Persistent Opioid Use and Concurrent Psychotropic Prescription Tied to Opioid-related Deaths

Pavankumar Kamat


August 20, 2021


  • Persistent opioid utilisation (POU) and concurrent psychotropic prescription (tricyclic antidepressants [TCAs], benzodiazepines [BZDs] and gabapentinoids) were associated with an increased risk of opioid-related deaths.

Why this matters

  • Findings suggest that health care providers should evaluate the history of POU rather than the daily opioid dose alone when considering the safety of prescribed opioids.

Study design

  • A nested case-control study of 902,149 opioid users from the UK Clinical Practice Research Datalink linked to the Office for National Statistics (ONS) death registration.

  • Of 902,149 opioid users, 230 opioid-related deaths (cases) were matched (1:4) to 920 control participants based on a disease risk score.

  • POU (opioid prescriptions ≥3 quarters/year and oral morphine equivalent dose ≥4500 mg/year) and psychotropic prescriptions were identified during the 3 patient-years before the date of opioid-related deaths.

  • Funding: None.

Key results

  • Compared with non-POU, POU during the 3 patient-years was significantly associated with a higher risk of opioid-related deaths (adjusted OR [aOR], 1.9; 95% CI, 1.2-2.9; P=.0057).

  • Compared with non-concurrent antipsychotic prescription, concurrent prescription of opioids and antipsychotics during the 3 patient-years was significantly associated with an increased risk of opioid-related deaths (aOR, 4.3; 95% CI, 2.5-7.3; P<.0001).

  • During the 3 patient-years, the risk of opioid-related deaths increased with the use of concurrent prescription of opioids and (aOR; 95% CI):

    • >1 defined daily dose (DDD) of gabapentinoids (6.2; 2.9-13.5; P<.0001);

    • >0.5 DDD of TCAs (2.0; 1.2-3.5; P=.0342); and

    • <1 DDD of BZDs (3.6; 2.1-6.2) or >1 DDD of BZDs (6.5; 4.0-10.4; P<.0001 for both).


  • Only 54.8% of all opioid users were registered in practices eligible for linkage to the ONS death registration.


Chen TC, Knaggs RD, Chen LC. Association between opioid-related deaths and persistent opioid prescribing in primary care in England: a nested case-control study. Br J Clin Pharmacol. 2021 Aug 09 [Epub ahead of print]. doi: 10.1111/bcp.15028. PMID: 34371521.  View abstract .

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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