Opioid use disorder

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

Treatment of opioid use disorder requires a multidisciplinary approach, is typically long term in nature (possibly lifelong), and involves modifying deeply ingrained behaviors through the use of maintenance pharmacotherapy and psychosocial treatments. There is extensive and high-quality evidence to support the combination of maintenance pharmacotherapy with psychosocial treatment for optimal management of opioid use disorders, both for suppressing illicit opioid use and for retaining people in treatment.[65][68][89][90][91][92] Note that terminology on treatment for opioid use disorder varies internationally; in the US, maintenance pharmacotherapy is increasingly known as “medication for opioid use disorder” (MOUD), but may also be known as medication-assisted treatment (MAT) or opioid substitution therapy (OST) in some parts of the world.

It is important to note that effective treatment is individualized based on the needs and preferences of the patient, and that there is no “one size fits all” approach.[93] In spite of the strong evidence in favor of long-term pharmacologic treatment, some people with opioid use disorder successfully recover using self-cessation, support groups, or treatment programs with or without pharmacotherapy.[68] Assessment of patient motivation for change, and evidence of family and social support, are important while planning treatment. Engagement and retention in substance use disorder treatment can be a major clinical challenge; it is recommended that healthcare providers proactively engage people who would benefit from treatment at all stages of readiness for change, including those who are uninterested or ambivalent about receiving treatment.[94]

Nonspecialists should consult and seek supervision from a practitioner experienced in treating addiction prior to prescribing pharmacotherapies to patients with opioid use disorders, particularly in special populations such as teenagers, pregnant women, and older adults.

In older patients, it is important to assess for cognitive impairment or dementia, as that can affect treatment, adherence, and aftercare. Current drug history including herbal medicines and supplements should be completely reviewed to avoid potential drug interactions.[95] In addition, doses of drug treatments may need to be adjusted based on a patient’s age, body mass index, renal function, liver function, and nutritional status (albumin). Safe storage of drug treatments for opioid use disorder is crucial to prevent accidental or intentional overdose, particularly if there are children in the household.

In the US, the levels of service for the treatment of opioid use disorder should follow the guidelines established by the American Society of Addiction Medicine criteria to determine whether a patient is appropriate for early intervention, outpatient services, intensive outpatient services, partial hospitalization services, residential services, inpatient services, or medically managed intensive inpatient services.[96]

Pharmacotherapy for opioid use disorder may be utilized on a short- or long-term basis as part of medically supervised withdrawal (formerly known as detoxification) or maintenance treatment. Maintenance treatment involves:[68]

Induction (transition from active opioid use or early withdrawal to pharmacotherapy)
Stabilization (dose adjustment to relieve withdrawal symptoms and cravings)
Long-term maintenance (continued treatment at a therapeutic dose)

Both approaches require safe induction and stabilization, careful monitoring and dosing, and attention to tolerance and withdrawal symptoms. While principles of induction and stabilization overlap, maintenance aims to stabilize patients on long-term pharmacotherapy, whereas withdrawal seeks tapering. Withdrawal alone in the absence of ongoing maintenance is not recommended due to high relapse and overdose risk from reduced tolerance (see below).[65][68] Some key principles of timing apply to both pharmacologic approaches.

Safe timing and initiation of pharmacologic treatment: general principles

First-line drug treatments for both medically supervised withdrawal and maintenance treatment are buprenorphine (a partial opioid agonist) and methadone (a full opioid agonist). Naltrexone, an opioid antagonist, is a second-line option for maintenance.[68] Pharmacologic differences among these treatments are important when planning the safe timing of induction, whether for maintenance or medically supervised withdrawal. Premature administration of buprenorphine or naltrexone in the presence of residual opioids can be dangerous, and cause precipitated withdrawal:[65][68]

Naltrexone requires complete opioid abstinence (at least 7 days after short-acting opioids and 10-14 days after long-acting opioids) to prevent precipitated withdrawal. This abstinent period is typically achieved through medically supervised withdrawal with an opioid agonist or partial agonist.
Buprenorphine does not require prior full abstinence, but it is important that induction begins only after moderate withdrawal symptoms appear in those physiologically dependent on opioids, to avoid triggering precipitated withdrawal. Some clinicians, including the authors of this topic, recommend waiting for a COWS score of 13 or higher before initiating buprenorphine, although evidence to guide the specific threshold is limited.[65] Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken. 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.
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.[65][68]

Medically supervised withdrawal

Supervised withdrawal (formerly known as detoxification) is not recommended as a standalone treatment due to high relapse rates and increased overdose risk from reduced tolerance; ongoing maintenance treatment, in combination with psychosocial treatment, is the standard of care.[65][68] Medically supervised withdrawal can occur after stabilization with maintenance therapy, or may be used early, with transition to maintenance therapy (e.g., buprenorphine or methadone) once withdrawal symptoms begin. It is not required before starting maintenance treatment, except for with naltrexone, which requires a period of opioid abstinence beforehand, which is in practice usually achieved with supervised withdrawal.[65][68]

Supervised withdrawal is preferred over abrupt cessation of opioids, which increases risks of severe symptoms and complications.[65] Ultra-rapid withdrawal (e.g., under anesthesia) is not recommended due to serious risks.[65][68][97]

Treatment decisions are individualized and patient-centered, using shared decision-making.[65] In select, clinically stable individuals pursuing abstinence, supervised withdrawal may be acceptable within a structured plan offering ongoing support and psychosocial care.[68][97] Patients must be informed that tolerance decreases post-withdrawal, elevating overdose risk, and should be advised to reenter treatment promptly if opioid use resumes or is considered.[68]

Withdrawal can be performed in an outpatient or inpatient setting, depending on the severity of intoxication and withdrawal symptoms, presence of comorbid conditions, and safety issues.[65]

The ideal duration of medically supervised withdrawal is unclear.[68] Clinical trials have led to the development of semi-standardized protocols.[98] There are two evidence-based withdrawal strategies: opioid agonist (i.e., methadone, buprenorphine with or without naloxone) substitution and taper, and use of an alpha-2 adrenergic agonist (i.e., clonidine [off-label use] or lofexidine) with or without naltrexone.[97][99] [ ] Methadone (alone) or buprenorphine (with or without naloxone) are first-line treatments for supervised withdrawal.[65][68][97][100] Clonidine and lofexidine (with or without naltrexone) are considered second-line agents.[65][68]

Buprenorphine (with or without naloxone)

A first-line option for medically supervised withdrawal in adults.[65][68][97][100][101]
For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[65]
Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone (a mu opioid receptor antagonist).
Buprenorphine/naloxone combination treatment was developed to deter parenteral misuse of buprenorphine.[102] When taken as sublingual tablets, buprenorphine’s opioid effects dominate and block opioid withdrawal.[102] If the sublingual tablets are crushed and injected, naloxone’s effects dominate and can precipitate withdrawal symptoms.[102]
It is unclear whether rapid reduction in the dose of buprenorphine is more effective than slow reduction and whether this depends on the context of withdrawal.[103]
Advantages: lower risk of lethal overdose compared to methadone, appropriate for home initiation, has a long duration of action, and withdrawal symptoms are relatively mild and less severe than those of methadone.[34][104][105][106] The effectiveness of buprenorphine is probably similar to tapered doses of methadone, but it is uncertain whether withdrawal symptoms resolve more quickly with buprenorphine.[103][107] Buprenorphine is superior to clonidine or lofexidine and comparable to methadone in terms of completion rates and withdrawal discomfort for opioid withdrawal.[103] [ ]
Disadvantages: potential for misuse, has been reported to cause fatal respiratory depression when combined with benzodiazepines and alcohol.[67]

Methadone

An alternative first-line option for medically supervised withdrawal in adults.[65][68][97][100][101] Shown to be safe and effective for withdrawal if used appropriately.[108]
There are two types of withdrawal methods: a short-term (<30 days) method for shorter-acting opioids, and a long-term (>180 days) method for methadone-maintained patients.
Induction is the most critical phase of treatment, and involves slow and careful titration to avoid potential accidental overdose. The induction phase lasts until the patient has been on a stable dose for 5-7 days.
Advantages: smoother taper than short-acting opioids (due to its longer half-life), and withdrawal symptoms are milder but prolonged compared with those of heroin.
Disadvantages: potential for misuse, possibly a longer taper than with buprenorphine or alpha-2-adrenergic agonists, unsafe in overdose and requires closer monitoring than with buprenorphine due to longer half-life and risk for respiratory depression, and needs to be dispensed at a licensed clinic in the US.[34][67]

Clonidine or lofexidine (with or without naltrexone)

Alpha-2-adrenergic agonists (clonidine [off-label use], lofexidine) are considered second-line agents for medically supervised withdrawal.[65][68]
They reduce the sympathetic nervous system response (i.e., noradrenergic release) to opioid withdrawal, reducing autonomic withdrawal symptoms. Lofexidine is a structural analog of clonidine and is generally associated with fewer side effects.[67]
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.
Studies have found that addition of the opioid antagonist naltrexone to clonidine can shorten the duration of withdrawal without increasing discomfort.[109][110]
Lofexidine may not suppress withdrawal symptoms as fully as clonidine, and may therefore contribute to poorer treatment retention.[67][99]
Advantages: less potential for misuse, may be used in treatment settings that prohibit use of controlled substances, shorter treatment duration, and avoidance of long-term residual withdrawal symptoms that can occur with methadone.[67]
Disadvantages: more adverse effects, higher dropout rate, and greater withdrawal discomfort (particularly hypotension and sedation) compared with opioid agonists.[67][99][107]

Supportive therapies

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, for example:[67]
- Ibuprofen for muscle cramps
- Bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues
- Trazodone for sleep disturbances
Benzodiazepines may be given in an inpatient setting on a time-limited basis for treatment of anxiety or muscle cramps.[67] 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 counseling 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 supervised withdrawal.[111][112] [ ]
Ongoing assessment for suicidality throughout the course of supervised withdrawal is strongly advisable. See Suicide risk mitigation.

Maintenance pharmacotherapy

Goals of long-term treatment are multiple, and include abstinence from illicit drugs, relapse prevention, reduction of HIV and hepatitis C risk, reduced mortality, restoration of functionality disrupted by opioid use, and decreased criminality.[113][114] In practice this can be achieved by drug treatment which prevents or reduces opioid withdrawal and craving, and which may also blunt and block the effects of illicit opioids.[68] Continuing maintenance treatment after completion of medically supervised withdrawal (if this has taken place) is strongly recommended due to the high risk of relapse.[65][68]

Data from observational studies suggest that all cause mortality may be reduced by up to 50% among people with opioid dependence who are enroled in any form of opioid agonist treatment.[115] Substantial evidence indicates that pharmacotherapy-assisted treatment is essential for a majority of patients with opioid use disorder.[116] 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 has no serious adverse effects.[65][68]

The choice of pharmacotherapy for maintenance treatment is determined by patient preferences, past history of response to treatment, and physician assessment of the short- and long-term effects of continued drug treatment.[65][68]

Buprenorphine maintenance therapy (BMT) can reduce opioid misuse compared with placebo. However, one Cochrane review found that methadone maintenance therapy (MMT) was more effective than BMT at both medium and high doses in retaining patients in treatment.[90] [ ] Both methadone and buprenorphine are associated with significantly lower all-cause mortality and overdose-related mortality when participants are on versus off treatment.[117] Cross-sectional studies suggest that the rate of mortality with BMT may be lower than that with MMT.

Methadone

A first-line option for maintenance therapy; may be preferred if both buprenorphine and methadone are equally suitable.[90][116][118] [ ] Has the largest and oldest evidence base of all treatment approaches to opioid use disorder.[68] High oral systemic bioavailability and a long half-life make it an effective agent for maintenance.[119] Methadone may be associated with a lower risk of discontinuation than buprenorphine.[90][120][121]
Induction should begin at a low dose and increase gradually with daily monitoring over days or weeks. The recommended approach to dosing is to “start low and go slow.” Dosing is highly individualized, given that the bioavailability, clearance and half-life of methadone varies considerably among patients. People with no or low opioid tolerance will need a lower than usual starting dose.[68]
Once a stable dose is reached after induction (based on suppression of craving and elimination of withdrawal), the maintenance phase begins. Patients are typically required to come to the treatment program daily for their methadone dosing and counseling.[68][122]
Patients who do well may be permitted to take methadone home for unsupervised dosing, dependent on the relevant legislation and clinical guidance in their area.
The first 4 weeks of treatment with methadone are associated with a higher risk of death (from all causes) compared with during the rest of treatment. This increase in mortality is reduced by persistent engagement with opioid substitution treatment and increased by dropping out of treatment, indicating a need to promote engagement with treatment during this initial "golden" month.[117]
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.[68][123]

Buprenorphine

A first-line option for maintenance therapy.[65][68][101][116][119][124]
Important properties that make it a good candidate for maintenance therapy include: less physical dependence and lower severity of withdrawal symptoms compared with methadone and heroin; due to a ceiling effect on respiratory depression and poor systemic bioavailability, it has reduced potential to produce lethal overdose, unlike methadone allows for flexibility of dosing. Dosing frequency depends on the formulation used and patient-specific factors.
Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone. Buprenorphine/naloxone combination treatment was developed to deter parenteral misuse of buprenorphine.[102] When taken as sublingual tablets, buprenorphine’s opioid effects dominate and block opioid withdrawal.[102] If the sublingual tablets are crushed and injected, naloxone’s effects dominate and can precipitate withdrawal symptoms.[102]
For patients who are currently opioid dependent, buprenorphine should not be initiated until there are objective signs of mild-moderate opioid withdrawal, to reduce the risk of precipitated withdrawal.[65]
For patients with moderate to severe opioid use disorder in need of rapid treatment, buprenorphine can be administered by subcutaneous injection. The 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 stabilized on buprenorphine.
Buprenorphine can also be used to detoxify patients from methadone maintenance and transition to buprenorphine maintenance or a drug-free state. Patients on lower doses of methadone generally tolerate transition to buprenorphine with relatively minimal discomfort, whereas patients on higher doses of methadone may experience significant discomfort in transitioning between drugs.[65] Therefore, a careful taper of methadone is recommended before initiating buprenorphine.[68] Do not start buprenorphine until the patient manifests signs of opioid withdrawal.[68]
Carefully consider the setting for initiation of buprenorphine based on individual patient factors; in the US, both office-based and home-based initiation are possible.

Parenteral naltrexone

A pure mu opioid receptor antagonist that is nonaddictive and produces no euphoria. An extended-release, parenteral formulation of naltrexone is available and is considered a useful treatment option following medically supervised withdrawal due to the lack of risk of physical dependence.[101] Patients must be willing to receive monthly intramuscular injections.[68]
For patients who wish to discontinue opioids but who are motivated to continue pharmacotherapy, maintenance treatment with naltrexone is a valuable option.[68] It is also a treatment for alcohol use disorder, and so may be useful when this is a co-occurring condition.[68]
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.[125] [ ]
Other studies suggest that, when initiated, extended-release naltrexone is as safe and effective as oral buprenorphine plus naloxone.[126][127]
In one 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.[91] Trials of extended-release injectable naltrexone show a consistent pattern of clinical efficacy for maintaining abstinence, achieving pharmacotherapy adherence, maintaining retention, protecting against re-establishment of opioid physical dependence, and possibly reducing craving for opioids for some individuals, while showing good safety and tolerability.[128][129]
Before initiation of any formulation of naltrexone, patients must be opioid abstinent for an adequate period of time after completing opioid withdrawal; this is usually achieved by medically supervised withdrawal.[68]
A naloxone challenge test could be considered prior to initiation of naltrexone maintenance therapy to verify opioid abstinence, if there is clinical uncertainty.[65][68]

The formulation can be used safely in patients with opioid use disorders, including those with underlying mild to moderate chronic hepatitis C virus and/or HIV infections, and is administered once monthly.[130]

Oral naltrexone

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).[68]
Has been found effective in treating specific groups of highly motivated individuals such as nurses, physicians, and prisoners in release programs.[131][132][133][134]
One systematic Cochrane review found no benefit of oral naltrexone over placebo or no treatment in retention, opioid misuse, or side effects.[135]

Supportive therapies

Psychosocial interventions and urine drug screen monitoring, as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders), should occur as a part of maintenance therapy.[136][137]
Psychosocial interventions are categorized into “standard” and “enhanced” care.[66] Standard care interventions offered by a key worker may include motivational interviewing, goal setting, recovery planning, and contingency management.[66][112][138] Enhanced care is offered if there is a poor response to standard care, or for patients with more complex needs.[66] This may include a residential rehabilitation program with high-intensity cognitive behavioral therapy.[66] 12-step-oriented groups such as Narcotics Anonymous may also be beneficial, preferably within a group supportive of pharmacotherapy.[68][139] Narcotics Anonymous Opens in new window
Pain self-management programs based on the principles of mindfulness and cognitive behavioral therapy may support moderate reductions in opioid use.[140][141]
For drug use among parents, a Cochrane review found that psychosocial interventions addressing both parenting skills and substance misuse may have the greatest impact on abstinence (low-quality evidence).[142]
Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counseling, as well as viral hepatitis screening and referral for treatment, should be integrated into a maintenance program.

Adolescents

In general, young people need closer monitoring and regular supervision by adults. Adolescents with opioid use disorder often benefit from services designed specifically for them.[65] There are also issues of consent and confidentiality with teenagers that differ from adults. Family and/or parental involvement is crucial for the evaluation and treatment of adolescents. Prior to commencing pharmacologic treatment, it is important to establish a safe environment for adolescents to rehabilitate. Experienced specialists should be the primary providers initiating treatments and supervising nonspecialists in the continuation of treatment.

The combination of buprenorphine with behavioral interventions is more efficacious in the treatment of opioid-dependent adolescents than the combination of clonidine and behavioral interventions.[143] However, further research is needed to evaluate the efficacy and safety of longer-term treatment with buprenorphine for young people with opioid use disorder.[144][145]

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. It appears that adolescents with established opioid use disorder should be treated similarly to adults with respect to induction and longer-term stabilization and maintenance with buprenorphine.

When prescribing drugs for opioid use disorder in adolescents, clinicians should be aware that age restrictions, consent requirements, and prescribing criteria vary not only by country and jurisdiction, but also according to the specific drug being used. For example 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.[146][147]

While buprenorphine and methadone are the most commonly used drugs for opioid use disorder in adolescents, other treatments, including those used in adults, may sometimes be used in practice depending on local availability and clinical context, under expert guidance.[65]

The usual supportive treatments should also be considered.

Pregnancy: prenatal management

Pregnant women with opioid use disorder experience increased obstetric and neonatal complications.[148] Medically supervised withdrawal is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[80][149][150][151] However, if absolutely necessary, medically supervised withdrawal should be carried out in an inpatient setting.

Methadone and buprenorphine (with or without naloxone) are the drugs of choice for withdrawal or maintenance therapy.[80][151][152]

There is limited evidence to suggest that methadone may be associated with a higher rate of birth defects compared to buprenorphine.[153][154] However, its use may be considered during pregnancy.[68] Methadone can lead to neonatal abstinence syndrome (NAS). 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 NAS).[80]

Buprenorphine with or without naloxone is a first-line alternative to methadone.[80][152] Buprenorphine monotherapy was previously recommended for pregnant women to avoid any potential prenatal exposure to naloxone.[80] However, studies evaluating buprenorphine in combination with naloxone have since found no adverse effects in pregnant women.[80] Buprenorphine appears to have a lower, but still significant, risk of NAS compared with methadone.[155][156][157] It also appears to result in improved birth weight due to longer gestation when compared with methadone treatment.[158] However, it should be noted that participants treated with buprenorphine in the study were required to present for daily dosing and received more intense psychosocial interventions than are typically offered in standard community care.[158] 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.[159]

A 2020 systematic review and meta-analysis found no significant differences in pregnancy outcomes between women receiving buprenorphine/naloxone compared with methadone or buprenorphine monotherapy.[160] Similarly, a Cochrane review published in the same year found methadone and buprenorphine to be comparable in efficacy and safety in pregnancy.[161]

Pregnant women receiving treatment with methadone should not transition to buprenorphine because of a significant risk of precipitating withdrawal.[80]

Data are insufficient to recommend initiation of naltrexone in pregnancy.[68][81][153] However, naltrexone may be continued in patients who are already on therapy and become pregnant after a careful assessment and risks/benefits discussion.[81]

Ancillary pharmacotherapy in therapeutic doses may be required for symptomatic relief. Treatments are generally the same as for nonpregnant women; however, certain drugs should be avoided or only used when the benefits outweigh the risks. For example, ondansetron should not be used as a first-line agent for treating vomiting in pregnant women owing to a possible increased risk of cleft palate with its use during the first trimester of pregnancy.[162][163][164] Consult a specialist for further guidance on the selection of suitable supportive therapies in pregnant women.

Pregnancy: delivery and postpartum management

Acute pain management is challenging in this population due to fear among providers and patients of triggering a relapse, and the fact that patients often have a high tolerance to opioid analgesics.[81]

Women should be encouraged to have an epidural or combined spinal-epidural in early labor or as soon as contractions become uncomfortable.[81] Inhaled nitrous oxide should be avoided during delivery as it may be less effective in opioid-dependent women and is associated with increased sedation risk when taken concurrently with opioids.[81]

First-line treatment for postpartum pain is oral or intravenous acetaminophen.[81] If pain persists for more than 24 hours, a full opioid agonist such as fentanyl or hydromorphone may be considered.[81]

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).[80][151]

Women with opioid use disorder may require additional prenatal care; for example, expanded STI testing and additional ultrasounds to assess fetal weight.[80] Babies born to mothers who used opioids during pregnancy (including methadone and buprenorphine) should be monitored after birth by a pediatrician for NAS, which neonates may develop shortly after birth.[80]

Duration of pharmacologic treatment and treatment discontinuation

There is no recommended time limit for pharmacologic treatment for opioid use disorder. Continued treatment with buprenorphine or methadone is associated with better outcomes than medically supervised withdrawal.[165] However, some patients may choose to stop opioid agonist therapy through gradually tapering the dose. Ensure that patients who discontinue pharmacologic treatment are made aware of the risks associated with opioid overdose, particularly if they return to illicit opioid use.[65] Discuss treatment alternatives (e.g., with another opioid agonist or an opioid antagonist) with all patients wishing to discontinue their maintenance treatment. For patients who wish to discontinue opioids but who are motivated to continue pharmacotherapy, maintenance treatment with naltrexone is a valuable option.[68]

Methadone produces strong physical dependence. Discontinuation of methadone maintenance can lead to a protracted withdrawal syndrome that can last over 4 weeks. For withdrawal from methadone maintenance, the tapering schedule depends on the reasons for withdrawal. Guidelines on tapering vary by country and by clinical setting. For stable patients, some evidence suggests that a slow taper (<5%/ week) improves outcomes and increases the possibility of abstinence.[166][167][168] Some studies suggest that only a minority of patients who discontinue methadone remain abstinent long term, particularly without ongoing psychosocial support.[98] Buprenorphine taper and discontinuation is also typically a slow process, generally accomplished over several months to years; close monitoring is recommended and patients should be encouraged to remain in treatment for ongoing monitoring past the point of discontinuation.[65]

Patients wishing to taper their opioid agonist should be offered psychosocial and recovery support.[68] Offer advice on overdose prevention with naloxone, and encourage patients to resume treatment with drug treatment quickly if they return to opioid use.[65][68] The first 4 weeks after cessation of maintenance treatment is associated with a higher risk of death than in the remainder of time out of treatment, indicating a need during this time to focus clinical strategies in order to mitigate this risk.[117]

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