​Safety considerations for clinicians prescribing other medicines to patients who are on the Opioid Treatment Program 

Last updated: 12 July 2023

People with opioid dependency often have other coexisting conditions, including chronic pain, mental health conditions, and sleep disorders. Prescribers managing these patients must be aware of the high risk of prescribing sedating medicines for patients on opioid agonist treatment (OAT).

Methadone and buprenorphine are safe and effective medicines for treating opioid dependence. However, there is an increased risk of harm from combining methadone or buprenorphine with other sedating medicines, including unintentional overdose and death from multiple drug intoxication. The combination of methadone or buprenorphine with alcohol or other pharmaceuticals such as opioid pain relievers, benzodiazepines, antidepressants, anticonvulsants and antipsychotics increases the risk of opioid-induced unintentional deaths.

Toxicology data insight

In NSW in 2020, pathology data of deaths referred for toxicology testing showed that where methadone or buprenorphine were detected, there was a high proportion of deaths co-detected with sedating medicines (a).

Drug group Number of deaths -
 Methadone with selected drug groups N (%)
Number of deaths -
Buprenorphine with selected drug groups N (%)
Benzodiazepine119 (70.8)25 (73.5)
Antidepressant64 (38.1)9 (26.5)
Opioid51 (30.4)16 (47.1)
Antipsychotic48 (28.6)10 (29.4)
Gabapentinoid42 (25.0)6 (17.6)
Total 168 34

Health care practitioners should consider the risks when patients on OAT are prescribed or using other medicines resulting in potentially harmful combinations.

How can prescribers reduce the risk of harm?

Review risks and consider appropriate actions

  • Ask the patient about all prescribed medicines they are taking, including medications prescribed for them by another doctor and ask if they have any health conditions being treated by another doctor. Consider recommending non-pharmacological alternatives if appropriate.
  • Access SafeScript NSW for information about a patient's prescribing and dispensing history. Some medicines are not safe to cease abruptly
  • Contact the SafeScript NSW Clinical Advice Linefor advice on clinical management options if needed.
  • Assess overdose risk, provide advice in case of overdose and access to take home naloxone when there is a potential risk of opioid toxicity/overdose.
  • Monitor regularly and adjust medicine regimen as necessary.

Review guidance and seek specialist advice on managing patients with complex needs

Identify individual risk factors:

  • Concurrent use of the OTP medication and benzodiazepines, antidepressants, antipsychotics or other sedating medicines.
  • Switching between opioids or adding opioids or other sedating medicines to existing treatment.
  • History of alcohol use disorder.
  • History of opioid overdose.
  • Recommencement of opioid use after a period of abstinence.
  • Presence of any respiratory problems / renal / liver disease.

Engage patients by discussing risks and management strategies

  • Only take your opioids (including OTP medication) as directed by your health care provider.
  • Inform your doctor or pharmacist about all current prescribed and non-prescribed medication including over-the-counter medicines.
  • Seek advice from your doctor or pharmacist before mixing your opioids with alcohol or sleeping pills, antianxiety drugs, antidepressants, and over the counter sedating medicines.
  • Know the signs of intoxication and opioid overdose.
  • Naloxone can reverse the effects of opioid overdose.
  • Store all medication in a safe and secure place, away from children.

Training and other resources


  1. Source: Forensic Toxicology Laboratory, NSW Health Pathology Forensic & Analytical Science Service (FASS). The data records toxicological results corresponding to unexplained and unexpected deaths in NSW referred for toxicology testing. The table shown is from an analysis of records where (i) the date of post-mortem was between 1 January 2020 to 31 December 2020 inclusive, and (ii) toxicological results found methadone (n=168) or buprenorphine (n=34); or where both were detected (n=6). Note that this data does not necessarily reflect prescribing practices, only toxicology findings.
  2. A NSW non-accredited prescriber is authorised to manage up to 30 patients including maximum 20 patients on buprenorphine/buprenorphine-naloxone and maximum 10 patients on methadone who have been referred by an accredited prescriber.

Current as at: Wednesday 12 July 2023