Erratum to: Deliberate Self-Poisoning: Real-Time Characterization of Suicidal Habits and Toxidromes in the Food and Drug Administration Adverse Event Reporting System (Drug Safety, (2023), 46, 3, (283-295), 10.1007/s40264-022-01269-x)

Dear Editor, On May 4th 2023, the article published in Drug Safety by Fusaroli et al. [1] was presented and discussed in a journal club hosted by the Italian chapter of the International Society of Pharmacovigilance (ISoP). In this interesting article, the authors analysed an impressive series of reports on the phenomenon of deliberate self-poisoning (DSP) using the US FDA Adverse Event Reporting System (FAERS) pharmacovigilance database [1]. This study highlighted, quantified, and characterised a drug safety issue, which is the DSP phenomenon, which may not be adequately examined using other available data sources, such as those cited by the authors (forensic autopsy records, forensic toxicology databases or the Office for National Statistics). We found it quite intriguing and somewhat surprising that a pharmacovigilance database was utilised to characterise such an event that, although closely associated with drug safety, does not seem to fit the conventional definition of an adverse event (AE) or a suspected adverse drug reaction ADR), specifically with regard to the concept of non-intentionality. An AE can happen during or after the use of a medical product, but it’s not necessarily caused by it, while an ADR is a harmful and unintended response specifically caused by the use of a medical product [2]. Both ‘adverse event’ and ‘adverse reaction’ are characterised by non-intentionality, meaning that they are not intentionally caused. The document ‘definitions and standards for expedited reporting E2A’ by the International Conference on Harmonisation (ICH E2A), reported a definition of ADR in the post-marketing context, based on the WHO Technical Report Series 498 [1972], which already incorporates the notion of non-intentionality: ‘A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function’ [3]. It’s important to note that the ICH E2A guidelines are reference documents of the US FDA [4]. The European Medicine Agency (EMA), the Good Pharmacovigilance Practice (GVP) Annex I—definitions state that an ADR is ‘a response to a medicinal product which is noxious and unintended’. Also, this definition emphasises that an ADR is a harmful response that is not intended or expected from the use of the medicinal product. Notably, an update of this definition states that ADRs can arise from use outside the terms of the marketing authorisation, including overdose, off-label use, misuse, abuse and medication errors and the occupational exposure [4]. About the overdose, the FDA clarifies that an AE can occur from drug overdose whether accidental or intentional [5]. However, DSP cases should not be confused with the concept of voluntary abuse or overdose in which the patient has a recreational purpose or seeks a greater therapeutic effect. Deliberate self-poisoning case is defined precisely by the voluntary search for the toxic effect of the drug, i.e., an AE of the drug for anti-conservative purposes, which would seem to be inconsistent with the definition of AE or a suspected ADR. It is also important to note that in their article, Fusaroli et al. [1] excluded from the analysis cases of suicidal ideation induced by drugs and accidental overdose, so we are essentially dealing with cases in which the drug is only the means used for self-harm. In light of the above, one may question whether collecting DSP cases through the pharmacovigilance system makes sense. Because FAERS database (and probably other large similar repositories) contain numerous reports of DSP cases, many reporters may answer yes. Nevertheless, to address this question, it is important to consider the overall goals of pharmacovigilance, which WHO defines as ‘the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine related problem’ [6]. Hence, pharmacovigilance should take an interest in any safety-related issues pertaining to the use of drugs, regardless of whether they align with the definition of an AE. This is especially important when it is possible to intervene through specific actions that can reduce the risks associated with the use of drugs. In our opinion, this type of event should be included in pharmacovigilance databases, because these can produce information that may support regulatory agencies and national governments to implement risk minimisation measures. For instance, restrictions (e.g., limited dispensable dose) can be placed on the ease of patient access to certain drugs that are prone to self-poisoning, with a particular caution for subjects with history of psychiatric disorders. Moreover, appropriate information campaigns can be implemented to raise awareness among health care providers and tutors about the drugs most frequently used for self-deliberated poisoning with recommendation for implementation of access restrictions at home (e.g., keeping drugs in locked drawer or boxes). In our opinion, it would be appropriate to initiate a discussion on formulating regulatory definitions that encompass drug-related SPD as reportable events in spontaneous reporting systems. Similar to AEs resulting from abuse, misuse, overdose, or medication errors, drug-related SPDs are significant events that warrant reporting. Including them in reporting systems can help to identify and characterise emerging drug safety concerns, improve surveillance, and ultimately defend patients who voluntarily self-harm.