Essay: Opioid use disorder (OUD)

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Opioid use disorder (OUD) is characterised by repeated use of opioids with harmful consequences (4). It is a complex and relapsing condition that may require long-term treatment and care. People with OUD should have access to medication for its management. Treatment including medication is associated with important social and clinical benefits, reduces overdose deaths and crime, and enables patients to positively contribute to society (10,18,24). Evidence-based, good quality treatment helps achieve recovery outcomes (3). In Europe, treatment options and guidelines differ by country; there is no common best practice guidance across Europe. Existing guidelines are not all up-to-date and do not provide day-to-day advice for physicians to inform best practice.

Access to pharmacotherapy should be made available to all patients with OUD. Opioid agonist therapy (OAT), including methadone, buprenorphine or buprenorphine/ naloxone fixed dose combination is effective treatment for OUD, (7,18,19,21,23,24). The focus of this work is limited to methadone and buprenorphine: these are the most widely available treatments throughout Europe and considered as the most appropriate agonist therapies for use in OUD. This recommendation focuses on only these treatments; other treatment options are not considered here.


A group of 15 European experts in the treatment of OUD (see Appendix 1) developed practical recommendations for the treatment of OUD. Recent national and international guidelines published between May 2014 and Dec 2016 were identified and reviewed by searching key national sources and following expert recommendations. Their content provides the basis of the recommendations, supplemented by expert consensus from the Faculty of experts. Where evidence-based information is not available, expert consensus recommendations are provided for optimal pharmacotherapeutic options.

In total 15 guidelines were reviewed (Appendix 2). The recommendations describe the two most widely used and effective treatments in OUD (methadone and buprenorphine or buprenorphine/ naloxone) and provide practical recommendations for their optimal use in general, and in patients with more complex and hard-to-treat problems.

Treatment objectives

Patients and physicians should reach an agreement on treatment objectives (3,21), which are goals that are expected to be achieved from the treatment program (11). The broad goal of treating OUD is to improve the physical and psychological health (3,18,23) and to reduce health, social and economic harm to individuals and community (18).

From a health of the individual point of view, short-term goals include to avoid serious risk to health (18), cease or reduce dangerous illicit opioid use (3,11,14,18,19,23), cease exposure to risk from unsafe injecting therefore reducing risk of blood-borne virus transmission (3,13,18,19,23), address pre-existing health concerns (11), reduce overdose risk (23). From a social aspect, OUD treatment reduces substance-related criminal activity (3,18,23), and promotes re-integration to society (3,14,23), for example working, studying or participation in other activities (18), as well as enhancing quality of life for families and communities (25).

An important long-term goal may be to reach complete abstinence (3,14,18), but the complexities of OUD mean that this is not necessarily achieved (18). This is not a reason to limit access to care. Over emphasis on abstinence may, to some, devalue other achievable short term goals (18). Extended treatment may benefit some people to achieve improved social functions without necessarily ceasing illicit drug use (18,23). Progress for patients is often progressive and individual with some aiming to cease all drug use, others may not choose this path.

A range of interventions or treatment options, including psychosocial and pharmacological interventions are available: there is no single treatment that is effective for all individuals with OUD (35). OAT represents an important component of the overall management program aiming to provide safe, effective and consistent therapy (13,29). It is pragmatic and focused on realisable goals (23), and has been shown to be superior to withdrawal management regarding retention, sustained abstinence, reduced risk of morbidity and mortality (32). OAT often controls withdrawal symptoms and minimizes the craving for additional opioids (19,21). It is the most effective long-term strategy and can allow a “return-to-normal” physiological, psychological and societal functioning (7,13,25). Some patients are able to reach abstinence with significant support from both medical intervention and community-based services (22,29). Treatment of strategies including OAT and a combination of professional and peer-based support to assist patients and families in achieving positive outcomes in OUD.

Appropriate quality OAT for OUD is cost-effective and the return on investment from good quality OAT is better than from poor quality. It is important for decision-makers to focus on retaining investment in OAT and treatment in the wider context while also improving the quality of OAT (for example by ensuring sufficient dosing levels).

Treatment option: Methadone

Methadone is a long-acting synthetic opioid which as an oral formulation is effective in treating OUD (21). It prevents opioid withdrawal, reduces opioid craving and mitigates the euphoric effects of opioids such as heroin (11). Methadone is rapidly absorbed following oral administration; effects starts in 15- 45 min (18), peak plasma concentration and clinical effect reached at 2-6 hours, and has a half-life average 24-36 hours (range 4-90 hours) at steady state (11,18).

The pharmacokinetics of methadone with the variable individual response make safety an important concern in OAT. Methadone may accumulate and cause sedation and respiratory depression (11), with an increased toxicity, potentially lethal, by concomitant ingestion of alcohol and sedative-hypnotics such as benzodiazepines and Z drugs (11). Respiratory depression, including deaths may occur on treatment initiation or conversion to methadone (19). Management should be limited to those knowledgeable in the use of methadone for maintenance treatment of OUD.

Tolerance to the various effects of methadone could develop at different rates: rapid to the euphoric effect, less rapid to respiratory depression and slowest to autonomic side effects (11). Tolerance is lost in as little as 3 days. Cross-tolerance between methadone and other opioids is unpredictable.

• Methadone is an indicated treatment OUD in patients who are physiologically dependent on opioids (21)

• Methadone is administered orally either as a liquid or as a tablet commonly in the supervised setting (21)

• Methadone use should be monitored to prevent misuse and diversion (11,18,21); unsupervised dosing should be considered after the patient’s clinical response and behaviour indicates this is safe and appropriate

• The extended pharmacokinetics and individual response to methadone make the process of induction and achievement of stability highly variable: it may take 2-4 weeks (33)

• Methadone dosage:

– Starting dose should not exceed 30 mg daily and is often lower in some patients (11)

– Increment of doses should be stepwise based on “go low, go slow” with 10% or 5-10 mg changes (11,21,23) no more frequently than every 5 to 7 days (11,13,21) (and may need to be longer) – increments driven by the clinical response

– It is not recommended to alter the dose without an assessment and after each dose change it may take up to 5 days for methadone plasma levels to reach steady state (11)

– Optimal dose is critical to outcome (3), which is the lowest dose where a patient experiences minimum withdrawal, is clinic
ally and socially stable, opioid-induced euphoria is prevented, and the patient is able to stay in treatment (21)

– The typical optimal dose is 60-120mg daily (13) but many factors (e.g. drug interactions, liver or renal failure) may affect methadone clearance so the optimal dose is highly variable (3)

– Doses of 60 mg/day or greater have been shown to be more effective than lower doses in patient retention, reduced unsanctioned opioid use, and less risk behaviour (11,13,18)

– Dividing doses is rarely used but may be beneficial for specific populations only such as during pregnancy, patients with rapid metabolism or pain management (13,23).

• Patients on methadone should be advised to avoid alcohol and over-the-counter sedating drugs (13). Depending on the individual case and risk profile, prescribers may limit or avoid prescribing any sedating drugs, including benzodiazepines, non-benzodiazepine hypnotics, anti-psychotics, antidepressants, and sedating antihistamines (13) and pay special attention to presence of such drugs in urine samples (33)

• Switching from methadone to another medication of OUD is appropriate if the patient experiences intolerable side effects or is not successful in attaining or maintaining treatment goals through the use of methadone (18,27)

• Advantages and disadvantages of methadone treatment (Table 1) should be considered in deciding if methadone is a suitable treatment

• Methadone is an important choice for treatment in patients who require treatment with daily monitoring, may continue to use other opioids or have intense addiction. Buprenorphine/ Naloxone is recommended in settings with increased risk of misuse or diversion

• Table 1 Advantages and disadvantages of methadone


Potent opioid agonist with extensive treatment experience (33)

Potentially improved treatment retention in some patients, for example unstable patients or those more likely to cease therapy (32)

For people with high opioid tolerance, may be more appropriate (32)

No precipitated withdrawal; initiating treatment may be easier in patients continuing to use other opioids (32)

For patients with anxiety or other concurrent mental health problems such as schizophrenia sedative effects may be beneficial (23)


Fatal overdose and toxicity risks (sedation and respiratory depression which in the most severe case may lead to hypoventilation, coma, bradycardia and death with risk of delayed toxicity occurring hours after exposure for the patient) (11,13,18,19,21,32,33)

May be associated with overdose risk in domestic settings for other parties including families and young children, with serious consequences (23)

Patients concurrently using alcohol, sedative hypnotics (e.g. benzodiazepines), stimulants, cocaine or any medication that interferes with methadone metabolism are at risk of methadone toxicity (18,19,33)

Unsupervised administration can lead to misuse and diversion (21)

Longer and more challenging initiation phase (11,13,19) with unpredictable patient responses over time which may be associated with increased induction treatment drop out (19)

Overdose risk high during first 2 weeks of initiation in the presence of sedatives and patients with low opioid tolerance or altered pharmacokinetics (11,13,19,23)

Associated with more clinically relevant drug interactions. Some medications (e.g., those used to treat HIV, tuberculosis and epilepsy) increase the clearance of methadone leading to a need for increased doses (18,32,33)

Liver & renal failure affect methadone clearance leading to requirement for variable doses (23)

Often requires daily supervision (18,21): this may limit autonomy and prevents patient undertaking work or participating in other daily activities such as study, caring, travel and socialising (32)

With office based treatment and “Take home dosing” there is risk of diversion & fatal toxicity (19,32) (e.g. if a child consumes it accidentally)

Cognitive impairment (18) and sedation may limit opportunities for work, study (7)

Risks for cardiac patients, (QTc prolongation and fatal torsades de pointes arrhythmia): Need for ECGs in patients using doses above 100 mg and patients with cardiac risk factors (11,13,18,19,33)

Other adverse effects include sleep apnoea, painful joints and bones, constipation, perspiration, endocrine effects, impact on sex hormones, dry mouth, dysphoria, dyspepsia, opioid-induced oedema, pruritus, weight gain, tooth damage (3,11,18,19,33)

Pharmacokinetics altered in pregnancy so increased need to alter dose during pregnancy (21)

Toxicity increased in the elderly (33)

Harder to transition from and longer more challenging discontinuation (18)

Treatment option: Buprenorphine and buprenorphine/ naloxone

Buprenorphine is a semi-synthetic opioid that is used to treat OUD (15). Buprenorphine is a partial opioid agonist which binds strongly at the mu opioid receptor with a higher binding affinity and lower intrinsic activity compared to most opioid agonists(23). For patients taking buprenorphine, the addition of other opioids may be ineffective in terms of euphoria (19).

It is recommended as an initial choice for patients requiring pharmacotherapy treatment for OUD primarily because of its favourable safety profile and potential for community-based management in the outpatient setting (7,18,22,33). The lower intrinsic activity of buprenorphine is associated with a ceiling effect of receptor activation – respiratory and central nervous system depression is significantly less with buprenorphine as compared to full opioid agonists. In adults, overdoses on buprenorphine alone are not normally fatal.

Buprenorphine exhibits a slower rate of association with, and dissociation from, opioid receptors resulting in a long duration of effect and limiting risk abstinence syndromes in adults on withdrawal. Buprenorphine may cause opioid withdrawal precipitation in individuals with tolerance to opioids higher than buprenorphine’s maximal effect (18,21). It also has a slow rate to associate with and dissociate from the opioid receptor, therefore preventing euphoria following additional opioid use on top (26).

Buprenorphine is available as a single agent or combined with naloxone. Buprenorphine-naloxone (Suboxone®, generics) combines buprenorphine and naloxone, an opioid antagonist (26). Naloxone administered intravenously to opioid-dependent persons, produces marked opioid antagonist effects and opioid withdrawal, reducing potential diversion and misuse. When naloxone is administered orally or sublingually to patients experiencing opioid withdrawal, little or no pharmacological effect is observed (26).

Buprenorphine is well absorbed when administrated sublingually, but has poor bioavailability when ingested orally due to first-pass hepatic metabolism (9,18). Sublingual administrated buprenorphine reaches peak concentration in 1-4 hours, with typical effects to continue to up to 12 hours at low does (2mg), but as long as 48-72 hours at higher doses (16 or 32mg) (18).

Buprenorphine and methadone when used at appropriate doses are equally effective in reducing illicit opioid use and risk behaviours (3). Evidence suggests buprenorphine and/ or buprenorphine/ naloxone is associated with reduced “on top” heroin use (3).

• Buprenorphine is administered as a sublingual tablet (18) and should be taken in conjunction with psychosocial therapy (21)

• Induction onto buprenorphine is normally relatively simple and is different to the induction with methadone, usually safer and easier (18,19,23); patients may reach maintenance doses more quic
kly (18,19,23,33)

• To reduce the risk of precipitated withdrawal symptoms, when starting buprenorphine, the first dose should be delayed until patients are experiencing mild or moderate withdrawal symptoms (18,21,23)

• Regular patient review is recommended for first few weeks to evaluate adequacy of dose and maintenance does should be achieved within the first one or two weeks (33)

• It has lower potential for misuse compared with full opioid agonists since it is effective in suppressing withdrawal symptoms but produces less euphoria (19,22). Kappa receptor antagonists may be beneficial in the treatment of mood and addictive disorder (18)

• It is recommended that physicians act to reduce chance of diversion, including frequent office visits, urine testing, and recalls visits for pill counts (21)

• Buprenorphine dosage:

– Optimal dose is critical to outcome (21)

– The starting dose is from 2-4mg up to 8 mg per day, depending on degree of tolerance to opioids and extent of opioid withdrawal at first dose (18,33)

– Dose should be increased by 2-4 mg each time. Once the initial dose is well tolerated it can be rapidly increased (19,23,33)

– Optimal doses following induction must be individualised according to patient responses and an optimal dose is critical to obtaining the best outcome (3)

– Doses of buprenorphine at the end of the first week to achieve stabilisation typically range from 12 to 24 mg/day (33) with the proportion of patients who relapse decreasing as the induction dose is increased

– Doses of at least 16 mg are associated with better outcomes, a greater reduction in on-top use of illicit drugs than doses <16 mg (1,16,28,36).

– Doses in excess of 24 mg per day may be reserved for a small group of patients with particular clinical profiles

– Once a stable daily dose is established, it may be appropriate in some cases to alter frequency of dosing to alternate day dosing or 3 times weekly (11,18)

• The advantages and disadvantages of buprenorphine and buprenorphine/ naloxone treatment (Table 2) should be considered in deciding if buprenorphine is a suitable treatment

• Buprenorphine treatment is recommended for patients as a component of a management plan for OUD; it is often the appropriate initial option based on its favourable safety profile, low risk of overdose, relatively easy induction and ability to treat in the community setting; expert management is required to avoid precipitated withdrawal

• Buprenorphine/ Naloxone is also recommended in settings with increased risk of misuse or diversion

• Table 2 Advantages and disadvantages of buprenorphine or buprenorphine/ naloxone


Safety profile: lower risk of fatal overdose (6,7,18,19,23,25,32,33)

Reduced risk of over-sedation and respiratory depression due to “ceiling effect” and less euphoric effect (19)

Fewer clinically relevant drug interactions (18)

Side effect profile more favourable (7,18,22,23)

Easier to switch to alternative therapies such as methadone (18); withdrawal symptoms are less severe (33)

Lower risks of misuse and diversion with buprenorphine/ naloxone combination (6,11,13,18)

Initiation can be completed more quickly and simply, potential to reach optimal stable maintenance dose more quickly (18,19,23)

Limited monitoring and supervision on therapy (18)

Can be offered in flexible treatment settings including “Take home dosing” (32), which can be started relatively quickly (even from the first dose) (19,21,33)

Reduced sedative effects, less impairment of cognitive function (18)

Treatment maybe more likely to allow patients to continue normally daily activities, work (18,19)

Fewer treatment related problems with patients with concomitant medical problems (7,23) (cardiology, limited risk of QTc prolongation), less likely need for dose adjustment in renal and liver impairment and in the elderly (18)

Withdrawal symptoms often less severe; treatment easier to discontinue (option for individuals with lower intensity opioid dependence) (33)


If dosed inappropriately may be associated with precipitated withdrawal

May be suboptimal for individuals with high opioid tolerance (21,32,33)

May block opioid analgesics used for concurrent pain treatment (32)

At lower doses, there may be lower rates of retention in treatment (18,32)

May not meet the needs of patients with seeking intense effects of opioids such as euphoria

May not provide sedation type effects where desired

Choice of opioid agonist treatment

Patients and healthcare professionals should review options and consider the choice of treatment for OUD based on individual needs (18). The best therapy for an individual should be decided by the patient and physician together as a shared decision (21). A clear set of treatment goals needs to be defined for each patient.

When administered at appropriate doses, both methadone and buprenorphine are effective treatments (7,19). To select the optimal opioid agonist therapy for each patient, the advantages and disadvantages of each treatment (Table 1 and Table 2) need to be considered as well as the following factors.

• Availability of each treatment may vary from country to country (11,19)

• Risk of overdose, especially during the first 2 weeks of treatment (19)

– Risk of overdose is higher with methadone than with buprenorphine (6,7,18,19,23,25,32,33)

• Concomitant therapies used by the patient, including the potential for drug interactions with opioid agonist therapy and their clinical relevance

– More clinically relevant drug interactions with methadone than with buprenorphine (18,32)

• Previous opioid overdose (19), opioid tolerance (18,33), intolerance symptoms and tendency to drop-out from treatment, challenge in induction phase of treatment (32)

• Patient need for supervised daily administration, treatment setting

– Buprenorphine treatment in the community is a recommended option for patients wishing to reduce contact with healthcare services (18)

– Take home treatment with buprenorphine may be preferred for patients at work, study, with busy lifestyles or children (18,19,21,33). It can save time, costs and reduce the stigma associated with opioid agonist therapy

– Supervised daily administration of methadone may be beneficial for chaotic, unstable, or injecting patients (32,33)

• Home environment – especially considered for patients with small children where risks from accidental ingestion need to be considered (23). Buprenorphine is recommended as risks from accidental ingestion higher for methadone than for buprenorphine

• Sedative effects

– Methadone has greater sedative effects than buprenorphine (19) Buprenorphine has an advantage for patients taking other sedative medications (18)

– Beneficial impact of sedative effects for people with psychological distress, anxiety and schizophrenia (19)

– Negative impact of sedative effects for people who require good cognitive function such as those employed or studying, looking after children, driving, and elderly patients with other conditions affecting cognition (7,18)

– Impact for those taking other sedative medications (18)

• Strong patient preference for a specific treatment (e.g., safety concern, take home doses, previous experience) (3)

• Clinical condition of the patient (e.g., patients with pain, comorbidities such as cardiac, renal, liver and
respiratory dysfunction, the elderly and depressed patients (19,23))

• Specific patient social circumstances

– People at work, study (18,19), or caring for others need rapid induction and fast stabilisation

– Slow induction for injecting heroin users is appropriate

– Prisoners will have additional considerations (19,21)

• Previous benefit on a particular opioid agonist therapy

• Age of the patient – elderly patients are likely to have a high level of co-morbidities whether or not associated with a long history of drug use

• Treatment flexibility: some patients move in and out of treatment and discontinue treatment regularly

• Ease of transition to another opioid therapy (18). It is easier to transition from buprenorphine to methadone. It is recommended to consider treatment commencement on buprenorphine first-line in many cases.

Additional recommendations for special population

Psychiatric comorbidities

Dual diagnosis of psychiatric comorbidity with OUD is common (31). Treatment of co-existence psychiatric disorders is important and, whenever possible, treatment of patients with OUD and other mental disorders should be provided by individuals or teams with expertise in the management of dual diagnoses (18,19,21,23,33).

An assessment of mental health status should be undertaken in patients with OUD (18,19,21,33). There may be a specific risk of suicide for some with dual diagnosis – this must be address urgently (21). OUD and co-existent psychiatric disorders must be treated as there is an increased risk of relapse and failed stabilisation rate in both disorders if only one condition is treated (18). Assessment and treatment for either disorder should begin as early as possible (21,33), without the imposition of arbitrary waiting periods of abstinence and without a requirement of psychiatric stabilization. Upon stabilisation of OAT, status of psychiatry disorder and management plan should be reassessed (21).

Treatment choice

• OUD should be treated in patients with psychiatric co-morbidities including consideration for pharmacotherapy (21)

• There is limited evidence for different efficacy outcomes to direct the selection of pharmacotherapy choices of OUD in patients with psychiatric comorbidities

• Treatment choice is influenced by potential interactions of concomitant medications with opioid agonist therapy (19,21); tricyclic antidepressants and fluvoxamine may interact with methadone (19)

• Effects of methadone, including hypotensive and sedative effects, may be potentiated by antipsychotic medication, thereby increasing the toxicity risk(19). Methadone, due to sedative effects, may be most appropriate for patients with concomitant schizophrenia

• Buprenorphine may be preferred by some experts for those with depression and borderline personality disorder, although there is neither extensive nor strong evidence (18)

Somatic disorders

• At initial assessment should be conducted by a clinician trained in the relevant somatic disorder

– Test for additional somatic disorders (11,19,23)

– Perform an ECG (11,19)

– Offer vaccinations (18,19) and provide information (23) about disease transmission

– Perform a thorough review of concomitant medication currently taken by the patient including a web search for up-to-date potential clinically relevant drug-drug interactions and dose adjustment (18,19)

– Refer to specialist treatments for specific medical conditions (18)

• Prioritise treatment for this population

– Offers the opportunity to improve patient’s adherence and management of a potentially complicated treatment regimen (13)

– Prevent disease transmission, minimising public and individual health consequences (11)

Treatment choice

• For safety reasons, buprenorphine is the preferred treatment in patients with specific somatic disorders.

– Few clinically relevant drug-drug interactions (18,19,33)

– A lower likelihood of QTc prolongation inducement (18). Patients with prolonged QTc intervals should have regular ECGs as clinically appropriate (11)

– For patients with advanced liver disease, monitor buprenorphine and methadone dose closely as there may be a need to reduce dose significantly through a gradual dose reduction (18,23)

Pregnant women

The highest risk to the unborn child is acute opioid withdrawal and/ or untreated opioid use disorder (33). It is recommended that a plan to start or continue OAT pharmacotherapy in conjunction with psychosocial treatment, is developed with expectant mothers with opioid use disorder (21,33).

Abstinence or management of withdrawal is not recommended in pregnancy. Detoxification is not recommended as the risk of miscarriage or preterm labour is increased with acute withdrawal of opioids(21,33).

Co-management by the obstetrician–gynecologist and addiction medicine specialist and of the neonate by the pediatrician and for comprehensive care of the opioid-dependent mother during pregnancy and postpartum should be the norm (2,21). It is important to evaluate all pregnant women to identify any medical conditions that require urgent referral for further clinical evaluation by other specialists, particularly obstetrician-gynecologist (21,33). Participation in an opioid agonist program may allow identification of other health and social needs and provide interventions to improve pregnancy outcomes (11,18). Breastfeeding should be encouraged in mothers treated with buprenorphine or methadone (22,33,34)

Treatment choice

• Buprenorphine and methadone may be used in pregnancy and during breastfeeding (13,14,18,21,22,33,34). Women treated with opioid agonists who become pregnant should be encouraged to remain on the current medication with appropriate dosing adjustments throughout pregnancy (34).

• Buprenorphine treatment has advantages over methadone for outcomes of foetal wellbeing (18) (based on assessments of fetal heart rate and movements in pre- and post-dosing of study drug-maintained mothers in the third trimester) as well as severity of NAS (18,19) and neonatal neurobehavioral functioning (18): buprenorphine is the recommended choice for treatment naïve patients in many situations (21,33)

• Mothers currently treated on buprenorphine should remain on this treatment in pregnancy: buprenorphine-stabilized women who become pregnant should not be transitioned to methadone (34); buprenorphine should be considered as an initial choice for opioid-dependent pregnant women who are naive to agonist treatment.

• Care must be taken with the initiation of buprenorphine treatment as this may be associated with precipitated withdrawal, which should be avoided (21).

• Buprenorphine/ naloxone should be used during pregnancy only if the potential benefit outweighs the potential risk to the foetus

• There is extensive historical experience with methadone in pregnancy (33). Doses of methadone may need to be increased during pregnancy: pharmacokinetics of methadone decrease progressively as the gestational age increases requiring increased doses, typically of 15% greater (11,13,19,21,33). It is often necessary to split methadone doses may be required as the pregnancy advances (11,13,19,21,33). Methadone-stabilized women who become pregnant should not be transitioned to buprenorphine (18,20,34)

• Assessment of methadone and buprenorphine risk profile in pregnancy (8,33), indicates that the risk of adverse effects has not been ruled out but potential benefits may warrant use of the drug in pregnant women despite potential risk (17,33)

The elderly

• For elderly patients w
ith difficulty in accessing drug treatment services (18), it may be appropriate to perform assessments and treatments at the patient’s preferred location (5)

• The elderly may be more likely to remain on treatment than younger patients (5)

• For elderly patients entering residential care ongoing OAT should continue and physicians must collaborate with care home staff for optimal transition (23)

• Elderly patients are likely to have a high level of co-morbidities whether associated or not with a long history of drug use (18)

– Co-ordinated care is necessary and co-morbidities should be reviewed when the patient attends any OUD treatment review (18,23)

– As patients may be taking a number of treatments for other conditions, close monitoring of all side effects is needed (18,23)

Treatment choice

• Due to the safety profile, reduced impact on cognition commencing treatment with buprenorphine and transferring existing elderly patients to buprenorphine may be provident in some groups (23)

• Risk of methadone toxicity has been found to increase in the elderly population (33)

– As drugs may be metabolised more slowly, slower dose titration and lower doses of methadone are likely to be required (18)

• Elderly patients may have been on treatment for many years so it could be risky to enforce methadone dose reductions, particularly without the patient’s agreement

Patients using opioids to manage pain

Patients with co-existing pain may be challenging to manage. For those who have lost control of their pain management, OAT offers an opportunity to regain healthy control (13). Correct diagnosis and identifying a target for treatment is a priority (21), without assuming that maintenance opioid treatment will manage co-existing pain (18).

• Medication choice and treatment goals should be approached comprehensively, with caution, planned clearly (18,19).

• Consultation with pain and addiction specialists is important to facilitate appropriate dispensing and to form a comprehensive management plan (13,18,19,23). This should be further developed between physician and patient

• Patients should be monitored closely (21,23), especially during rapid introduction of high dose opioids to manage acute pain (19)

• Physicians should assess and manage the risk of misuse or diversion carefully (19)

Treatment choice

• Either methadone or buprenorphine may be considered for treatment, along with psychosocial treatment (21)

• Patients with pain typically have a higher tolerance to opioids (18). It is likely the dose for a typical patient will be less effective and to be optimal this may mean a 30% higher dose in acute care (18). Suboptimal doses should be avoided (19)

– Patients could benefit from dosing 2-3 times daily during maintenance (19,23) due to the shorter analgesic activity of methadone over its half-life

• Physicians should try to avoid opioid analgesia. However, an opioid analgesic can be added on top of the opioid agonist treatment if necessary (18)

• Additional regional anesthesia should be considered (21)

• Patients on buprenorphine during an emergency surgical situation

– Clinical data is limited. In this population buprenorphine should be continued throughout elective surgery with additional short-acting opioids, or split dosing, or switching to methadone (23)

• For acute pain

– Patients already on methadone for severe acute pain will need additional methadone and those facing surgery may need additional opioid pain relievers at a higher dose (21)

– Patients with mild acute pain may find buprenorphine effective by temporarily increasing dosing (21). However, for more severe acute pain it is recommended to switch to a high-potency opioid (21)

• For chronic pain

– Specialists should be consulted for recommendations due to the potential complexity of managing both conditions (13,18)

– Some patients could benefit from dosing 2-3 times daily during maintenance due to the shorter analgesic activity of methadone over its half-life (19,23)

Polydrug users (including use of alcohol)

Patients with alcohol, sedative, hypnotic, or anxiolytic use disorder or those regularly consuming alcohol or sedatives (“downers”) are a challenging group to manage (19) safely as treatment with methadone or buprenorphine is undermined and benefits of opioid agonist therapy reduced (11).

• Interventions to reduce or cease alcohol and polydrug misuse should be instituted (19) since such activities affect methadone and buprenorphine metabolism, risking overdose, death from toxicity, intoxication, liver damage, blood-borne disease, drug interactions, street drinking and a drug misusing lifestyle (11,18,19,33)

• A breathalyser test should be taken when opioid is prescribed and consumption should be supervised (19)

• Injecting equipment should be offered to injecting drug users and support to address housing and other negative social problems (19)

• Opioid agonist treatment can be offered if an alcohol/ polydrug misuse management plan is put in place and conducted simultaneously. Treatment continuation is only recommended in the presence of clear benefits (11)

Treatment choice

• There is no consensus on whether methadone or buprenorphine is more favourable in this population: either treatment is reasonable to use with caution (18)


Due to their social circumstances and environmental pressures, prisoners are considered to be at risk of receiving sub-optimal treatment for OUD.

• Regardless of the length of their sentence, prisoners should be offered OAT alongside psychosocial treatment and rehabilitation support (13,19)

• OAT should be available immediately on the first night in prison (19)

• Prisoners should be managed in the same way as any other patient with OUD.

– Treatment should not be discontinued for disciplinary reasons, as this is not clinically justified (18,19)

• Coordinated care between prison staff and the community health services should be a priority, consulting the local pharmacist for a dispensing history (18). However, if prisoners have been storing or diverting prescribed medication, they will be less tolerant of opioid medication than expected from a medical history (19)

• Review prisoners frequently (twice daily) during initial days in prison (particularly during stabilisation and withdrawal stages) for toxicity, overdose, suicide and self-harm (19)

• If the patient is actively psychotic or has suicidal ideation or intent, mental health services will need to act immediately. Safe cells may be necessary to facilitate intensive supervision, monitoring and assessment (19)

– There is a high risk of overdose for prisoners with OUD on their release from prison as they may have developed a reduced tolerance to opioids during their time incarcerated (18,19)

– Re-toxification may be required for prisoners with a relapse history who have been detoxified in prison (19)

– Prisoners who gained stability on opioid agonist therapy in prison may require a higher dose upon release to maintain stability; the prison dose may not prove sufficient (19)

– Advice and support and continued treatment in the community setting are important if outcomes are to be improved and gains made in prison continued (18,19)

• Treatment choice

• If a person on stable maintenance therapy in the community is arrested, this should be continued during custody (13,19)

• Where history is unknown a low potency opioid at a lo
w dose may be given and buprenorphine may be considered with good monitoring. There is evidence for buprenorphine’s effectiveness for improving opioid withdrawal in custody (19)

• Methadone is offered in most prisons on the first night unless a community prescription is known when this prescription should be continued (19)

• The potential for diversion in prisons is great and thus methadone may be preferred (supervised dosing) (19)

• Due to its low risk of diversion, buprenorphine/ naloxone is recommended

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