Dear Editor,
With great interest we read the article of Tardelli et al. about the perceived increase of overdose-deaths “due to” non-benzodiazepine hypnotics including gabapentinoids (GPT) over the last two decades extrapolated from USA National Center for Health Statistics data.1 We have not seen comparable phenomena in Germany, despite the highest Western-European rate of non-medical GPT-use.2 German addiction medicine experts have recently characterized GPT as low-harm drugs (despite abuse potential)3 which stands in striking contrast to concerns emanating from countries experiencing opioid epidemics.4
That distinction may in itself provide an explanation for this regional variation; the opioid epidemic experienced by North-America and other Western nations (but not prevalent in Germany!) may serve as an amplifier of GPT-misuse and GPT-toxicity. Epidemiologically, geographic variation in GPT-misuse seems to overlap with that of opioid-analgesics in the USA5 perhaps reflecting changing prescribing and self-medication behaviors utilizing GPT as one solution to curb excess opioid-use, as well as opioid-withdrawal. Biologically, supratherapeutic GPT-doses may not only augment opioid-induced sedation but have also been suspected to reverse tolerance to opioid-induced respiratory depression.6 Both mechanisms may act synergistically to increase the risk of respiratory failure and accidents, an assumption however still awaiting verification by controlled clinical studies.
Finally, supranormal post-mortem drug-concentrations do not comprise sufficient grounds to establish a causal relation to death without an in-depth analysis of each individual case (i.e., an assessment by an experienced toxicologist). The reported rise in post-mortem GPT-samples might therefore be confounding with not identified more toxic drugs and/or severe comorbidity comprising the actual cause of death.
Declaration of interests
The authors have no conflict of interest to declare.
References
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