Overview of medication-assisted treatment of opioid dependence (MATOD)

Faggiano, 2003 Mattick, 2014 Mattick, 2009 Victoria Department of Health

Medication-assisted treatment of opioid dependence (MATOD) is also known as chronic opioid therapy (COT), medication for opioid use disorder (MOUD), opioid agonist therapy (OAT), opioid replacement therapy (ORT), opioid substitution therapy (OST) and opioid treatment program (OTP). It involves the use of one of the following opioids to help patients reduce or stop using other opioids:

buprenorphine—as a sublingual film or tablet taken daily (or on every 2 or 3 days), or a modified-release subcutaneous injection given weekly or monthly
methadone—as an oral liquid taken daily.

Both buprenorphine and methadone are opioid receptor agonists. Buprenorphine is a partial mu-receptor agonist; methadone is a full mu-receptor agonist.

Naltrexone¹ is generally not used for the treatment of opioid dependence, because of very poor adherence. If a patient requests oral naltrexone for opioid dependence, seek specialist advice. No long-acting naltrexone depot injections are registered for use in Australia. Naltrexone implants are not registered or recommended because of inadequate safety data on their use.

Comparison of medication-assisted treatment of opioid dependence (MATOD) with planned withdrawal to manage opioid dependence compares MATOD with planned opioid withdrawal. Although planned withdrawal may initially appeal to a patient, encourage the patient to consider MATOD because it is more effective and safer.

Table 1. Comparison of medication-assisted treatment of opioid dependence (MATOD) with planned withdrawal to manage opioid dependenceGowing, 2014
	MATOD	Planned withdrawal
Advantages	decreases mortality highly effective in reducing use of nonprescribed opioids reduces risk of bloodborne viral infections improves quality of life avoids withdrawal in patients who are ill or unstable widely available (in metropolitan centres)	short-term commitment access may be easier entry point to other treatments
Considerations	for sublingual buprenorphine or oral methadone: consider travel costs and dispensing fees for the patient, and restrictions of supervised dosing [NB1] long-term opioid adverse effects stigma possibly prolonged withdrawal on stopping	increased opioid overdose risk following withdrawal because of reduced tolerance poor long-term outcomes if used as a standalone treatment can destabilise other conditions (eg chronic pain, mental health)
Note: NB1: These issues are less relevant for injectable weekly or monthly buprenorphine treatment.

Note: MATOD is more effective and safer than planned withdrawal in the treatment of opioid dependence.

Robust evidence with a high level of certainty supports the use of MATOD in combination with psychosocial interventions toFaggiano, 2003 Mattick, 2014 Mattick, 2009 Victoria Department of Health:

decrease the reinforcing euphoric effects of other opioids that may be used concurrently
reduce use of other opioids and the risk of overdose
reduce risk of bloodborne infections
prevent opioid withdrawal symptoms
reduce cravings
improve health and social functioning, including ability to work and stay in stable accommodation.

Note: MATOD therapy is the most effective treatment for opioid dependence; it can improve health and restore ability to work or study.

Use shared decision-making to help a patient decide the aim of MATOD for them. Some patients continue MATOD in the long term, while others have a period of maintenance before gradually reducing the dose to stop.

Factors to consider when deciding whether to stop MATOD therapy are discussed in Factors to consider when planning to stop medication-assisted treatment of opioid dependence. Planning to stop MATOD requires support with relapse prevention strategies. It is common for patients to want to stop MATOD early; encourage them from the start of treatment to continue MATOD for a minimum of 12 months (although longer treatment is likely to offer more benefit); this allows time for the patient to develop strategies to reduce the risk of relapse. Discuss the fact that relapse can happen (particularly if a patient requires opioids for surgery) and recommend that patients seek treatment again early if relapse should occur.

Indications to seek specialist advice if a patient is considering starting MATOD therapy include:

pregnancy and breastfeeding
polysubstance use (use of more than one substance)
acute medical illness
comorbidities such as liver disease, respiratory or central nervous system depression or chronic pain
mental illness
recent release from prison.

These issues are also discussed in more depth in Section A2.1 of the National Guidelines for MATOD Gowing, 2014.

Monitoring is more intensive at the start of MATOD; sublingual buprenorphine and liquid methadone require each dose to be supervised (observation of the dose being taken at a pharmacy or clinic). Once the patient’s condition stabilises, the frequency of reviews can be reduced and some of the doses can be unsupervised (‘takeaways’)². Signs of stability include negative urine screens for illicit drugs; involvement in education, training, employment or childcare; punctual attendance at appointments; signs of self-care, and positive interactions with staff. The timing and frequency of takeaway doses varies with state and territory regulations.

Buprenorphine and methadone each have features that influence the choice of drug, as summarised in Comparison of buprenorphine and methadone in medication-assisted treatment of opioid dependence (MATOD).

Table 2. Comparison of buprenorphine and methadone in medication-assisted treatment of opioid dependence (MATOD)Gowing, 2014
	Buprenorphine	Methadone
Considerations when starting	therapeutic doses can be achieved more quickly with buprenorphine than when starting methadone	methadone is less likely to precipitate withdrawal than buprenorphine when starting [NB1]
Requirement for attendance for dosing	more flexible with buprenorphine; daily or alternate daily sublingual dosing can be used. Weekly and monthly injectable formulations free patients to focus on other life activities [NB2]	attendance for daily oral dosing is less convenient than for injectable buprenorphine and has more travel cost and stigma
Overdose risk	overdose less likely with buprenorphine than with methadone	higher risk of toxicity, especially when starting methadone
Drug interactions	fewer drug interactions occur with buprenorphine than with methadone	clinically relevant drug interactions increase or decrease the metabolism of methadone methadone can increase the QTc interval
Impact on cognitive function	buprenorphine may have less impact than methadone on cognition	distressed patients may prefer the sedative effects of methadone
Ease of stopping	may be easier to stop buprenorphine than methadone	symptomatic withdrawal is more prolonged after stopping methadone
Note: NB1: Buprenorphine can precipitate withdrawal if started too soon after the last use of a more potent opioid; this is because buprenorphine can displace the other opioid from mu receptors but results in less stimulation of the receptor (partial agonism). NB2: Preparations of buprenorphine for medication-assisted treatment of opioid dependence (MATOD) outlines characteristics of the available preparations of buprenorphine.

¹ Naltrexone is an opioid antagonist, not to be confused with another, naloxone. Naloxone is used for reversal of opioid overdose.Return

² Most jurisdictions allow more unsupervised treatment with buprenorphine than with methadone because overdose risk is less with buprenorphine than methadone.Return