Medicines used in the treatment of opioid dependence

SUMMARY

Opioid dependence is a chronic condition that can lead to significant harm if left untreated. People who experience opioid dependence and the treatments themselves are highly stigmatised. Person-centred trauma-informed services are critical to therapeutic engagement and effectiveness.

Buprenorphine and methadone are highly effective, evidence-based medicines for opioid dependence. In recent years, long-acting injectable buprenorphine has emerged as a safe and effective treatment option, offering flexible weekly or monthly dosing.

The long-term treatment of opioid dependence can be undertaken in primary care settings. General practitioner and nurse practitioner prescribing, and community pharmacist dispensing, are essential for ongoing care.

Australian jurisdictions have differing regulations that guide the prescribing of medicines for opioid dependence. Health professionals should be familiar with their local jurisdiction’s guidelines as well as the national guidelines. Drug and alcohol telephone services are available in each jurisdiction and can provide advice to health professionals.

Introduction

Opioid dependence is a chronic relapsing medical condition.¹ It is a cluster of behavioural, cognitive and physical phenomena that commonly occurs with repeated or continued use of opioids.² Not everyone who uses opioids develops dependence; the risk of dependence is influenced by biological, sociological and psychological factors, which may be protective or may increase risk.³ Factors that increase risk include adverse childhood experiences,^4,5 chronic health conditions including mental health conditions, and long-term use of prescribed opioids.

According to the World Health Organization’s International Classification of Diseases 11th revision (ICD-11), the diagnosis of opioid dependence has 3 main facets: loss of control, salience, and physiological factors of neuroadaptation (tolerance and withdrawal) (Box 1). The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders 5th edition refers to this condition as ‘opioid use disorder’ and uses 11 separate criteria for diagnosis and to determine the severity of the disorder.⁷ This article uses the term ‘opioid dependence’.

People can develop opioid dependence from illicit and pharmaceutical opioids, both prescribed and non-prescribed.² Like other chronic conditions, such as asthma or diabetes, it cannot be cured and, while sometimes it may remit, relapse is common and requires long-term management.³ Untreated opioid dependence can lead to significant harm, including impaired ability to engage in everyday life, increased risk of bloodborne viruses due to injecting use, and increased risk of injuries and death from violence or overdose.⁸

Opioid dependence is a stigmatised condition. The experience of stigma and discrimination adversely affects health and prevents people from disclosing behaviours and accessing or staying in treatment.⁹ Person-centred trauma-informed approaches are encouraged to promote safety and trust, and to support adherence to treatment.¹⁰

Opioid dependence treatment (ODT) with long-term prescribed opioids, such as buprenorphine or methadone, is highly effective and reduces the health, social and economic harms for people experiencing opioid dependence,³ as well as for their families, communities and Australia as a whole.³

Prescribing in primary care

In Australia, nearly 75% of ODT is provided in primary care settings. Most prescribers are general practitioners (GPs) with a small but increasing number of nurse practitioners (NPs).¹¹ Currently, it is likely that fewer than 43% of people who may benefit from ODT are able to access treatment.¹¹ GPs and NPs in primary care have an important role in the management of opioid dependence. People with low complexity may start treatment in primary care in some jurisdictions, while those with complex physical and mental health conditions, ideally, would have access to alcohol and other drug (AOD) specialist support to start treatment.

As ODT is highly effective, many people will greatly improve and can transition to ongoing treatment in primary care. Treatment in the primary care setting reduces stigma and enables better management of people’s general health care. A core role for primary care is the long-term management of people particularly whose ODT has stabilised. Ensuring good connections and collaboration between GPs, NPs, community pharmacists and local AOD specialist settings for consultation, advice and support, which may be virtual, is essential.

Planned opioid withdrawal

Planned opioid withdrawal may be suitable for people who are using low doses of opioids (i.e. oral morphine equivalent daily dose less than 60 mg) or have a short history of opioid dependence (weeks to months); however, this approach is associated with a high risk of relapse and overdose due to loss of opioid tolerance.³ Planned opioid withdrawal is best undertaken with short-term buprenorphine,* which provides better symptom control than a combination of medications used to relieve individual opioid withdrawal symptoms (e.g. antiemetics, nonsteroidal anti-inflammatory drugs, anti-diarrhoeals, sedating antihistamines, hyoscine). Planned withdrawal requires close follow-up and may best be seen as a tool to engage people in long-term treatment. The use of a validated tool, such as the Clinical Opiate Withdrawal Scale (COWS), can assist in the evaluation of opioid withdrawal symptoms (see Appendix).

It is essential to consider the optimal setting for withdrawal for each person. People with other morbidities, experiencing homelessness or needing intensive psychological support, may do better in a supported setting, for example, in a public or non-government drug and alcohol inpatient unit. For support and more information, contact the AOD specialist advisory service in your jurisdiction.

Medicines used in the treatment of opioid dependence

Medicines approved in Australia for the treatment of opioid dependence include methadone and buprenorphine (Table 1). Both are equally effective.^12-16 ODT is only indicated for people with diagnosed opioid dependence. People may have opioid dependence without opioid tolerance and, while they can benefit from ODT, this group requires careful commencement with low doses. ODT should not be used in opioid-naive people and is not a treatment for other drug dependencies (e.g. alcohol, stimulants). People with comorbid risky, hazardous or dependent poly-drug use may be best referred for AOD specialist assessment. For many people, psychological and social support plays an important role in recovery.¹⁷

Table 1 Medications used to treat opioid dependence in Australia^3,18

ODT requires supervised medication administration (dosing). This can occur in drug and alcohol clinics, and in hospital or community pharmacies. Generally, people who commence oral or sublingual therapies will start with daily supervised dosing and be given doses to take away, to administer themselves at home, once they are stable in treatment. Stability is indicated by stable social conditions, stable physical and mental health, no high-risk drug use, attendance at planned appointments and good adherence to medication. Safe storage of takeaway medicines to prevent child poisoning is important.^3,19 People accessing ODT should be counselled on storing takeaway doses in a locked box in a locked high cupboard and not taking doses in front of children.²⁰

Generally, the choice of treatment should be a shared decision between the prescriber and the person seeking treatment, taking into account their unique needs, comorbidities, medications and preferences.

Buprenorphine

Buprenorphine, a partial opioid agonist, has a high affinity for opioid receptors and only partially activates them. This means that if a person with opioid dependence has high concentrations of opioid agonists (e.g. morphine, heroin) in their body, adding buprenorphine will displace the other opioid from the receptors, triggering opioid withdrawal symptoms (a condition called precipitated withdrawal). In contrast, if an opioid-dependent person presents with opioid withdrawal symptoms, buprenorphine will relieve these. Given the pharmacology of buprenorphine, care is needed to ensure that the person is in mild to moderate opioid withdrawal (COWS score of at least 10 to 15; refer to Appendix) before starting treatment to avoid precipitated withdrawal. Once above a certain daily dose, usually 16 mg, buprenorphine blocks the effects of other opioids, so it may be suitable for people who do not want to continue using other opioids. Buprenorphine may also assist with clarity of thought, making it a good option for those who need better cognitive function.³

Buprenorphine+naloxone

Buprenorphine can be prescribed as a sublingual tablet or film and is usually combined with naloxone (Table 1). Naloxone, an opioid antagonist, may deter injecting use and, when injected, can lead to opioid withdrawal symptoms.²¹ Buprenorphine has poor oral absorption, hence it is taken sublingually. The sublingual preparation is usually administered daily; however, some people can take sublingual buprenorphine as a double or triple dose every second or third day (the total daily dose cannot exceed 32 mg).¹⁹ Generally, people are started on a dose of 2 to 8 mg on day one, and the dose is increased daily as needed to between 16 and 32 mg daily, though some people may stabilise on a lower dose. Some jurisdictions allow liberal takeaway dosing of up to 28 days for buprenorphine+naloxone combined preparations once treatment is stabilised.

Long-acting injectable buprenorphine

Long-acting injectable buprenorphine (LAIB) was first introduced in Australia in 2018. It is available as weekly or monthly subcutaneous injections.¹⁸ The injection must be administered by a health professional (pharmacist, medical practitioner, NP or nurse). Its longer duration of action allows greater flexibility, avoiding the need for daily site attendance or takeaway dosing. This is an important factor that improves access to treatment in rural, regional and remote settings.

There are 2 formulations, with the trade names Buvidal and Sublocade (Table 1). They are both highly effective treatments; however, they are not interchangeable. While Buvidal provides greater dose flexibility with several weekly (8, 16, 24 and 32 mg) and monthly dose strengths (64, 96, 128 and 160 mg), Sublocade is available in 2 monthly strengths (100 and 300 mg) and may be preferred for its simpler dosing. Sublocade may be more useful for people with comorbid chronic pain or a high level of opioid dependence. Sublocade has a larger needle and injecting may be more painful; local anaesthetic or ice can be used to decrease discomfort.

Generally, sublingual buprenorphine+naloxone is started before transitioning the person to a LAIB. However, practice is evolving, and it is likely in the future that people may be started directly on a LAIB, with those who have not previously been exposed to buprenorphine receiving a test dose of sublingual buprenorphine+naloxone to exclude allergy prior to starting a LAIB. For further details on how to start LAIBs, refer to your jurisdiction’s guidelines.

Methadone

Methadone is a full opioid agonist (Table 1). It is a potent opioid with complex pharmacodynamics and pharmacokinetics. While highly effective for the treatment of opioid dependence, its safety profile means it needs to be managed with a high degree of supervision and caution.³ The allowable takeaway doses vary, with some jurisdictions permitting up to 6 takeaways per week. Ongoing close engagement with pharmacists through frequent supervised dosing can be an important therapeutic experience for some people; however, it can limit full participation in tasks of daily life and travel and has been described by some as ‘liquid handcuffs’.²² It may be useful for people who want to continue using other opioids, have comorbid chronic pain, or have psychological distress as methadone may dull cognition.³

There are 2 oral formulations of methadone: methadone syrup and Biodone liquid. Injected use is associated with infection and vein damage.

Naltrexone

Naltrexone is an opioid antagonist with limited use in ODT. It may be used as adjunctive therapy in the maintenance of abstinence from opioids for people with a history of opioid dependence who have fully withdrawn from opioids. It has increased overdose risk and is not subsidised on the Pharmaceutical Benefits Scheme (PBS) for opioid dependence. Oral naltrexone is more commonly used in Australia for alcohol dependence relapse prevention.

Adverse effects and precautions

Like other opioids, methadone and buprenorphine can cause sedation, light-headedness, nausea, vomiting, dry mouth, hypotension and, rarely, biliary or renal tract spasm. There is an increased risk of sedation and respiratory depression when methadone is used with other sedatives (e.g. benzodiazepines, alcohol). Buprenorphine is less sedating and is preferred if a particular risk of sedation exists.

Methadone, and to a lesser extent buprenorphine, can cause QT interval prolongation, increasing the risk of cardiac arrhythmias and sudden death. Therefore, methadone and buprenorphine must be used with caution, and electrocardiogram monitoring and AOD specialist advice sought when used in combination with other medications or substances that also prolongate the QT interval (e.g. alcohol, cocaine, amphetamines).

Methadone and buprenorphine are both metabolised by hepatic cytochrome P450 (CYP) enzymes. Medicines that induce or inhibit CYP enzymes (e.g. antiepileptics, steroids, antibiotics, nicotine, omeprazole, cimetidine) can result in under- or overdosing of methadone or buprenorphine. The impact of hepatic metabolism is less marked in buprenorphine and there appear to be fewer clinically relevant drug interactions with buprenorphine compared with methadone.¹⁹ Methadone can potentially increase the risk of serotonin syndrome with other serotonergic drugs (e.g. selective serotonin reuptake inhibitors, tramadol).²³

Completing treatment

ODT is long term, and for some, it is lifelong. Some people may wish to gradually stop treatment. This is best done when people have stable mental and physical health and are housed with good social connections and purpose. LAIBs may be preferred due to their long duration of action after the last dose which can mitigate the experience of withdrawal. Discharge planning should include advice and education around relapse prevention, overdose risk management, and follow-up as needed.

State and territory programs

There are ODT programs in every state and territory in Australia. These programs provide controlled supply of ODT under robust legal and regulatory frameworks to facilitate access to treatment and minimise unsanctioned supply and leakage into informal drug markets. The programs’ fundamental approach involves significant supervision of patient progress and medication administration.

In some jurisdictions, there are state-funded services that focus on people presenting with complex issues (e.g. multimorbidity, polysubstance use, unstable mental and physical health) and provide free care by multidisciplinary teams. Policies, guidelines and training requirements vary between jurisdictions. Health professionals should refer to their local jurisdiction’s guidelines and requirements for prescribing and training (Box 2).

Role of the pharmacist and community pharmacy

Community pharmacists and pharmacies are integral to ODT, providing 85% of ODT (supply, dispensing and administration) across Australia.¹¹ By embracing a person-centred non-stigmatising approach, they can help make ODT part of mainstream health care. Prescribers and pharmacists are encouraged to regularly communicate with each other and to access the real-time prescription monitoring tool in their jurisdiction, which helps to assess high-risk medicine use. In some jurisdictions, this is mandatory prior to prescribing.²⁴ The Pharmaceutical Society of Australia’s website contains information for pharmacists on ODT provision in each jurisdiction.

Changes to the cost of ODT medicines

Prior to July 2023, the cost of supplying, dispensing and administering ODT medicines in the community pharmacy setting was borne by the person in treatment. This typically costed between $120 and $210 per month. In July 2023, ODT medicines became part of the Section 100 Highly Specialised Drugs Program (Community Access) arrangements, allowing eligible people to pay the PBS co-payment for up to 28 days supply and a maximum of 5 repeats.²⁵ This includes free access through the ‘Closing the Gap’ program for Aboriginal and Torres Strait Islander peoples.²⁶

Currently, there are no Medicare item numbers for LAIB administration for medical or nurse practitioners; however, pharmacists are able to claim fees for supplying ODT medicines and administering LAIBs under the ODT Community Pharmacy Program. Pharmacists cannot charge additional private fees for this service.

Drug and alcohol information services

Each jurisdiction in Australia has drug and alcohol telephone services that can provide information, support and clinical advice in real time to health professionals (Table 2).

Table 2 Drug and alcohol telephone services in Australia

Conclusion

Buprenorphine and methadone are highly effective, evidence-based treatments for people experiencing opioid dependence. Most people can be effectively managed by GPs and NPs working in primary care, while those with more complex needs may benefit from initial AOD specialist care and transfer to primary care once their complexity has settled. It can be highly rewarding work for the health professionals involved. Support and advice through local AOD specialist services and jurisdictional telephone lines are available. Health professionals should refer to jurisdictional regulations and guidelines when providing care. Access to treatment remains limited, and the engagement of GPs, NPs and pharmacists is crucial to ensure all who need it can receive treatment in the setting most suited to their needs.

*The use of buprenorphine in planned withdrawal in the community setting generally needs to be authorised by the ODT program in each state and territory.

This article was finalised on 26 May 2025.

Conflicts of interest: Hester Wilson is the Chair of The Royal Australian College of General Practitioners’ Addiction Medicine Specific Interest Group and a member of the expert group for Therapeutic Guidelines: Addiction version 2 (under review).

Jillian Kanck has no conflicts of interest to declare.

This article is peer reviewed.

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Appendix