Delirium Induced by Quetiapine and the Potential Role of Norquetiapine

Almeida, Filipe Félix; Albuquerque, Elisabete; Murta, Ilda

doi:10.3389/fnins.2019.00886

Cited by 9 publications

(3 citation statements)

References 27 publications

(27 reference statements)

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“…In fact, increased NDQ was suggested to be the plausible explanation of causing delirium in an elderly female patient using 100 mg quetiapine tablets in combination with carbamazepine, which induce the metabolism of QUE to NDQ. 27 The metabolism of QUE to NDQ is mainly mediated by CYP3A. 1,13 However, in the subgroup of patients who had been CYP3A4/5 genotyped, we did not find any significant impact of the CYP3A4*22 or CYP3A5*3 variants on the MPR, or on the C:D ratios of QUE and NDQ.…”

Section: Variables Valuesmentioning

confidence: 54%

“…As female sex and old age are associated with increased likelihood of polypharmacy and increased anticholinergic burden in general, 10 the increased serum levels of NDQ observed in elderly females may leave them particularly vulnerable to anticholinergic adverse effects. In fact, increased NDQ was suggested to be the plausible explanation of causing delirium in an elderly female patient using 100 mg quetiapine tablets in combination with carbamazepine, which induce the metabolism of QUE to NDQ 27 …”

Section: Discussionmentioning

confidence: 99%

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Impact of age, sex and cytochrome P450 genotype on quetiapine and N‐desalkylquetiapine serum concentrations: A study based on real‐world data from 8118 patients

Solhaug

Tveito

Waade

et al. 2023

Brit J Clinical Pharma

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AimsTo investigate the effect of aging, sex and cytochrome P450 (CYP) genotypes on the exposure of quetiapine (QUE) and the pharmacologically active metabolite N‐desalkylquetiapine (NDQ).MethodsPatients with serum concentrations of QUE and NDQ were included retrospectively from a therapeutic drug monitoring service. The outcome measures were concentration:dose (C:D) ratios of QUE and NDQ, and NDQ:QUE metabolic ratio. Linear mixed model analyses were used to evaluate the effects of age, sex and, subsequently, CYP2D6/3A genotypes.ResultsThe average age of the included population (n = 8118 patients) was 44 years (13.5% ≥65 years). The C:D ratio of QUE and NDQ gradually increased in patients aged >50 years compared to those aged 18–30 years, with 28 and 29% increase, respectively, for patients aged >70 years (P < .001). Compared to males, females had 15% lower QUE C:D ratio and 10% higher C:D ratio of NDQ (both P < .001). The NDQ:QUE metabolic ratio was 30% higher in females than in males (P < .001). For females ≥65 years, the NDQ C:D ratio was 36% higher compared to males <65 years (P < .001). A significantly higher NDQ C:D ratio was observed for CYP2D6 intermediate (+7%, P = .012) and poor (+17%, P = .001) compared to normal metabolizers. No effects of CYP3A4*22 and CYP3A5*1 allele variants were observed.ConclusionThis study shows an increase of the QUE and NDQ exposures during aging. Old age, female sex and CYP2D6 allele variants encoding reduced activity are factors associated with high NDQ exposure. Therefore, females ≥65 years carrying CYP2D6 allele variants encoding reduced activity have the highest risk of dose‐dependent side effects of NDQ during QUE treatment.

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Section: Variables Valuesmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Impact of age, sex and cytochrome P450 genotype on quetiapine and N‐desalkylquetiapine serum concentrations: A study based on real‐world data from 8118 patients

Solhaug

Tveito

Waade

et al. 2023

Brit J Clinical Pharma

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“…Antipsychotics are known to be associated with delirium, potentially mediated by their anticholinergic properties 43 . Case reports have shown quetiapine and its metabolite norquetiapine have strong anticholinergic effects and may induce delirium in older adults 44 . Case reports have also highlighted delirium associated with olanzapine secondary to its anticholinergic effects 26 …”

Section: Discussionmentioning

confidence: 99%

Identifying frequent drug combinations associated with delirium in older adults: Application of association rules method to a case‐time‐control design

Chyou

Nishtala

2021

Pharmacoepidemiology and Drug

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Background Older adults are at an increased risk of delirium because of age, polypharmacy, multiple comorbidities, frailty, and acute illness. Although medication‐induced delirium in older adults is well understood, limited population‐level evidence is available, particularly on combinations of medications associated with delirium in older adults. Objectives We aimed to apply association rule analysis to identify drug combinations contributing to delirium risk in adults aged 65 and older using a case‐time‐control design. Method We sourced a nationwide representative sample of New Zealander's aged ≥65 years from the pharmaceutical collections and hospital discharge information. Prescription records (2005–2015) were obtained from New Zealand pharmaceutical collections (Pharms). Medication exposures were coded as binary variables (exposed vs. not exposed) at the individual drug level. All medications, including antimicrobials, antihistamines, diuretics, opioids, and nonsteroidal anti‐inflammatory medications, were considered drugs of interest. The first‐time coded diagnosis of delirium was extracted from the National Minimal Dataset (NMDS). A unique patient identifier linked the prescription dataset to the event dataset to set up a case‐time‐control cohort, indexed at the first delirium event. Association rules were then applied to identify frequent drug combinations in the case and the control periods (l‐day with a 35‐day washout period) that are statistically associated with delirium, and the association was tested by computing a time‐trend adjusted matched odds‐ratio (MOR) and its 95% confidence interval (CI). Results We identified 28 503 individuals (mean age 84.1 years) from 2005 to 2015 with delirium. Our combined association rule and case‐time‐control analysis identified several drug classes, including antipsychotics, benzodiazepines, opioids, and diuretics associated with delirium. Our analysis also identified frequently used drug combinations that are associated with delirium. Examples include combined exposures to quetiapine and furosemide (MOR = 6.17; 95%CI = [2.05–18.54]), haloperidol (MOR = 4.81; 95%CI = [3.16–6.69]), combined exposures to furosemide, omeprazole, and lorazepam (MOR = 3.94; 95%CI = [3.03–5.10]), and fentanyl exposure (MOR = 3.46; 95%CI [2.05–9.21]). Conclusion The association rule method applied to a case‐time‐control design is a novel approach to identifying drug combinations contributing to delirium with adjustment for any temporal trends in exposures. The study provides new insight into the combination of medicines linked to delirium.

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Carbamazepine/diazepam/quetiapine

2019

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Delirium Induced by Quetiapine and the Potential Role of Norquetiapine

Cited by 9 publications

References 27 publications

Impact of age, sex and cytochrome P450 genotype on quetiapine and N‐desalkylquetiapine serum concentrations: A study based on real‐world data from 8118 patients

Impact of age, sex and cytochrome P450 genotype on quetiapine and N‐desalkylquetiapine serum concentrations: A study based on real‐world data from 8118 patients

Identifying frequent drug combinations associated with delirium in older adults: Application of association rules method to a case‐time‐control design

Carbamazepine/diazepam/quetiapine

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