Bisphosphonate-associated psychiatric adverse events: a signal from the Italian pharmacovigilance database

Background: Oral and intravenous bisphosphonates (alendronate, risedronate, pamidronate, ibandronate and zoledronate), used in oncology and for the treatment of osteoporosis, have been associated with different types of adverse reactions (ADRs) as oesophageal ulcer, influenza-like illness, hypocalcaemia, musculoskeletal pain, osteonecrosis of the jaw and ocular events. The frequency of these reactions is variable, in relation to the different single bisphosphonates, type of use, route of administration, dosage and duration of therapy. In literature no case of psychiatric disorders related to bisphosphonates is reported. The summary of product characteristics of pamidronate and zoledronate lists some psychiatric disorders as anxiety and sleep disturbances, all reported among uncommon events. No psychiatric adverse events are mentioned for the other bisphosphonates. Aim: To describe and discuss the spontaneous reports of psychiatric disorders associated to bisphosphonates in the Italian Pharmacovigilance Database. Methods: The database holds reports of suspected ADRs submitted since 1988. Within spontaneous reporting system in Italy the database is analysed twice in a year to filter out potential signals. Signal detection is done by qualitative case-by-case analysis and by using quantitative methodology like Proportional Reporting Ratio (PRR). Results: The database actually holds 110 497 reports, 90.1% of them coming from physicians, 4.9% from pharmacists, 1.4% from nurses and 0.3% from consumers. In 1260 reports a bisphosphonate is reported among the suspected drugs. Among these reports, 29 (2.3%) referred at least one psychiatric disorders. [...]