Phd in PHARMACOLOGY AND TOXICOLOGY

Thesis title: SOGGETTI ANZIANI E CON DEMENZA: STUDI FARMACOEPIDEMIOLOGICI SULL’USO E LA SICUREZZA D’IMPIEGO DI FARMACI E PRODOTTI DI ORIGINE NATURALE

Title: Elderly people and patients with dementia: pharmacoepidemiological studies on the use and safety of medicines and natural products Introduction: From a public health perspective, epidemiological studies need to be planned to improve scientific knowledge on the appropriate use of drugs and the safety of natural products in frail individuals, such as the elderly. The aim of this PhD thesis is to describe the in-depth studies carried out during the doctoral period, which had the common objective of describing the characteristics of the elderly population in Italy, with a focus on individuals with dementia, a neurodegenerative disease typical of ageing. Specifically, the first study (two in-depth analyses) concerned descriptive studies on the use of anti-dementia drugs and cannabis-based magistral preparations, while the second study (two other in-depth analyses) concerned the safe use of cannabis magistral preparations and food supplements. Material and methods: For the descriptive study at the national level, the pharmaceutical prescription database (e.g OsMed flow) and a platform coordinated by the Italian National Institute of Health were used, respectively, for anti-dementia drugs and for cannabis preparations. The main indicators of consumption and intensity of use were DDD/1000 inhabitants per day and prescriptions per user, respectively. For the two studies on the safety of natural products (cannabis and food supplements), data from the VigiErbe platform coordinated by the Italian National Institute of Health were analysed. When possible, reports were evaluated using a standardised assessment scale adapted from the World Health Organisation system. Results: The consumption of drugs indicated for dementia at the national level remained stable over the three years considered (2018-2020) at ~9 DDD/1000 inhabitants per day. The consumption of Acetylcholinesterase inhibitors (AChEIs) was just over 5 DDD/1000 inhabitants per day (donepezil accounting for 60% of the total). Memantine consumption was almost 4 DDD/1000 inhabitants per day (40% of the total), which increased steadily over the three years studied. Among all users (more than 185,500), 50% received at least one AChEI, 37% received memantine, and 13% received a combination of two or more drugs, with an average of 7.4 prescriptions per user. The total number of cannabis prescriptions for patients over 65 during the study period was 65,598, accounting for approximately 80% of total cannabis prescriptions on the platform. The analysis shows that, overall, the number of prescriptions decreases with age. Females are more likely to receive a prescription than males (71.8% vs. 27.4%) for all age groups. During the study period, an average of 3.2 prescriptions per user were issued. From 1st January 2002 to 31st July 2025, the VigiErbe platform collected 83 reports of suspected adverse reactions following the use of cannabis-based magistral preparations, none of which related to patients with dementia. Moreover, 541 reports indicated food supplements as suspected products, and 11 reports referred to patients with dementia. In all investigations, reports were more frequent among females (approximately 70%) than among males, and the majority of reports came from healthcare professionals. The most frequent cannabis reactions were neurological (22.6%) and psychiatric (20.4%), followed by gastrointestinal reactions (15.3%), while those related to supplements were mainly related to gastrointestinal disorders (23.7%) and skin and subcutaneous tissue disorders. A causal link was established for reports of cannabis (44% probable, 56% possible) and for reports of supplements in patients with dementia (45.5% probable, 54.5% possible). In all safety investigations, reports indicated a high number of concomitant medications. Specifically, all but two patients with dementia were taking concomitant medications in addition to supplements, which may have led to interactions that could have caused the adverse reactions. Conclusions: Understanding doctors' prescribing habits and older people's consumption habits for medicines and food supplements is the basis for implementing corrective measures, focusing attention on potential adverse events that may arise after use. These insights can provide useful information for assessing the benefit/risk ratio, raising awareness that a drug or natural product is not necessarily safe or useful for the treatment of elderly patients by definition.