUSIONS
The meta-analysis revealed perioperative application of haloperidol could decrease the occurrence of postoperative delirium without obvious side effects in elderly people, and high-dose haloperidol (5 mg daily) possessed a greater positive effect.
Topics: Humans; Aged; Haloperidol; Antipsychotic Agents; Emergence Delirium; Delirium; Hospitalization
PubMed: 38308229
DOI: 10.1186/s12871-024-02434-8