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Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j760 (Published 14 March 2017) Cite this as: BMJ 2017;356:j760

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Drugs Pharmacodynamics’ make predictable the dangerous association of benzodiazepines with opioids. Re: Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis

This very interesting paper is the epidemiological evidence of the respiratory depressant effect of opioids potentiated by associated benzodiazepines. But, it may be useful to look also for the pharmacodynamics of the drugs associated, to understand the rational (or its absence) of this drug association to treat pain, and also to understand the synergic mechanisms that lead to the respiratory depression, in order to avoid future predictable toxic associations.
Opioids are strong analgesics with the great risk of respiratory depression.
Benzodiazepines are GABAergic drugs that don’t have any analgesic activity, excluding the case of some muscular spasm (by its muscle relaxant activity), or the case of clonazepan on the trigeminal neuropathic pain. So it seems that there is no rational to justify the association of benzodiazepine with analgesics like opioids.
On the other side, this association increases the risk of respiratory depression of opioids, since benzodiazepines are also central nervous system depressors, and although their depressive effect is lower than that of barbiturates, they are may even depress the activity of the respiratory center when in overdose, and surely they potentiate the effect of other depressant agents such as opioids. Furthermore, by their relaxant effect on muscle tone may be dangerous on patients with obstructive sleep apnea.
All these reasons make very dangerous the association of these 2 kind of drugs, as it is emphasized by the recent guidelines (JAMA. 2016;315(15):1624-1645. doi:10.1001/jama.2016.1464 ).

Competing interests: No competing interests

23 March 2017
Fernando Martins do Vale
Prof. Pharmacology and Clinical Pharmacologist
Instituto de Farmacologia/Neurociências, Centro Bioética, IMM of Faculdade de Medicina da Universidade de Lisboa
Faculdade de Medicina da Universidade de Lisboa. 1649-028 Lisboa, Portugal