In the 25 years since the inception of the Harvard Review of Psychiatry, enormous strides have been made in understanding the etiology and neurobiological underpinnings of addiction and in demonstrating evidence-based pharmacologic and behavioral treatments. Yet we have made minimal progress in closing the gap between the overall prevalence of substance use disorders (SUDs) and the proportion of individuals with these disorders who ever receive any treatment in the course of their lifetimes.1 When the first issue of HRP was published, the United States was just emerging from a cocaine epidemic, and now as the Review’s 25th anniversary volume goes to press, the United States is in the midst of a ravaging opioid epidemic. During this interval, the neurobiology underlying these disorders has become increasingly clarified; behavioral interventions such as cognitive-behavioral therapy (CBT), relapse prevention, motivational interviewing, brief interventions, 12-step facilitation, contingency management, and others have demonstrated effectiveness; and new medication-assisted treatments for alcohol, opioid, and nicotine use disorders have received approval from the Food and Drug Administration (FDA). However, the United States’ treatment system has struggled to disseminate these lifesaving treatments to the approximately 20% of the U.S. population who would benefit from them. The gap between available evidence-based treatments and the delivery of these treatments to the majority of patients in need of them is the focus of the 2016 landmark report Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health.1
In its first publishing year, HRP published five articles on addiction that were emblematic of the state of the field at that time,2–6 including: evidence for adaptations to chronic drug administration in the brain’s ventral tegmental area and nucleus accumbens;2 clinical and preclinical studies of buprenorphine treatment of opioid and cocaine dependence;3 the role of psychotherapy in the treatment of substance use disorders;4 emerging evidence of gender differences in alcohol-related disorders;5 and the importance of treating co-occurring psychiatric disorders.6 There has been a rapid acceleration of new knowledge in each of these areas over the last two decades.
Basic and translational research has expanded our understanding of the reward circuitry underlying addiction, including brain circuits that mediate substance-induced reward pathways, stress-related changes during withdrawal, and craving and compulsion.7 These interconnected neural circuits are disrupted through the chronic use of substances, and affect the pathways of reward, learning, and control. A convergence of data over the past two decades also demonstrates that 40% to 60% of the risk for addiction is conferred by genetics. The array of gene variants implicated in the development of SUDs grows each year. In addition, in the past decade new research has highlighted epigenetic mechanisms that can switch on genes implicated in the development of addiction. Early childhood trauma may be a particularly powerful environmental stressor that produces potentially heritable epigenetic changes that confer greater risk for addiction in later life. To provide even greater understanding of the developmental risks for SUDs, a new ten-year longitudinal study, the Adolescent Brain Cognitive Development study, was launched by the National Institutes of Health in 2016 to investigate the effects of substance use at critical stages of adolescent brain development.
Parallel to discoveries in the areas of neuroscience and genetics, treatment research has expanded the evidence base for effective medications and behavioral treatments across different substances of abuse and levels of SUD severity. In 2003, the National Institute on Alcohol Abuse and Alcoholism published Helping Patients Who Drink Too Much: A Clinician’s Guide,8 with updates in 2005 and 2008 to keep pace with outcomes of alcohol treatment studies, including the multisite, randomized, controlled trial of combinations of medications and behavioral treatments for alcohol dependence, COMBINE.9 In 1993—when HRP was first published—disulfiram was the only FDA-approved medication for alcohol dependence. Since then, the FDA has approved naltrexone (in both oral and extended-release depot injection forms) and acamprosate for treating alcohol use disorders (AUDs), and research studies have shown promise for topiramate10–12 and gabapentin,13 although they are not currently approved by the FDA. The ten-question Alcohol Use Disorders Identification Test (AUDIT) had just been published in 1992,14 and over the past 25 years, countless studies have demonstrated its effectiveness as a screening tool to detect AUDs in patients presenting for treatment in primary care and mental health settings. In addition, three-question and one-question AUDIT screeners have been shown to be time-efficient and effective,15,16 and brief, effective screening questions for special populations such as adolescents17 and pregnant women18 have also been developed. Screening, Brief Intervention, and Referral to Treatment (SBIRT) for alcohol misuse and emerging hazardous drinking is now considered an important component of care delivery in primary care and emergency medicine.19 In 1991, as the AUDIT was nearing its initial publication, the first edition of Motivational Interviewing was published,20 with updated editions in 200221 and 201322—a reflection of the many clinical trials supporting the use of this innovative approach to engaging people in substance use treatment. Indeed, the shift away from an emphasis on confrontation to the collegial, empathy-based motivational interview is one of the major advances in SUD treatment over the past 25 years.
In addition to motivational interviewing—an approach that is now used for both alcohol and drug use disorders—other behavioral treatments have been demonstrated as effective in the treatment of SUDs. These approaches include CBT, relapse prevention, motivational enhancement therapy, contingency management, and 12-step facilitation, all in group and individual formats as well as, more recently, computerized formats such as CBT4CBT23 and other Web-based formats added to usual care.24 A multisite study of one of these Web-based treatment interventions25 was conducted through the National Institute on Drug Abuse National Clinical Trials Network, a national collaboration of researchers and clinicians that was initiated in 2000 to conduct multisite trials in community-based SUD treatment programs and, more recently, in general medical settings. Seventeen years later the Clinical Trials Network has completed multiple large, multisite, randomized clinical trials demonstrating the effectiveness of a range of medications, behavioral treatments,26 and their combination. These have included a study demonstrating the effectiveness of buprenorphine/naloxone in adolescents and young adults27 and the largest study yet conducted of prescription opioid addiction treatment, examining optimal combinations of buprenorphine/naloxone and counseling.28
The enactment of the Drug Addiction Treatment Act of 2000 heralded a sea change in the treatment of opioid use disorders (OUDs) in that it allowed trained and waivered physicians, for the first time, to prescribe agonist treatment (the partial agonist buprenorphine) for OUDs as part of office-based practice. Prior to 2000, methadone was the only agonist medication available for the treatment of OUD, and it could be dispensed only in opioid treatment programs.29 In 2010, the FDA approved depot naltrexone for the treatment of OUD and allowed it to be prescribed in office-based practice. In 2016, the FDA approved a buprenorphine implant30 for the treatment of OUD. Thus, the landscape of OUD treatment has changed dramatically since 1993. At that time, physicians could only refer their patients for agonist (methadone) treatment in an opioid treatment program or prescribe oral naltrexone in the office, which had a very low acceptance rate among patients with OUDs. Now, physicians have the ability to prescribe buprenorphine in either sublingual or implant form, and can prescribe extended-release, injectable naltrexone. Another significant advance in the treatment of OUDs occurred as a result of a multisite clinical trial that demonstrated the relative safety and effectiveness of buprenorphine compared to methadone in treating pregnant women with OUDs.31
A number of advances have also occurred in the treatment of cigarette smoking. Studies have demonstrated the effectiveness of single and combined behavioral and medication treatment for tobacco cessation, including varenicline, bupropion, nicotine-replacement treatments, and brief counseling.32 Despite the fact that the effectiveness of these treatments has been demonstrated in the last 25 years, the prevalence of nicotine-dependence treatment among smokers remains low,33 and one group who are especially affected are individuals with mental health disorders.34
Over the last 25 years, epidemiologic, treatment-outcome, and biological research studies have demonstrated sex differences in the risk, onset, progression, and treatment outcomes of SUDs.35 In the United States, the gap between males and females in the prevalence of alcohol and drug use disorders has narrowed significantly in the last 30 years, and in the younger birth cohorts, the current prevalence of some substance use disorders is approximately the same. The “telescoping course” of addiction—the more rapid acceleration of adverse consequence of SUDs in women versus men—has been demonstrated for a number of substances, including alcohol and opioids. Compared to men, women with SUDs are also more likely to have co-occurring depressive, anxiety, eating, and posttraumatic stress disorders. Studies during the last two decades have shown the importance of providing integrated treatment of psychiatric and substance use disorders,35 which may be especially important in improving addiction treatment outcomes in women. Indeed, the term addiction psychiatry, once seen as oxymoronic, is now commonplace, emblematic of the dramatic shift in the past 25 years, in which the central role of psychiatry in treating patients with SUDs has become well recognized.
Emerging epidemics of drugs of abuse provide ongoing challenges. Recent epidemiologic studies indicate that while alcohol use is decreasing among youth, cannabis use has been increasing, as its perceived dangerousness declines in the wake of state legalization efforts.36 Opioid use disorders—involving prescription opioids, heroin, and fentanyl, along with an ongoing rise in opioid overdose deaths—continue to challenge the health system and U.S. society at every level. The critical and sustained need for public health and health care system interventions to prevent and treat SUDs in the United States has been brought into high relief by the recent opioid crisis. By the same token, the health care system’s capacity in addiction treatment needs to be sharply increased.
Over the last 15 years, the field has struggled to train adequate physician prescribers to meet the rising demand for OUD treatment. In 2016, the Substance Abuse and Mental Health Services Administration responded by passing new regulations to increase the number of patients for whom qualified providers can prescribe buprenorphine.37 In general, however, medical specialties have been slow to implement training of physicians to screen for and treat SUDs. In the mid 1990s, psychiatry became the first medical specialty to initiate specialty training in addiction psychiatry—in particular, by establishing addiction psychiatry fellowship programs approved by the American Board of Medical Specialties (ABMS). But it was not until 2015 that other primary care specialties gained approval by the ABMS for addiction medicine fellowships in primary care specialties. Other health care professions such as nursing are now also emphasizing the need for additional training and education in SUD treatment.
As HRP marks its 25th year, legislation passed by Congress in 2016 could have the potential to increase treatment among individuals with SUDs. The Comprehensive Addiction and Recovery Act, signed into law in July 2016, was the first major federal legislation in 40 years, authorizing $181 million each year in new funding to fight the opioid epidemic. Congress will need to appropriate funds annually, however, if it is to provide a coordinated and much needed response through prevention, treatment, recovery, law enforcement, criminal justice reform, and overdose reversal. In December 2016, Congress also passed the 21st Century Cures Act, which provides $1 billion in grants to help states provide treatment for OUDs. The Affordable Care Act, through mandatory coverage and parity enforcement, has expanded access to treatment services to many patients with OUD and other SUDs. Such legislation has enabled millions of Americans with SUDs and other mental health conditions to gain coverage and access to treatment. Changes to the ACA could potentially erode these recent gains. Beyond these legislative initiatives, the U.S. surgeon general’s report on addiction in America,1 as mentioned above, highlights even more broadly the need for increased attention by the U.S. health system to the treatment of SUDs.
The last 25 years has seen a remarkable explosion of knowledge in neuroscience and genetics, and research has generated an expanded compendium of evidence-based treatments that can be used to provide early intervention, treatment, and recovery for patients and their families. It remains to be seen, however, whether social and political forces can join together to provide sustained and meaningful change to the U.S. health system so that the majority of individuals with SUDs can gain access to, and benefit from, the ever expanding array of effective treatments now available for these health conditions that are responsible for such great morbidity and mortality.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
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