Misuse of the Naranjo Adverse Drug Reaction Probability Scale in toxicology.

CONTEXT: When an adverse event occurs in an overdose patient, it may be difficult to determine whether the event was caused by the ingested drug or by medical therapy. Naranjo et al. developed a probability scale, the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale), to assess the probability that a drug administered in therapeutic doses caused an adverse event thereby classifying the event as an adverse drug reaction (ADR). Although Naranjo et al. specifically excluded the application of this scale to adverse events in overdose patients, case reports demonstrate that authors continue to apply the Naranjo Scale to events in these patients.
OBJECTIVE: The World Health Organization defines an ADR as occurring only when drugs are administered in therapeutic doses. Yet ADRs continue to be reported in overdose patients. We sought to examine the use of the Naranjo scale in case reports of overdose patients to assess the potential consequences of that application.
METHODS: A Medline search via PubMed without language limits, through September 2012, using the search terms "Naranjo" and "overdose" or "poisoning" yielded 146 publications. Additional searches were performed to find articles with keywords of the Naranjo Scale development, current applications and validity of application in specific populations such as critically ill and overdose patients.
RESULTS: From the 146 publications, we identified 17 case reports or case series of overdose patients in which the Naranjo Scale was applied to a clinical complication to support a causal relationship between an administered drug and the clinical complication and thereby classify the clinical complication as an ADR. We also identified a recent publication in which the Naranjo Scale was applied to a new treatment modality (lipid emulsion) that is currently administered to overdose patients. Original publication of the Naranjo Scale and studies evaluating its use in critically ill patients or those with drug-induced disease were also retrieved.
CONCLUSION: Adverse events that occur in overdose patients are excluded from the definition of ADR. Yet in case reports or series of overdose patients, the Naranjo Scale has been applied to assess the probability an event was caused by the ingested drug or therapeutic modality. This application of the Naranjo Scale is not scientifically valid and may lead to erroneous conclusions. There is no evidence to support the application of the Naranjo scale to any events that occur in overdose patients.