Issues Women often Face at the Time of Treatment Entry

Women who use opioids as well as other licit and illicit psychoactive substances during pregnancy often do so in the context of intricately complex social, environmental, and internal individual factors that are not usually mutually exclusive, and may be operating at varying levels and varying intensities [1]:

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  Social/community/external

  
  
  
  
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    Gender inequality/male-focused society

    
    
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    Legal involvement

    
    
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    Unstable and/or poor housing conditions

    
    
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    Exposure to environmental toxins and diseases

    
    
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    Food insecurity

  
  
  
  
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  Family/home environment

  
  
  
  
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    Generational drug use

    
    
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    Limited parenting skills/resources

    
    
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    Child abuse and neglect history

    
    
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    Lack of positive/supportive relationships

  
  
  
  
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  Internal/biological/psychological

  
  
  
  
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    Multiple drug exposures

    
    
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    Violence and trauma exposure

    
    
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    Lack of formal education

    
    
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    Lack of job acquisition and maintenance skills

    
    
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    Multiple psychiatric issues (e.g., depression, anxiety)

    
    
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    Lack of nutrition

    
    
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    Extreme stress

  
  

While the odds are often stacked against a pregnant woman with an opioid use disorder (OUD), each patient is unique and each patient must be viewed in the context of her own risk and protective factors to optimize her treatment and outcomes for herself and her child.

Opioid Use in Women Who Become Pregnant

Opioid use among women who become pregnant must be seen in the context of substance use among pregnant and nonpregnant women. The most recent data from the National Survey on Drug Use and Health [2] are shown in Figure 10.1. Relative to alcohol and tobacco, that may have a more profound and lasting impact on both mother and neonate, opioid use can be seen to be relatively infrequent. Moreover, no marked difference appears between pregnant and nonpregnant women’s use, as does, say, alcohol or tobacco.

Figure 10.1 National study of drug use and health data for women

The past decade has witnessed a striking increase in the use and misuse of prescription opioids by pregnant women, rising from 1.2 per 1,000 in 2000 to 5.6 per 1,000 hospital live births in 2009. The incidence of neonatal abstinence syndrome (NAS) has increased from 1.2 to 3.4 per 1,000 hospital live births during this same period [3]. More recent research has suggested that misuse of prescription analgesics (e.g., oxycodone) has risen over the period from 2009 to 2011, and suggests the possibility of a prescription opioid epidemic among pregnant women.

Assessment of the Pregnant Woman with Opioid Use Disorder

Substance Abuse and Mental Health Services Administration (2016)[4] provides guidelines for the assessment of pregnant women with OUD. The primary aim of an assessment is to evaluate a woman’s current life circumstances and her physical, psychological, and social history to determine specific treatment needs. In order to obtain as complete a picture of the patient and her past and current functioning, a thorough assessment will utilize multiple sources to obtain the necessary information, including:

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  Self-report

  
  
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  Clinical records

  
  
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  Structured assessment instruments

  
  
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  Third-party reports

  
  
• 
  

  An assessment is often the beginning of a therapeutic relationship.

  
  
• 
  

  An assessment interview requires both time and sensitivity in order to elicit the necessary information from the patient. Pregnant women with opioid use disorder often have histories not only of substance use but also of trauma, physical abuse, and mental health disorders that they may be hesitant to disclose.

  
  
• 
  

  Assessment should be a fluid process throughout the course of treatment – given changes in physical and psychological functioning as a result of treatment, it is critical to assess a pregnant woman periodically throughout pregnancy and the postpartum period.

The Addiction Severity Index [5] can be used in both treatment planning and assessment of treatment response, and is in wide use with pregnant patients with OUD. It gathers information in seven domains:

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  Alcohol use

  
  
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  Drug use

  
  
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  Employment/finances

  
  
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  Family/social

  
  
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  Medical

  
  
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  Legal

  
  
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  Psychiatric

The ASI has been shown to be a valid measure with pregnant patients with OUD [6].

The prescription opioid epidemic in the USA has brought to light an economically diverse sample of pregnant women who present for treatment of OUD. They may have unique needs that are not captured by current assessment tools – and, importantly, may not be addressed by the current service models provided in comprehensive care programs. Future research is needed to determine the utility of measures such as the ASI in more affluent and diverse populations, and the potential needs for other assessment measures tailored to these groups.

Assessment of Medication History

Pregnant women with OUD come to treatment with varied histories and experiences with medications for treatment of their OUD. Medications that might interact with opioid agonist medications merit attention in any history. Some pregnant women with OUD will be seeking treatment for the first time, and will have no prior experience with opioid agonist medications, while others may have had prior experience with one or the other medication, or both. It is important to assess not only their prior history with the medication, but also importantly, their view of the reasons for success and failure with the medication. Careful discussion with the patient can help to chart a successful choice of pharmacotherapeutic agent on the part of both patient and provider.

Other pregnant women with OUD will be seeking healthcare services for their pregnancy while already maintained on an opioid agonist. In such cases, it is likely the best course of treatment to maintain these women on their current medication, because switching medications may lead to a period of vulnerability for relapse and instability without careful patient management.

It is also the case that many women, whether or not they are currently maintained on an opioid agonist medication, wish to undergo medically assisted withdrawal (“detoxification”), often because they do not wish to expose their fetus to opioids. In these cases, it is important to discuss with these women their fears regarding opioid agonists, and in particular, how neonatal abstinence syndrome (NAS) requiring treatment does not always occur following prenatal exposure to opioid agonists, and, if it does, is a medically manageable condition.

In the final analysis, it is the patient who expresses her treatment preference. It is the role of the health care provider to ensure that the patient is fully informed as she is making her choice, and to fully engage with her regardless of her choice of treatment.

Co-occurring Mental Health Issues

Pregnant women with OUD often have a co-occurring psychiatric disorder, and routine screening for such disorders is strongly recommended.

• 
  

  Although precise estimates are lacking, it is likely that 65–73 percent of pregnant women with OUD have a co-occurring psychiatric disorder – likely a mood- or anxiety-related disorder [7, 8].

  
  
• 
  

  Pregnant women with co-occurring psychiatric disorders are more likely to drop out of substance use disorder treatment, and to have poorer treatment outcomes.

  
  
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  Research is insufficient to recommend specific treatment choices for the co-occurring disorder for pregnant women with OUD and thus should be individualized and patient-centered.

  
  
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  The general clinical consensus is to pursue concurrent treatment of OUD and the co-occurring psychiatric disorder.

  
  
• 
  

  Psychological treatments (psychotherapy, behavior therapy) may be beneficial for many patients, depending on the disorder.

  
  
• 
  

  Use of psychotropic medications during pregnancy must weigh the maternal benefits of the potential reduction in the psychiatric disorder with the potential risks to the fetus of exposure to the medication.

Comprehensive Treatment for Pregnant Women with Substance Use Disorders

Pregnant women with OUD very often have multiple problems that require attention, beyond the need for effective treatment for OUD. Thus, treatment programs for pregnant women with OUD in pregnancy in which the focus is on the mother–fetus dyad are likely to maintain these women in treatment, and minimize problems in delivery for both mother and infant. Such comprehensive programs integrate obstetric/gynecological care with substance use treatment, psychiatric care, case management services, and assistance with such services as transportation, housing, and parenting and create a recovery-oriented system of care that provides an ongoing system of support that extends beyond the formal treatment phase [9]. Figure 10.2 conceptualizes what a recovery-oriented system of care would look like for pregnant and/or parenting women. UNC Horizons, www.med.unc.edu/obgyn/Patient_Care/unc-horizons-program is an example of such a model in action.

Figure 10.2 Recovery-oriented system of care for women and children

As seen in Figure 10.2, the main components of a recovery-oriented system of care for mothers and children are outlined below [10].

Staffing would be provided by obstetricians, psychiatrists, psychologists, social workers, family physicians, neonatologists, pediatricians, nurses, doulas, who would provide support and services throughout pregnancy and the postpartum period.

A comprehensive care approach considers the needs of women in all aspects of program design and delivery, including location, staffing, and program development, program content, and program materials. It provides safe and comfortable environments in which women develop supportive relationships that allow them to address their recovery needs.

Trauma-Informed Treatment

Trauma-informed treatment is not trauma-specific treatment. Trauma-specific treatment is a response to trauma experienced by the patient. In contrast, trauma-informed approach to treatment of pregnant women with OUD incorporates three key elements:

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  Realizing the prevalence of trauma

  
  
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  Recognizing how trauma affects all individuals involved with the program, organization, or system, including its own workforce

  
  
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  Responding by putting this knowledge into practice

This topic is discussed in detail in Chapter 5.

Treatment Objectives with Opioid Agonist Medication

Treatment objectives for pregnant women with OUD do not differ from treatment objectives for nonpregnant individuals. Opioid agonist medication should not be considered a cure for OUD. Methadone and buprenorphine, if used properly, can effectively suppress other opioid use. Both medications serve as critical components in a comprehensive care program for pregnant women with OUD. However, they do not change the behaviors associated with illicit opioid use. Therefore, behavioral and psychosocial interventions are needed to address the myriad of problems that pregnant women with OUD face. Moreover, such intervention can facilitate bonding between the mother and her neonate.

Treatment Approaches to Opioid Use Disorder in Pregnant Women

Although there are certain exceptions to this general statement, there are three distinct approaches to the treatment of pregnant women with OUD:

1. 
   

   1. medically assisted withdrawal (“detoxification”)

   
   
2. 
   

   2. opioid agonist pharmacotherapy

   
   
3. 
   

   3. opioid antagonist therapy (not currently recommended for treatment of OUD during pregnancy)

Until recently, with the widespread licit and illicit use of opioid pain relievers (e.g., oxycodone), treatment for OUD in pregnant women had largely focused on treatment for heroin use. A critical component of such treatment has often been opioid agonist pharmacotherapy, that can include either methadone or buprenorphine [11].

Medically Assisted Withdrawal

Medically assisted withdrawal (“detoxification”) from opioids has a long and generally unsuccessful history in the treatment of OUD. Early systematic efforts to provide medically assisted withdrawal to males and nonpregnant females focused on varying short durations, often 21 days [12], although shorter (rapid and ultra-rapid) and longer [13] periods have been assessed. The general conclusion has been that medically assisted withdrawal has been a failure – although such a conclusion is now often based on the fact that some form of opioid agonist pharmacotherapy has relatively longer rates of treatment retention and less risk of overdose than medically assisted withdrawal. Slow tapering with long-acting opioids can reduce withdrawal severity; however, the majority of patients relapse to opioid use [14].

The use of medically assisted withdrawal for pregnant women with OUD has been consistently considered to be an inferior treatment choice since the initiation of opioid agonist treatment for heroin in the late 1960s in this population.

This general rejection of medication-assisted withdrawal for the treatment of OUD for pregnant women is largely based on two publications. Zuspan and colleagues [15] reported on the results of fetal monitoring of a single mid-trimester woman undergoing methadone-assisted withdrawal. Using serial amniotic fluid epinephrine and norepinephrine levels, to show a fetal-stress response, authors concluded that medication-assisted withdrawal should not be attempted without biochemical fetal monitoring. Similarly, Rementeria and Nunag [16] examined stillbirths in pregnant women addicted to heroin in a retrospective uncontrolled study. They reported a stillbirth rate of 6.4 percent for this population – there was no control or comparison condition. Also reported was N = 1 pregnant woman who used both heroin and methadone illicitly, and at 39 weeks, delivered a stillborn infant. She had not undergone medication-assisted withdrawal. Nonetheless, they suggested that stillbirth in pregnant women undergoing medication-assisted withdrawal may be due to oxygen insufficiency due to maternal and fetal withdrawal. These two studies laid the foundation for the recommendation found in Center for Substance Abuse Treatment’s TIP # 45 [17] “… that methadone stabilization [rather than detoxification] is the treatment of choice for patients who are pregnant and opioid dependent.”

Recent research has suggested that medically assisted withdrawal may be considered an appropriate treatment for pregnant women with OUD. However, there are significant limitations to this line of research [18] including:

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  Research is largely case series that suffer from significant loss to follow-up assessment of the participants

  
  
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  Relapse rates in these studies range from 17 percent to 96 percent, with an average of 48 percent, a likely underestimate given the loss to follow-up

  
  
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  Findings do not support a reduction in the incidence of neonatal abstinence syndrome signs and symptoms (NAS) as a result of medically assisted withdrawal

  
  
• 
  

  Medically assisted withdrawal is known to be associated with a higher risk of maternal relapse to opioid use, lower treatment engagement, and their attendant ancillary health risks

  
  
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  There is evidence in at least two states (MD and CO) that opioid overdose is a leading cause of maternal death in the first year after delivery. Whether this increased risk of overdose is due to relapse to opioid use after a period of abstinence needs to be explored.

At present, this line of research does not support the benefits of medically assisted withdrawal in comparison to opioid agonist pharmacotherapy. Nor, has it addressed the potential longer term benefits and risks of medically assisted withdrawal for either mother or child in comparison to opioid agonist pharmacotherapy. In summary, while it may be possible to provide medically assisted withdrawal of medication to women with OUD who are pregnant, the most important questions to ask are what goals would be accomplished and at what risks to the mother, fetus, and child? Overall, the use of an acute intervention to address a chronic medical condition is not a beneficial approach for the majority of patients.

Opioid Agonist Pharmacotherapy

There are two principal opioid agonists in wide use in the treatment of pregnant women with OUD – methadone and buprenorphine. The Food and Drug Administration’s (FDA) Pregnancy and Lactation Labeling Final Rule (PLLR) went into effect on June 30, 2015. This rule discontinued the pregnancy risk letter categories (A–D and X) on prescription and biological drug labeling and now uses updated information to be more clinically meaningful to both patients and healthcare providers. The new labeling system allows better patient-specific conversations and informed decision making for pregnant women seeking medication treatment. The pregnancy letter category must be removed by June 29, 2018 [19].

Pregnant women with OUD can be effectively treated with either medication, and their use in the treatment of pregnant women with OUD should not be considered “off-label” because both medications have been approved for the treatment of OUD [20].

Methadone

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  Schedule II opioid

  
  
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  Synthetically derived

  
  
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  μ-Opioid receptor agonist

  
  
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  Also uniquely a δ-opioid receptor agonist

  
  
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  Antagonist at NMDA receptors

  
  
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  Half-life estimated to fall in the range of 24–36 hours

  
  
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  Can be provided in inpatient or outpatient settings

  
  
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  Patients typically begun on methadone when they are in mild withdrawal from opioids

  
  
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  Patients cannot be using benzodiazepines and alcohol before beginning methadone treatment in order to minimize chances of over-sedation

  
  
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  Patients typically begin their methadone dosing under observation; first dose is small; observe for possible negative effects

  
  
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  Assuming no negative reactions to initial doses of methadone, dose is systematically increased until it prevents withdrawal, cravings, and possible continued use of illicit opioids

  
  
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  There is no “correct” dose; optimal dose varies greatly between patients

  
  
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  Blood concentrations of patients on an equivalent dose, adjusted for body weight, have been estimated to vary between 17- and 41-fold

  
  
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  Dosing does not have to be more complicated for pregnant patients

Research on the treatment of pregnant women with OUD with methadone began in 1975, following the FDA’s reversal of its initial decision that pregnant women with OUD should undergo 21-day medication-assisted withdrawal, given research that suggested that there was increased risk to the fetus associated with medication-assisted withdrawal [21]. Initial recommendations were that pregnant women with OUD were to be maintained on a low dose in order to protect the fetus, and to minimize the potential for neonatal abstinence syndrome. Subsequent research suggested that low doses were ineffective in protecting pregnant women with OUD from withdrawal symptoms, and often led to illicit opioid use. Current recommendations have been to maintain a pregnant woman on a methadone dose that effectively treats her withdrawal symptoms. In line with this consensus regarding methadone dosing of pregnant women with OUD, an NIH Consensus Panel [22] declared methadone the standard of care for pregnant women with OUD.

Buprenorphine Mono Product

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  A derivative of the opioid alkaloid thebaine

  
  
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  Schedule III opioid

  
  
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  μ-Opioid receptor partial agonist

  
  
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  Primarily antagonistic actions on κ-opioid and δ-opioid receptors

  
  
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  Half-life estimated to fall in the range of 24–60 hours

  
  
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  Patient must already be in withdrawal or buprenorphine may precipitate withdrawal

  
  
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  Patients dependent on short-acting opioids (e.g., heroin, most prescription narcotics) will not take as long to enter withdrawal as patients dependent on long-acting opioids (e.g., methadone)

  
  
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  Induction typically then takes places over a 3-day period, beginning with either 2 mg or 4 mg, with a maximum dose of:

  
  
  
  
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    8–12 mg on Day 1

    
    
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    12–16 mg on Day 2

    
    
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    16 mg up to 32 mg on Day 3

  
  

As a partial agonist, higher doses of buprenorphine can be given with lower risk of adverse effects (e.g., respiratory depression) than are seen with higher doses of full agonist opioids. Due to its partial-agonist effects, past a certain dose (commonly 24 mg), increasing doses of buprenorphine do not further increase the pharmacological effects of the drug but do increase its duration of withdrawal suppression and opioid blockade. Buprenorphine has a slow dissociation rate from the μ-opioid receptor, which gives rise to its prolonged suppression of opioid withdrawal and blockade of exogenous opioids. This enables buprenorphine dosing to occur on a less frequent basis than full μ-opioid agonists. Thus, buprenorphine can be given as infrequently as three times per week. Common adverse events experienced by pregnant women undergoing buprenorphine pharmacotherapy are constipation, sweating, nausea, headache, dizziness, hypotension, hypoventilation, and myosis. The most commonly prescribed formulation of the buprenorphine mono product in pregnancy is the sublingual tablet, available in 2 and 8 mg tablets.