Introduction

The main cause of death among people with opioid use disorder (OUD) is drug overdose. OAT is a proven intervention to reduce both drug-related and all-cause mortality. The advantages of OAT can be negated by using other prescribed and non-prescribed substances at the same time during OAT, such as heroin, cocaine or street benzodiazepines and/or other prescribed medications. Polysubstance use is associated with treatment discontinuation and is known as a risk factor for drug overdose. Despite this, there is limited research on the effects of polysubstance use among patients in OAT.

An Irish study sought to address this gap in the research by aiming to (1) examine trends in drug positivity rates in amphetamines, benzodiazepines, cannabis, cocaine and opioids (heroin, morphine and codeine); and (2) identify trends in polysubstance positivity rates for drug combinations associated with increased risk of drug overdose including (a) methadone and benzodiazepines; (b) methadone, benzodiazepines and opioids; (c) methadone, benzodiazepines and cocaine; and (d) methadone, benzodiazepines, opioids and cocaine.1

Methods

A cross-sectional study design was employed using anonymised individual-level urine drug test (UDT) results from the National Drug Treatment Centre (NDTC) laboratory between 2010 and 2020. The NDTC is the largest specialist addiction clinic in Ireland, with approximately 750 patients attending OAT (primarily methadone) services each year. In line with national guidelines, all patients attending OAT services must provide regular urine samples for drug testing throughout the course of their treatment.

Samples from OAT patients were included if the patient had a minimum of five valid samples, one of which must have been positive for methadone. All urine samples were tested for benzodiazepines, methadone, other opioids, and cocaine using immunoassay testing. Annual positivity rates were calculated by dividing the number of samples tested for each substance and multiplying by 100. In order to evaluate trends in polysubstance positivity rates for drug combinations, mixed-effects logistic regression models were employed. Sensitivity analysis was carried out to assess the impact of COVID-19 on these observed trends.

Findings

A total of 221,564 samples were included over the study period, with an average of 114 samples per patient.

The results showed that methadone was the most commonly detected substance followed by benzodiazepines, cannabis, other opioids, cocaine, and amphetamines. The magnitude of increase was greatest for cocaine, reflecting a weighted annual positivity rate of 12% in 2015, compared with 37% in 2020. In contrast, the detection of opioids decreased from 50% in 2015 to 39% in 2020.

For patterns in polysubstance positivity rates for drug combinations associated with increased risk of drug overdose, the main findings were as follows:

1. Combination of methadone and benzodiazepines was common over the period.
2. Combination of methadone and benzodiazepines with cocaine increased over the period.
3. Combination of methadone, benzodiazepines, opioids and cocaine increased between 2010 and 2020.
4. Combination of methadone and benzodiazepines with opioids decreased over the study period.
5. Patients aged 36 years and over were less likely to test positive for multiple substances.

Limitations

This research only included patients attending the NDTC and focused on drugs that are routinely tested by the NDTC laboratory; therefore, they may not be generalisable outside this setting. In addition, immunoassay tests can be limited in scope, e.g. cannot detect prescription opioids such as tramadol, which could underestimate concurrent opioid use. Another issue which may affect the results is that cannabis and amphetamine testing was at the request of individual doctors, which may have led to some selection bias; moreover, it was not possible to ascertain whether the benzodiazepines were prescribed by a doctor or were sourced at street level. It should also be noted that there was an increase in the number of patients enrolled in OAT during the COVID-19 pandemic, but a decrease in the number of urine samples taken in that period.

Conclusions

The authors state that given the prevalence of polysubstance use among patients in OAT, and its associated risk with overdose fatality, there is a need to introduce measures to address the persistently high use of benzodiazepines and cocaine among this group. They also state that information from urine sampling can be very useful in relation to identifying changes in the trends of drug use over time and that it can inform interventions to help reduce polysubstance use in patients on OAT.

1    Durand L, O’Kane A, Stokes S, Bennett KE, Keenan E and Cousins G (2024) Trends in polysubstance use among patients in methadone maintenance treatment in Ireland: evidence from urine drug testing 2010–2020. J. Subst. Abuse Treat. 167, 209507. https://doi.org/10.1016/j.josat.2024.209507. https://www.drugsandalcohol.ie/41799/