Associations Between Biological Adverse Effects and Antidepressants in the Elderly: Investigations Using an Analysis of the Worldwide Pharmacovigilance Database

• Published in: Drug safety Vol. 46; no. 11; p. 1244
• Main Authors: Richard, H, Boulouard, L V, Meurant, A, Fedrizzi, S
• Format: Journal Article
• Language: English
• Published: Auckland Springer Nature B.V 01.11.2023
• Subjects: Antidepressants; Bayesian analysis; Biological effects; Citalopram; Diuretics; Dyslipidemia; Fluoxetine; Hypercholesterolemia; Hyperglycemia; Hyponatremia; Neutropenia; Older people; Paroxetine; Pharmacovigilance; Risk; Sertraline; Side effects; Subgroups; Thrombocytopenia
• ISSN: 0114-5916; 1179-1942

Introduction: Antidepressant (ATD) induced hyponatremia is well-known particularly in the elderly. Concerning other biological adverse drug reactions (ADR), some of them (hypo/hyperglycemia, hypercholesterolemia, agranulocytosis, thrombocytopenia) are mentioned in the summary product characteristics (SPCs) but few data exist in the literature regarding their risk of occurrence, particularly in patients over 75 year old (y.o.) Aim: The aim of our study is to identify ATD associated with all biological ADRs in patients over 75 y.o using a disproportionnality analysis in Vigibase. A comparison with under 75 y.o with a second disproportionality analysis in age subgroups to compare the associations is performed. Method: The inclusion period was from January 1987 to December 2021.Vigibase uses a Bayesian disproportionnality method. The strenght of the ATD/ADR association is defined by the logarithmic measure of disproportionnality (information component « IC »). For each ATD, the IC0.25 was calculated. Events of interest were identified by the 9 Standardized MedDRA Queries (SMQ) relating to a biological ADR. 16 ATD were selected. An additionnal analysis of the 10 most frequently co-prescribed drugs associated with the SMQ hypokaliemia is performed. Results: Data of the literature are confirmed with 4 SMQ (hyponatremia, agranulocytosis, hematopoietic cytopenias, dyslipidemia). Only one new association is identified after 75 y.o with the SMQ hypokaliemia with 5 SRIs: citalopram IC0.25 = 0.98, escitalopram IC0.25 = 0.50, sertraline IC0.25 = 0.9, paroxetine IC0.25 = 0.82, fluoxetine IC0.25 = 0.29. No association is found with the SMQs « hypoglyceamia », « hyperglycemia » and « other hematopoietic effects » whereas these ADR are expected with ATD. 6 out of the 10 most frequently co-prescribed drugs associated with hypokaliemia are diuretics after 75 y.o. Conclusions: This study reinforces certain previously described associations, notably with hyponatremia. For hypokaliemia, this ADR is known only with citalopram and escitalopram, a class effect may be suspected. No mechanism has been identified to explain the link between SRI use and hypokaliemia. Hypokaliemia in the elderly is favored by the use of diuretics with wich hypokaliemia is expected [2]. The combination of SRIs and diuretics should be taken into account in elderly patients, regarding the risk of hypokaliemia. The risk of torsade de pointe (described with SRIs and favored by hypokaliemia) should also be considered. This analysis is only a screening of the biological ADR that may occur with ATD, and the results found need to be confirmed by data with a higher level of evidence.