Pain is a common symptom reported by patients in both medical and surgical settings [1, 2]. Given the multidimensional and subjective nature of pain, together with the large variability in response to medications, many prescribers are guided in their therapeutic choices essentially by pain severity scores [1]. The World Health Organization (WHO) has developed a pain ladder, conceived for patients with cancer, based on three steps where the degree of pain divided into (1) mild, (2) mild-to-moderate, and (3) moderate-to-severe, corresponds with the matching therapeutic recommendations.

Pain management involves a comprehensive approach, including pharmacological, non-pharmacological, and interventional therapies [4, 5]. In patients with mild pain, non-opioid drugs such as paracetamol, aspirin, or alternatively non-steroidal anti-inflammatory drugs (NSAIDs) are considered as adequate. In patients with moderately severe pain, if adequate relief is not achieved with non-opioids administered on a regular basis, codeine is suggested as an alternative weak opioid. In patients with severe pain, morphine is the drug of choice, with proper dose adjustment, although opioids are now used cautiously due to addiction concerns [3, 6].

However, it has been reported that, in more the half of the cases (52.6%), pain medications are administered with a possible prescription appropriateness [1, 7]. In particular, the possible misuse of NSAIDs, especially in the older and frail population [7], still represents an open issue in the assessment of potentially inappropriate prescribing, and suggests the need for the re-evaluation of pain management strategies. In this context, one point to be noted is that paracetamol, the analgesic of choice for tolerability and manageability, especially in patients with non-neoplastic pain, is less commonly utilized in Italy than in other European countries: the international comparison of the top 20 active ingredients revealed that paracetamol occupies the eighth rank in Italy, with respect to the first rank in Belgium, France, Portugal, Spain and Sweden, and the second rank in UK and the whole of Europe [8]. In addition, the increased use of NSAIDs might also be related to some cultural barriers for opioid drugs in Mediterranean countries [9, 10], together with a suboptimal awareness and insufficient patient education on the safety profile of NSAIDs [11]. In a nutshell, while NSAIDs offer significant benefits in pain and inflammation management, it is crucial to balance these advantages against the potential risks, in terms of possible cardiovascular, gastrointestinal, hepatic, and renal side effects. Healthcare providers should conduct thorough assessments to ensure the safe and effective use of NSAIDs, tailoring treatment plans to individual patient needs and risk profiles [12,13,14].

The use of NSAIDs to treat both acute and chronic pain has grown significantly over the last years in Italy. The OsMed report of the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) on the national drug utilization in 2022 revealed that approximately 16 out of 100 citizens received at least one prescription of NSAIDs, with higher exposure levels in females (18.1%) than in males (13.7%) [15]. Moreover, based on the epidemiology of certain clinical conditions such as arthritis and osteoarthritis, for which these drugs are used, consumption increases with age reaching the maximum value of defined daily dose (DDD) in the 75–84 age group, up to 53.3 DDD/1000 people in women and 37.6 DDD/1000 people in men [15]. These rising trends have been confirmed in the most recent OsMed report (released on November 12, 2024) which showed a delta increase between 2022 and 2023 of 2.8% for DDD of NSAIDs and 8% delta for the expenses per capita [16].

During the last decade, Italy emerged as the European country with the highest consumption of NSAIDs with a markedly larger proportion of pain symptoms controlled through the administration of an NSAID compared to other nations [17].

This poses the question of whether NSAIDs are prescribed without a proper assessment of the origin of the pain and of the actual need for an anti-inflammatory drug, also resulting in incorrect dosage and duration of treatment [18, 19]. According to the scientific literature and the indications of the regulatory authorities, the use of NSAIDs should be limited to the minimum effective dosage and the shortest possible time because of the cardiovascular, gastrointestinal, hepatic, and renal side effects that chronic use can induce [12,13,14].

An even more extensive utilization of NSAIDs was observed during the pandemic period, most probably due to the recommendations for use in the symptomatic treatment of patients with COVID-19 at home [20]. This trend has remained constant in the subsequent period, with a 7.1% increase of NSAID prescriptions in Italy during 2021 [5].

The prescription of NSAIDs covered by the Italian National Health Service (NHS) is limited to the list of pathologies defined in last update of the Note 66 released by AIFA in 2018, which includes arthropathy, osteoarthritis, neoplastic pain, and acute gout attack. The rationale of AIFA Note 66 is to ensure the appropriate use of NSAIDs, with the ultimate goal of encouraging clinicians to weigh the risks and benefits of these medications. This approach is meant to reduce unnecessary drug use, to ensure that NSAIDs are prescribed only when needed, and to minimize adverse health outcomes related to inappropriate use [22].

With the exception of the above-mentioned conditions, all the other indications included in the summary of product characteristics are not reimbursed by the NHS and therefore are paid by the patient (out-of-pocket).

This analysis was conducted in normal Italian clinical practice to describe the use of NSAIDs with respect to the latest update of the AIFA Note 66, focusing on the following objectives: (1) describing the main characteristics of patients treated with NSAIDs, namely age, sex distribution and conditions for which NSAIDs were prescribed; (2) assessing NSAID consumption in the period 2019–2023, in terms of main active ingredients prescribed, number of patients treated, and dosage (DDD/1000 inhabitants); and (3) defining the therapeutic pathways and drug utilization in patients treated with NSAIDs, with a focus on the most prescribed molecules, duration of treatment, sequence of treatments, combinations, and dosages.