Hyponatraemia as an adverse drug reaction of antipsychotic drugs: a case-control study in VigiBase.

BACKGROUND: Hyponatraemia due to antipsychotic use is a potentially serious problem; however, it is not known whether it is an adverse drug reaction (ADR) to antipsychotic use or is due to the underlying psychiatric disease. OBJECTIVE: To estimate the strength of the association between antipsychotics and hyponatraemia or syndrome of inappropriate antidiuretic hormone secretion (SIADH), using information reported to the WHO Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre (UMC). SETTING: The WHO global individual case safety report database system (VigiBase) maintained by the UMC. STUDY DESIGN: Case-control study, with cases being reports of hyponatraemia/SIADH, and controls being reports of other ADRs. Each case was sampled with ten controls sequencing in time from the date the corresponding case was entered into the database. The potential contribution of the chemical structures and receptor affinity (dopaminergic and/or serotonergic) of the antipsychotics was studied, as was the influence of concomitant use of other medications known to cause hyponatraemia. MAIN OUTCOME MEASURES: The strength of the association between antipsychotic use and hyponatraemia in comparison with other drugs was expressed as reporting odds ratio (ROR), a measure of disproportionality, with corresponding 95% CIs, adjusted for age, sex and concomitant medication associated with hyponatraemia. In addition, stratification by the presence or absence of concomitant medication was performed. RESULTS: Up to August 2008, 3 881 518 suspected ADRs were reported and filed in VigiBase, with 912 reports on hyponatraemia related to antipsychotics. The adjusted ROR for the association between antipsychotic use and hyponatraemia was 1.58 (95% CI 1.46, 1.70). The adjusted RORs did not vary for the different chemical structures or dopamine D(2) and serotonin 5-HT(2A) receptor affinity profiles. The ROR was 3.00 (95% CI 2.65, 3.39) for the association between hyponatraemia and antipsychotic use in the absence of concomitant medication associated with hyponatraemia, and 1.16 (95% CI 1.06, 1.28) in the presence of concomitant medication associated with hyponatraemia. CONCLUSIONS: Antipsychotic use may be associated with reporting of hyponatraemia. Moreover, the concomitant use of medication associated with hyponatraemia potentially leads to under-reporting of antipsychotic-associated hyponatraemia. We advise testing patients whose psychiatric and/or physical condition deteriorates while on antipsychotics for hyponatraemia

Contribution of adverse drug reactions to hospital admission of older patients

OBJECTIVE: To describe the severity of adverse drug reactions as a factor in hospital admission of older patients, and to identify risk indicators for severe adverse drug reactions in these patients. DESIGN: Observational cross-sectional study. SETTING: Five wards in a university hospital in The Netherlands. SUBJECTS: Patients aged 70 and over admitted to general medical wards. METHODS: Use of statistical comparison and Kramer's algorithm. RESULTS: A severe adverse drug reaction was present in 25 (24%) of 106 patients. Thirteen patients (12%; 95% confidence interval 6.1-18.6%) were admitted probably because of an adverse drug reaction. Risk indicators for a severe adverse drug reaction were a fall before admission (odds ratio 51.3, P = 0.006), gastrointestinal bleeding or haematuria (odds ratio 19.8, P < 0.001) and the use of three or more drugs (odds ratio 9.8, P = 0.04). CONCLUSION: Adverse drug reactions are an important cause of hospital admissions in older people. A fall before admission may indicate a severe adverse drug reaction

Do older hospital patients recognize adverse drug reactions?

OBJECTIVE: To establish the relationship between subjective complaints of side effects of drugs and the objective presence of adverse drug reactions in older patients. DESIGN: Observational cross-sectional study. SETTING: Five medical wards at the University Hospital Rotterdam Dijkzigt. SUBJECTS: Patients aged 70 and over admitted to the general medical wards over a 3-month period. METHODS: Statistical comparison and Kramer's algorithm. RESULTS: Of 106 patients, 102 used medication, and 93 of these were able to report whether they believed they were experiencing drug side effects. Thirty-six [39% (95% confidence interval 28.8-48.6)] believed that they were experiencing side effects and the number of diagnoses per patient and the proportion of patients with chronic obstructive pulmonary disease was higher in these 36 'complainers' than in the group of the 'non-complainers'. We found a correct opinion (true positive and negative) about the objective presence or absence of mild or severe adverse drug reactions in 79% (95% confidence interval 70.2-86.8). Asking the patient about side effects of drugs had a sensitivity of 0.70 and a specificity of 0.85 patients. The severe adverse drug reactions in 21 patients were not recognized by 14 of them. CONCLUSION: At hospital admission, older patients should be asked about drug side effects because they are often correct in recognizing them. However, severe adverse drug reactions are not easily recognized