Treatment algorithm

Your Organisational Guidance

ebpracticenet urges you to prioritise the following organisational guidance:

GeneesmiddelenverslavingPublished by: Domus Medica | SSMGLast published: 2011Assuétude aux médicamentsPublished by: Domus Medica | SSMGLast published: 2011

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 medically supervised withdrawal programme

1st line – medically supervised withdrawal regimen: buprenorphine ± naloxone

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

medically supervised withdrawal regimen: buprenorphine ± naloxone

Medically supervised withdrawal (formerly known as detoxification) involves short-term pharmacotherapy to manage symptoms but is not recommended as standalone treatment due to high relapse and overdose risk; ongoing maintenance therapy with psychosocial support is standard of care.[66][69] Supervised withdrawal may occur after stabilisation with maintenance therapy, or be used early with transition to substitution therapy once withdrawal begins. Withdrawal is not required before starting maintenance, except with naltrexone, which requires prior abstinence.[66][69] Treatment should be individualised using shared decision-making. In select stable, well-supported individuals pursuing abstinence, supervised withdrawal may be acceptable within a structured plan offering ongoing psychosocial support.[66][69]​​[96]​​ Patients must be warned that post-withdrawal tolerance is reduced, increasing overdose risk, and should be advised to return to treatment if opioid use resumes or is anticipated.[69]

Buprenorphine is one first-line option for medically supervised withdrawal.[66][69]​​[96][99][100]​​​​ Buprenorphine is a schedule III controlled drug. For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66] Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken.[68] For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.[68]

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.[66] 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.[34]

There are insufficient data on the duration of taper with buprenorphine, with studies ranging from 36 hours to 13 days.[102][168][169]

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.[104]

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 medically supervised withdrawal 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 medically supervised withdrawal, adequate hydration and food intake should be ensured.

Ancillary pharmacotherapy 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).[68]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[68] 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 medically supervised withdrawal, and it is desirable to develop adjunct psychosocial approaches that might make withdrawal more effective. For example, psychosocial treatments such as contingency management can reduce dropout rates from medically supervised withdrawal.[110] [ Cochrane Clinical Answers logo ]

Ongoing assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

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 – medically supervised withdrawal regimen: methadone

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

medically supervised withdrawal regimen: methadone

Medically supervised withdrawal (formerly known as detoxification) involves short-term pharmacotherapy to manage symptoms but is not recommended as standalone treatment due to high relapse and overdose risk; ongoing maintenance therapy with psychosocial support is standard of care.[66][69] Supervised withdrawal may occur after stabilisation with maintenance therapy, or be used early with transition to substitution therapy once withdrawal begins. Withdrawal is not required before starting maintenance, except with naltrexone, which requires prior abstinence.[66][69] Treatment should be individualised using shared decision-making. In select stable, well-supported individuals pursuing abstinence, supervised withdrawal may be acceptable within a structured plan offering ongoing psychosocial support.[66][69]​​[96]​​ Patients must be warned that post-withdrawal tolerance is reduced, increasing overdose risk, and should be advised to return to treatment if opioid use resumes or is anticipated.[69]

Methadone is an alternative first-line option to buprenorphine for supervised withdrawal.[66][69]​​​[96][99][100]​​ Methadone is a schedule II controlled drug. 

Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration to avoid accidental overdose. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66][69]

Dose should be titrated against withdrawal symptoms. Initial dose should not exceed 30-40 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.[170][171]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[67]

Methadone may prolong the QT interval and patients should be informed of the potential risk of arrhythmia.[66] A history of structural heart disease, arrhythmia, or syncope should be taken.[66] An ECG should be performed for high-risk patients.[66]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adults in inpatient/outpatient medically supervised withdrawal 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 medically supervised withdrawal, adequate hydration and food intake should be ensured.

Ancillary pharmacotherapy 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).[68]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[68] 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 medically supervised withdrawal, and it is desirable to develop adjunct psychosocial approaches that might make withdrawal more effective. For example, psychosocial treatments such as contingency management can reduce dropout rates from medically supervised withdrawal.[110][111]​​ [ Cochrane Clinical Answers logo ]

Ongoing assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

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 – medically supervised withdrawal regimen: clonidine or lofexidine ± naltrexone

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

medically supervised withdrawal regimen: clonidine or lofexidine ± naltrexone

Medically supervised withdrawal (formerly known as detoxification) involves short-term pharmacotherapy to manage symptoms but is not recommended as standalone treatment due to high relapse and overdose risk; ongoing maintenance therapy with psychosocial support is standard of care.[66][69] Supervised withdrawal may occur after stabilisation with maintenance therapy, or be used early with transition to substitution therapy once withdrawal begins. Withdrawal is not required before starting maintenance, except with naltrexone, which requires prior abstinence.[66][69] Treatment should be individualised using shared decision-making. In select stable, well-supported individuals pursuing abstinence, supervised withdrawal may be acceptable within a structured plan offering ongoing psychosocial support.[66][69]​​[96]​​ Patients must be warned that post-withdrawal tolerance is reduced, increasing overdose risk, and should be advised to return to treatment if opioid use resumes or is anticipated.[69]

Clonidine and lofexidine are alpha-2-adrenergic agonists that reduce the sympathetic nervous system response (i.e., noradrenergic release) to opioid withdrawal. They are considered second-line agents for supervised withdrawal.[66][69]​ Clonidine is generally not recommended for medically supervised withdrawal by the National Institute for Health and Care Excellence (NICE) in the UK.[96]​ Lofexidine is a structural analogue of clonidine and is generally associated with fewer side effects.[68] However, it may not suppress withdrawal symptoms as fully as clonidine, and may therefore contribute to poorer treatment retention.[68]

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

Transdermal clonidine patches can also be used for medically supervised withdrawal, 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.[108][109]​ After withdrawal 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 medically supervised withdrawal 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 medically supervised withdrawal, adequate hydration and food intake should be ensured.

Ancillary pharmacotherapy 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).[68]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[68] 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 medically supervised withdrawal, and it is desirable to develop adjunct psychosocial approaches that might make withdrawal more effective. For example, psychosocial treatments such as contingency management can reduce dropout rates from medically supervised withdrawal.[110][111]​​ [ Cochrane Clinical Answers logo ]

Ongoing assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

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 medically supervised withdrawal programme

1st line – medically supervised withdrawal regimen: buprenorphine ± naloxone

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

medically supervised withdrawal regimen: buprenorphine ± naloxone

Medically supervised withdrawal (formerly known as detoxification) involves short-term pharmacotherapy to manage symptoms. In adults, it is not recommended as standalone treatment due to high relapse and overdose risk; maintenance therapy with psychosocial support is standard of care.[66][69]​ In adolescents, similar principles may apply, although the evidence base on pharmacotherapy in adolescents is not extensive.[66][143]

This is a specialised area, and treatment decisions should be guided by expert consultation; adolescents with opioid use disorder often benefit from services designed specifically for them.[66]

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.

For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66] Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken.[68] For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.[68]

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.[66] 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.[34]

There are insufficient data on the duration of taper with buprenorphine, with studies ranging from 36 hours to 13 days.[168][169]

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.[104]

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 medically supervised withdrawal 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 medically supervised withdrawal, adequate hydration and food intake should be ensured.

Ancillary pharmacotherapy 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).[68]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[68] 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 medically supervised withdrawal, and it is desirable to develop adjunct psychosocial approaches that might make withdrawal more effective.[110] [ Cochrane Clinical Answers logo ]

Ongoing assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

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 – medically supervised withdrawal regimen: methadone

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

medically supervised withdrawal regimen: methadone

Medically supervised withdrawal involves short-term pharmacotherapy to manage symptoms. In adults, it is not recommended as standalone treatment due to high relapse and overdose risk; maintenance therapy with psychosocial support is standard of care.[66][69]​ In adolescents, similar principles may apply, although the evidence base on pharmacotherapy in adolescents is not extensive.[66][143]​ This is a specialised area, and treatment decisions should be guided by expert consultation; adolescents with opioid use disorder often benefit from services designed specifically for them.[66]

Methadone is 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 medically supervised withdrawal or short-term rehabilitation.[145][146]

Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration to avoid accidental overdose. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66][69]

Dose should be titrated against withdrawal symptoms. Initial dose should not exceed 30-40 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.[170][171]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[67]

Methadone may prolong the QT interval and patients should be informed of the potential risk of arrhythmia.[66] A history of structural heart disease, arrhythmia, or syncope should be taken.[66] An ECG should be performed for high-risk patients.[66]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
non-pregnant adolescents in inpatient/outpatient medically supervised withdrawal 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 medically supervised withdrawal, adequate hydration and food intake should be ensured.

Ancillary pharmacotherapy 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).[68]

Benzodiazepines may be given in an inpatient setting on a time-limited basis (e.g., 3 days) for treatment of anxiety or muscle cramps.[68] 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 medically supervised withdrawal, and it is desirable to develop adjunct psychosocial approaches that might make withdrawal more effective.[110] [ Cochrane Clinical Answers logo ]

Ongoing assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

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 medically supervised withdrawal programme

1st line – medically supervised withdrawal regimen: methadone

Back
ACUTE
|
pregnant women in inpatient/outpatient medically supervised withdrawal programme
1st line – 

medically supervised withdrawal regimen: methadone

Methadone is a schedule II controlled drug.

Medically supervised withdrawal (formerly known as detoxification) is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[81][148][149][150]​​​ However, if absolutely necessary, medically supervised withdrawal should be carried out in an inpatient setting. It involves short-term pharmacotherapy to manage symptoms but is not recommended as standalone treatment due to high relapse and overdose risk; ongoing maintenance therapy with psychosocial support is standard of care.[66][69]

Methadone is a first-line option for withdrawal.[150][151][172][173]​​​

Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration to avoid accidental overdose. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66][69]

Dose should be titrated against withdrawal symptoms. Initial dose should not exceed 30-40 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.[170][171]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[67]

Methadone may prolong the QT interval and patients should be informed of the potential risk of arrhythmia.[66] A history of structural heart disease, arrhythmia, or syncope should be taken.[66] An ECG should be performed for high-risk patients.[66]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
pregnant women in inpatient/outpatient medically supervised withdrawal programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Ancillary pharmacotherapy 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 assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

1st line – medically supervised withdrawal regimen: buprenorphine ± naloxone

Back
ACUTE
|
pregnant women in inpatient/outpatient medically supervised withdrawal programme
1st line – 

medically supervised withdrawal regimen: 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.[81] However, studies evaluating buprenorphine in combination with naloxone have since found no adverse effects in pregnant women.[81]

Medically supervised withdrawal is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[81][148][150]​​​ However, if absolutely necessary, medically supervised withdrawal should be carried out in an inpatient setting. It involves short-term pharmacotherapy to manage symptoms but is not recommended as standalone treatment due to high relapse and overdose risk; ongoing maintenance therapy with psychosocial support is standard of care.[66][69]

Buprenorphine is a first-line alternative to methadone.[81][150]​​[151]

For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66] Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken.[68] For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.[68]

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.[158]

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.[66] 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.[34]

There are insufficient data on the duration of taper with buprenorphine, with studies ranging from 36 hours to 13 days.[168][169]

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.[104]

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 medically supervised withdrawal programme
Consider – 

supportive therapies

Additional treatment recommended for SOME patients in selected patient group

Ancillary pharmacotherapy 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 assessment for suicidality throughout the course of medically supervised withdrawal is strongly advisable. See Suicide risk mitigation.

non-pregnant adults after medically supervised withdrawal or suitable for initial or early maintenance therapy

1st line – maintenance therapy: methadone

Back
ACUTE
|
non-pregnant adults after medically supervised withdrawal or suitable for initial or early maintenance therapy
1st line – 

maintenance therapy: methadone

Preferred if both buprenorphine and methadone are equally suitable, and for patients with very high-dose opioid addiction.[89][115]​​[117] [ Cochrane Clinical Answers logo ] Has the largest and oldest evidence base of all treatment approaches to opioid use disorder.[69]

A schedule II controlled drug.

Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66][69]​ Once a stable dose is reached after induction, based on suppression of craving and elimination of withdrawal, the maintenance phase begins. During maintenance, patients are typically required to come to the treatment programme daily for their methadone dosing and counselling.[69][121]

Higher doses of methadone (>60 mg/day) are superior to lower doses for maintenance.[105] A dose of 60-100 mg/day 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.[174]

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[170][171]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[67] Concurrent use of benzodiazepines or alcohol is common in patients with opioid use disorder and increases the risk of respiratory depression. However, opioid agonist treatment should not be withheld solely due to benzodiazepine use, given the high risk associated with untreated opioid use disorder. Coordinated care between prescribers (with patient consent) is advised. Patients should be counseled on the risk of respiratory depression and overdose when combining methadone with alcohol, benzodiazepines, or other central nervous system depressants. Assess the need for medically supervised withdrawal or tapering of alcohol or benzodiazepines.[69][122]​​​

Treatment should be continued as long as the 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
ACUTE
|
non-pregnant adults after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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, preferably within a group supportive of pharmacotherapy.[67][69]​​[138] 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.[175]

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

1st line – maintenance therapy: buprenorphine ± naloxone

Back
ACUTE
|
non-pregnant adults after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[66][69]​​[100][115][118]​​[123]​​

Buprenorphine is a schedule III controlled drug.

For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66] Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken.[68] For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.[68]

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone. Dosing frequency depends on the formulation used and patient-specific factors.

For patients with moderate to severe opioid use disorder in need of rapid treatment, buprenorphine can be administered by subcutaneous injection. The US Food and Drug Administration (FDA) has approved both a weekly and monthly extended-release buprenorphine injection for moderate to severe opioid use disorder to eliminate the need for daily administration. The weekly formulation is suitable for patients who are initiating treatment with a single dose of transmucosal (i.e., sublingual or buccal) buprenorphine or are already receiving buprenorphine, while the monthly version is for patients who are already stabilised on  buprenorphine.

Treatment should be continued as long as the patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.[66][69]​ 

Can be used to detoxify patients from methadone maintenance and transition to buprenorphine maintenance or a drug-free state. Patients on lower doses of methadone (e.g., 30-40 mg/day or less) generally tolerate transition to buprenorphine with relatively minimal discomfort, whereas patients on higher doses of methadone may experience significant discomfort in transitioning between drugs.[66] Therefore, a careful taper of methadone is recommended before initiating buprenorphine.[69] Do not start buprenorphine until the patient manifests signs of opioid withdrawal.[69]

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 after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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 the 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, preferably within a group supportive of pharmacotherapy.[67][69]​​​[138] 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.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

2nd line – maintenance therapy: naltrexone

Back
ACUTE
|
non-pregnant adults after medically supervised withdrawal or suitable for initial or early maintenance therapy
2nd line – 

maintenance therapy: naltrexone

Before initiation of any formulation of naltrexone, patients must be opioid abstinent for an adequate period of time; this is usually achieved by prior medically supervised withdrawal.[69]​ A naloxone challenge test could be considered prior to initiation of naltrexone maintenance therapy to verify opioid abstinence, if there is clinical uncertainty.[66][69]​ Patient may then be transitioned from supervised withdrawal therapy to naltrexone maintenance therapy. Naltrexone maintenance can be a valuable option for those who wish to discontinue opioids but who are motivated to continue pharmacotherapy.[69] It is also a treatment for alcohol use disorder, and so may be useful when this is a co-occurring condition.[69] See Alcohol use disorder.

An extended-release, parenteral formulation of naltrexone is available and is considered a useful treatment option due to the lack of risk of physical dependence. Patients must be willing to receive monthly intramuscular injections.[69]

One Cochrane review concluded that parenteral naltrexone shows mixed and uncertain effects across outcomes for opioid dependence, with possible benefits over oral naltrexone and treatment as usual, but may increase adverse events compared to opioid agonists; significant evidence gaps remain.[124] [ Cochrane Clinical Answers logo ] ​ Other studies suggest that, when initiated, extended-release naltrexone is as safe and effective as oral buprenorphine plus naloxone.[125][126]

In one randomised controlled trial, opioid-dependent adults who had completed medically supervised withdrawal and who were voluntarily seeking treatment and received this formulation had more opioid-free days compared with those who received placebo, and it was found to be generally well-tolerated.[90][179]​ ​

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.[129]

Patient preference for oral naltrexone is low, because of its lack of agonist effects. This leads to reduced treatment adherence and low retention rates, which limits its use in the clinical setting. Consequently it is infrequently used, and expert guidance recommends against the use of oral naltrexone except in certain limited circumstances (e.g., for those not permitted to have opioid agonist treatment).[69]​ A Cochrane review found no benefit of oral naltrexone over placebo or no treatment in retention, opioid misuse, or side effects.[134]

Treatment should be continued as long as the 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
ACUTE
|
non-pregnant adults after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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, preferably within a group supportive of pharmacotherapy.[67][69]​​[138] 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.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

non-pregnant adolescents after medically supervised withdrawal or suitable for initial or early maintenance therapy

1st line – maintenance therapy: buprenorphine ± naloxone

Back
ACUTE
|
non-pregnant adolescents after medically supervised withdrawal or suitable for initial or early maintenance therapy
1st line – 

maintenance therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug.

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

For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66] Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken.[68] For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.[68]

Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone. Dosing frequency depends on the formulation used and patient-specific factors.

Treatment should be continued as long as the patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.[66][69]

Can be used to detoxify patients from methadone maintenance and transition to buprenorphine maintenance or a drug-free state. Patients on lower doses of methadone (e.g., 30-40 mg/day or less) generally tolerate transition to buprenorphine with relatively minimal discomfort, whereas patients on higher doses of methadone may experience significant discomfort in transitioning between drugs.[66]​ Therefore, a careful taper of methadone is recommended before initiating buprenorphine.[69] Do not start buprenorphine until the patient manifests signs of opioid withdrawal.[69]

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 after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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 the 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, preferably within a group supportive of pharmacotherapy.[67][69]​​[138] 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.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

2nd line – maintenance therapy: methadone

Back
ACUTE
|
non-pregnant adolescents after medically supervised withdrawal or suitable for initial or early maintenance therapy
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 medically supervised withdrawal or short-term rehabilitation.[145][146]

Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66][69]

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[170][171]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[67] Concurrent use of benzodiazepines or alcohol is common in patients with opioid use disorder and increases the risk of respiratory depression. However, opioid agonist treatment should not be withheld solely due to benzodiazepine use, given the high risk associated with untreated opioid use disorder. Coordinated care between prescribers (with patient consent) is advised. Patients should be counselled on the risk of respiratory depression and overdose when combining methadone with alcohol, benzodiazepines, or other central nervous system depressants. Assess the need for medically supervised withdrawal or tapering of alcohol or benzodiazepines.[69][122]

Treatment should be continued as long as the 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
ACUTE
|
non-pregnant adolescents after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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 the 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, preferably within a group supportive of pharmacotherapy.[67][69]​​[138] 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.[175]

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

pregnant women after medically supervised withdrawal or suitable for initial or early maintenance therapy

1st line – maintenance therapy: methadone

Back
ACUTE
|
pregnant women after medically supervised withdrawal or suitable for initial or early maintenance therapy
1st line – 

maintenance therapy: methadone

A schedule II controlled drug.

Medically supervised withdrawal is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[81][148]​ However, if absolutely necessary, medically supervised withdrawal should be carried out in an inpatient setting.

Methadone is a first-line option for maintenance in pregnancy.[151][172][173]​​ There is limited evidence to suggest that methadone may be associated with a higher rate of birth defects compared to buprenorphine.[152][153]​ However, its use may be considered during pregnancy.[69]

Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66][69]

Once a stable dose is reached after induction, based on suppression of craving and elimination of withdrawal, the maintenance phase begins. During maintenance, patients are typically required to come to the treatment programme daily for their methadone dosing and counselling.[69][121]

Higher doses of methadone (>60 mg/day) are superior to lower doses for maintenance.[105] A dose of 60-100 mg/day 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.[174] Methadone can lead to neonatal abstinence syndrome.

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).[81]

May be used safely in patients with mild to moderate hepatic disease and patients with chronic renal disease.[170][171]

Overdose is potentially fatal due to no ceiling effect on respiratory depression and sedation.[67] Concurrent use of benzodiazepines or alcohol is common in patients with opioid use disorder and increases the risk of respiratory depression. However, opioid agonist treatment should not be withheld solely due to benzodiazepine use, given the high risk associated with untreated opioid use disorder. Coordinated care between prescribers (with patient consent) is advised. Patients should be counseled on the risk of respiratory depression and overdose when combining methadone with alcohol, benzodiazepines, or other central nervous system depressants. Assess the need for medically supervised withdrawal or tapering of alcohol or benzodiazepines.[69][122]

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

In general, 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).[81][150]​ 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.[81]

Primary options

methadone: see local protocols for guidance on dosing regimen

Consider – supportive therapies

Back
ACUTE
|
pregnant women after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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, preferably within a group supportive of pharmacotherapy.[67][69]​​[138] 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.[175]

Compared with standard outpatient services, additional psychosocial services (e.g., counselling, medical, psychiatric, employment, and family therapy) improved overall outcomes in opioid-dependent patients.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

1st line – maintenance therapy: buprenorphine ± naloxone

Back
ACUTE
|
pregnant women after medically supervised withdrawal or suitable for initial or early maintenance therapy
1st line – 

maintenance therapy: buprenorphine ± naloxone

Buprenorphine is a schedule III controlled drug. Medically supervised withdrawal is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[81][148][149][150]​​ However, if absolutely necessary, medically supervised withdrawal should be carried out in an inpatient setting.

Buprenorphine (with or without naloxone) is an alternative first-line option for maintenance in pregnancy.[81][150]​​[151]

For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66]​ Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken.[68] For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.​[68]

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.[81] However, studies evaluating buprenorphine in combination with naloxone have since found no adverse effects in pregnant women.[81]

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.[158]

Dosing frequency depends on the formulation used and patient-specific factors.

Treatment should be continued as long as the patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.[66][69]

Pregnant women receiving treatment with methadone should not transition to buprenorphine because of a significant risk of precipitating withdrawal.[81]

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).[81][150]​ 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.[81]

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 after medically supervised withdrawal or suitable for initial or early maintenance therapy
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.[135]

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 the 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, preferably within a group supportive of pharmacotherapy.[67][69]​​[138] 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.[176][177]

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 people with opioid use disorder treated with buprenorphine maintenance.[178]

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