Methadone Treatment during Pregnancy - Assignment Example

Introduction Methadone, a synthetic opioid receptor agonist, is used as maintenance therapy in pregnant heroin addicts. The main rationale for its use is that it prevents abuse of other illicit drugs and has other beneficial effects. However, its use is controversial, and neonates can still develop a severe withdrawal syndrome. This study aims to explore these facts and to find if the continued use of methadone is justified and the ethical implications. Review of Literature Heroin and methadone treatment Heroin is a potent opiate drug processed from morphine (NIDA ). With repeated administration of heroin, an addict can develop a high level of tolerance. (Bashore RA, Ketchum JS, Staisch KJ, et al, 1981). In most study series, “the pregnant addicts were young (median age about 22), unmarried or separated, lacking in social supports and disproportionately concentrated in minority ethnic groups.” (Bashore RA, Ketchum JS, Staisch KJ, et al, 1981) Methadone is a synthetic µ-opioid receptor agonist opiate. The uses of methadone include detoxification and maintenance in those dependent on opiates (especially heroin) and in the treatment of chronic severe pain. The rationale for prescribing methadone as maintenance therapy for heroin addicts is because of its long half-life, which delays the abstinence syndrome, thereby making Heroin’s effects less severe, and also because it blocks the euphoric effects and cravings for heroin. Methadone use has also shown to decrease both illicit heroin use and the incidence of infectious disease among addicts. Methadone maintenance therapy is usually started at 10 to 20 mg, and increased in 10-mg increments till the withdrawal symptoms are controlled. The requirement may go up to 80-100 mg daily to minimize illicit intravenous heroin use. In pregnancy, fetal dependence is caused by the ability of methadone to cross the placental barrier. (American Family Physician, 2000.) Neonatal abstinence syndrome (NAS) This refers to the various signs and symptoms seen in infants with drug dependencies. There are two major types of NAS, prenatal NAS and postnatal NAS. Prenatal NAS is caused by maternal substance abuse (Belik J, Belik J.) NAS is a generalized disorder and presents with CNS hyperirritability, high-pitched cry, rapid breathing, gastrointestinal dysfunction, respiratory distress, ineffective sucking even when the baby is hungry and excessive wakefulness. Although symptoms generally begin during the first 24 hours after birth, it can be delayed by up to five or more days. “Newborns exposed to methadone are more likely to experience symptoms and more often require treatment than those exposed to heroin” (Ford C, Barnard J, Bury J, et al., n.d). It has been observed that the effects of methadone on the fetus are similar to the effects of heroin. Since methadone’s half-life is longer than 24 hours, acute withdrawal occurs within the first 48 hours after birth and up to 7-14 days later. “The severity of methadone withdrawal, in relation to dose, is difficult to establish, but higher maternal doses are associated with more significant withdrawal symptoms in the neonate, especially if the maternal dose is higher than 20 mg/d” (Belik J, Belik J.) Controversies in methadone therapy The treatment of heroin addiction remains controversial. Since the introduction of methadone maintenance programs, numerous debates have surfaced in the medical community. Some studies of treatment of pregnant addicts with methadone and the effect on their offspring have expressed concern over a higher rate of complications and greater severity of withdrawal symptoms in the newborns. (Bashore RA, Ketchum JS, Staisch KJ, et al, 1981) Kashiwagi M, Arlettaz R, Lauper U, et al., 2005, in their study observed that methadone maintenance is not efficient in preventing pregnancy exposure to additional illicit drug consumption, and that a Heroin-assisted treatment may be a more effective method of minimizing the use of street drugs. Another study observed that women receiving methadone maintenance are likely to abuse other illicit drugs (Brown HL, Britton KA, Mahaffey D, et al., 1998.) Arlettaz R, Kashiwagi M, Das-Kundu S, et al., 2005, aimed to analyze the neonatal impact in a methadone maintenance program in pregnancy, and the social resources of the families involved. They observed that newborns of women on methadone had a higher incidence of prematurity, intrauterine growth retardation (IUGR), and microcephaly when compared with the normal population. Pharmacological treatment for abstinence syndrome was required in 62% and 42% required placement. Many studies, however, have found methadone therapy to be beneficial. Studies have shown that, methadone therapy in addicts is advantageous, which include longer gestational periods, higher birth weights, and a more moderate abstinence syndrome in the neonate (American Family Physician, 2000.) Stimmel B, Adamsons K, 1976, studied the course of pregnancy and delivery in 28 women under closely supervised methadone maintenance (group 1). This was compared with 57 women using heroin or methadone under less controlled circumstances (group 2) and with 30 women free of mood-altering medications (group 3). The women in group 1 had the lowest incidence of coexisting medical problems. The incidence of fetal distress was statistically the same as that of women in group 3. The highest incidence of fetal distress was seen in infants born to women group 2. These findings suggest, “maintenance of the pregnant addict under closely supervised methadone therapy is compatible with an uneventful pregnancy and birth of a healthy infant whose withdrawal symptoms in the neonatal period are readily controllable.”(Stimmel B, Adamsons K, 1976.) Dashe JS, Sheffield JS, Olscher DA, 2002, in a retrospective cohort study of pregnant women with opioid addiction who delivered live-born babies, aimed to determine whether maternal methadone dosage affects the duration and degree of neonatal narcotic withdrawal. It was observed that in select pregnancies, a low maternal methadone dosage was associated with both decreased incidence and severity of neonatal withdrawal. Another study reported a similar finding of significant reduction in the frequency of withdrawal symptoms in infants born to mothers whose methadone dose at the time of delivery was less than 20 mg (Madden JD, Chappel JN, Zuspan F, et al., 1977.) When compared to women who used only methadone in later pregnancy, women who used Heroin had babies who developed more severe NAS and required a longer hospital stay. McCarthy JJ, Leamon MH, Parr MS, Anania B, 2005.) Currently, the methadone-maintenance treatment program is probably the most satisfactory approach, with complications of pregnancy similar to those of the average obstetric population. However, low birth weight at term is still frequent for those on methadone maintenance (Blinick G, Wallach RC, Jerez E, Ackerman BD, 1976). Methadone treatment appears to benefit fetal growth and survival, and there is less risk of prematurity. However, these improved outcomes may be related to improved antenatal care and improved diet and not due to methadone alone. There is still a debate on the best approach in methadone use in pregnancy. It has been recommended that a stable dose of methadone is preferable than a dose reduction, due to the high risk of relapse to illicit opioid use and possible loss of stability. Maintaining a steady dose, which the patient is comfortable on and sufficient to get the positive benefits of methadone maintenance therapy is advisable. It is better to avoid an abrupt withdrawal of methadone due to the possible risks like miscarriage, fetal distress and premature labor. However, at all doses there is a risk of NAS (Ford C, Barnard J, Bury J, et al. n.d.) Statement From the above facts, there seems to be a benefit in using methadone in the pregnant heroin abuser, and a low or stable methadone maintenance therapy combined with prenatal care and a comprehensive drug treatment program can improve many of the detrimental maternal and neonatal outcomes associated with untreated heroin abuse. Ethical Implications Clinical studies in pregnant patients always evoke a lot of ethical concerns as well as fear of litigation. Therefore, getting approval from institutional review board (IRB) is difficult. The IRBs have a significant responsibility and authority in reviewing a research protocol. In order to approve research, the IRB must determine that risks to the subjects in a clinical trial are minimized. There is also reluctance on the part of pharmaceutical companies to develop medications for this study population because of concerns over financial feasibility as well as fear of litigation. “Federal Government agencies should encourage research in this area by providing sufficient funds to scientific communities, by facilitating IRB approval, and by actively collaborating with industry and interacting with FDA to advance medications development” (NIDA research monograph series.) Sometimes, persons who are not allowed in drug trials or who do not meet the inclusion criteria are able to get drugs like methadone used in the drug trial. In order to prevent this, The Food and Drug Administration (FDA) has expanded access and created a parallel track. FDA has also reversed its recommendation against including women of childbearing potential in early trials. But still, “there is a need to balance the exposure of vulnerable groups with their access to new modalities”(NIDA research monograph series.) There is always a possibility that clinical trials may expose pregnant women or the fetus to additional risks. Therefore, every effort must be taken to reduce the risks and to maximize the benefits. More research is also definitely indicated to develop alternate, safer treatments or modify treatments for pregnant drug dependent women and their infants. (NIDA research monograph series). Most methadone programs are monopolized by hospitals with the result that patients have limited options to leave the program. “Methadone providers are open to charges of paternalism as they exercise power in what they perceive as the best interests of their clients. Paternalism can be justifiable in treatment where a patient faces serious risks that can be reliably predicted, where these risks are irreversible and where patients have impairment in their autonomy.” (Townshend PL, Sellman JD, Coverdale JH, 2001.) In preventive ethics, the program structure is examined to identify and eliminate factors that may lead to unacceptable treatment for patients (Townshend PL, Sellman JD, Coverdale JH, 2001.) Conclusion Currently, methadone is the drug commonly used for treating pregnant Heroin addicts, and the methadone-maintenance treatment program is also probably the most satisfactory approach. Many studies have shown that methadone treatment appears to benefit fetal growth and survival and there is less risk of prematurity. A low maternal methadone dosage is associated with both decreased incidence and severity of neonatal withdrawal. These are the main reasons why a pregnant heroin addict is started on methadone therapy despite its effects on the neonate. However, this is still a controversial topic. Methadone, like heroin, produces a neonatal withdrawal syndrome, irrespective of the dose used. More research is needed to determine the best treatment strategy for using methadone in pregnancy. The areas of research that is urgently required include pharmacokinetic and pharmacodynamic studies to determine the proper dosage regimen, when and how withdrawal is to be safely performed, and a follow-up study to investigate the effects of methadone in children exposed in utero. A substitute medication that would produce little or no withdrawal would also be a significant achievement. ***************************************************************************** References Arlettaz R, Kashiwagi M, Das-Kundu S, et al., 2005. Methadone maintenance program in pregnancy in a Swiss perinatal center (II): neonatal outcome and social resources. Acta Obstet Gynecol Scand. Feb; 84(2): 145-50. American Family Physician, 2000. Public Health Issue: Methadone Maintenance Therapy. Retrieved November 25, 2005 from, http://www.aafp.org/afp/20000715/tips/1.html Blinick G, Wallach RC, Jerez E, Ackerman BD, 1976. Drug addiction in pregnancy and the neonate. Am J Obstet Gynecol. May 15; 125(2): 135-42. Bashore RA, Ketchum JS, Staisch KJ, et al, 1981: Heroin addiction and pregnancy Interdepartmental Clinical Conference, UCLA School of Medicine (Specialty Conference). West J Med 134:506-514.) Brown HL, Britton KA, Mahaffey D, et al., 1998. Methadone maintenance in pregnancy: a reappraisal. Am J Obstet Gynecol. Aug; 179(2): 459-63 Belik J, Belik J, Neonatal Abstinence Syndrome. Retrieved November 25, 2005 from, http://www.emedicine.com/ped/topic2760.htm Dashe JS, Sheffield JS, Olscher DA, 2002. Relationship between maternal methadone dosage and neonatal withdrawal. Obstet Gynecol.; 100(6): 1244-9 Ford C, Barnard J, Bury J, et al., n.d. Guidance for the use of methadone for the treatment of opioid dependence in primary care. Retrieved November 25, 2005 from, http://www.smmgp.org.uk/download/guidance/guidance015.pdf Kashiwagi M, Arlettaz R, Lauper U, et al., 2005. Methadone maintenance program in a Swiss perinatal center: (I): Management and outcome of 89 pregnancies. Acta Obstet Gynecol Scand. Feb; 84(2): 140-4 McCarthy JJ, Leamon MH, Parr MS, Anania B, 2005. High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes. Am J Obstet Gynecol. Sep; 193(3 Pt 1): 606-10 Madden JD, Chappel JN, Zuspan F, et al., 1977. Observation and treatment of neonatal narcotic withdrawal. Am J Obstet Gynecol. Jan 15;127(2):199-201. NIDA research monograph series. Retrieved November 25, 2005 from, http://www.drugabuse.gov/pdf/monographs/149.pdf Stimmel B, Adamsons K, 1976. Narcotic dependency in pregnancy. Methadone maintenance compared to use of street drugs. JAMA; 235(11): 1121-4. Townshend PL, Sellman JD, Coverdale JH, 2001. A preventive ethics approach to methadone maintenance programmes. N Z Bioeth J. Oct;2(3):7-13 Read More