Address for correspondence: Dr. E-mail: ten. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. This article has been cited by other articles in PMC. Abstract Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. Keywords: Addiction, buprenorphine, detoxification, maintenance, methadone, opiate. Introduction Illicit heroin use is an international problem.
In this article we will: Compare buprenorphine and methadone in terms of efficacy; Examine the relative safety of both drugs; and Explore the issues relating to when clinicians should consider prescribing one over the other. Mode of action of opioid drugs Opiate drugs, such as heroin diamorphine , are natural derivates from opium, whereas opioids, such as methadone and buprenorphine, are synthetic derivates of opiates.
Table 1 Activity of opioid receptor subtypes. Open in a separate window. Mode of action of buprenorphine Due to its unique pharmacologic profile, buprenorphine has, in principle, a number of advantages over methadone for use as an opioid replacement therapy.
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Table 2 Comparison of buprenorphine and methadone in the treatment of opioid dependence. Efficacy of opioid replacement therapies Maintenance therapy Twenty-four randomized controlled trials RCTs comparing buprenorphine to methadone in the maintenance treatment of opioid dependence with a total number of participants were included in a Cochrane systematic review and meta-analysis.
Detoxification Fewer data exist for direct comparisons of buprenorphine vs methadone for detoxification from heroin dependence. Cost-effectiveness A number of studies have addressed the issue of the cost-effectiveness of buprenorphine and methadone. Safety of opioid replacement therapies The safety features of pharmacotherapies for heroin dependence must be weighed up against the benefits of continued illicit drug use. Overdose liability Buprenorphine causes less respiratory depression than methadone due to its ceiling effect and, thus, has lower overdose potential.
Abuse potential Like all opioid drugs, buprenorphine has the potential for misuse. Serious side effects Although buprenorphine has been used as an analgesic for over three decades it is a relatively new compound in terms of the treatment of opioid dependence, certainly in comparison with methadone. Indian perspective India has a substantial opiate dependence problem with reports of up to 2 million addicts in the Sub-continent although this must be considered in the light of a huge population pushing 1 billion people.
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Risk of divergence If the risk of divergence is considered high with a given patient then one should consider methadone prescription due to the previously highlighted difficulties supervising the consumption of buprenorphine. Conclusion Despite the obvious benefits conferred by the ceiling effect, buprenorphine prescriptions have failed to overtake methadone in the UK. Acknowledgments The author would like to thank Drs. Footnotes Source of Support: Nil. References 1. Shooting up: Infections among injecting drug users in the United Kingdom London: Health Protection Agency; Health Protection Agency.
Deaths of drug addicts in the United Kingdom Parker H, Newcombe R. Heroin use and acquisitive crime in an English community. Br J Sociol. World Health Organization, Department of mental health and substance misuse. Proposal for the inclusion of buprenorphine in the WHO model list of essential medicines. United Nations Drug Control Programme. United Nations Office on Drugs and Crime. World Drug Report. Clinical practice guidelines for management of opioid dependence. Indian Psychiatr Soc. Mortality associated with New South Wales methadone programs in lives lost and saved.
Med J Aust. Wolff K.
Characterization of methadone overdose: clinical considerations and the scientific evidence. Ther Drug Monit. An open-label study of a functional opioid kappa antagonist in the treatment of opioid dependence. J Subst Abuse Treat. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. Post-marketing surveillance of buprenorphine. Pharmacoepidemiol Drug Saf. Assessment of differential doses of buprenorphine for long term pharmacotherapy among opiate dependent subjects.
The decision whether or not to continue naltrexone treatment for a woman already using naltrexone before pregnancy should involve a careful discussion with the patient that compares the limited safety data versus the potential risk of relapse with treatment discontinuation. Naloxone is a short-acting opioid antagonist that can rapidly reverse the effects of opioids and can be life-saving in the setting of opioid overdose. Naloxone can be administered intravenously or subcutaneously by health care or emergency medical professionals.
Additionally, an autoinjectable form and prepackaged nasal spray can be administered by family members or other bystanders when overdose is suspected Patients at risk of overdose, such as those with long-term use or high doses of opioids, may benefit from having a naloxone kit available at all times.
Many states authorize prescribing naloxone to a third party, such as a family member or caregiver, who may be able to assist in an overdose www. Several issues to consider include the following:. Women taking methadone or buprenorphine who are in labor should have their maintenance opioid agonist dose continued and should receive additional pain relief 68 , Epidural or spinal anesthesia should be offered, when appropriate, for management of pain in labor or for delivery.
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Opioid agonist—antagonist drugs such as butorphanol, nalbuphine, and pentazocine should be avoided because they can precipitate acute withdrawal in patients taking an opioid agonist. Some patients who are physiologically dependent on opioids may not disclose their substance use and health care providers may, therefore, not be aware of their opioid use.
Because of this, some units have opted to remove these medications from their formularies because of inadvertent precipitation of withdrawal. Buprenorphine should not be administered to a patient who takes methadone. Pediatric staff should be notified of all infants exposed to opioids to ensure appropriate screening for neonatal abstinence syndrome. In general, patients taking methadone or buprenorphine will require higher doses of opioids to achieve analgesia than other patients because they are tolerant to their maintenance treatment dose.
Injectable nonsteroidal antiinflammatory agents, such as ketorolac, also are highly effective in postpartum and postcesarean delivery pain control. Dividing the usual daily treatment dose of buprenorphine or methadone into three or four doses every 6—8 hours may provide partial pain relief; however, additional analgesia will be required The pain management of intrapartum and postpartum patients on opioid agonist therapies can be challenging because of their increased drug tolerance and hypersensitivity to pain.
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When resources are available, a consultation with an anesthesiologist can be beneficial in pregnant women with substance use disorder or chronic opioid use to formulate a pain management plan tailored to the individual patient. A multimodal pain control approach with neuraxial analgesia and nonsteroidal antiinflammatory drugs and acetaminophen typically is needed to provide effective intrapartum and postpartum pain relief 69, Breastfeeding is beneficial in women taking methadone or buprenorphine and has been associated with decreased severity of neonatal abstinence syndrome symptoms, less need for pharmacotherapy, and a shorter hospital stay for the infant In addition, breastfeeding contributes to attachment between a woman and her infant, facilitates skin-to-skin care, and provides immunity to the infant.
Breastfeeding should be encouraged in women who are stable on their opioid agonist, who are not using illicit drugs, and who have no other contraindications, such as HIV infection 73 , Women should be counseled about the need to suspend breastfeeding in the event of a relapse.
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The American Academy of Pediatrics recommends breastfeeding for women taking methadone and buprenorphine regardless of maternal dose, as transfer of these medications into breast milk is minimal In nursing women, the ultra-rapid conversion of codeine to morphine can result in high and unsafe levels of morphine in blood and breast milk.
Food and Drug Administration has strengthened the label warning to state that breastfeeding is not recommended while using medicines containing codeine or tramadol because of the potential for serious adverse effects in the infant due to opioid overdose However, if a codeine-containing medication is considered the preferred choice, the risk and benefits of this drug and the reasoning behind the FDA warning should be discussed with each family. Although most pregnant women who take methadone will experience dosage increases during pregnancy, and a need for dosage reduction might be expected postpartum, one study demonstrated little need for immediate postpartum methadone dosage reduction Significant dose reductions postpartum should not be done routinely but should be titrated to signs and symptoms of sedation, particularly at the peak of the dose 2—6 hours.
Most women taking buprenorphine will not experience large dosage adjustments during their pregnancies and most may continue the same dosages after delivery Other medications that can produce sedation eg, benzodiazepines, zolpidem, antihistamines should be used with caution, as they may add to the risk of maternal respiratory depression Women with substance use disorder should continue their opioid agonist pharmacotherapy postpartum. The postpartum period represents a time of increased vulnerabilities, and women with opioid use disorder relapse far more often in the postpartum period compared with during pregnancy Triggers for relapse may include loss of insurance and access to treatment, demands of caring for the new baby, sleep deprivation, and threat of loss of child custody.
Psychiatric disorders such as depression, anxiety, bipolar disorder, and posttraumatic stress disorder are prevalent among women with opioid use disorder. Screening for postpartum depression should be routine, and assessing for other comorbid mental health conditions should be considered if there is a prior history or if concern exists 78, Substance use and overdose are increasingly found to be major contributing factors to pregnancy-associated deaths in the United States 9, Access to adequate postpartum psychosocial support services, including substance use disorder treatment and relapse prevention programs, should be made available In addition, postpartum women with opioid use disorder should receive overdose training and preferably, coprescribing of naloxone for overdose prevention Use of reliable contraception is also lower among this group of women when compared with a nondrug-using comparison population Therefore, discussion of a full range of contraceptive options should begin prenatally with these patients.
In particular, obstetric care providers should counsel women about the option of immediate postpartum long-acting reversible contraception, which has few contraindications and is highly effective and convenient Neonatal abstinence syndrome is characterized by disturbances in gastrointestinal, autonomic, and central nervous systems, leading to a range of symptoms including irritability, high-pitched cry, poor sleep, and uncoordinated sucking reflexes that lead to poor feeding. In infants exposed to methadone, symptoms of withdrawal may begin anytime in the first 2 weeks of life, but usually appear within 72 hours of birth and may last several days to weeks Infants exposed to buprenorphine who develop neonatal abstinence syndrome generally develop symptoms within 12—48 hours of birth that peak at 72—96 hours and resolve by 7 days Recent evidence indicates that other substances such as nicotine, selective serotonin reuptake inhibitors, and benzodiazepines may increase the incidence and severity of neonatal abstinence syndrome Use of validated screening assessments such as the Finnegan Scale to diagnose neonatal abstinence syndrome and protocols that standardize treatment using methadone or morphine have been associated with improved outcomes for these infants Each nursery should develop an evidence-based written policy to assess and treat an infant with neonatal abstinence syndrome, and women should be informed of key components of these policies eg, any delayed discharge of the infant or reporting requirements.
Families should be encouraged to visit and care for their infants and women should be supported in their effort to breast feed their infants, if appropriate. Several perinatal collaborative quality initiatives have developed valuable resources for health care providers and patients to optimize the diagnosis and treatment of neonatal abstinence syndrome and promote collaboration between obstetric and neonatal care providers www.
Long-term outcomes of infants with in utero opioid exposure have been evaluated in several observational studies. A major challenge in assessing these outcomes is isolating the effects of opioid agonists from other confounding factors such as use of other substances tobacco, alcohol, nonmedical drugs and exposure to environmental and other medical risk factors eg, low socioeconomic status, poor prenatal care For the most part, studies have not found significant differences in cognitive development between children up to 5 years of age exposed to methadone in utero and control groups matched for age, race, and socioeconomic status, although scores were often lower in both groups compared with population data Preventive interventions that focus on supporting the woman and other caregivers in the early and ongoing parenting years, enriching the early experiences of children and improving the quality of the home environment are likely to be beneficial Contraceptive counseling and access to contraceptive services should be a routine part of substance use disorder treatment among women of reproductive age to minimize the risk of unplanned pregnancy.
Pregnancy in women with opioid use disorder should be co-managed by the obstetric care provider and a health care provider with addiction medicine expertise, and appropriate 42 CFR Part 2-compliant consent for release of information should be obtained from the patient to allow exchange of information between the health care providers.
Continuity of care, including ensuring consistent daily dosing of buprenorphine or methadone, is critical to success. For women, including pregnant women, with an opioid use disorder, opioid agonist pharmacotherapy is the recommended therapy and is preferable to medically supervised withdrawal because withdrawal is associated with higher relapse rates, which lead to worse outcomes.
More research is needed to assess the safety particularly regarding maternal relapse , efficacy, and long-term outcomes of medically supervised withdrawal.