Dataset Information

Incidence of hospital contacts with acute kidney injury after initiation of second-generation antipsychotics in older adults: a Danish population-based cohort study.

ABSTRACT:

Purpose

To investigate the association between acute kidney injury (AKI) and use of second-generation antipsychotics (SGA) in older adults.

Methods

In a population-based cohort study using Danish national registries, new users of SGAs (aged ≥ 65) were identified during 2005-2015. Each SGA user was matched to 10 population controls on age, sex, and the SGA initiation date. The outcome was incident AKI within 90 days after the index date. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders.

Results

In the study, 36,581 new SGA users and 365,810 controls were included. The 90-day incidence rate of AKI was 4.38 and 1.70 per 1000 person-years among SGA users and controls, respectively, corresponding to a crude HR of 2.57 (1.79-3.68). The fully adjusted HR (aHR) was 1.43 (0.89-2.27) for all SGAs. The risk differed among individual drugs with aHRs for olanzapine 3.50 (1.20-10.23), quetiapine 1.62 (0.81-3.26), and risperidone 0.68 (0.28-1.64). In sensitivity analyses, the aHR declined to 1.24 (0.95-1.61) at 1-year follow-up.

Conclusions

Olanzapine use was associated with a significantly increased 90-day AKI risk. For quetiapine, the risk was elevated but not significant, and risperidone had no association. CIs were wide and confounder adjustment largely impacted the estimates. Main limitations included residual confounding and incomplete recording of AKI diagnoses.

SUBMITTER: Sharon R

PROVIDER: S-EPMC9283184 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:OBJECTIVES:To examine the association between use of second-generation antipsychotics (SGA) and the risk of chronic kidney disease (CKD). DESIGN:Population-based case-control study. SETTING:Routinely collected laboratory, prescription and diagnostic information on all inhabitants with creatinine measurements residing on the island of Funen, Denmark (2001 to 2015). PARTICIPANTS:21 434 cases with incident CKD matched with 85 576 CKD-free population controls by risk-set sampling using age, sex and calendar year. PRIMARY AND SECONDARY OUTCOME MEASURES:CKD was defined as an estimated glomerular filtration rate below 60?mL/min/1.73?m2 in a period longer than 3?months. Information on drug exposure and comorbidities were obtained from the Danish National Prescription Register and the Danish National Patient Register. We calculated OR for the association between SGA use and CKD using conditional logistic regression. RESULTS:Use of SGAs was associated with increased risk of CKD among ever users (OR 1.24, 95%?CI: 1.12 to 1.37) and current users (OR 1.26, 95%?CI: 1.12 to 1.42). We found no clear evidence of dose-response relationship. Both short duration (one to two antipsychotic prescriptions; OR 1.22, 95%?CI: 1.01 to 1.48) as well as long-term use (>30 prescriptions; OR 1.45, 95%?CI 1.19 to 1.76) were associated with an increased risk of CKD. Both use of SGAs with mild and high risk of metabolic disturbances was associated with increased risk of CKD (OR 1.21, 95%?CI: 1.06 to 1.39 and OR 1.36, 95%?CI: 1.11 to 1.68, respectively). Recent use of non-steroidal anti-inflammatory drugs, prior use of lithium, hypertension or prior acute kidney injury were not clearly associated with development of CKD connected to SGA exposure. The highest risk of CKD was found for clozapine (OR 1.81, 95%?CI: 1.22 to 2.69). CONCLUSION:Use of SGA is associated with a small-to-moderately increased risk of incident CKD. All investigated SGAs, except for aripiprazole, were associated with an increased risk of CKD.

Project description:Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting ?6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pooled relative risk (RR) (±95% confidence intervals (CIs)) was calculated using random-effects model, with numbers-needed-to-treat (NNT) calculations where appropriate. Across 23 studies (n=4504, mean duration=61.9±22.4 weeks), none of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone's superiority at 3 and 6 months when requiring ?3 trials. Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR=0.80, CI: 0.70-0.91, P=0.0007, I(2)=37%; NNT=17, CI: 10-50, P=0.003). SGAs were also superior regarding relapse at 3, 6 and 12 months (P=0.04, P<0.0001, P=0.0001), treatment failure (P=0.003) and hospitalization (P=0.004). SGAs showed trend-level superiority for dropout owing to intolerability (P=0.05). Superiority of SGAs regarding relapse was modest (NNT=17), but confirmed in double-blind trials, first- and multi-episode patients, using preferentially or exclusively raw or estimated relapse rates, and for different haloperidol equivalent comparator doses. There was no significant heterogeneity or publication bias. The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualized considering patient- and medication-related factors.

Project description:AIM:To investigate whether differential influence on the QTc interval exists among four second generation antipsychotics (SGAs) in psychosis. METHODS:Data were drawn from a pragmatic, randomized head-to-head trial of the SGAs risperidone, olanzapine, quetiapine, and ziprasidone in acute admissions patients with psychosis, and with follow-up visits at discharge or maximally 6-9 wk, 3, 6, 12 and 24 mo. Electrocardiograms were recorded on all visits. To mimic clinical shared decision-making, the patients were randomized not to a single drug, but to a sequence of the SGAs under investigation. The first drug in the sequence defined the randomization group, but the patient and/or clinician could choose an SGA later in the sequence if prior negative experiences with the first one(s) in the sequence had occurred. The study focuses on the time of, and actual use of the SGAs under investigation, that is until treatment discontinuation or change, in order to capture the direct medication effects on the QTc interval. Secondary intention-to-treat (ITT) analyses were also performed. RESULTS:A total of 173 patients, with even distribution among the treatment groups, underwent ECG assessments. About 70% were males and 43% had never used antipsychotic drugs before the study. The mean antipsychotic doses in milligrams per day with standard deviations (SD) were 3.4 (1.2) for risperidone, 13.9 (4.6) for olanzapine, 325.9 (185.8) for quetiapine, and 97.2 (42.8) for ziprasidone treated groups. The time until discontinuation of the antipsychotic drug used did not differ in a statistically significant way among the groups (Log-Rank test: P = 0.171). The maximum QTc interval recorded during follow-up was 462 ms. Based on linear mixed effects analyses, the QTc interval change per day with standard error was -0.0030 (0.0280) for risperidone; -0.0099 (0.0108) for olanzapine; -0.0027 (0.0170) for quetiapine, and -0.0081 (0.0229) for ziprasidone. There were no statistically significant differences among the groups in this regard. LME analyses based on ITT groups (the randomization groups), revealed almost identical slopes with -0.0063 (0.0160) for risperidone, -0.0130 (0.0126) for olanzapine, -0.0034 (0.0168) for quetiapine, and -0.0045 (0.0225) for ziprasidone. CONCLUSION:None of the SGAs under investigation led to statistically significant QTc prolongation. No statistically significant differences among the SGAs were found.