OBJECTIVES To investigate the combined effect of two policies for reducing prescription opioid supply in Australia on hospital use by people prescribed opioids in primary care.

STUDY DESIGN Retrospective data linkage study; controlled interrupted time series analysis of linked primary care electronic medication records and hospital admissions data.

SETTING Three Victorian health care networks (Monash Health, Eastern Health, Peninsula Health); pre-intervention period: 1 April 2018 - 31 March 2020; intervention period: 1 April 2020 - 31 March 2022.

PARTICIPANTS People prescribed opioid medications at least twice during the preceding six months (opioid group) and propensity score-matched patients, based on age, gender, comorbidity, and residential postcode-based socio-economic status (control group); matching was undertaken for each month of the study period.

INTERVENTION Mandatory prescription drug monitoring (from 1 April 2020); tighter restriction criteria for the subsidisation of opioid medications by the Pharmaceutical Benefits Scheme (PBS) (from 1 June 2020).

MAIN OUTCOME MEASURES Differences between the opioid and control groups in immediate changes after start of the intervention in rates of emergency department (ED) presentation and hospital admission related to opioid use, non-opioid substance use, self-harm, or mental health problems; differences between the two groups in the change in trend for these rates between the pre-intervention and intervention periods.

RESULTS Propensity matching was undertaken for 179 091 people in the opioid group and a total of 389 061 people in the control group. The opioid-related ED presentation rate for the opioid group had been increasing prior to the intervention, but declined after its introduction at a rate not significantly different from that of the control group. The immediate change in non-opioid substance-related ED presentation rate was greater for the opioid group than the control group (β, 11.1 [95% confidence interval, 1.7-20.5] presentations per 100 000 patients); by 31 March 2022, the rate had declined to below the pre-intervention level. Differences between groups in changes to self-harm- and mental health-related presentations, and in all hospital admission rates, were not statistically significant.

CONCLUSION Following implementation of two prescription opioid supply-restricting polices in 2020, the opioid-related ED presentation rate declined among people prescribed opioids; the non-opioid substance-related presentation rate initially increased, but was lower than the pre-intervention level by the end of the study period. Our findings suggest that some opioid-restricting policies can reduce opioid-related harm without increasing long term non-opioid substance- or mental health-related harm.

STUDY REGISTRATION European post-authorisation study register (EUROPAS), EUPAS104005 (prospective).