The United States is in the midst of one of the worst public health crises of modern times. Drug overdose is now the number one cause of death for all Americans younger than age 50 years. More people lose their lives annually to overdose than to the peak number of deaths from motor vehicle accidents, firearms, or HIV/AIDS.1 The impact of this crisis has been so profound that life expectancy in the US has declined for two consecutive years.2 If this trend continues for a third year, as is expected, it will be the first time since the Spanish influenza epidemic of 1916 that the US will see such a continuous decline in life expectancy.
Because opioid-related deaths are largely driving overdose mortality, this crisis has been termed the opioid epidemic. The opioid epidemic has seen a dynamic progression of deaths related to different types of opioid drugs played out in three distinct waves. The first wave, which began in 1999, consisted of a steady rise in deaths due to prescription (opioid) pain relievers, such as oxycodone. By 2010, the second wave appeared with a rising rate of heroin-related deaths. Finally, the third, and current wave, has seen a rapid increase in synthetic opioid-related deaths, driven predominantly by illicitly manufactured fentanyl (Figure 1).3 This dramatic and rapid increase in opioid overdose deaths has garnered much attention in the media, among policy makers, and in the scientific literature. However, alcohol-related mortality in the United States has also increased significantly since 1999; in addition, cocaine-related deaths are also on the rise, particularly among non-Hispanic Black populations.4,5 Addressing the current crisis of substance use and related mortality requires a comprehensive response that is grounded in a scientific understanding of addiction and effective interventions for treatment and harm reduction.
Opioid overdose deaths in the United States. From the Centers for Disease Control and Prevention3 (in the public domain; permission is not required).
Understanding the Current Overdose Crisis
The current crisis began in the late 1990s with a rising rate of opioid prescriptions and then with an increasing number of admissions for treatment of addictions.6 However, since 2010, overdose deaths involving illicit opioids increased by more than 200%.7 Although this trend was initially driven by heroin-related deaths, contamination of the street-opioid supply with illicitly manufactured fentanyl has driven the rise in opioid-related overdose deaths.
This transition highlights the nuance of the crisis and the need for a multifaceted approach. Interventions that have focused solely on reducing access to prescription opioids are unlikely to help people who have developed an opioid use disorder and may increase the risk of death. Decreasing availability of prescription opioids has been linked with a rising mortality rate from illicit opioids, suggesting that supply side shortages may push people toward using heroin or illicitly manufactured fentanyl.8 This is also seen in the changing nature of opioid initiation; in one study of people entering treatment for an opioid use disorder, use of prescription opioids decreased from more than 90% in 2005 to 67% in 2015.9 A subsequent study found that in 2005 only 8.7% of people upon entry into addiction treatment reported heroin was the opioid used initially; in contrast 31.6% of entrants in 2015 identified heroin as their first-used opioid.10
Although opioids have driven the increasing rate of overdose mortality overall, cocaine-related deaths are also on the rise. This is particularly true among non-Hispanic Black men and women, in whom cocaine has been the largest contributor to drug overdose deaths between 2000 and 2015.5 From 2015 to 2016, deaths involving cocaine increased 52.4%, the second largest increase next to fentanyl.11 Cocaine-related-deaths involving opioids increased from 0.37 in 2000 to 1.36 per 100,000 people in 2015, which may reflect that these deaths are due in part to contamination of the drug supply with illicitly manufactured fentanyl and unintentional opioid exposure among people who use cocaine.12 This has resulted in a mortality impact in some communities that is on a par with the opioid overdose crisis, and yet it has received relatively little attention. In addition, there are parts of the country where opioid-related deaths are highest among African Americans (eg, in West Virginia, the District of Columbia, and Wisconsin).13 The lack of attention paid to overdose deaths in African Americans is consistent with our historical racial disparity in approaches toward those with addiction, where the responses to drug use and addiction in communities of color have generally been punitive.13
Effective solutions to address the overdose crisis will rely on empirically proven interventions. To quote Volkow and Collins,14 “As we have seen repeatedly in the history of medicine, science is one of the strongest allies in resolving public health crises. Ending the opioid epidemic will not be any different.” The past several decades have seen numerous advances in our understanding of the neurobiology, epidemiology, and treatment of addiction. Yet, despite scientific advances, much of what is called addiction treatment looks nothing like what we deem appropriate for a person with another type of chronic illness; we have approached addiction as a social problem or a criminal justice issue, rather than as a medical matter.15
Although most people who use alcohol or other drugs never develop addiction, some people considered to be at-risk will. A person's risk for developing addiction is based on genetic vulnerability (which accounts for 40%–60% of the equation), and environmental factors or exposure (such as adverse childhood experiences).16 Addiction, a chronic illness, is characterized by the compulsive seeking and use of substances despite harmful consequences. Although addiction is a recognized and well-described term, it is not specific. The Diagnostic and Statistical Manual of Mental Disorders, fifth edition,17 uses the term substance use disorder (SUD), which is subclassified as mild, moderate, or severe. The diagnosis of a SUD refers to a problematic pattern of substance use leading to clinically significant impairment related to impaired control, social impairment, risky use, and physiological dependence, which is notably not sufficient in isolation to make the diagnosis. The term “addiction” correlates with moderate-to-severe SUDs.18 There are a range of important medical complications associated with SUD (Table 1).
Medical Complications of Substance Use Disorders
Several important concepts are embedded in the definition of addiction. First, addiction is a chronic illness; thus, the goal is not cure, but rather engagement and retention in treatment to achieve remission and to minimize the frequency and duration of recurrences. Second, this illness is defined by doing something compulsively in a fashion that causes harm. This defining hallmark of the illness can be incredibly difficult for health care providers, family members, and policy makers to comprehend. It is often tempting to look at someone in the throes of active addiction and to wonder why the person cannot stop the self-destructive behavior. Amid mounting negative consequences, observers frequently grapple with understanding why a compulsive behavior that so clearly results in harm is continuing. Nonetheless, this is the sine qua non of addiction. We need to think more about how our policies and our treatment programs (which have often sought to punish people into getting well) are designed. Despite recent rhetoric around approaching addiction as a public health issue, many of our societal policies penalize people who use drugs; this results in incarceration, termination of treatment, loss of housing, loss of employment, or loss of parental rights.19 If the hallmark of this illness is not being able to stop using substances despite negative consequences, then making more bad things happen to a vulnerable person—particularly when continued substance use is often a strategy for coping with stressful situations—will often worsen outcomes.
Understanding Addiction Treatment
When we recognize addiction as a chronic illness, much like diabetes, hypertension, or HIV infection, we can begin to match appropriate clinical interventions and treatment models to the disease. Treatment outcomes and rates of recurrence are similar between drug addiction and other chronic medical conditions.20 Successful treatments for addiction mirror approaches toward other chronic illnesses. Effective treatment involves a menu of options that include medications, behavioral interventions, and ongoing follow-up; treatment selection should be tailored to individual patients based on clinical presentation, patient preference, and treatment history. The goal of treatment becomes engagement and retention in care to reduce or eradicate symptoms of active illness and to minimize both the acute and chronic complications of untreated disease. With illnesses like diabetes, our health care system is better prepared to recognize these nuances. For example, although medication is a cornerstone of treatment for type 2 diabetes, not all patients require long-term medication management, and some are able to control their illness with behavioral changes alone. This doesn't mean that one modality of treatment is morally superior to the other, but rather that all treatments should be available and appropriately matched to the person. Unfortunately, although the clinical situation is similar for an illness like opioid use disorder, there tend to be strongly held opinions about the use of medications versus use of behavioral treatments;21 this has deeply influenced access to care.
Effective medication treatments exist for opioid, alcohol, and tobacco use disorder; these may be used in conjunction with a range of effective psychosocial interventions, such as cognitive-behavioral therapy, motivational enhancement therapy, or contingency management.22 Recovery supports are not considered formal treatment, but they can offer invaluable support. Recovery supports include mutual help organizations, such as Alcoholics or Narcotics Anonymous or SMART (Self-Management and Recovery Training) Recovery, as well as recovery coaching, which is the use of peer-support specialists who have a shared lived experience of addiction and recovery. The existing research on recovery coaches is limited; however, a qualitative study found that patients view this role to be valuable, with patients identifying several important features of recovery coaching (including accessibility, shared experiences, motivation of behavior change, and links to social services).23 Treatment for SUD can be started in inpatient medical settings as well as in emergency departments with higher treatment retention rates than when patients are simply referred to treatment at the time of discharge.24–26
For opioid use disorder, the evidence overwhelmingly supports the use of medication treatments as the foundation of treatment, with decades of research demonstrating superior efficacy with medication as opposed to behavioral-only treatments. There are three US Food and Drug Administration (FDA)-approved medications for opioid use disorder: methadone (a full opioid agonist); buprenorphine (a partial opioid agonist); and naltrexone (an opioid antagonist).27 Methadone maintenance has been shown to be superior to psychosocially enriched, medically supervised withdrawal and to behavioral-only treatments with regards to increasing treatment retention and reducing ongoing opioid use.28,29 Buprenorphine has similarly been shown to be more effective at retaining people in treatment and preventing ongoing opioid use. A small but notable study in which randomized people with heroin addiction were steered to either medically supervised withdrawal followed by 1 year of intensive psychosocial counseling or to buprenorphine maintenance plus psychosocial counseling, found that no patients were retained in the medically supervised withdrawal arm and 20% died within 1 year, compared to a 75% retention rate, 75% abstinence rate, and no deaths in the buprenorphine arm.30 At medium or high doses, buprenorphine appears to be as effective as methadone in retaining people in treatment and suppressing illicit opioid use.31 Both methadone and buprenorphine, when used for ongoing treatment, significantly reduce mortality.31 A meta-analysis of studies that included 122,885 people receiving methadone for 1.3 to 13.9 years, and 15,831 people treated with buprenorphine for 1.1 to 4.5 years found that all-cause mortality decreased from 36.1 to 11.3 per 1,000-person years when patients were engaged in methadone treatment and from 9.5 to 4.3 per 1,000-person years for patients receiving buprenorphine.32 Overdose-specific mortality was reduced even more, from 12.7 to 2.6 per 1,000-person years for methadone treatment and 4.6 to 1.4 per 1,000-person years for buprenorphine treatment.32 Although outpatient use of methadone in the US must be delivered in a strictly regulated opioid treatment program (unless it is used for pain management), buprenorphine can be offered by specially trained physicians, nurse practitioners, or physician assistants in an office-based setting. Treatment in primary care has been effective with or without the addition of trained addiction counselors.33 Extended-release naltrexone is a third medication option for opioid use disorder; it has been shown to be more effective than nonmedication treatment.34,35 In a randomized trial of patients recruited from a detoxification setting, extended-release naltrexone was less effective at preventing relapse than was buprenorphine, in large part because of the difficulty people had in initiating treatment. A per-protocol analysis of that study found that among patients who successfully completed medically supervised withdrawal and started extended-release naltrexone, relapse rates were comparable to those of buprenorphine.36 Real-world evidence also highlights the challenges faced by initiation and adherence to extended-release naltrexone. A cohort study in Massachusetts that examined medication treatment for opioid use disorder after nonfatal overdose found that the median duration of treatment with extended-release naltrexone was 1 month as compared to 4 months for buprenorphine and 5 months for methadone.37 Importantly, methadone and buprenorphine treatment were both associated with significant reductions in all-cause and overdose-specific mortality, whereas there was no mortality benefit from extended-release naltrexone treatment.31 Recommendations by the Substance Abuse and Mental Health Administration concluded that all people with opioid use disorder should have access to medication treatment and individualized psychosocial supports, which can range from medication management and supportive counseling by the patient's provider to adjunctive addiction counseling.38
The details of opioid agonist treatment with methadone and buprenorphine, which are federally regulated, are important to understand. Opioid agonist therapy consists of daily methadone or buprenorphine treatment with a goal of achieving a stable level of opioid effect, which is experienced as neither intoxication nor withdrawal, but rather allows the patient to feel “normal.” Buprenorphine treatment can be delivered in an office-based setting; however, prescribers are required to complete 8 hours of training if they are a physician, or 24 hours of training if they are a nurse practitioner or a physician assistant to receive a waiver from the Drug Enforcement Agency. Methadone can only be prescribed for opioid addiction in federally licensed opioid treatment programs, which have strict requirements to mandate daily-observed therapy for the first months or longer of care.39 Naltrexone prescribing does not require any special licensure. Buprenorphine can be initiated in an observed manner in the office or at home, generally starting with a 4-mg dose and treating with supplemental doses based on withdrawal symptoms or craving to a usual first daily dose of 16 mg or less.40 Maintenance dosing of buprenorphine range from 8 to 24 mg daily, with some recent evidence suggesting greater treatment retention with higher doses.27 Methadone is usually started at 30 mg per day and up-titrated to a therapeutic dose that can range from 60 to 120 mg or higher.41
Although the evidence strongly supports the use of medications for treatment of opioid use disorder compared to no treatment or behavioral treatments alone, not all patients want to take medications. Access to psychosocial interventions and recovery supports should be readily available to all patients, in addition to medication treatment. Because patient preference could be influenced by pervasive stigma about the use of medications in addiction treatment, careful education about the risks and benefits of treatment (with or without medication) and an exploration of reasons why a patient may choose to not use medication treatments is warranted.
Motivational interviewing is a crucial tool for engagement with patients with SUDs across settings. Motivational interviewing is a technique for interacting with people with a SUD that is grounded in acceptance and partnership and positions the clinician as a helper in a patients' change process. Motivational interviewing seeks to help resolve the natural ambivalence that patients have around substance use by identifying patients' goals and eliciting self-motivational statements and behavioral change from the patient. This can identify discrepancy between patients' behaviors and their self-identified goals to enhance motivation for positive change.42
For alcohol use disorder, there are also three FDA-approved medications (eg, naltrexone, acamprosate, and disulfiram) as well as a range of effective behavioral interventions and recovery supports. In addition, several medications (such as topiramate and gabapentin) that are used off-label to treat alcohol use disorder, have been effective.43 Although the evidence supporting the use of medications in alcohol use disorder does not demonstrate the same dramatic effectiveness as those used to treat opioid use disorder, these medications reduce heavy drinking days and modestly improve abstinence rates.44 They are also safe, generally well tolerated, and require no additional training to prescribe; yet, they remain vastly underutilized by physicians.
For cocaine, other stimulant, sedative/hypnotic, and cannabis use disorders there are no FDA-approved medications. Although a vast range of pharmacotherapies has been studied, some with modest efficacy, the cornerstone of treatment remains psychosocial interventions and recovery supports.
Effectively Responding to the Overdose and Addiction Crisis
There are three frameworks (a patient-centered approach, an evidence-based care approach, and a systems-based approach) that could be used to conceptualize a comprehensive approach to the crisis of addiction and overdose.
Patient-centered care includes recognition of the bio-psychosocial influences on health, an acknowledgement of the subjective health needs and experiences of patients, shared power and decision-making between patients and providers, and a promotion of communication and relationships based on mutual trust.45 This model has generally not been applied to the care of people with addiction in health care settings, where numerous barriers and stigma have resulted in poor outcomes. This is reflected in the language health care providers commonly use when referring to people with addiction, including terms like “substance abuser” or “addict,” which have increased stigma and negatively impact providers' clinical decision-making.46 One proposed approach to hospital treatment based on a qualitative study conducted with people with addiction who had been discharged against medical advice, suggested a number of changes that could promote patient-centered care. These included prioritizing care retention and risk reduction, increasing responsiveness to subjective health needs, and fostering “cultural safety” by promoting nonjudgmental, nonstigmatizing interactions and refocusing providers' attention on patients' “personhood.”45 A general framework for a patient-centered care approach to addiction could include respecting the dignity, humanity, and autonomy of each patient; delivering compassionate care that is guided by science; using person-first, medically accurate language; and involving people who are affected in the design of systems of care.
An evidence-based care framework for addressing the addiction and overdose crisis could incorporate the range of empirically backed treatments delivered in a model that is consistent with management of other chronic illnesses. This would include ensuring that all patients have immediate access to treatment, which is triaged appropriately by a trained health care provider to their clinical needs. For people with an opioid use disorder this must include the opportunity to initiate medication treatment immediately, without barrier. As with other chronic illnesses, treatment ought to be based on clinical need and be guided by a patient's preferences, values, culture, and prior experiences, rather than a one-size-fits-all approach. Lastly, the mutual goal of clinicians and patients should be on retaining patients in care. Outdated approaches that discharge symptomatic patients from treatment, even when disguised by an unrealistic recommendation to “seek a higher level of care,” are no more clinically appropriate than discharging a patient with heart disease from care for having ongoing chest pain.
A systems-based approach to the ongoing crisis must incorporate strategies that focus on prevention, treatment, and harm reduction. Effective prevention efforts for addiction largely occur in the community and include efforts to build resiliency in young people. Identifying and proactively addressing adverse childhood experiences and co-occurring psychiatric illness is an important prevention strategy. Although efforts to reduce inappropriate opioid prescribing may ultimately impact prevention, it remains to be seen whether these efforts will effectively reduce the incidence of opioid addiction over the long term. From a treatment standpoint, developing systems of care that rapidly increase access to low-barrier addiction care that are available on demand are crucial to meet the needs of those suffering from this illness. Doing so will require enhancing the competency of health care providers in identifying and treating addiction, while simultaneously creating the necessary system changes to bring addiction treatment back into the medical mainstream. Lastly, harm reduction is a critical component to the equation and can be thought of as a component of prevention and treatment, rather than as something separate. Harm reduction is a philosophy and an approach that focuses on reducing the negative consequences of substance use and promoting health. Numerous harm-reduction interventions (including syringe service programs, supervised consumption sites, naloxone distribution, safer use education, and low-threshold treatment models) have been effective. The general principles of harm reduction can inform policies and approaches that are grounded in an understanding that people who use substances deserve equitable and dignified health care.
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Medical Complications of Substance Use Disorders
|Type of Substance
||Liver disease (eg, acute alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis); cardiovascular disease (eg, hypertension, cardiomyopathy); gastrointestinal illnesses (eg, pancreatitis, gastritis, esophagitis); bone marrow suppression; peripheral neuropathy; chronic infectious diseases (eg, pneumonia); several types of cancer (eg, of the mouth, esophagus, throat, liver, and breast); associated with psychiatric and behavioral conditions (eg, depression sleep disturbance); alcohol withdrawal
||Local infections (eg, abscesses, cellulitis); blood-borne infections, including bacterial (eg, endocarditis, pneumonia, osteomyelitis, septic arthritis) and viral (eg, HIV infection, hepatitis C and B)
||Injection-related risks (see above); nausea and constipation; hypothalamic-pituitary-adrenal axis suppression (eg, amenorrhea, low bone density, loss of libido); opioid-related hyperalgesia; respiratory depression and overdose
||Cardiac ischemia; cerebrovascular and renal disease; chronic rhinitis and perforation of the nasal septum associated with intranasal use; acute and chronic pulmonary complications associated with smoked use (eg, acute pulmonary toxicity involving diffuse alveolar damage and hemorrhagic alveolitis)
||Cardiotoxicity; acute behavioral effects (eg, irritability, anger, panic, and psychosis); neurotoxicity and cognitive decline; oral health issues (eg, tooth decay)
||Chronic bronchitis; cannabis-related hyperemesis; possible association between heavy marijuana use and reduced cognitive function as well as onset of schizophrenia (although controversy remains)
||Synthetic cannabinoids are associated with seizures, acute renal failure, and myocardial infarction; cathinones or “bath salts” are associated with muscle spasm, bruxism, cardiac arrhythmias, myocarditis, hyponatremia, rhabdomyolysis, and psychiatric effects