Paracetamol: A History of Assumptions, Errors, and Evidence Reversals in Pain Management
Abstract
Purpose of review: Paracetamol (acetaminophen) is among the most widely used medications in the history of humanity for treatment of pain conditions. For more than half a century, it has occupied a unique position as the archetypal first-line analgesic and antipyretic, recommended across age groups, clinical settings, and healthcare systems. Its remarkable success has been based on three fundamental assumptions: it is effective for common painful conditions, substantially safer than alternative analgesics, and suitable for broad population use with minimal restrictions. Over the last two decades, however, these assumptions have been increasingly challenged by accumulating evidence from randomized trials, systematic reviews, pharmaco-epidemiological studies, and regulatory analyses.
Recent findings: The history of paracetamol represents an instructive example of evidence reversal in modern medicine and pain management. Originally introduced as a safer successor to phenacetin, paracetamol benefited from a favorable safety reputation that often exceeded the available scientific evidence. Subsequent investigations have revealed a more complex reality. Hepatotoxicity has emerged as a leading cause of acute liver failure worldwide, efficacy in chronic musculoskeletal disorders has proved substantially lower than previously assumed, and concerns regarding long-term safety and use during pregnancy have generated ongoing scientific debate. Simultaneously, clinical practice and…
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