Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization's global pharmacovigilance database.

BACKGROUND: Psychoactive drugs frequently cause delirium adverse events in older adults. However, few data on the relationship between antidepressants and delirium are available. Here, we investigated the association between antidepressant prescription and pharmacovigilance reports of delirium in older adults. METHODS: Using the World Health Organization's VigiBase® global pharmacovigilance database from 1967 to 2022, we performed a disproportionality analysis in order to probe the putative associations between each antidepressant class (non-selective monoamine reuptake inhibitors (NSMRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), alpha-2-adrenergic receptor antagonists, and other antidepressants) and reports of delirium in people aged 65 or over. We calculated the reporting odds ratios (r-OR) and their 95% confidence interval ([95%CI]) with logistic regression models before and after adjustment for confounding factors. Secondary analyses were performed for each drug and within each class by age group (65-74, and 75 and over). We also studied the reports of concomitant delirium and hyponatremia. RESULTS: Our main analysis included 87,524 cases of delirium. After adjustment for confounders, a significant association was found between delirium and all antidepressant classes other than SNRIs. Intraclass disparities were found for the association between the most frequently prescribed antidepressants and reports of delirium. An elevated risk of reports of concomitant delirium and hyponatremia was found for SSRIs (4.46 [4.01-4.96]), SNRIs (1.25 [1.07-1.46]), MAOIs (1.72 [1.41-2.09]), and the "other antidepressants" class (1.47 [1.30-1.65]). CONCLUSIONS: There was a significant association between reports of delirium and antidepressant classes (other than SNRIs). However, this association varied from one drug to another within a given antidepressant class. Moreover, this association could not always be explained by antidepressant-induced hyponatremia.

NSAIDs for Pain Control During the Peri-Operative Period of Hip Fracture Surgery: A Systematic Review.

BACKGROUND: Hip fracture (HF) mostly affects older adults and is responsible for increased morbidity and mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the peri-operative multimodal analgesic management, but their use could be associated with adverse events in older adults. This systematic review aimed to assess outcomes associated with NSAIDs use in the peri-operative period of HF surgery. METHODS: This systematic review was conducted according to the PRISMA guidelines. Three databases (PubMed/EMBASE/Cochrane Central) were used to search for clinical trials and observational studies assessing efficacy, safety and impact of NSAIDs use on non-specific post-operative outcomes, such as functional status and post-operative complications. RESULTS: Among the 1320 references initially identified, four provided data on efficacy, four on safety and six on non-specific post-operative outcomes (three randomized controlled clinical trials, three observational studies). Mean study population ages ranged from 68 to 87 years. Two studies found that NSAIDs were effective on pain control, but two studies found conflicting results on opioid sparing. No increased risk of acute kidney injury was observed, while results concerning bleeding risk and delirium were conflicting. No study has found any effect of NSAIDs use on walk recovery. Quality of evidence was high for pain control, but low to very low for all the other studied outcomes. CONCLUSIONS: The use of NSAIDs may be effective for pain control in the peri-operative period of HF surgery. However, safety data were conflicting with low levels of certainty. Further studies are needed to assess their benefit-risk balance in this context. The research protocol was previously registered on PROSPERO (registration number: CRD42021237649).

Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization's database.

Importance: Endocrine therapies (ETs) and inhibitors of cyclin-dependent kinases-4/6 (iCDK4/6s) are a standard treatment in breast cancer. However, data on potential neurocognitive impacts remain inconsistent for ET and are scarce for iCDK4/6s. Objective: To evaluate whether ET and iCDK4/6s are associated with neurocognitive impairment (NCI). Methods: We used observational, real-world cases of NCI from the World Health Organization's database VigiBase® to perform disproportionality analysis. Cases were defined as any symptom of NCI in females treated with ETs or iCDK4/6s. The study period was from the date of the first adverse event reported in VigiBase® with iCDK4/6s (1 January 2014) until the date of data extraction (16 March 2022). In our primary analysis, we calculated the reporting odds ratio (ROR) adjusted for age to identify a potential association between NCI and individual ETs in isolation or in combination with iCDK4/6s. We also performed subgroup analyses by the NCI class. Results: We identified 2.582 and 1.943 reports of NCI associated with ETs and iCDK4/6s, respectively. NCI was significantly associated with each ET [anastrozole: n = 405, aROR = 1.52 (95% CI: 1.37-1.67); letrozole: n = 741, aROR = 1.37 (95% CI: 1.27-1.47); exemestane: n = 316, aROR = 1.37 (95% CI: 1.22-1.53); tamoxifen: n = 311, aROR = 1.25 (95% CI: 1.12-1.40); and fulvestrant: n = 319, aROR = 1.19 (95% CI: 1.06-1.33)] and only with palbociclib for iCDK4/6s [n = 1,542, aROR = 1.41 (95% CI: 1.34-1.48)]. Conclusion: These findings suggest that in females treated for breast cancer, all ETs may be associated with NCI. However, amongst iCDK4/6s, NCI may be specific to palbociclib. NCI most frequently involved learning and memory as well as language. Neurocognitive impact of treatments requires better consideration and management.