Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels.

BACKGROUND: Serotonin syndrome is a rare and potentially fatal adverse drug reaction caused by serotonergic drugs and is due to an increase in serotonin concentration or activation of the 5-HT receptor in the central nervous system. We analysed adverse events in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data set to investigate the main drug classes related to reports of serotonin syndrome and the reporting risk in relation to age and sex. METHODS: We analysed data from the FAERS database to evaluate the main drug classes related to reports of the serotonin syndrome, and the reporting risk in relation to age and sex. RESULTS: We found 8,997 cases of serotonin syndrome; selective serotonin reuptake inhibitors (SSRIs) was the class of drugs with most reports, followed by opioids and other antidepressants. The highest Reporting Odds Ratios (ROR) for drug classes was for monoamine oxidase (MAO) inhibitors (45.99, 95% confidence interval (CI): 41.21-51.33) and SSRIs (32.66, 95% CI: 31.33-34.04), while the ten active substances with the highest ROR were moclobemide, isocarboxazid, oxitriptane, tranylcypromine, melitracen, phenelzine, linezolid, amoxapine, reboxetine and tryptophan; with values of ROR ranging from 44.19 (95% CI: 25.38-76.94) of tryptophan to 388.36 (95% CI: 314.58-479.46) of moclobemide. The ROR for the most commonly involved drugs was higher in the group of older adults (65 > years old), and higher in males. CONCLUSION: Prescribers need to be vigilant about drugs that can raise serotonin concentration or influence serotonergic neurotransmission, also when using drugs with less well-known risk for serotonin syndrome, like linezolid and triptans.

Anticholinergic Burden and Cognitive Impairment in Nursing Homes: A Comparison of Four Anticholinergic Scales.

BACKGROUND: Medications with anticholinergic effects are commonly used in nursing homes, and their cumulative effect is of particular concern for the risk of adverse effects on cognition. OBJECTIVE: The relation between cognitive function and anticholinergic burden measured with four scales, the Anticholinergic Cognitive Burden (ACB) Scale, the Anticholinergic Risk Scale, the German Anticholinergic Burden Scale, and the CRIDECO Anticholinergic Load Scale, is assessed according to the hypothesis that a higher anticholinergic burden is associated with reduced cognitive performance. METHODS: This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term-care nursing homes (NH). Sociodemographic details, diagnosis, and drug treatments of each NH resident were collected using medical records four times during 2018 and 2019. Cognitive status was rated with the Mini-Mental State Examination (MMSE). The prevalence of anticholinergic use and its burden were calculated referring to the last time point for each patient. A longitudinal analysis was done on NH residents with at least two MMSE between 2018 and 2019 to assess the relation between the anticholinergic load and decline in MMSE. The relationship between drug-related anticholinergic burden and cognitive performance was analyzed using Poisson regression model theory. Multivariate analyses were adjusted according to the known risk factors of reduced cognitive performance available [age, sex, history of stroke or transient ischemic attack (TIA), and number of non-anticholinergic drugs] and for cholinesterase inhibitors. In view of the high number of subjects with an MMSE score = 0 among residents with dementia, for this group a zero-inflated Poisson regression model was used to give more consistent results. The association of anticholinergic burden with mortality was examined from each patient's last visit using a multivariate logistic model adjusted for age, sex, and Charlson Comorbidity Index (CCI). RESULTS: Among 1412 residents recruited, a clear direct relationship was found between higher anticholinergic burden and cognitive impairment only for the Anticholinergic Cognitive Burden Scale. Residents taking an anticholinergic who scored 5 or more had 2.5 points more decline than those not taking them (p < 0.001). Among residents without dementia there was a trend toward direct relationship for the Anticholinergic Cognitive Burden Scale and the Anticholinergic Risk Scale. Residents with higher scores had about 2 points more decline than residents not taking anticholinergic drugs. No relation was found between anticholinergic burden and cognitive decline or mortality. CONCLUSIONS: The cumulative effect of medications with modest antimuscarinic activity may influence the cognitive performance of NH residents. The anticholinergic burden measured with the ACB scale should help identify NH residents who may benefit from reducing the anticholinergic burden. A clear direct relationship between anticholinergic burden and cognitive impairment was found only for the ACB Scale.

Factors Associated with a High-Risk Profile for Developing Pressure Injuries in Long-Term Residents of Nursing Homes.

OBJECTIVES: Pressure injuries are a health problem of special concern for older adults, and different scales are used to assess the risk of developing these ulcers. We assessed the prevalence of residents at high risk of pressure injuries using a Norton scale and examined its relationships with the most important risk factors in a large sample of Italian nursing homes (NHs). METHOD: This was a cross-sectional cohort study in a sample of Italian long-term care NHs with data collected between 2018 and 2020. RESULTS: We recruited 2,604 NH residents; 1,252 had Norton scale scores, 41 (3.3%) had a diagnosis of pressure injuries, 571 (45.6%) had a Norton score ≤9, and 453 (36.2%) had a score between 10 and 14. The univariate model showed a relationship between female sex, age, dementia, and cerebrovascular disease with a Norton scale score ≤9. The significant associations were confirmed in the multivariate model with stepwise selection. CONCLUSION: The prevalence of NH residents at high risk of pressure injuries was very high using the Norton scale, but the percentage of residents who develop these ulcers is lower. Female NH residents with advanced age, dementia, and a history of cerebrovascular disease should be carefully monitored.

Prevalence of Pharmacologic Treatments for Chronic Obstructive Pulmonary Disease in Relation of Diagnosis of Dementia Among Nursing Homes Residents.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a chronic disease affecting millions of older adults. We investigated the prevalence of nursing home (NH) residents with COPD and their pharmacologic treatment in relation to the diagnosis of dementia and the prevalence of potentially severe drug-drug interactions (DDIs) of COPD medications with drugs prescribed to treat comorbidities. DESIGN: Retrospective cross-sectional multicentre study. SETTING AND PARTICIPANTS: Individuals living in long-term care NHs. METHODS: This cross-sectional cohort study was conducted in a sample of Italian long-term care NHs located throughout the country. Information on drug prescriptions, diseases, and sociodemographic characteristics was collected using medical records between 2018 and 2020. Potentially severe DDIs were analyzed using INTERCheck, developed by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS. RESULTS: Among the 2604 residents living in 27 NHs (mean age 86.4 ± 8.5 years; women 1995, 76.6%; number of drugs 7.3 ± 3.6), 306 had a diagnosis of COPD (11.8%) and 84 (27.5%) of them were treated with at least 1 medication for COPD (27.5%). Those without dementia had a higher prevalence of drugs for COPD than those with dementia (48% vs 20%, P < .0001). The most used classes for COPD were adrenergics in combination with corticosteroids (16.7%) and inhalant anticholinergics (14.7%). Among those receiving medications for COPD, 45 had at least 1 potentially severe DDI with medications for comorbidities (53.6%) and most of them were associated with an increased risk of QTc prolongation, as beta2 agonists with diuretics, antipsychotics or antidepressants. CONCLUSIONS AND IMPLICATIONS: Most NH residents with COPD did not receive any medication for this disease despite the potential benefits. Residents with dementia received fewer COPD medications probably because of their compromised physical and cognitive status. One-half of the NH residents taking medication for COPD were exposed to an increased risk of QTc prolongation and torsades de pointe because of pharmacodynamic DDIs with medication for comorbidities. Close monitoring of electrocardiograms for NH residents with COPD is recommended.

Anemia in nursing homes, proton pump inhibitors and prescribing cascade of antianemic drugs.

PURPOSE: Some medications can cause anemia through their effect on gastrointestinal function, such as proton pump inhibitors and H2-antagonists, and on the risk of bleeding, such as anticoagulants and antiplatelet agents. The main aim of this study is to evaluate how anemia is related with the most commonly used drugs in a large sample of NH residents. METHODS: This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term care NHs distributed throughout the country. RESULTS: In all, 2602 NH residents recruited from 27 Italian long-term NHs (mean age ± SD: 88.4 ± 8.5) and 441 (16.9%) had a diagnosis of anemia. The unadjusted model showed a significant relation with PPI (OR 1.71, 95% CI 1.39-2.11, p < 0.0001). This relation was maintained in the model adjusted for age, sex, CKD, atrophic gastritis, peptic ulcer and rheumatic disease (OR 1.61, 95% CI 1.31-1.99, p < 0.0001). PPI users were also at higher risk of being treated with antianemic drugs-iron supplements, folate, vitamin B12 and erythropoietin (OR 2.03, 95% CI 1.67-2.48, p < 0.0001)-even if they did not have anemia (OR 1.94, 95% CI 1.55-2.42, p < 0.0001). CONCLUSION: Proton pump inhibitors are associated with anemia in NH residents. PPIs are also related with an increased probability of receiving drugs to treat anemia, such as iron supplements, folate or cyanocobalamin and erythropoietin, as the effect of a prescribing cascade. Optimization of PPI prescription is needed to avoid adverse events and promote rational drug prescription.

Laxative Agents in Nursing Homes: An Example of Prescribing Cascade.

OBJECTIVES: Laxatives are among the most prescribed medications to nursing home (NH) patients, and we evaluated the hypothesis that laxative agents could be prescribed as a result of a prescribing cascade. The aims of the study are (1) to investigate the use of laxative drugs in a large sample of Italian NHs and (2) to assess the relationship between medications that can induce constipation and laxative use. DESIGN: Retrospective cross-sectional multicenter study. SETTING AND PARTICIPANTS: Individuals living in long-term care NHs. METHODS: Study conducted in a sample of Italian long-term care NHs distributed throughout the country. Information on drug prescriptions, diseases and sociodemographic characteristics collected 4 times during 2018 and 2019. RESULTS: Among the 2602 patients recruited from 27 NHs (mean age ± standard deviation: 88.4 ± 8.5; women: 1994, 76.6%), 1248 were receiving laxatives (48%). Parkinson disease, cerebrovascular disease, and hemiplegia were associated with laxative prescription, and diabetes was associated with a decrease. Benzodiazepines, anti-Parkinson dopaminergic agents, and antidepressants (tricyclic antidepressants and mirtazapine) were associated with laxative treatment in univariate and adjusted models. Tricyclic antidepressants users were 3 times more likely to be taking laxatives than nonusers (odds ratio 2.98, 95% confidence interval 1.31-6.77, P = .0093). A larger number of drugs that can induce constipation was associated with laxative use (P = .0003). In all, 2002 individuals had at least 2 different prescription times: from the first to the last visit laxative use rose from 46.1% to 49.9%. Time of stay was also associated with laxative use (P = .016). CONCLUSIONS AND IMPLICATIONS: Laxatives are among the most prescribed medications in Italian NHs. Medications that can induce constipation, such as antidepressants, anti-Parkinson dopaminergic agents, and benzodiazepines, are often used together with laxatives, and combinations of these drugs further increase the use of laxatives. Optimizing the prescription of psychotropic drugs could help reduce the "prescribing cascade" with laxatives. The length of stay in NHs is often proportional to laxative use and chronic treatment is very common.

Comparison between drug therapy-based comorbidity indices and the Charlson Comorbidity Index for the detection of severe multimorbidity in older subjects.

BACKGROUND: To know burden disease of a patient is a key point for clinical practice and research, especially in the elderly. Charlson's Comorbidity Index (CCI) is the most widely used rating system, but when diagnoses are not available therapy-based comorbidity indices (TBCI) are an alternative. However, their performance is debated. This study compares the relations between Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), Chronic Disease Score (CDS), and severe multimorbidity, according to the CCI classification, in the elderly. METHODS: Logistic regression and Receiver Operating Characteristic (ROC) analysis were conducted on two samples from Italy: 2579 nursing home residents (Korian sample) and 7505 older adults admitted acutely to geriatric or internal medicine wards (REPOSI sample). RESULTS: The proportion of subjects with severe comorbidity rose with TBCI score increment, but the Area Under the Curve (AUC) for the CDS (Korian: 0.70, REPOSI: 0.79) and MCI (Korian: 0.69, REPOSI: 0.81) were definitely better than the DDCI (Korian: 0.66, REPOSI: 0.74). All TBCIs showed low Positive Predictive Values (maximum: 0.066 in REPOSI and 0.317 in Korian) for the detection of severe multimorbidity. CONCLUSION: CDS and MCI were better predictors of severe multimorbidity in older adults than DDCI, according to the CCI classification. A high CCI score was related to a high TBCI. However, the opposite is not necessarily true probably because of non-evidence-based prescriptions or physicians' prescribing attitudes. TBCIs did not appear selective for detecting of severe multimorbidity, though they could be used as a measure of disease burden, in the absence of other solutions.

Inappropriate use of antiplatelet agents for primary prevention in nursing homes: An Italian multicenter observational study.

AIM: The benefits of antiplatelets to prevent cardio- and cerebrovascular disease are recognized and appropriate only for "secondary prevention." This multicenter retrospective study was designed to (i) examine the prevalence of residents receiving antiplatelets for primary and secondary cardio- and cerebrovascular prevention, and (ii) evaluate the predictors of inappropriate antiplatelet prescription. METHODS: This study was conducted in a sample of Italian long-term care nursing homes (NHs). Appropriate use of antiplatelets was defined in accordance with the strongest evidence-based indications. RESULTS: Among the 2579 patients recruited from 27 long-term care NHs (age mean ± SD: 86.8 ± 7.3; women: 1995; 77.4%), 1092 were treated with antiplatelets (42.3%) and 619 (56.7%) were receiving antiplatelet agents for inappropriate primary prevention of cardio- or cerebrovascular atherothrombotic events. Age, dementia or cerebral atherosclerosis, congestive heart failure, peripheral vascular disease, diabetes without chronic complication and hypertension were predictors of inappropriate prescription of antiplatelets. Patients inappropriately treated with antiplatelets also had a higher risk of receiving proton pump inhibitors than those appropriately not treated in univariate (OR 95% CI = 2.79 (2.25-3.46, p < 0.0001) and multivariate models (OR 95% CI 2.71 (2.16-3.40, p < 0.0001). CONCLUSIONS: Most patients receiving antiplatelet agents in NHs are being inappropriately treated for primary prevention of cardio- or cerebrovascular disease. NH residents with diagnosis of dementia or cerebral atherosclerosis, congestive heart failure, peripheral vascular disease, diabetes without chronic complication and hypertension seemed more likely to receive antiplatelets inappropriately. Patients without an evidence-based indication for antiplatelets also received proton-pump inhibitors in an unnecessary "prescribing cascade," which should be assessed for de-prescribing. Geriatr Gerontol Int 2020; 20: 828-832.

Overuse of proton pump inhibitors in nursing homes: An Italian multicenter observational study.

PURPOSE: To examine the prevalence of residents receiving proton pump inhibitors (PPIs) for evidence-based indications in a large sample of Italian nursing homes (NHs) and to assess the predictors of potentially inappropriate prescriptions. METHODS: This study was conducted in a sample of Italian long-term care NHs. Information on drug prescription, diseases, and socio-demographic characteristics of NH residents was collected three times during 2018. Appropriate use of PPI was defined in accordance with the strongest evidence-based indications and the Italian criteria for PPI prescription. RESULTS: Among the 2579 patients recruited from 27 long-term care NHs, 1177 (45.6%) were receiving PPIs; 597 (50.7%) were taking them for evidence-based indications. Corticosteroids, anticoagulants, and mean number of drugs were the most important predictors of inappropriate PPIs prescriptions. NH residents receiving ≥13 drugs had about 10 times the risk of receiving a PPI than those taking 0 to 4 drugs. Similarly, residents with more comorbidity had about 2.5 times the risk of receiving a PPI than those in better health. The prevalence of residents inappropriately treated with PPI in individual NHs varied widely, ranging from 22% to 63%. CONCLUSIONS: Number of drugs, comorbidity, corticosteroids, and anticoagulants are the most important predictors of the inappropriate use of PPI in NHs. The wide variability between NHs in the appropriate use of PPIs suggests the need for thorough drug review in this fragile and vulnerable population. Prescribing patterns linked to evidence-based guidelines and national recommendations are essential for rational, cost-effective use of PPIs.