Opioid-related deaths continue to rise ever year in the United States and around the world. According to the CDC, in 2016 drug overdoses claimed the lives of over 63,000 people in the United States. Of those deaths, two-thirds were attributable to opioid use. The DSM V criteria for a substance abuse disorder requires the following criteria to be met: taking the substance in larger quantities or for longer periods than intended; along with a desire to reduce intake with failed attempts to do so.
Additional criteria include spending excessive time obtaining, using or recovering from use, substantial cravings to use which interfere with several areas of functioning, and continued use despite known consequences of use that are understood to even be potentially fatal. DSM V substance abuse disorder requires that the individual continue problematic use despite the understanding that use could cause or make a physical or psychological problem worse. Additionally, criteria is met when tolerance and withdrawal symptoms have been achieved. Opioid use often begins with treatment for chronic and escalates to misuse generally due to inaccurate prescribing practices or well intentioned dosing. The problem began in the early 90’s with the assurance from manufacturers that opioids were non-habit forming medications that were “the answer” to chronic pain problems. It is estimated that at least 80 percent of heroin users, began with misuse of prescription opioids.
Between 2004 and 2008, the number of patients seeking care in emergency rooms for side effects of opioid misuse rose from 144,000 to over 300,000. According to DrugAbuse.gov (2018), approximately 4 to 6 percent of individuals who misuse prescription opioids will eventually transition to heroin use. It is estimated that at least 80 percent of heroin users, began with misuse of prescription opioids. Opioids become drugs of abuse through their mechanism of action which decreases the perception of pain, while producing a greater sense of well-being and euphoria. Between 2004 and 2008, the number of patients seeking care in emergency rooms for side effects of opioid misuse rose from 144,000 to over 300,000. Prescription opioids account for approximately 70% of fatal prescription drug overdoses.
In 2016, 45 of 52 states saw a 30 percent or greater rise in opioid overdoses. understand the magnitude and distribution of the economic burden of prescription opioid overdose, abuse and dependence to inform clinical practice, research and other decision makers.
The total economic burden of opioid abuse is estimated to be around $75 billion. Over one third of this amount is due to increased health care and substance abuse treatment costs. Approximately one quarter of the cost is borne by the public sector in health care, substance abuse treatment, and criminal justice costs.
The Neuroscience of Addiction
Addiction is a persistent, uncontrollable pattern of risky behaviors aimed at obtaining an object for pleasurable use regardless of the detrimental consequences of misuse. Drug abuse literally teaches the brain to repeat risky behaviors, regardless of the consequences on health, responsibilities or commitments. Dopamine is at the center of addiction responses. When pleasurable activities are experienced through a surge of dopamine, the brain actually “remembers” and signals occur that cause similar neurotransmission easier to repeat without forethought which leads to habit formation. Just as drugs produce intense euphoria, they also produce much larger surges of dopamine, powerfully reinforcing the connection between consumption of the drug, the resulting pleasure, and all the external cues linked to the experience.
The euphoria associated with drug use occurs in three distant areas within the brain: the basal ganglia, the amygdala and the prefrontal cortex. The basal ganglia influences motivation and pleasure. Activities like socializing and sexual experiences trigger the basal ganglia and initiate triggers that becomes habits and routines. Drugs overactivate the basal ganglia and produce a euphoric high; however, the repeated drug use diminishes the sensitivity of the drug and results in a diminished high with repeated use. The amygdala is responsible for anxiety and irritability which make up the feelings of withdrawal. Over time, the drug user is actually using drugs to relieve a discomfort of oversensitized neurotransmitters instead of for the eupohria.
General Opioid Pharmacology
Molecules on the surface of cells that attach to opioids are opiod receptors. Three different types of opioid receptors exist: the mu, kappa and delta. Mu and kappa receptors are responsible for transmitting pain signals. Thus, opioid abuse involves the mu receptor; as it is responsible for the analgesic effects, the euphoric highs and the addictive properties of opioids. There are three different types of biochemical receptor interactions that interact with neurotransmitters. Full agonist substances activate mu receptors and have the greatest abuse potential. Examples of full agonist drugs are morphine, oxycodone, methadone, heroine and hydromorphone. Antagonists function to block receptors instead of activating them.
A great example of how an antagonist works is to imagine that an antagonist is a key that does not quit fit into a lock but at the sometime it also blocks another key from being able to fit. Examples of opioid antagonists are the drugs naltrexone and naloxone. Naltrexone and naloxone compete to occupy space on a receptor. Partial agonists have the same function of an agonists with the exception that they do not activate receptors to a full degree. Interestingly, for people who are not addicted to opioids, partial agonists and full agonist drugs have indistinguishable effects. Overtime, the repeated exposure to a mu opioid agonist drug results in tolerance or decreased drug response and increased dose requirements and physical dependence (USDepartmentofHealthandHospitals, 2009).
Medication Assisted Treatment Options
Medication are becoming the preferred treatment for opioid use disorders. Currently, three medications are approved by the US Food and Drug Administration, to target the μ-opioid receptor and effectively treatment opioid use disorders. Methadone and buprenorphine have agonist effects and act to address cravings and symptoms of withdrawal without producing the euphoric highs associated with drug use.Methadone is a long acting opioid agonist. Methadone works by dampening the ‘high’ of drug abuse, while preventing withdrawal symptoms. Buprenorphine also known as Subutex or Suboxone, is a partial opioid agonist. Buprenorphine relieves drug cravings without producing the euphoric high or dangerous side effects of opioids. Suboxone is a new formulation that can be administered orally or sublingually and is combined with naloxone to prevent diversion by injection. If suboxone were to be injected, the naloxone part of the combination therapy would induce withdrawal symptoms. Buprenorphine has rarely been linked to overdoses outside of concurrent alcohol or other sedative abuse and lacks the QTc prolongation and drug-drug interactions of methadone.
Naltrexone is an opioid antagonist that blocks the action of opioids. Naltrexone is a non-addictive and non-sedating option for opioid dependence. Vivitrol is a long acting injectable formulation of naltrexone with the indication of preventing relapse after opioid detoxification treatment. By contrast, naltrexone is an antagonist agent that is approved for long term use and acts to prevent opioids from having an addictive effect.
Research has proven that medication assisted treatment of opioid addiction is associated with lower numbers of overdoses from heroin use, increased participation in treatment, decreased drug use, reduced incidences of infectious disease transmission, and lower overall criminal activities. For example, studies of criminal offenders who many of which enter the prison system with a substance abuse problem, have demonstrated reduced drug use, remained in treatment and had a three fold reduced recidivism rate when they were discharged on medication assisted treatment medications. Interestingly and too often not considered, is the financial impact that medication assisted treatment provides to the economy.
According to a 2005 published study that examined methadone patients and included such variables as heroin use, treatment for heroin use, criminal behavior, job status, and healthcare costs, every dollar spent on methadone treatment produced approximately $38 in related economic benefits. Another similar study followed opioid dependent patients for 42 months after treatment in order to assess the long term outcomes as compared to treatment entry assessments. It was discovered that 32% of the participants were abstinent from drugs and not on any type of agonist therapies, while 29% were prescribed medication for opioid abuse and remained abstinent. At the conclusion of the study, the patients on medication assisted treatments were associated with a greater likelihood of sobriety.
Abstinence and Relapse
In one controlled study, oral naltrexone was compared to placebo and at 6 months the results were actually similar in relapse rates and were 3 times higher in relapse rates when compared to buprenorphine (Velander, J., 2018). Several recent studies indicate that buprenorphine and extended-release naltrexone are equally effective in maintaining soberity. Relapse rates for people treated for substance use disorders are not often compared with those for people treated for high blood pressure and asthma but should be compared to any similar chronic disease process. Relapse is common and similar across all of these illnesses and therefore, should be treated like any other chronic illness. Relapse serves as a signal for the need for resumed care, modified plans, or new treatment ideas all together. Strikingly, patients undergoing short term inpatient treatment for opioid use disorders were associated with higher rates of relapse (Nunes et al., 2018). These important findings suggest that withdrawal treatments should be accompanied by medication assisted treatments on an outpatient basis in order to improve the chances of successful abstinence.
However, while relapse is a normal part of recovery, for some drugs and drug users, it can be very dangerous and even fatal (Treatment and Recovery, 2018). It is extremely important to educate drug users who are in jeopardy of relapse that if they were to begin to use again, they should do so with extreme caution. If a person uses as much of the drug as they did before quitting, they can easily overdose because they have lost their previous levels of tolerance making overdose more likely to occur. their bodies are no longer adapted to their previous level of drug exposure.
Misconceptions About Medication Assisted Treatments
Commonly, it is said that Suboxone and other medication therapies for opioid dependence are an exchange of one addiction for another, however, this is simply inaccurate. If used as directed, buprenorphine-naloxone, is an FDA approved medication, not a substance of abuse. It is a stable, safe, long-acting medication with a ceiling effect. It is prescribed to improving patients’ physical and mental health, prevent communicable diseases and reduce the risk of relapse and death. Therefore, like any prescription medication it has a clear indication, unlike substances of abuse. Treatment with a partial agonist has been proven effective for stabilization of opioid receptors so that patients are able to make changes in lifestyle, behaviors, and psychiatric condition to allow ultimate recovery rather than cycles of relapses. The mortality associated with any relapse on opioids is too high to not consider all possible alternatives and to not prepare every patient for the associated risks.
Medication Assisted Treatment of Opioid Addiction
Medication are becoming the preferred treatment for opioid use disorders. Currently, three medications are approved by the US Food and Drug Administration (FDA), to target the μ-opioid receptor and effectively treatment opioid use disorders. Methadone and buprenorphine have agonist effects and act to address cravings and symptoms of withdrawal without producing the euphoric highs associated with drug use. By contrast, naltrexone is an antagonist agent that is approved for long term use and acts to prevent opioids from having an addictive effect.
Research has proven that medication assisted treatment of opioid addiction is associated with lower numbers of overdoses from heroin use, increased participation in treatment, decreased drug use, reduced incidences of infectious disease transmission, and lower overall criminal activities. For example, studies of criminal offenders who many of which enter the prison system with a substance abuse problem, have demonstrated reduced drug use, remained in treatment and had a three fold reduced recidivism rate when they were discharged on medication assisted treatment medications. Interestingly and too often not considered, is the financial impact that medication assisted treatment provides to the economy.
According to a 2005 published study that examined methadone patients and included such variables as heroin use, treatment for heroin use, criminal behavior, job status, and healthcare costs, every dollar spent on methadone treatment produced approximately $38 in related economic benefits. Another similar study followed opioid dependent patients for 42 months after treatment in order to assess the long term outcomes as compared to treatment entry assessments. It was discovered that 32% of the participants were abstinent from drugs and not on any type of agonist therapies, while 29% were prescribed medication for opioid abuse and remained abstinent. At the conclusion of the study, the patients on medication assisted treatments were associated with a greater likelihood of sobriety.
Strikingly, patients undergoing short term inpatient treatment for opioid use disorders were associated with higher rates of relapse. These important findings suggest that withdrawal treatments should be accompanied by medication assisted treatments on an outpatient basis in order to improve the chances of successful abstinence.
APRN Role in Substance Abuse Treatment
The federal government has advocated that improving access to medication assisted treatments for individuals with opioid use disorders is the best answer in addressing the opioid epidemic.
This year several US senators propositioned the Department of Health and Human Services, urging them to increase access to buprenorphine treatment as a solution to the opioid epidemic, and specifically requesting that nurse practitioners and physician assistants be allowed to join physicians in prescribing buprenorphine.
In 2012, there were just over 16,000 physicians with a DEA waiver licensed to prescribe buprenorphine for up to 30 patients with a diagnosis of an opioid use disorder, and only an additional 6000 physicians were licensed for the 100-patient limit. These numbers would only support a national buprenorphine treatment capacity of one million patients. Even more discouraging, was that only an estimated 700,000 patients were actually prescribed buprenorphine leaving significant gaps in treatment. APRNs that receive the appropriate training and certification have recently been permitted to prescribe medications and deliver counseling for persons with opioid use disorders. Increasing the total medication assisted treatment providers, APRNs continue to provide enhanced options in improving the health of the nation.
