Pharmacotherapy for Opioid Use Disorders in Special Populations

Three populations are most at risk for opioid use disorder: adolescents, pregnant women, and those with comorbid psychological or psychiatric disorders. Opioid use disorders present throughout the life course of an individual, often developing during adolescence. For women, these disorders commonly occur during peak childbearing years. In addition, the twin vulnerabilities of genetics and adverse childhood events often interact to impart a greater chance for co-occurring psychiatric conditions. Caring for the pregnant woman, the adolescent, or the person with a co-occurring mental disorder presents special challenges. This chapter focuses on special considerations when treating opioid use disorders in these populations.

Use of Buprenorphine for the Treatment of Opioid Use Disorder

Buprenorphine is a mu-opioid partial agonist that was first developed as a parenteral analgesic and subsequently as a treatment for opioid dependence. In the United States, the first two products approved by the US Food and Drug Administration (in 2002) for the latter indication were buprenorphine (Subutex) and buprenorphine/naloxone (Suboxone) tablet formulations for sublingual administration. Since that time, additional products for both sublingual and buccal administration have also been approved, as well as a subcutaneous injection for once-monthly administration for the treatment of moderate or severe opioid use disorder (OUD) and a subdermal implant for the maintenance treatment of opioid dependence that delivers buprenorphine over a 6-month period. Under the Drug Addiction Treatment Act of 2000 (DATA 2000), qualified practitioners may apply for waivers to treat opioid dependence/OUD with approved buprenorphine products in any setting in which they are qualified to practice. Like other opioids, buprenorphine has the potential for being misused and abused.

Stress and Substance Misuse

Stress is both a critical contributor and consequence of substance use disorder (SUD). First, exaggerated subjective stress responses are characteristic of affective symptomatology such as depression, bipolar disorder, generalized anxiety, and posttraumatic stress disorder (sometimes stemming from histories of abuse) that have been prognostic of development of addiction in longitudinal studies. Substance use is negatively reinforced in many at-risk and addicted individuals because it may acutely alleviate stress. Second, chronic administration of commonly abused substances alters physiological stress response systems, especially during acute withdrawal. Third, acute stress responses blunt the addicted individual’s frontocortically mediated behavioral repertoire (solution space) in favor of reflexive behavioral biases toward relief-based substance use. Therefore, acute stress responses are a strong trigger for relapse to substance use during extended recovery. These findings have collectively led to approaches to SUD relapse prevention that pharmacologically blunt components of the stress response, but these agents have not reliably shown success in human clinical trials. This chapter reviews these different relationships between stress and addiction and offers future avenues for additional research.

Impulsivity and Drug-Seeking Behavior in Substance Misuse

Vulnerability to initiate use of psychoactive drugs as well as relapse to drug-seeking in patients with established substance use disorders are precipitated by behavioral disinhibition or impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to negative consequences) and attentional bias toward drug cues (cue reactivity). These behavioral phenotypes are not independent mechanistically nor neurobiologically, and preclinical analyses have demonstrated the complex nature of the interactions between these interlocked phenotypic behaviors, including aspects of their shared neurobiology and circuitry. This chapter focuses on impulsivity and drug-seeking behaviors from a preclinical perspective and summarizes studies exploring the impact of substances of abuse in the context of the neurobiology of impulsivity and drug-seeking behaviors in rodents.

Turn the Next Page

Contemporary research has enriched our knowledge of mechanisms involved in the generation and persistence of the debilitating disorders characterized by an “addictive dimensionality,” such as substance use disorders and binge eating disorder. Personalized treatment strategies for addictive disorders might include one or a combination of medications at important stages in detoxification and recovery to reduce craving, assist in establishing a substance-free state, and open the optimal window to allow cognitive restructuring and enhanced inhibitory control of substance-seeking. The overlapping neural systems and brain circuitry involved across addictive disorders have elevated interest in the metabolic and neural regulators serotonin (5-hydroxytryptamine; 5-HT) and ghrelin. This chapter focuses on these systems as examples of how we can broaden our horizons for advancing future therapeutic and biomarker initiatives.

Evidence-Based Pharmacotherapy for Cocaine, Amphetamine, and Methamphetamine Use Disorders

Cocaine use disorder is one of the important stimulants use disorders worldwide, and amphetamine/methamphetamine misuse is a growing epidemic. There are no pharmacotherapy treatments approved by the US Food and Drug Administration (FDA) available for these illnesses. Numerous treatments based on a variety of strategies from psychotherapy, pharmacotherapy, to neuromodulation have been tested to date. Clinical efficacy of the trialed treatments, including both negative and positive outcomes. are reviewed and discussed in this chapter. In summary, many agents and interventions showed promising therapeutic potential in preclinical and early phase clinical trials but eventually failed in later larger trials. Thus, behavioral interventions and supportive therapy focusing on detoxification, initial recovery, and relapse prevention remain the major therapeutic approach due to lack of targeted treatment. New strategies and models are urgently needed to develop effective treatments for these detrimental disorders.

Overview

Substance use disorders (SUDs) are a significant cause of morbidity and mortality in the United States. In spite of the significant public health impacts of SUDs, medications approved by the US Food and Drug Administration (FDA) are underutilized for the treatment of SUDs. This chapter reviews the history of FDA-approved medications for alcohol, nicotine, and opioid use disorders and provides some background on barriers to use of these medications to treat patients with SUDs. Suggestions are provided to guide clinicians on a path forward to reduce these barriers and increase the use of FDA-approved medications for the treatment of SUDs.

Epidemiology of Substance Use Disorders

Nearly 3 million Americans have a current or previous opioid use disorder, and recent data indicate that 10.2% of US adults have ever misused pain relievers. In 2015, approximately 800,000 individuals used heroin, while 4 million misused prescription opioids. Although use of other drugs such as alcohol and cannabis is more prevalent, opioid use contributes to significant morbidity, mortality, and social and economic costs. While the current US opioid overdose epidemic began with prescription opioids, since 2015, heroin and synthetic opioids (e.g., fentanyl) have driven continued increases in opioid overdose deaths, contributing to a recent decline in overall life expectancy in the United States. Policies to address the opioid epidemic by changing clinical practice include provider education, monitoring prescribing practices, and expanding the clinical workforce necessary to treat opioid use disorders. The opioid epidemic appears to be largely a US phenomenon and a consequence of both structural challenges in the US healthcare system and growing socioeconomic disparities, and thus it will require policies including and beyond delivery system reforms to resolve it.

Evidence-Based Pharmacotherapy for Alcohol Use Disorders

Pharmacotherapy is a vital component of alcohol use disorder (AUD) treatment. From a biopsychosocial perspective, the use of pharmacotherapy alone and in combination with various therapeutic and psychosocial modalities to reduce harmful drinking behaviors is supported by a strong evidence base. This chapter presents an overview of the use of both US Food and Drug Administration (FDA)-approved and off-label treatments for AUD, and it provides practical information and evidence for the use of pharmacotherapy. Comprehensive reviews of medications are undertaken with an emphasis on evidence-based practice and clinical utility to aid in the treatment of AUD and harmful drinking behaviors.

Evidence-Based Behavioral Therapies for Substance Use Disorders

A variety of pharmacological and psychosocial interventions have demonstrated efficacy in the treatment of substance use disorders (SUDs). This chapter focuses on evidence-based behavioral and psychosocial interventions for the treatment of alcohol use disorder and other SUDs. Among the interventions discussed are screening, brief intervention, and referral to treatment (SBIRT); motivational interviewing (MI); cognitive behavioral therapy (CBT); and contingency management (CM). Additionally, one promising intervention for SUD, Transcending Self Therapy (TST), is spotlighted. The importance of comprehensive care is noted by the authors, as is the importance of recognizing gender differences in the selection of therapies and the need to address barriers to care for specific populations.