Same-day use of opioids and other central nervous system depressants amongst people who tamper with pharmaceutical opioids: A retrospective 7-day diary study

Highlights

• 437 people who tamper with pharmaceutical opioids completed 7-day drug use diary.

• Half reported same-day opioid with benzodiazepines/alcohol use (typically 1–3 days).

• One-fifth reported high opioid intake with high benzodiazepine and/or alcohol intake.

• This group generally used both prescribed and diverted/illicit opioids.

• Pervasive but erratic other sedative use warrants attention in opioid prescribing.

Abstract

Objective

The aims were to determine: (i) quantity and frequency of same-day use of opioids with benzodiazepines and/or alcohol amongst people who regularly tamper with pharmaceutical opioids; and (ii) socio-demographic, mental health, harms and treatment profile associated with same-day use of high doses.

Method

The cohort (n = 437) completed a retrospective 7-day diary detailing opioid, benzodiazepine, and alcohol intake. Oral morphine equivalent (OME) units and diazepam equivalent units (DEU) were calculated, with >200 mg OME, >40 mg DEU and >4 standard alcoholic drinks (each 10 g alcohol) considered a “high dose”.

Results

One-half (47%) exclusively consumed opioids without benzodiazepines/alcohol; 26% had days of opioid use with and without benzodiazepines/alcohol; and 26% always used opioids and benzodiazepines/alcohol. Same-day use of opioids with benzodiazepines/alcohol typically occurred on 1–3 days in the past week. Six in ten (61%) participants reported high dose opioid use on at least one day; one in five (20%) reported high dose opioid and high dose benzodiazepine/alcohol use on at least one day. The latter group were more likely to use prescribed opioid substitution therapy, often alongside diverted pharmaceutical opioids. Socio-demographic and clinical profiles did not vary according to high dose opioid, alcohol and benzodiazepine use, and there was no association with harms.

Conclusions

Same-day use of opioids with benzodiazepines/alcohol, and high dose combinations, are common amongst people who tamper with pharmaceutical opioids. Assessment of concomitant benzodiazepine/alcohol use during opioid therapy, implementation of real-time prescription monitoring systems, and research to clarify upper safe limits for polydrug depressant use, are potential implications.

Introduction

There has been an increase in opioid prescriptions, partly attributable to greater chronic non-cancer pain (CNCP) prevalence and a greater number of opioids registered for CNCP treatment (Berterame et al., 2016, Karanges et al., 2016). Increased pharmaceutical availability has seen greater prevalence of extra-medical use and tampering (i.e., manipulating a dosage form to change its drug delivery in a way not specified by the manufacturer, and may include dissolving, crushing, chewing, snorting and injecting; Katz et al., 2011, Katz et al., 2007), which in turn has led to greater rates of opioid-related harms (Hall et al., 2008, Manchikanti et al., 2012b).

Use of other central nervous system depressants, such as benzodiazepines and alcohol, with opioids may have an interactive or synergistic effect, increasing the risk of acute harms such as overdose (Warner-Smith et al., 2001, White and Irvine, 1999). An increasing proportion of unintentional overdoses have been observed involving the use of benzodiazepines, alcohol and other depressant drugs with opioids (Calcaterra et al., 2013, Jones et al., 2013), with death primarily attributed to respiratory depression (Gudin et al., 2013). As tolerance to the depressant effects of opioids is slower than tolerance to euphoric effects, consumers with a long history of opioid use are still often unknowingly at risk, although the underlying pathophysiology is complex and poorly understood (White and Irvine, 1999).

In addition, combined depressant use may contribute to increased sedation, greater motor impairment (e.g., falls or injuries) and enhanced abuse liability of these substances. Benzodiazepine or alcohol use enhances the euphoric effects of opioid analgesics (Chen et al., 2011, Lintzeris et al., 2007, Zacny and Gutierrez, 2011) and acute alcohol co-administration may increase maximum plasma concentrations and reduce time to maximum concentration for long-acting opioids (Fiske et al., 2012, Johnson et al., 2012, Sathyan et al., 2008).

Few studies have conducted in-depth investigation of concurrent use (specifically, same-day use) of opioids and benzodiazepines and/or alcohol among people who use opioids (e.g., Brands et al., 2008, Cropsey et al., 2015, Fleming et al., 2007, Lavie et al., 2009, Nielsen et al., 2007, Saunders et al., 2012). This is particularly the case for people regularly engaging in extra-medical pharmaceutical opioid use, a group at greater risk of opioid-related harms and among whom use of a range of substances is prevalent (Becker et al., 2008, Jones, 2013). As such, the aims of this study were to apply a novel methodology, a retrospective self-report daily drug diary, to determine:

• Frequency of same-day opioid use with benzodiazepines/alcohol, and typical quantities consumed, by people who regularly tamper with prescription opioids; and

• Demographic, mental/physical health, drug use, harms and treatment profile correlates of same-day use of opioids, benzodiazepines, and alcohol at high doses.