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Opioid use disorder during pregnancy

Current Psychiatry. 2011 March;10(03):35-46
March 1, 2011|Current Psychiatry
Shannon C. Miller, MD;Fasam, FAPA
Author and Disclosure Information

Shannon C. Miller, MD, FASAM, FAPA
Medical Director, Integrated Dual Diagnosis and Outpatient Addiction Psychiatry/Medicine, Program Director, VA Advanced Fellowship in Addiction Medicine/Research, Veterans Affairs Medical Center, Cincinnati, Associate Professor of Clinical Psychiatry, Associate Director of Education, Training, and Dissemination, Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD),Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH
Lisa Fernandez, MD
Addiction Psychiatry Fellow, University Hospital/University of Cincinnati, CeTREAD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH
Roberto Soria, MD
Medical Director, Opiate Addiction Recovery Services, Assistant Professor of Clinical Psychiatry, Co-Director, Clinical Services, CeTREAD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH

Nonjudgmental identification and treatment can maximize maternal/fetal outcomes

Table 2

Medical complications common to pregnancy and substance abuse

Anemia
Bacteremia/sepsis
Endocarditis
Cellulitis
Depression/anxiety
Gestational diabetes
Hepatitis (chronic and acute)
Hypertension/tachycardia
Phlebitis
Pneumonia
Gingivitis/poor oral hygiene
Sexually transmitted diseases
  • chlamydia
  • gonorrhea
  • condyloma acuminata
  • herpes
  • HIV/AIDS
  • syphilis
Tetanus
Cystitis
Pyelonephritis
AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus
Source: Reference 6

Table 3

Obstetric complications in women with addiction disorders

Placental abruption
Chorioamnionitis
Placental insufficiency
Intrauterine growth restriction
Hypoxic/ischemic brain injury
Meconium passage
Neonatal abstinence syndrome
Spontaneous abortion
Intrauterine fetal death
Premature labor and delivery
Preterm, premature rupture of membranes
Postpartum hemorrhage
Hypertensive emergencies/preeclampsia
Source: Reference 6

Opioid agonist therapy

Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).20

Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:

  • their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
  • their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
  • research on the use of naltrexone during pregnancy is lacking.
Methadone has been used to treat OUD during pregnancy since the late 1970s.5 It requires adherence to strict federal regulations and is FDA pregnancy class C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate well-controlled studies in humans, but potential benefits may warrant use in pregnant women despite potential risks). Pregnant women have been safely maintained on methadone without adverse long-term maternal or fetal effects, and the National Institutes of Health recommends it as the standard of care for pregnant women with OUD. A woman steadily maintained on methadone is more likely to have a healthy pregnancy and infant than a woman who uses alcohol or other drugs.21 Further, the structure and services of methadone maintenance treatment can improve compliance with prenatal care and help prepare patients for parental responsibilities.

Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24

Clinical Point

Methadone dosages should be based on a woman’s relapse risk, experience with methadone, and other factors

Buprenorphine is FDA pregnancy class C. Although not approved for use during pregnancy, it has been used successfully for pregnant patients with OUD.12,25 It is a partial agonist of the mu opioid receptor and an antagonist of the kappa opioid receptor, which may reduce its abuse liability and NAS severity.

The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.

Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.

In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29

Table 4

Opioid agonist treatment objectives for addicted patients who are pregnant

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