Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

non-pregnant adults in inpatient/outpatient detoxification programme

1st line – induction therapy: buprenorphine ± naloxone

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient detoxification programme
1st line – 

induction therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug.

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone.

Dose is titrated according to signs and symptoms of withdrawal. Dose should be sufficient to enable patients to discontinue opioid use. Evidence suggests that doses ≥16 mg/day may be more effective than lower doses. However, there is limited evidence for the efficacy of doses ≥24 mg/day.[46] Consult a specialist or your local protocols for further guidance on dosing.

Microdosing protocols using successive small doses (i.e., 2 mg) may be appropriate for patients taking opioids with a high lipophilicity such as fentanyl, as they allow slow displacement from the opioid receptor.[22]

There are insufficient data on the duration of taper with buprenorphine, with studies ranging from 36 hours to 13 days.[73][133][134]

When buprenorphine is stopped abruptly, the exact duration of withdrawal is not known and may vary considerably from patient to patient. After receiving 8 mg/day for 10 days (without taper), mild symptoms peaking at 3 to 5 days and disappearing after 10 days have been reported.[75]

Primary options

buprenorphine: see local protocols for guidance on dosing regimen

OR

buprenorphine/naloxone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

While there is no evidence of any specific nutrition or diet to aid detoxification, adequate hydration and food intake should be ensured.

Ancillary medications in therapeutic doses may be required for symptomatic relief (e.g., ibuprofen for muscle cramps; bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues; and trazodone for sleep disturbances).[41]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[41] Monitoring for respiratory depression is required. Use caution if prescribing on an outpatient basis. Oxazepam and chlordiazepoxide are generally the benzodiazepines of choice in clinical practice.

Psychosocial counselling is primarily given during the maintenance phase; however, support and reassurance should be provided during detoxification, and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective.[85] [ Cochrane Clinical Answers logo ]

Primary options

Pain

ibuprofen: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

Nausea/vomiting

prochlorperazine: 5-10 mg orally every 6-8 hours when required, maximum 40 mg/day

OR

Nausea/vomiting

ondansetron: 8 mg orally/intravenously every 8 hours when required

OR

Diarrhoea

bismuth subsalicylate: 524 mg (2 tablets) orally every hour when required, maximum 4200 mg/day

OR

Insomnia

trazodone: 25-50 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150-200 mg/day

OR

Anxiety

oxazepam: 15-30 mg orally three to four times daily when required

OR

Anxiety

chlordiazepoxide: 50-100 mg orally every 4-6 hours when required, maximum 300 mg/day

1st line – induction therapy: methadone

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient detoxification programme
1st line – 

induction therapy: methadone

Alternative first-line option to buprenorphine.

A schedule II controlled drug.

Dose should be titrated against withdrawal symptoms. Initial dose should not exceed 30 to 40 mg/day on the first day. Ideally the patient should be observed 3 to 4 hours after the initial dose, when peak levels are reached. Dose can be increased by up to a maximum of 10 mg/day if patient is not comfortable at 3 to 4 hours.

Dose increases during induction should be gradual, with urine drug screens to monitor illicit drug use and regular assessments.

Blood levels of methadone can help to optimise dosing. Levels >1.29 micromol/L (>400 nanograms/mL) are considered optimal to provide cross-tolerance to illicit opioids. The peak (4 hours after dose) to trough (24 hours after last dose) level ratio is considered important to determine split dosing in fast metabolisers. An ideal peak:trough ratio is 2 or less. Higher ratios suggest rapid metabolism and require divided dosing.

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[135][136]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[40]

Methadone may prolong the QT interval and patients should be informed of the potential risk of arrhythmia.[46] A history of structural heart disease, arrhythmia, or syncope should be taken.[46] An ECG should be performed for high-risk patients.[46]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

While there is no evidence of any specific nutrition or diet to aid detoxification, adequate hydration and food intake should be ensured.

Ancillary medications in therapeutic doses may be required for symptomatic relief (e.g., ibuprofen for muscle cramps; bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues; and trazodone for sleep disturbance).[41]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[41] Monitoring for respiratory depression is required. Use caution if prescribing on an outpatient basis. Oxazepam and chlordiazepoxide are generally the benzodiazepines of choice in clinical practice.

Psychosocial counselling is primarily given during the maintenance phase; however, support and reassurance should be provided during detoxification, and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective.[85] [ Cochrane Clinical Answers logo ]

Primary options

Pain

ibuprofen: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

Nausea/vomiting

prochlorperazine: 5-10 mg orally every 6-8 hours when required, maximum 40 mg/day

OR

Nausea/vomiting

ondansetron: 8 mg orally/intravenously every 8 hours when required

OR

Diarrhoea

bismuth subsalicylate: 524 mg (2 tablets) orally every hour when required, maximum 4200 mg/day

OR

Insomnia

trazodone: 25-50 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150-200 mg/day

OR

Anxiety

oxazepam: 15-30 mg orally three to four times daily when required

OR

Anxiety

chlordiazepoxide: 50-100 mg orally every 4-6 hours when required, maximum 300 mg/day

2nd line – induction therapy: clonidine or lofexidine ± naltrexone

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient detoxification programme
2nd line – 

induction therapy: clonidine or lofexidine ± naltrexone

Clonidine and lofexidine are alpha-2-adrenergic agonists that reduce the sympathetic nervous system response (i.e., noradrenergic release) to opioid withdrawal. Lofexidine is a structural analogue of clonidine and is generally associated with fewer side effects.[41] However, it may not suppress withdrawal symptoms as fully as clonidine, and may therefore contribute to poorer treatment retention.[41]

Usual doses of opioids should be given on the day prior to detoxification, with opioids discontinued abruptly the day clonidine or lofexidine is started.

Transdermal clonidine patches can also be used for detoxification, but require oral clonidine supplementation for first 2 days. They are not widely used.

Studies have found that addition of the opioid antagonist naltrexone to clonidine can shorten the duration of withdrawal without increasing discomfort.[79][80] After detoxification was completed, patients could be transitioned to naltrexone maintenance treatment.

Primary options

clonidine: see local protocols for guidance on dosing regimen

OR

lofexidine: see local protocols for guidance on dosing regimen

Secondary options

clonidine transdermal: see local protocols for guidance on dosing regimen

OR

clonidine: see local protocols for guidance on dosing regimen

and

naltrexone: see local protocols for guidance on dosing regimen

OR

lofexidine: see local protocols for guidance on dosing regimen

and

naltrexone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

While there is no evidence of any specific nutrition or diet to aid detoxification, adequate hydration and food intake should be ensured.

Ancillary medications in therapeutic doses may be required for symptomatic relief (e.g., ibuprofen for muscle cramps; bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues; and trazodone for sleep disturbance).[41]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[41] Monitoring for respiratory depression is required. Use caution if prescribing on an outpatient basis. Oxazepam and chlordiazepoxide are generally the benzodiazepines of choice in clinical practice.

Psychosocial counselling is primarily given during the maintenance phase; however, support and reassurance should be provided during detoxification, and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective.[85] [ Cochrane Clinical Answers logo ]

Primary options

Pain

ibuprofen: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

Nausea/vomiting

prochlorperazine: 5-10 mg orally every 6-8 hours when required, maximum 40 mg/day

OR

Nausea/vomiting

ondansetron: 8 mg orally/intravenously every 8 hours when required

OR

Diarrhoea

bismuth subsalicylate: 524 mg (2 tablets) orally every hour when required, maximum 4200 mg/day

OR

Insomnia

trazodone: 25-50 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150-200 mg/day

OR

Anxiety

oxazepam: 15-30 mg orally three to four times daily when required

OR

Anxiety

chlordiazepoxide: 50-100 mg orally every 4-6 hours when required, maximum 300 mg/day

non-pregnant adolescents in inpatient/outpatient detoxification programme

1st line – induction therapy: buprenorphine ± naloxone

Back
ACUTE
|
non-pregnant adolescents in inpatient/outpatient detoxification programme
1st line – 

induction therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug.

Buprenorphine is generally preferred over methadone for induction and maintenance in adolescents because of its safety profile, except in instances of prior inadequate response to buprenorphine.

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone.

Dose is titrated according to signs and symptoms of withdrawal. Dose should be sufficient to enable patients to discontinue opioid use. Evidence suggests that doses ≥16 mg/day may be more effective than lower doses. However, there is limited evidence for the efficacy of doses ≥24 mg/day.[46] Consult a specialist or your local protocols for further guidance on dosing.

Microdosing protocols using successive small doses (i.e., 2 mg) may be appropriate for patients taking opioids with a high lipophilicity such as fentanyl, as they allow slow displacement from the opioid receptor.[22]

There are insufficient data on the duration of taper with buprenorphine, with studies ranging from 36 hours to 13 days.[133][134]

When buprenorphine is stopped abruptly, the exact duration of withdrawal is not known and may vary considerably from patient to patient. After receiving 8 mg/day for 10 days (without taper), mild symptoms peaking at 3 to 5 days and disappearing after 10 days have been reported.[75]

Primary options

buprenorphine: see local protocols for guidance on dosing regimen

OR

buprenorphine/naloxone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adolescents in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

While there is no evidence of any specific nutrition or diet to aid detoxification, adequate hydration and food intake should be ensured.

Ancillary medications in therapeutic doses may be required for symptomatic relief (e.g., ibuprofen for muscle cramps; bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues; and trazodone for sleep disturbance).[41]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[41] Monitoring for respiratory depression is required. Use caution if prescribing on an outpatient basis. Oxazepam and chlordiazepoxide are generally the benzodiazepines of choice in clinical practice.

Psychosocial counselling is primarily given during the maintenance phase; however, support and reassurance should be provided during detoxification, and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective.[85] [ Cochrane Clinical Answers logo ]

Primary options

Pain

ibuprofen: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

Nausea/vomiting

prochlorperazine: 5-10 mg orally every 6-8 hours when required, maximum 40 mg/day

OR

Nausea/vomiting

ondansetron: 8 mg orally/intravenously every 8 hours when required

OR

Diarrhoea

bismuth subsalicylate: 524 mg (2 tablets) orally every hour when required, maximum 4200 mg/day

OR

Insomnia

trazodone: 25-50 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150-200 mg/day

OR

Anxiety

oxazepam: 15-30 mg orally three to four times daily when required

OR

Anxiety

chlordiazepoxide: 50-100 mg orally every 4-6 hours when required, maximum 300 mg/day

2nd line – induction therapy: methadone

Back
ACUTE
|
non-pregnant adolescents in inpatient/outpatient detoxification programme
2nd line – 

induction therapy: methadone

A schedule II controlled drug.

Methadone treatment is not usually given as a first-line treatment option in those <18 years of age. In the US, methadone treatment in patients <18 years is allowed only if they have relapsed to opioid use after two documented attempts at detoxification or short-term rehabilitation.[119][120]

Dose should be titrated against withdrawal symptoms. Initial dose should not exceed 30 to 40 mg/day on the first day. Ideally the patient should be observed 3 to 4 hours after the initial dose, when peak levels are reached. Dose can be increased by up to a maximum of 10 mg/day if patient is not comfortable at 3 to 4 hours.

Dose increases during induction should be gradual, with urine drug screens to monitor illicit drug use and regular assessments.

Blood levels of methadone can help to optimise dosing. Levels >1.29 micromol/L (>400 nanograms/mL) are considered optimal to provide cross-tolerance to illicit opioids. The peak (4 hours after dose) to trough (24 hours after last dose) level ratio is considered important to determine split dosing in fast metabolisers. An ideal peak:trough ratio is 2 or less. Higher ratios suggest rapid metabolism and require divided dosing.

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[135][136]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[40]

Methadone may prolong the QT interval and patients should be informed of the potential risk of arrhythmia.[46] A history of structural heart disease, arrhythmia, or syncope should be taken.[46] An ECG should be performed for high-risk patients.[46]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adolescents in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

While there is no evidence of any specific nutrition or diet to aid detoxification, adequate hydration and food intake should be ensured.

Ancillary medications in therapeutic doses may be required for symptomatic relief (e.g., ibuprofen for muscle cramps; bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues; and trazodone for sleep disturbance).[41]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[41] Monitoring for respiratory depression is required. Use caution if prescribing on an outpatient basis. Oxazepam and chlordiazepoxide are generally the benzodiazepines of choice in clinical practice.

Psychosocial counselling is primarily given during the maintenance phase; however, support and reassurance should be provided during detoxification, and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective.[85] [ Cochrane Clinical Answers logo ]

Primary options

Pain

ibuprofen: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

OR

Nausea/vomiting

prochlorperazine: 5-10 mg orally every 6-8 hours when required, maximum 40 mg/day

OR

Nausea/vomiting

ondansetron: 8 mg orally/intravenously every 8 hours when required

OR

Diarrhoea

bismuth subsalicylate: 524 mg (2 tablets) orally every hour when required, maximum 4200 mg/day

OR

Insomnia

trazodone: 25-50 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150-200 mg/day

OR

Anxiety

oxazepam: 15-30 mg orally three to four times daily when required

OR

Anxiety

chlordiazepoxide: 50-100 mg orally every 4-6 hours when required, maximum 300 mg/day

pregnant women in inpatient/outpatient detoxification programme

1st line – induction therapy: methadone

Back
ACUTE
|
pregnant women in inpatient/outpatient detoxification programme
1st line – 

induction therapy: methadone

A schedule II controlled drug.

Detoxification is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[52][122][123] However, if absolutely necessary, opioid detoxification should be carried out in an inpatient setting.

Methadone is a first-line option for detoxification or maintenance.[124][137][138]​​

Dose should be titrated against withdrawal symptoms. Initial dose should not exceed 30 to 40 mg/day on the first day. Ideally the patient should be observed 3 to 4 hours after the initial dose, when peak levels are reached. Dose can be increased by up to a maximum of 10 mg/day if patient is not comfortable at 3 to 4 hours.

Dose increases during induction should be gradual, with urine drug screens to monitor illicit drug use and regular assessments.

Blood levels of methadone can help to optimise dosing. Levels >1.29 micromol/L (>400 nanograms/mL) are considered optimal to provide cross-tolerance to illicit opioids. The peak (4 hours after dose) to trough (24 hours after last dose) level ratio is considered important to determine split dosing in fast metabolisers. An ideal peak:trough ratio is 2 or less. Higher ratios suggest rapid metabolism and require divided dosing.

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[135][136]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[40]

Methadone may prolong the QT interval and patients should be informed of the potential risk of arrhythmia.[46] A history of structural heart disease, arrhythmia, or syncope should be taken.[46] An ECG should be performed for high-risk patients.[46]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
pregnant women in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Ancillary medications in therapeutic doses may be required for symptomatic relief. Treatments are generally the same as for non-pregnant women; however, certain drugs should be avoided or only used when the benefits outweigh the risks. Consult a specialist for further guidance on the selection of suitable supportive therapies in pregnant women.

1st line – induction therapy: buprenorphine ± naloxone

Back
ACUTE
|
pregnant women in inpatient/outpatient detoxification programme
1st line – 

induction therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug.

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone.

Buprenorphine monotherapy was previously recommended for pregnant women to avoid any potential antenatal exposure to naloxone.[52] However, studies evaluating buprenorphine in combination with naloxone have since found no adverse effects in pregnant women.[52]

Detoxification is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[52][122] However, if absolutely necessary, opioid detoxification should be carried out in an inpatient setting.

Buprenorphine is a first-line alternative to methadone.[52][124]

Multiple small case series have examined maternal buprenorphine concentrations in human milk. All concur that the amounts of buprenorphine in human milk are small and are unlikely to have short-term negative effects on the developing infant.[130]

Dose is titrated according to signs and symptoms of withdrawal. Dose should be sufficient to enable patients to discontinue opioid use. Evidence suggests that doses ≥16 mg/day may be more effective than lower doses. However, there is limited evidence for the efficacy of doses ≥24 mg/day.[46] Consult a specialist or your local protocols for further guidance on dosing.

Microdosing protocols using successive small doses (i.e., 2 mg) may be appropriate for patients taking opioids with a high lipophilicity such as fentanyl, as they allow slow displacement from the opioid receptor.[22]

There are insufficient data on the duration of taper with buprenorphine, with studies ranging from 36 hours to 13 days.[133][134]

When buprenorphine is stopped abruptly, the exact duration of withdrawal is not known and may vary considerably from patient to patient. After receiving 8 mg/day for 10 days (without taper), mild symptoms peaking at 3 to 5 days and disappearing after 10 days have been reported.[75]

Primary options

buprenorphine: see local protocols for guidance on dosing regimen

OR

buprenorphine/naloxone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
pregnant women in inpatient/outpatient detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Ancillary medications in therapeutic doses may be required for symptomatic relief. Treatments are generally the same as for non-pregnant women; however, certain drugs should be avoided or only used when the benefits outweigh the risks. Consult a specialist for further guidance on the selection of suitable supportive therapies in pregnant women.

ONGOING

non-pregnant adults after detoxification programme

1st line – maintenance therapy: buprenorphine ± naloxone

Back
ONGOING
|
non-pregnant adults after detoxification programme
1st line – 

maintenance therapy: buprenorphine ± naloxone

First-line agent for maintenance therapy with relatively safe adverse effect profile and partial agonist properties, except in patients with very high-dose opioid addiction.

Buprenorphine is a schedule III controlled drug.

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone.

Due to its prolonged duration of action (24 to 60 hours), it can be given once daily or even three times weekly.[93]

For patients stabilised on buprenorphine, it can be administered via a subdermal implant that delivers a consistent dosage of buprenorphine over 6 months. It can also be administered as a once-monthly injection for patients who have been on a stable dose of buprenorphine for a minimum of 7 days; the US Food and Drug Administration have approved it for the treatment of moderate to severe opioid use disorder in adults who have initiated treatment with a transmucosal buprenorphine-containing product.

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects. An ongoing large, multi-site, 2-phase, randomised controlled trial will provide more data on optimal length of maintenance treatment and outcomes associated with prescription opioid addiction.[139]

Can be used to detoxify patients from methadone maintenance and transition to buprenorphine maintenance or a drug-free state.[95][96]

Primary options

buprenorphine: see local protocols for guidance on dosing regimen

OR

buprenorphine subdermal: see local protocols for guidance on dosing regimen

OR

buprenorphine/naloxone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
non-pregnant adults after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments such as motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, and HIV risk reduction.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

1st line – maintenance therapy: methadone

Back
ONGOING
|
non-pregnant adults after detoxification programme
1st line – 

maintenance therapy: methadone

Preferred if both buprenorphine and methadone are equally suitable, and for patients with very high-dose opioid addiction.[88] [ Cochrane Clinical Answers logo ] ​

A schedule II controlled drug.

Once a stable dose is reached after induction, based on suppression of craving and elimination of withdrawal, the maintenance phase begins. During maintenance, patients have to come to the treatment programme daily for their methadone dosing and counselling.

Higher doses of methadone (>60 mg/day) are superior to lower doses for maintenance.[76] A dose of 60 to 100 mg daily is the consensus goal for treatment. Higher doses may be considered for individuals with continued illicit drug use, but data are limited and the risk to benefit ratio must be carefully considered.[143]

For withdrawal from methadone maintenance, the tapering schedule depends on the reasons for detoxification. For stable patients, a slow taper (5% to 10% per week) over 4 to 6 months is preferable to a faster detoxification. Once doses of 30 mg/day are reached, taper may have to be slowed to <5% per week.

In some countries, patients who do well according to local guidelines may be permitted to take methadone home for unsupervised dosing.

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[135][136]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[40]

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
non-pregnant adults after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments such as motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

While methadone has been shown to be effective in controlling baseline cravings, patients continue to be at risk for cue-induced cravings.[144]

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, and HIV risk reduction.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

2nd line – maintenance therapy: naltrexone

Back
ONGOING
|
non-pregnant adults after detoxification programme
2nd line – 

maintenance therapy: naltrexone

Patient may be transitioned from clonidine or lofexidine (with or without naltrexone) detoxification therapy to naltrexone maintenance therapy.

A Cochrane review found no benefit of oral naltrexone over placebo or no treatment in retention, opioid abuse, or side effects.[103]

Medication compliance and retention are strong barriers to using oral naltrexone for opioid use disorder, as there is no euphoria associated with this regimen.

There is no additional benefit from higher doses of naltrexone compared with lower doses in reducing opioid use. There is also no significant difference in adverse effects between low and high doses.[145]

An extended-release, parenteral formulation of naltrexone is now available and is considered a useful treatment option due to the lack of risk of physical dependence. In one randomised controlled trial of 250 participants, detoxified, opioid-dependent adults voluntarily seeking treatment who received this formulation had more opioid-free days compared with those who received placebo, and it was found to be generally well-tolerated.[146] When initiated, extended-release naltrexone has been shown to be as safe and effective as oral buprenorphine plus naloxone.[108][109]

The extended-release formulation can be used safely in patients with underlying mild to moderate chronic hepatitis C virus and/or HIV infections, and is administered once monthly.[107]

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.

Primary options

naltrexone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
non-pregnant adults after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments such as motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, and HIV risk reduction.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

non-pregnant adolescents after detoxification programme

1st line – maintenance therapy: buprenorphine ± naloxone

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ONGOING
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non-pregnant adolescents after detoxification programme
1st line – 

maintenance therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug.

Buprenorphine is generally preferred over methadone for induction and maintenance in adolescents because of its safety profile, except in instances of prior inadequate response to buprenorphine.

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone.

Due to its prolonged duration of action (24 to 60 hours), it can be given once daily or even 3 times weekly.[93]

For patients ≥16 years of age stabilised on buprenorphine, it can be administered via a subdermal implant that delivers a consistent dosage of buprenorphine over 6 months.

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects. An ongoing large, multi-site, 2-phase, randomised controlled trial will provide more data on optimal length of maintenance treatment and outcomes associated with prescription opioid addiction.[139]

Can be used to detoxify patients from methadone maintenance and transition to buprenorphine maintenance or a drug-free state.[95][96]

Primary options

buprenorphine: see local protocols for guidance on dosing regimen

OR

buprenorphine subdermal: see local protocols for guidance on dosing regimen

OR

buprenorphine/naloxone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
non-pregnant adolescents after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Adolescents need support with safe accommodation, education, family relationships, mitigating risk factors for self-harm, and treatment of other comorbid addictions. Treatment on an individual and group or family basis are needed.

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments such as motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, HIV risk reduction, and criminal behaviour.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

2nd line – maintenance therapy: methadone

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ONGOING
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non-pregnant adolescents after detoxification programme
2nd line – 

maintenance therapy: methadone

A schedule II controlled drug.

Methadone treatment is not usually given as a first-line treatment option in those <18 years of age. In the US, methadone treatment in patients <18 years is allowed only if they have relapsed to opioid use after two documented attempts at detoxification or short-term rehabilitation.[119][120]

Higher doses of methadone (>60 mg/day) are superior to lower doses for maintenance.[76] A dose of 60 to 100 mg daily is the consensus goal for treatment. Higher doses may be considered for individuals with continued illicit drug use, but data are limited and the risk to benefit ratio must be carefully considered.[143]

For withdrawal from methadone maintenance, the tapering schedule depends on the reasons for detoxification. For stable patients, a slow taper (5% to 10% per week) over 4 to 6 months is preferable to a faster detoxification. Once doses of 30 mg/day are reached, taper may have to be slowed to <5% per week.

In some countries, patients who do well according to local guidelines may be permitted to take methadone home for unsupervised dosing.

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[135][136]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[40]

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
non-pregnant adolescents after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Adolescents need support with safe accommodation, education, family relationships, mitigating risk factors for self-harm, and treatment of other comorbid addictions. Treatment on an individual and group or family basis are needed.

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments such as motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

While methadone has been shown to be effective in controlling baseline cravings, patients continue to be at risk for cue-induced cravings.[144]

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, HIV risk reduction, and criminal behaviour.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

pregnant women after detoxification programme

1st line – maintenance therapy: methadone

Back
ONGOING
|
pregnant women after detoxification programme
1st line – 

maintenance therapy: methadone

A schedule II controlled drug.

Detoxification is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[52][122] However, if absolutely necessary, opioid detoxification should be carried out in an inpatient setting.

Methadone is a first-line option for detoxification or maintenance.[124][137][138]​​

Higher doses of methadone (>60 mg/day) are superior to lower doses for maintenance.[76] A dose of 60 to 100 mg daily is the consensus goal for treatment. Higher doses may be considered for individuals with continued illicit drug use, but data are limited and the risk to benefit ratio must be carefully considered.[143] Methadone has not been associated with birth defects; however, it can lead to neonatal abstinence syndrome.[125] The American Academy of Pediatrics states that maternal use is compatible with breastfeeding.

Women treated with a stable methadone dose before pregnancy may require dose adjustments, especially in the third trimester, although this is not required in all women and should be determined on an individual clinical basis. Rapid metabolism may develop in pregnancy, particularly in the third trimester, and in this scenario split (rather than daily) dosage may be best at controlling withdrawal symptoms (and may be associated with a reduced risk of neonatal abstinence syndrome).[52]

For withdrawal from methadone maintenance, the tapering schedule depends on the reasons for detoxification. For stable patients, a slow taper (5% to 10% per week) over 4 to 6 months is preferable to a faster detoxification. Once doses of 30 mg/day are reached, taper may have to be slowed to <5% per week.

In some countries, patients who do well according to local guidelines may be permitted to take methadone home for unsupervised dosing.

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[135][136]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[40]

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.

Breastfeeding should be encouraged in women who are stable on opioid agonist treatment who are not using illicit drugs and who have no other contraindications (e.g., HIV).[52] Women should be advised to stop breastfeeding if they develop a relapse of their opioid use disorder.

Babies born to mothers who used opioids during pregnancy (including methadone) should be monitored after birth by a paediatrician for neonatal abstinence syndrome, which neonates may develop shortly after birth.[52]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
pregnant women after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments targeted at supporting mothers, babies, fathers, and/or families. Therapies include motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

While methadone has been shown to be effective in controlling baseline cravings, patients continue to be at risk for cue-induced cravings.[144]

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, HIV risk reduction, and criminal behaviour.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

1st line – maintenance therapy: buprenorphine ± naloxone

Back
ONGOING
|
pregnant women after detoxification programme
1st line – 

maintenance therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug.

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone.

Buprenorphine monotherapy was previously recommended for pregnant women to avoid any potential antenatal exposure to naloxone.[52] However, studies evaluating buprenorphine in combination with naloxone have since found no adverse effects in pregnant women.[52]

Detoxification is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[52][122] However, if absolutely necessary, opioid detoxification should be carried out in an inpatient setting.

Buprenorphine is a first-line alternative to methadone.[52][124]

Multiple small case series have examined maternal buprenorphine concentrations in human milk. All concur that the amounts of buprenorphine in human milk are small and are unlikely to have short-term negative effects on the developing infant.[130]

Due to its prolonged duration of action (24 to 60 hours), it can be given once daily or even 3 times weekly.[93]

Treatment should be continued as long as patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects. An ongoing large, multi-site, 2-phase, randomised controlled trial will provide more data on optimal length of maintenance treatment and outcomes associated with prescription opioid addiction.[139]

Pregnant women receiving treatment with methadone should not transition to buprenorphine because of a significant risk of precipitating withdrawal.[52]

Breastfeeding should be encouraged in women who are stable on opioid agonist treatment who are not using illicit drugs and who have no other contraindications (e.g., HIV).[52] Women should be advised to stop breastfeeding if they develop a relapse of their opioid use disorder.

Babies born to mothers who used opioids during pregnancy (including buprenorphine) should be monitored after birth by a paediatrician for neonatal abstinence syndrome, which neonates may develop shortly after birth.[52]

Primary options

buprenorphine: see local protocols for guidance on dosing regimen

OR

buprenorphine/naloxone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ONGOING
|
pregnant women after detoxification programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Urine drug screening as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders) should occur.[110]

Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as hepatitis C screening and referral for treatment, should be integrated into maintenance programme.

Patients can benefit from psychosocial treatments targeted at supporting mothers, babies, fathers, and/or families. Therapies include motivational interviewing, individual and group drug counselling, contingency management, cognitive therapy, supportive expressive therapy, and 12-step-oriented groups such as Narcotics Anonymous.[40][112] UK Narcotics Anonymous Opens in new window

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[140][141]

Combination of behavioural and pharmacological treatments improves outcomes in abstinence, compliance, needle risk reduction, HIV risk reduction, and criminal behaviour.

Intensive counselling (i.e., three times per week) was no better than once-weekly counselling for opioid addicts treated with buprenorphine maintenance.[142]

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