The History of the Current Opioid Epidemic
Sam Quinones’s Dreamland  details the current opioid epidemic and is an excellent read. Since the early 1990s, opioid use in the United States and Canada has increased more than fivefold, starting with the release of Oxycontin® by Purdue Pharmaceuticals in 1996. A half page communication by Porter and Jick  in The New England Journal of Medicine showed that among hospitalized patients (emphasis mine) treated with opioids, less than 1 percent developed addiction. Using this study, Purdue Pharmaceuticals marketed this new extended-release opioid to primary-care physicians as the Holy Grail for the treatment of chronic pain, a safe, non-addictive opioid. Doctors were urged and incentivized to prescribe this new wonder drug, but not trained in its safe use, leaving many of their patients vulnerable to developing addictive behaviors and resulting in death due to overdose. Later studies showed that approximately 35 percent of people treated with opioids for chronic pain go on to develop an opioid-use disorder . In addition, for-profit pill mills were opened in many localities, where a patient could get a month’s worth of potent opioids with a minimal history of pain and cursory exam. In addition, there was no oversight of these clinics or the patients, and patients could and frequently would frequent more than one “pain clinic,” leading to huge numbers of “legal” opioids circulating around communities which had been devastated by the loss of manufacturing jobs.
Simultaneously, the American (National) Pain Society first suggested that pain be treated as the fifth vital sign, and the Joint Commission for Accreditation of Hospital Organizations (JACHO) put forth hospitals that executed this as an example of good patient care . Hospital satisfaction scores have been partially based on whether or not a patient’s pain was treated “adequately.” This led to hospitals and emergency rooms dispensing increasing numbers of opioids, especially to white patients  and surgeons prescribing prolonged courses of opioids, even though the majority of patients require opioids for only three days after discharge from the hospital.
By 2010, doctors prescribed sufficient opioid(s) so that “every person in the United States could be medicated around the clock for a month” (Figure 1.1) . Unlike previous opioid epidemics involving heroin, this epidemic targeted mostly white and middle class people, with many of them being women of childbearing age. Women were more likely to be prescribed opioids for pain relief than men; indeed, during the 1800s, the majority of people with opium-use disorders were women who were prescribed opium for pain relief by their physicians . Physicians also prescribed higher doses of opioids and for longer periods, leading to higher overdose death rates among women . Women are most likely prescribed opioids for migraine, fibromyalgia, and osteoarthritis, i.e., for all conditions for which they are not effective. The great majority of women who received prescription opioids were of childbearing age, which leads to our current epidemic of infants needing treatment for neonatal abstinence syndrome (NAS) (Figure 1.2).
Figure 1.1 Rates* of opioid pain reliever (OPR) overdose death, OPR treatment admissions, and kilograms of OPR sold in the United States, 1999–2010 
*Age-adjusted rates per 100,000 population for OPR deaths, crude rates per 10,000 population for OPR abuse treatment admissions, and crude rates per 10,000 population for kilograms of OPR sold.
Figure 1.2 Incidence of neonatal abstinence syndrome per 1,000 hospital births in the United States, 2000–12 
At the same time that the prescription opioid use epidemic came to the attention of public health officials and other authorities, another opioid was reemerging as a threat. Potent black tar heroin was smuggled from Mexico and delivered like pizza by small cells in several major cities and small towns that had never seen heroin before. This black tar, so named because it was the unrefined sticky substance directly extracted from the poppy plants, was several times more potent than the powdered heroin previously sold by dealers in big East Coast cities and was also cheap. An addict could satisfy their cravings for less than $20 per day, while Oxycontin and other opioids cost much more (if not covered by insurance). Once the pump had been primed by prescription opioids, and then the well ran dry as insurance companies refused to cover the extended-release options and pill mills were closed, heroin was there to take over this deadly trend. Recently, the heroin has been adulterated with synthetic opioids such as fentanyl and sufentanil which are hundreds of times more potent, leading to a skyrocketing rate of overdose deaths, including Phillip Seymour Hoffman and Prince.
Safe Treatment of Pain
Opioids still have a place in the treatment of pain, though the treatment of chronic non-cancer pain with opioids is controversial. There are several safeguards that need to be used for anyone using opioids for the treatment of pain. The CDC published these guidelines in May 2016 . They include the use of prescription drug monitoring systems (PDMPs), which 49 states have implemented, and some states mandate their use by physicians before the prescription of controlled substances. Urine drug monitoring is recommended to confirm that the patient is taking the medication that is prescribed and not taking other illicit or licit substances (such as benzodiazepines) that increase the risk of overdose death. Prescribers are encouraged not to prescribe opioid for more than 3 days for acute pain, and while treating chronic pain, caution must be exercised when prescribing above 50 MME (morphine milligram equivalents) and not to exceed 90 MME .
There are limitations to these guidelines, and given that 35 percent of individuals treated with opioids for chronic pain will develop an opioid-use disorder, practitioners are advised to treat with care while using opioids. Ideally, the treatment of chronic pain should occur in specialized multidisciplinary pain clinics with the use of multimodal treatment options, including nonopioid medications, physical therapy, chiropractic care, psychological treatments, pain blocks, and acupuncture, as well as someone specialized in the treatment of addiction. Unfortunately, insurance coverage for such comprehensive pain clinics is inadequate, and thus there is a nationwide shortage.
Pregnant Women and Pain
There are unfortunately few nonopioid medications that are safe in pregnancy. In addition, pregnancy increases stress on the musculoskeletal system, which can increase low back pain and other pain syndromes. Pregnancy intention should be discussed with all women being treated for chronic pain and attempts to control pain without opioids should be maximized before pregnancy. Weaning of opioids during pregnancy will be addressed in subsequent chapters, but it is important that women should not be abruptly withdrawn from opioids, as this can increase the risk of intrauterine fetal death (stillbirth), abruption, and preterm birth. All providers treating pregnant women with opioid-use disorders reported seeing an all-too-common phenomenon among women being treated at pain clinics; the prescriber, who has been managing the woman with opioids, will stop prescribing upon learning of the pregnancy, as if that will insure that the fetus is not exposed. This is a poor clinical practice, bordering on malpractice. With adequate counseling of NAS risks, many women can safely be continued on opioids during pregnancy, especially if there are no better options for treatment. Focus on nonmedication treatment of pain should be optimized (e.g., physical therapy, massage, acupuncture, and psychologic counseling such as cognitive-behavioral therapy). Unfortunately, insurance coverage for such adjunctive therapies are lacking, limiting its effectiveness in disadvantaged women (who are more vulnerable to chronic pain). Family planning will be addressed in Chapter 13, but it is of paramount importance to the optimal treatment of women with pain and with opioid-use disorders.
Pain and Addiction: Common Threads
The vulnerability of women treated with opioids to developing an opioid-use disorder stems from many factors, including genetic vulnerability, exposure to early childhood adverse events, poverty, physical trauma, and interpersonal violence.
The American Society of Addiction Medicine (ASAM) defines addiction as a primary, chronic disease of brain reward, motivation, memory, and related circuitry. Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors, and interpersonal relationships, and a dysfunctional emotional response . Vulnerability to addiction is thought to be multifactorial, comprising a complex interplay of genetic and environmental causes (Figure 1.3).
Figure 1.3 Determinants of addiction
Twin studies have demonstrated that genetic vulnerability comprises about 60 percent of an individual’s risk of developing a substance use disorder. Interestingly studies looking at possible genetic causes of both opioid addiction and vulnerability to chronic pain have found several genes in common [10, 11]. One of these gene targets, the COMT gene, which regulates the metabolism of catecholamines, was found to be associated with opioid-use disorder (OUD) only in women . Target gene studies comparing dependent vs. nondependent opioid users found a polymorphism in the delta opioid receptor gene OPRD1 associated with dependent opioid use . Activation of this receptor decreases persistent pain and reduces negative emotional states ; thus this could be a compelling target for drug development studies. Other genetic factors include polymorphisms in ADRB2 that are associated with resilience to posttraumatic stress after trauma , which we will see in Chapter 5 as a major factor in the development of substance use disorders.
The relationship between exposure to adverse childhood events (ACE) and substance use was first reported in 1998 . Since then other studies have looked at the role of poverty , sexual abuse , and interpersonal violence . All of these factors contribute to higher rates of opioid-use disorders. As we’ll see in Chapters 5 and 6, trauma and interpersonal violence remain two of the greatest risk factors for the development of opioid- and other substance use disorders. These factors are also determinants of chronic pain [19–21]. Women with substance use disorders and chronic pain suffer from multiple social and health disparities and thus these disparities need to be addressed if we are to help these women, their families, and their communities recover.
Traditional Approaches to Substance Use in Pregnancy
Focus on the risk of substance use solely on the fetus, lack of understanding of the role of the maternal-fetal dyad, and misunderstanding of the disease model of addiction have led to several public policy approaches to pregnant women with substance use disorders that have proven to be disastrous to public health as well as individual women and their families. Most of the public policy focus has been on the largely overstated and unproven risks of illicit drugs, while ignoring the real and well-known risk of the licit substances, such as alcohol and tobacco. These policies serve to prevent women from getting the prenatal care and addiction treatment they need and that has been shown to improve pregnancy outcomes and ameliorate the effects of the drugs.
Traditional Approach 1: Take Away Her Children: Women with Substance Use Disorders are Unfit to Parent
There is a pervasive notion in our society that women who use illicit drugs are unfit to parent children. This is reflected in policies where children under threatened harm are removed from the home even if no child abuse or neglect is proven. Threatened harm can include a positive drug test at delivery or at any time during her prenatal course. Women with a single, positive, drug urine test have been subject to child welfare involvement and infant removal, even if confirmatory drug testing was not done, and even if she was not aware of the pregnancy at the time of her drug use. This involvement serves to place the perceived needs of the fetus above those of the pregnant woman, ignoring the rights of the pregnant woman, and the role her health plays on that of the developing fetus. It also puts the prenatal care provider into an adversarial role with the pregnant woman, as drug testing is often done without the consent or even knowledge of the pregnant woman. Instead of talking to the woman about her drug use, her social situation and other factors that can affect her and her family’s health, and provided with necessary medical care (which includes addiction treatment), she is subject to unlawful search and subsequent infant abduction, which serves to perpetuate the inter-generational cycle of trauma. Women who have children removed from them, even temporarily, are more likely to get pregnant again . As one mother eloquently said “I have a hole in my heart from missing those 2 months with my son. I want to go have another baby just to fill it.” This can be one reason women with substance use disorders have more pregnancies and live births.
Perhaps this approach could be justified if it were shown to be effective in protecting the fetus and child from the effects of maternal drug use, but this is not the case. Policies that stress child welfare involvement actually worsen pregnancy outcomes, in that they serve as a large barrier to women obtaining prenatal care , which has been shown to ameliorate the effects of the substances and normalize pregnancy outcomes . A single drug test does not predict parenting ability ; Susan Boyd found no differences between women who use drugs and those who do not in their childrearing practices . In addition, in 1976, as Michael Wald said , “Removing a child from his family may cause serious psychological damage – damage more serious than the harm intervention was supposed to prevent.”
Keeping children with the mother while she undergoes drug treatment improves the outcomes of the entire family . Since the early 1990s, this model of comprehensive care has been supported by the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Center for Substance Abuse Treatment (CSAT), and has demonstrated success in many states . Despite the success of this approach, funding was drastically cut to this program and these facilities are still available in less than half of states.
On a practical note to providers who care for women with substance use disorders, current state laws are influenced by the Child Abuse Prevention and Treatment Act (CAPTA), which was originally enacted in 1974 and most recently updated and reauthorized in 2010. The purpose of this act is to provide funding to states for child welfare services. A new CAPTA state grant eligibility requirement modifies earlier CAPTA language that mandates identifying and making “appropriate referrals” by healthcare providers to CPS – and developing service “plans for safe care” of the child – of newborns affected by prenatal drug exposure. Various states have interpreted these requirements in various ways, both in reporting requirements and what is meant by newborns affected by prenatal drug exposure. The most recent requirements also include infants affected by NAS and fetal alcohol syndrome (FAS). Knowledge of your own state laws is imperative while taking care of women with substance use disorders. Counseling women during the course of prenatal care as to the requirements of the law and your own role in reporting can help allay her fears to some extent. For example, in Hawai’i, I’m not required to report drug use during the pregnancy, so that I am able to reassure the woman I’m providing prenatal care for that I won’t report her unless there are other concerns about child abuse or neglect. I do explain that if her child has NAS or if the pediatrician has concerns, she may be referred, but that the purpose of the referral is to ensure access to resources, not to remove the child from custody if she has been attending prenatal care and treatment for her substance use disorder. Providers in states with more punitive laws should fight to change the laws and advocate for your patient’s rights.