Dataset Information

Cytochrome P450 (CYP450) Interactions Involving Atypical Antipsychotics are Common in Community-Dwelling Older Adults Treated for Behavioral and Psychological Symptoms of Dementia.

ABSTRACT: Treatment of behavioral and psychological symptoms of dementia (BPSD) and comorbidities often necessitates the concomitant use of antipsychotics and non-antipsychotic drugs, thereby potentiating the risk for drug-drug interactions (DDIs).The primary objective of our study was to identify potentially clinically relevant cytochrome P450 (CYP)-mediated DDIs involving antipsychotics among participants enrolled in the Program of All-Inclusive Care for the Elderly (PACE) with BPSD. Additionally, we wanted to determine the prevalence of antipsychotic use in this population. The study included 10,001 PACE participants. The practice setting used a proprietary clinical decision support system (CDSS) to analyze simultaneous multidrug interactions. A retrospective analysis of pharmacy claims data was conducted to identify DDIs involving antipsychotics prescribed for BPSD, using snapshots of medication profiles paired with the CDSS. Of the participants who met inclusion criteria, 1190 (11.9%) were prescribed an antipsychotic; of those, 1071 (90.0%) were prescribed an atypical antipsychotic. Aripiprazole commonly caused (being a perpetrator drug 94.6% of the time) potential DDIs with antidepressants (e.g., duloxetine, venlafaxine, mirtazapine), opioids (e.g., hydrocodone, oxycodone, tramadol) and metoprolol via the CYP2D6 isoform. Risperidone commonly caused (85.7%) potential DDIs with donepezil, lamotrigine and trazodone via the CYP3A4 isoform. Quetiapine exclusively suffered (100%) from potential DDIs with amlodipine, buspirone, omeprazole or topiramate via the CYP3A4 isoform. Antipsychotics are commonly prescribed to PACE participants for BPSD treatment and they may interact with other drugs used to treat comorbidities. A thorough review of concomitant medications will help mitigate the likelihood of potentially dangerous CYP-mediated DDIs involving antipsychotics.

SUBMITTER: Matos A

PROVIDER: S-EPMC7355621 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Cytochrome P450 (CYP450) Interactions Involving Atypical Antipsychotics are Common in Community-Dwelling Older Adults Treated for Behavioral and Psychological Symptoms of Dementia.

Matos Adriana A Bain Kevin T KT Bankes David L DL Furman Anna A Skalski Briana B Verzicco James J Turgeon Jacques J

Pharmacy (Basel, Switzerland) 20200408 2

Treatment of behavioral and psychological symptoms of dementia (BPSD) and comorbidities often necessitates the concomitant use of antipsychotics and non-antipsychotic drugs, thereby potentiating the risk for drug-drug interactions (DDIs).The primary objective of our study was to identify potentially clinically relevant cytochrome P450 (CYP)-mediated DDIs involving antipsychotics among participants enrolled in the Program of All-Inclusive Care for the Elderly (PACE) with BPSD. Additionally, we wa ...[more]

PMID: 32276526

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Project description:ImportanceAtypical antipsychotics offer modest effectiveness compared with placebo but with serious safety risks, including a boxed warning for the risk of death in the treatment of behavioral and psychological symptoms of dementia (BPSD). Their comparative effectiveness and safety are not fully known.ObjectiveTo assess the relative benefits and safety of atypical antipsychotics in the treatment of BPSD shown in randomized clinical trials using network meta-analysis.Data sourcesPubMed/MEDLINE, Embase, PsychINFO, and Cochrane Library were searched from their inception until May 31, 2018. Key terms included dementia and atypical antipsychotics.Study selectionRandomized clinical trials comparing any atypical antipsychotic with another atypical antipsychotic or with placebo were included in the analysis.Data extraction and synthesisTwo independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% CIs. In addition to ORs, the surface under the cumulative ranking curve (SUCRA) was ascertained, which represents the percentage of the effectiveness or safety for each treatment compared with a hypothetical treatment that would be ranked first without uncertainty.Main outcomes and measuresThe primary effectiveness outcome assessed was the Neuropsychiatric Inventory (NPI); secondary effectiveness outcomes were the Brief Psychiatric Rating Scale (BPRS) and Cohen-Mansfield Agitation Inventory (CMAI). The primary safety outcomes were death and cerebrovascular adverse events (CVAEs). Secondary safety outcomes were extrapyramidal signs/symptoms; somnolence/sedation; falls, fracture, or injury; and urinary tract infection/incontinence.ResultsSeventeen studies (5373 patients) were included. The mean (SD) age of all participants was 80.8 (3.1) years, and most were women (3748 [69.8%]). Compared with placebo, aripiprazole was associated with improvement in outcomes on the NPI (SMD, -0.17; 95% CI, -0.31 to -0.02), BPRS (SMD, -0.20; 95% CI, -0.35 to -0.05), and CMAI (SMD, -0.30; 95% CI, -0.55 to -0.05); quetiapine was associated with improvement in outcomes on the BPRS (SMD, -0.24; 95% CI, -0.46 to -0.01), and risperidone was associated with improvement in outcomes on the CMAI (SMD, -0.26; 95% CI, -0.37 to -0.15). Differences between atypical antipsychotics were not significant for effectiveness, death, or CVAE. Compared with placebo, risperidone (OR, 3.85; 95% CI, 1.55-9.55) and olanzapine (OR, 4.28; 95% CI, 1.26-14.56) were associated with increased risk of CVAEs. The SUCRA estimated relative ranking of treatments suggested that aripiprazole might be the most effective and safe atypical antipsychotic and that olanzapine provides the least benefit overall; however, these results should be interpreted with caution where point estimates (OR and SMD) show that there is no statistically significant difference.Conclusions and relevanceThis network meta-analysis supports the existence of a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of BPSD and confirms that a single most effective and safe treatment option does not exist. Clinicians should individualize the assessment of safety risks against expected benefits when prescribing these medications to patients with dementia.

Project description:Background: Identifying the characteristics of behavioral and psychological symptoms of dementia (BPSD) associated with different dementia types may be a promising strategy to effectively deal with BPSD. We aimed to synthesize the prevalence rates of BPSD characteristics in community-dwelling dementia patients. Methods: We searched Medline, EMBASE, and PsycARTICLES databases for original clinical studies published until December 2020 that enrolled at least 300 community-dwelling dementia patients. The methodological qualities of prevalence studies were assessed using the Joanna Briggs Institute's critical appraisal checklist. Results: Thirty studies were included. The prevalence of the BPSD characteristic ranged from 4 (elation and mania) to 32% (apathy) in the pooled samples. The prevalence of delusions, anxiety, apathy, irritability, elation and mania, and aberrant motor behavior in Alzheimer's disease patients was 1.72-2.88 times greater than that in vascular dementia (VD) patients, while the prevalence of disinhibition in VD patients was 1.38 times greater. The prevalence of anxiety, irritability, and agitation and aggression, delusion, hallucinations, apathy, disinhibition, and aberrant motor behavior tended to increase as the severity of dementia increased, while that of depression, eating disorder, sleep disorders, and elation and mania tended to stable. In community-dwelling patients with dementia, the pooled prevalence of apathy, depression, anxiety, irritability, agitation and aggression, sleep disorders, and eating disorder was higher than 20%, while that of disinhibition and elation and mania was lower than 10%. Conclusion: Overall, the pooled prevalence of apathy, depression, anxiety, irritability, agitation and aggression, sleep disorders, and eating disorder was generally high in patients with dementia. Also, the prevalence of some BPSD characteristics differed according to the type and the severity of dementia. The methodological quality of the included studies is not the best, and high heterogeneity may affect the certainty of the findings. However, the results of this review can deepen our understanding of the prevalence of BPSD. Systematic Review Registration: https://osf.io/dmj7k, identifier: 10.17605/OSF.IO/DMJ7K.

Dataset Information

Cytochrome P450 (CYP450) Interactions Involving Atypical Antipsychotics are Common in Community-Dwelling Older Adults Treated for Behavioral and Psychological Symptoms of Dementia.

Publications

Cytochrome P450 (CYP450) Interactions Involving Atypical Antipsychotics are Common in Community-Dwelling Older Adults Treated for Behavioral and Psychological Symptoms of Dementia.

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