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Epidemiology of Opioid Misuse/Opioid Use Disorder (OUD)

From 1999 to 2018, 446,032 Americans died from an opioid overdose, making misuse and dependence on opioid medications a public health crisis.^1,2 Although opioid-related overdose deaths in the United States decreased by 4.1% from 2017 to 2018, opioids are still the primary cause of drug overdoses.^2,3 In 2018, opioids played a role in 46,802 of 67,367 overdose deaths (69.5%). Most of the opioid-related deaths were caused by synthetic opioids other than methadone (67.0%). While overall deaths due to opioids and prescription opioids reduced by 2% and 13.5% from 2017 to 2018, deaths due to synthetic opioids (excluding methadone) increased by 10%, likely as a result of illicitly manufactured fentanyl. The Centers for Disease Control and Prevention (CDC) reports that there are 3 waves of opioid overdose deaths.¹ The first wave involved deaths due to prescription opioids starting in the 1990s. The second wave involved heroin beginning in 2010. The third wave involved synthetic opioids (in particular illicitly manufactured fentanyl) beginning in 2013. Illicitly manufactured fentanyl can unfortunately be found in other illicit substances including heroin, counterfeit pills, and cocaine.

Reasons for the opioid crisis

Reasons for the opioid crisis generally included advocacy to treat pain as the “fifth vital sign” in the 1990s along with campaigns by pharmaceutical companies to emphasize benefits of opioid treatment while downplaying potential risks of treatment (ie, addiction).⁴ This led to overprescribing of opioids, which is illustrated by a striking statistic: in 2012, the prescribing rate of opioids per 100 US people was 81.3. This has since decreased to 58.7 by 2017. Further, the rate of misuse in patients taking opioids is 21% to 29%, while the rate of opioid use disorder (OUD) is 8% to 12%. Even more alarming is that many people who go on to use heroin were first prescribed opioids.

Addressing the opioid crisis

Because of its severity, the US Department of Health and Human Services declared a public health emergency with a 5-point strategy for addressing the crisis: 1) improve access to prevention, treatment, and recovery support services; 2) target the availability and distribution of overdose-reversing drugs; 3) strengthen public health data reporting and collection; 4) support cutting-edge research on addiction and pain; and 5) advance the practice of pain management.⁵ Pharmacists can provide leadership on multiple points of this strategy including the prevention and management of OUD, which is the focus of this module.

Definition of OUD, abuse, and misuse

Importantly, opioid dependence, opioid misuse, and OUD are defined differently. Physical dependence on opioids is not equivalent to opioid addiction. Physical dependence refers to patients who exhibit symptoms of withdrawal upon discontinuation or tapering of opioids.⁶ Withdrawal symptoms may last for days or even weeks after discontinuation and may include insomnia, cramps, diarrhea, nausea, vomiting, body aches, dysphoria, anxiety, and irritability. Patients who are using opioids for treatment may become physically dependent on them, even without misuse. Misuse of opioids refers to utilization in a manner other than that prescribed. Importantly, opioid misuse can take several forms. Opioid misuse is commonly thought of as use via inappropriate administration routes, such as snorting or injecting; however, opioids may also be misused via the oral route of administration by taking high doses or administering in combination with other drugs. Opioid misuse is not synonymous with opioid addiction; however, opioid addiction may be more likely if people are misusing opioids by repeatedly taking them, using higher doses, or injecting them.

The Diagnostic and Statistical Manual of Mental Disorders, 5^th edition (DSM-5) defines OUD as: “a problematic pattern of opioid use leading to clinically significant impairment or distress” occurring over 12 months.^7,8 Patients must experience at least 2 criteria listed in Table 1. OUD is preferred over the terms “opioid abuse or dependence” or “opioid addiction.”⁹ Patients who experience addiction become conditioned to the opioid because of factors including rewarding or analgesic properties, prevention of withdrawal symptoms, or dysphoria.⁶ OUD risk factors include genetic predisposition, younger age at the start of opioid use, and adverse social environments (unemployment, lower education level, lower income).^6,10 Pain and mood disorders are common comorbid conditions in people with OUD.⁶ In addition, patients with OUD are at higher risk of suicide. OUD is also commonly comorbid with infectious diseases because of the risk of infections due to injection drug use, including HIV, hepatitis C virus infection, and endocarditis. Generally, patients with OUD do not show specific symptoms.¹⁰

Interventions to Detect or Reduce Opioid Misuse

As accessible health care providers and experts on drug therapy, pharmacists can positively impact the care of patients taking opioids who may be at risk for OUD. Interventions that pharmacists can take to detect or reduce opioid misuse are discussed within the CDC Guideline for Prescribing Opioids for Chronic Pain.⁷

Opioid risk tools

Screening tools for opioid abuse are available to identify patients who may be at risk for misusing or abusing opioids. Screening tools are available on the National Institute on Drug Abuse website (https://www.drugabuse.gov/nidamed-medical-health-professionals/screening-tools-resources/chart-screening-tools).^4,11 An example of a screening tool is the Opioid Risk Tool, which is a 1-minute screening questionnaire meant for primary care settings to determine risk for opioid abuse in those with chronic pain.¹² Other screening tools listed by the CDC guideline are the Screener and Opioid Assessment for Patients with Pain (SOAPP)-Version 1, SOAPP-R, and Brief Risk Interview.⁷ However, evidence for screening tools is inconsistent, and the CDC guideline notes these tools suffer from insufficient accuracy. Pharmacists should keep in mind the limitations of screening tools to prevent underestimating a patient’s risk of opioid misuse. The CDC does recommend regularly screening patients with questions on drug and alcohol use (eg, “How many times in the past year have you used an illegal drug or prescription medication for nonmedical reasons?”).

Prescription drug monitoring programs (PDMP)

A prescription drug monitoring program (PDMP) is a statewide electronic database that is a powerful tool for monitoring prescriptions for controlled substances, including opioids.¹³ PDMPs are available in all states, and most states mandate prescriber utilization of these databases.⁴ Most prescribers may also use the National Association of Boards of Pharmacy prescription monitoring program (NABP PMP) Interconnect to communicate PDMP data from state to state. PDMPs can be utilized in several ways to improve patient safety and identify patients who may be at risk for OUD or an overdose.^7,13 Clinicians can access the PDMP to determine whether patients are receiving controlled substances from multiple providers, determine the total daily dose of opioids (ie, morphine milligram equivalents [MME]/d), and identify concurrent medications that may increase a patient’s risk of adverse events (eg, benzodiazepines).¹³ Other concerning factors related to OUD risk may be the presence of nonsensical drug regimens, increasing opioid doses, or various methods of payment.⁴

The CDC provides guidance for pharmacists who identify patients whose PDMP data indicate they fall into one of the broad categories (ie, multiple providers, high dosage, or drug interactions), and pharmacists can take further steps to ensure patient safety.⁷ If the PDMP data indicate that the patient is obtaining prescriptions from multiple providers, the pharmacist can counsel the patient on the importance of obtaining controlled substances from one provider. The pharmacist can also discuss these concerns with the prescribers. If the patient continues to fill prescriptions from multiple providers, the pharmacist can work with the prescriber(s) to taper or discontinue the opioid. There are also laws directed at preventing doctor shopping in many states.⁴ For example, patients cannot withhold information related to previous opioid prescriptions from other providers in some states.

If the PDMP indicates that the patient is taking a high daily opioid dosage (defined by the CDC as ≥ 50 MME/d), then the pharmacist can counsel the patient on the potential risks of high doses, including respiratory depression and overdose.⁷ Additional steps that the pharmacist can take include working on a plan to taper the opioid dose as well as potentially prescribing naloxone. If the pharmacist identifies concerning drug interactions between opioids and benzodiazepines, communication with the original prescriber may result in changes to medications and an increase in patient safety. The CDC recommends checking the PDMP every 3 months at least, and to consider checking the PDMP before filling each opioid prescription. It is important to note that the CDC does not recommend dismissing a patient from a clinician’s care based on information from the PDMP.

If a health care professional finds concerning information in the PDMP, additional steps should be taken.¹³ First, there could be mistakes with data entry such as use of a nickname, maiden name, or identity theft. Second, patients who meet criteria for OUD can be offered medication-assisted treatment. If the results of the PDMP suggest diversion, a urine drug test may be helpful. Finally, concerning results should be discussed with the patient as part of a framework regarding concern for the patient’s overall safety. Pharmacists can educate providers and one another on the importance of using PDMP to improve patient safety.

Medication reviews, medication therapy management services, and pill counts

Medication reviews and medication therapy management (MTM) are essential services that pharmacists perform to ensure patients are receiving optimal drug therapy. Further, medication reviews and MTM allow pharmacists the opportunity to review a patient’s medication history for potential signs of medication misuse or inappropriate prescribing.⁴ Pharmacists can use information gleaned from medication reviews and MTM to discuss potential changes in opioid prescribing and possible treatment for OUD with prescribers. The CDC guideline also discusses pill counts as a risk mitigation practice, primarily for adherence concerns.^4,7,14

Opioid exit plans and discharge preparation

While many interventions are directed at outpatient pharmacists, hospital pharmacists also have an important role in ensuring appropriate opioid use. In addition to performing medication reviews and MTM, pharmacists can play an active role in preparing patients for discharge from the hospital by reviewing the opioid discharge plan, recommending potential changes to prescribers, and counseling patients.⁴ Further, pharmacists may play a role in creating opioid exit plans. In a 2017 publication, pharmacists performed preoperative medication reconciliation with patients taking high-dose opioids, created inpatient postoperative and discharge treatment plans, and counseled the patients on the opioid exit plan as part of a pain management team.¹⁵

Storage and disposal of opioids

Pharmacists can provide valuable knowledge to patients and other health care professionals regarding the appropriate storage and disposal of opioids. Because many people obtain opioids from an acquaintance and because opioids are a danger to children and adolescents, these agents require storage “out of sight and out of reach.”¹⁶ The Food and Drug Administration (FDA) currently has a public education campaign for patients (eg, videos, print handouts) regarding how to properly dispose of opioids on the Remove the Risk website (www.FDA.gov/RemoveTheRisk). The FDA recommends counseling patients to remove any unused or expired opioids from one’s home in order to reduce the risk of misuse and potential harm of accidental ingestion by one’s child or pet. If available, opioids should be returned to a community medicine take-back program.¹⁷ Take back locations can be identified on the FDA or Drug Enforcement Agency (DEA) websites, and may include local pharmacies or law enforcement facilities. If a take back center is unavailable, the FDA recommends flushing the opioid down the toilet if the medication falls on the FDA’s flush list (Table 2).¹⁸ Opioids are included on this list as even 1 dose may cause life-threatening harm with misuse or accidental ingestion. For medications unable to be returned via a take back program and not on the FDA flush list, the FDA recommends mixing them with substances like dirt, cat litter, or used coffee grounds in a container such as a sealed plastic bag and subsequent placement in the household trash. Remind patients to remove their personal information from medicine bottles prior to throwing them away.¹⁹

Urine drug screen testing

The CDC recommends urine drug testing prior to starting opioid therapy and at least annually thereafter to check for prescribed and nonprescribed opioids.^7,20 The CDC recommends that a thorough patient/provider discussion occur prior to the initial test. This discussion should encompass the following topics: that the urine drug test is standardized for all patients (and therefore does not indicate lack of trust), the purpose of the test, the time and dose of the patient’s most recent opioids, all the patient’s drugs (both prescribed and nonprescribed), potential cost, and actions that may be taken depending on the test results.²⁰ Additionally, patients should be informed that random repeat testing may occur based on a treatment agreement. If the results of the urine drug test are unexpected, the CDC has helpful tips for discussion with the patient including keeping the patient’s safety at the forefront and being candid with possible explanations for the unexpected result. Further, a local laboratory can be consulted with questions on interpretation of the laboratory result if necessary. Detection of a nonprescribed opioid (or other nonprescribed controlled substance) may warrant referral to treatment for addiction.²¹ Importantly, the CDC recommends that a positive urine drug test should not result in patient dismissal from care.^7,20 Instead, results can help determine whether monitoring should be increased, while keeping continuity in patient care.

Urine drug tests are categorized as either immunoassays or liquid or gas chromatography/mass spectrometry.^20,22 Immunoassays are screening assays used in most settings, such as hospital laboratories, and are comparatively less expensive, fast, and easy to use. These tests provide a positive or negative result only instead of quantitative measurements of drug concentrations. While immunoassays screen for various drugs including natural opiates (morphine, codeine), these tests do not distinguish between opiates and typically do not detect semisynthetic and synthetic opioids such as hydrocodone, oxycodone, fentanyl, and tramadol. Additional assays must be added to detect these drugs. Further, because heroin metabolizes into morphine, a separate screening assay specific to heroin should be used to detect its presence. Another potential limitation with immunoassays is that there may be both false-negative and false-positive results. Drugs that may result in false-positive results for opiates include diphenhydramine, fluoroquinolones, poppy seeds, rifampin, chlorpromazine, verapamil, and dextromethophan.^20-22 Gas chromatography/mass spectrometry tests are more expensive and require more advanced laboratory ability; however, these tests provide minimal false-negative and false-positive results. Gas chromatography/mass spectrometry tests are more specific, so they identify and measure levels of individual drugs and metabolites in order to confirm a positive result. Compared to immunoassays, these tests more accurately identify semisynthetic and synthetic opioids.

Appropriate Pain Management

Extended-release and long-acting formulations

Selection of an appropriate opioid formulation can help prevent opioid overdose risk, as extended-release and long-acting opioid formulations have been shown to have a higher risk of overdose compared with use of immediate-release formulations.⁷ The CDC recommends that clinicians initiate opioid therapy with immediate-release agents at the lowest dose to effectively treat pain. Extended-release and long-acting opioid formulations should be reserved for patients who have been prescribed immediate-release opioid formulations for at least 1 week. When administering extended-release and long-acting opioids, pharmacists should assess the potential for renal or hepatic dysfunction, which may lead to drug accumulation in affected patients. Another consideration with extended-release or long-acting formulations is the unique challenges presented by methadone and fentanyl. The CDC recommends that methadone not be used as a first-line choice and that, if it is prescribed, patients should be educated regarding its numerous drug-drug interactions and closely monitored for hepatic dysfunction and risk of QT prolongation. Transdermal fentanyl should only be prescribed by clinicians familiar with its use in opioid-tolerant patients.

Abuse-deterrent formulations

Abuse-deterrent opioid formulations have been developed in order to attempt to deter abuse and misuse.⁷ These formulations have properties (eg, physical or chemical barriers, agonist/antagonist combinations, aversion, unique delivery systems) that make an opioid more difficult to abuse or less rewarding for the abuser. The 2016 CDC guideline did not provide a specific recommendation related to abuse-deterrent opioid administration. Overall, abuse-deterrent opioid formulations are used uncommonly compared to other opioid formulations, likely due to high cost.⁶

Opioid monitoring

Initial and ongoing monitoring of patients receiving opioid therapy is an essential aspect of appropriate pain management. The CDC recommends evaluating the risks and benefits of opioid therapy for chronic pain 1 to 4 weeks after initiating therapy and at every dosage increase.⁷ Because the risk of OUD increases after patients receive opioids for 3 months, the CDC recommends that risks and benefits be reevaluated at least every 3 months in patients receiving extended therapy.

Academic detailing

Academic detailing refers to outreach to health care professionals to provide them with information on optimal medical care.^23,24 The term originates from pharmaceutical company drug “detailers” who were historically sent with information on company products to health care professionals. In academic detailing, pharmacists, nurses, or physicians visit with health care professionals one-on-one to present evidence-based data on the appropriate treatment of a disease state. The CDC recommends academic detailing to educate prescribers on appropriate opioid prescribing, counseling patients on pain management options, and proper use of naloxone.^25,26 Academic detailing has been shown to improve outcomes such as increasing prescriber use of PDMP and urine screening, and pharmacist dispensing of naloxone.^4,27

Overdose Prevention: Naloxone

Naloxone is an opioid antagonist recommended to be prescribed or dispensed to people at increased risk for opioid overdose.^7,28 Pharmacists are in an excellent position to identify patients who may be at overdose risk such as those with a history of overdose or substance use disorder, those receiving concurrent benzodiazepines or other respiratory antidepressants (eg, sedatives), patients prescribed high opioid doses (defined as ≥ 50 MME/d), those with opioid prescriptions at multiple pharmacies or from multiple clinicians, or those who purchase over-the-counter sterile syringes.^7,29 Recently, the FDA also identified that breathing problems may also occur when opioids are used in conjunction with gabapentin or pregabalin.³⁰ The CDC emphasizes the importance of pharmacies dispensing naloxone in order to prevent opioid overdose.²⁶ Pharmacists may dispense naloxone to patients across the country as a result of a standing order (43 states), prescriptive authority (6 states and the District of Columbia), or dispensation without a prescription (1 state [Nebraska]).⁴ Many states have protections against civil and criminal liability for prescribers and dispensers of naloxone in order to further promote and increase access to naloxone.

Naloxone formulations

Naloxone is available as a solution for injection (0.4 mg/mL and 1 mg/mL), nasal spray (4 mg/0.1 mL), and a pre-filled intramuscular and subcutaneous auto-injector (2 mg/0.4 mL).^4,31-34 The nasal spray and pre-filled auto-injector may be used by patients themselves or caregivers and family members for emergency treatment of an opioid overdose. Pharmacists must be prepared to counsel patients, family members, or caregivers regarding administration issues (Table 3). Individuals should also be cautioned regarding the potential risk for opioid withdrawal symptoms after naloxone administration.^7,33,34

Counseling on naloxone

Pharmacists have an important role in counseling patients, family members, and caregivers on appropriate naloxone use. Initial counseling may focus on the respiratory risks of opioids and naloxone’s use as an antidote.²⁹ The American Pharmacist’s Association (APhA) recommends explaining the purpose of naloxone in easy to understand terms include comparing it to items that are only used if necessary in case of an emergency, such as a fire extinguisher or epinephrine. APhA naloxone counseling tips include advising the patient that you are speaking out of concern for their safety, asking open-ended questions, using clear, nontechnical words, and asking permission before giving advice. Pharmacists should also advise patients to administer naloxone anytime they feel an “opioid emergency” is present and counsel on signs and symptoms that may necessitate naloxone administration including extreme somnolence (inability to waken), respiratory depression (slow or shallow breathing), or miosis (pinpoint pupils) with concurrent somnolence or respiratory depression.^33,34 Patients and caregivers should also immediately call emergency medical assistance after administration of the initial naloxone dose as negative opioid effects may last longer than naloxone reversal effects. Prescribetoprevent.org provides comprehensive material on naloxone for prescribers, pharmacists, and patients. Specific material for pharmacists includes counseling resources, billing and ordering instructions, and compounding and storage information.³⁵ Other helpful tips on language to use and avoid while counseling on naloxone is located on the APhA website (https://www.pharmacist.com/lets-talk-about-naloxone).²⁹

Managing Patients with OUD

Managing withdrawal

Opioid withdrawal symptoms typically present 6 to 12 hours (short-acting opioids) or 24 to 48 hours (long-acting opioids) after the last dose of opioid and last for 7 to 10 days (short-acting opioids) to several weeks (long-acting opioids).³⁶ In patients with OUD, society guidelines recommend managing patients who experience opioid withdrawal with medication treatment (termed medically supervised withdrawal) instead of allowing abrupt discontinuation of opioids.^14,37 Methadone or buprenorphine are recommended in place of the opioid to reduce acute withdrawal symptoms in a patient receiving medically supervised withdrawal.^14,36 Patients should be counseled that maintenance therapy with medication-assisted treatment (MAT) for OUD after withdrawal is necessary to prevent relapse, and withdrawal alone is not sufficient treatment for OUD. However, if MAT is not possible, tapering methadone by 5 to 10 mg daily or buprenorphine by 2 mg daily over at least 3 to 5 days (and ideally longer) is recommended. Unfortunately, most patients will not pursue MAT long-term and will go back to taking opioids. The α-adrenergic agonists clonidine and lofexidine may be used to prevent withdrawal symptoms including tachycardia, hypertension, hyperthermia, diaphoresis, lacrimation, rhinorrhea, piloerection, mydriasis, and yawning.³⁶ Other medications are also typically used for symptomatic management of withdrawal (eg, antiemetics, antidiarrheals). Importantly, risk of opioid overdose increases in patients after medically supervised withdrawal.³⁷

Medication-assisted treatment

Pharmacists have an essential role in referring patients to, and monitoring patients on, medication-assisted treatment (MAT). MAT refers to use of medications (eg, methadone, buprenorphine, or naloxone), in conjunction with counseling and behavioral therapies, to treat OUD.^4,28 This treatment approach has been shown to reduce relapse and overdose risk, infectious disease transmission, and illicit drug use.^6,37 Pharmacists can assist patients who are appropriate MAT candidates receive optimal therapy as clinical studies have shown that MAT are often underutilized, underdosed, and not administered for an appropriate duration.⁶ Characteristics of MAT options are summarized in Table 4.

Selection of an appropriate agent is patient-specific and should take into consideration prior MAT experience, treatment setting, and patient or family/caregiver preferences. For example, naltrexone is an opioid antagonist so its use is limited by the requirement that the patient undergo opioid detoxification prior to starting therapy.⁶ Patients may require a “naloxone challenge” to determine whether they are still physically dependent on opioids prior to starting therapy with naltrexone.¹⁴ Initiation of buprenorphine requires that the patient experience the first signs and symptoms of withdrawal due to the potential of buprenorphine to precipitate withdrawal.³⁷ Buprenorphine requires an induction to ensure the patient tolerates the drug and to monitor for adverse events including sedation. Induction may occur in the clinician’s office, or may occur increasingly more common at a patient’s home for clinicians and patients experienced with buprenorphine.^14,37 If the induction occurs at home, the patient must be counseled on assessing and managing withdrawal, the timing of the first dose, and taking the medication correctly.³⁷

Due to risk of misuse, MAT prescribing restrictions vary. Buprenorphine is only available through clinicians who are trained and receive a waiver to prescribe.^6,7 Methadone is available through federally licensed opioid treatment programs.^6,28 A waiver is not required for prescribing naltrexone since it does not pose a risk of misuse. Pharmacists can refer patients to an opioid treatment program certified by the Substance Abuse and Mental Health Services Administration (SAMHSA). A buprenorphine physician locator and opioid treatment program directory is located on the SAMHSA site.^38,39 Because buprenorphine has a potential risk of misuse, monitoring may include increased frequency of office visits, urine drug testing, and pill counts.¹⁴ Patients receiving methadone also undergo significant supervision, since patients must obtain methadone in-person from an opioid treatment program. For example, initially, patients must come to clinic 6 days per week to receive their doses (with 1 dose to take home); over time, they may be eligible to come in less often (eg, 3 days per week with 4 take-home doses; 1 day per week with 6 take-home doses).⁴⁰ Monitoring also includes urine drug testing and potential breathalyzer tests.

Overall, consensus recommendations on the appropriate duration of MAT are lacking.⁶ SAMHSA recommends that the decision on length of treatment and decision to taper MAT is patient-specific.³⁷ MAT should continue for as long as it provides benefit and patients wish to continue. Even if MAT is tapered gradually to prevent withdrawal, many patients who discontinue MAT relapse. Generally, longer treatment increases likelihood of continued abstinence. If the decision is made to discontinue the MAT, a gradual taper of opioid agonist therapy is recommended.

Special populations

OUD treatment in pregnancy is essential. Opioid use during pregnancy can lead to neonatal abstinence syndrome, characterized by opioid withdrawal after birth requiring treatment with opioids (that are eventually tapered).¹⁰ In pregnant patients with OUD, guidelines recommend treatment with methadone or buprenorphine without naloxone.^7,14,3 The combination of buprenorphine with naloxone is generally not recommended due to the potential to precipitate opioid withdrawal; however, limited data suggest that the combination product may be safe.^14,37,40 Methadone or buprenorphine should be started as soon as possible in pregnant patients identified as having OUD, with consideration of hospitalizing the patient while starting therapy.¹⁴

Like in nonpregnant patients, buprenorphine should be started when pregnant women experience signs and symptoms of withdrawal.¹⁴ Buprenorphine dosing is similar to nonpregnant patients, but clinicians may split dosing if patients experience craving later in the day. Buprenorphine should not be discontinued prior to elective cesarean section due to the risk of fetal withdrawal. In contrast, methadone pharmacokinetics may significantly change during pregnancy. As pregnancy continues, patients more rapidly metabolize methadone, resulting in decreased plasma concentrations of methadone. Patients may require higher and/or split doses (eg, dividing the daily dose into twice-daily dosing) of methadone.³⁷ The methadone dose will need to be adjusted after delivery, requiring reduced or less frequent dosing as the metabolism of methadone returns to the previous level. In women already using naltrexone who become pregnant, American Society of Addiction Medicine (ASAM) recommends that the patient and provider should consider stopping therapy based on relapse risk. If the patient desires to continue naltrexone, the risks of continuation should be addressed. Breastfeeding is recommended in women receiving methadone or buprenorphine.

Another population recommended to be treated with MAT for OUD are those in the criminal justice system.^6,14 Unfortunately, incarcerated individuals are at higher overdose risk upon release; therefore, treatment for OUD prior to release should be considered.

Pain management in patients on MAT

Patients receiving treatment for OUD may have challenges related to pain management. ASAM and SAMHSA have published recommendations on the treatment of pain in patients with OUD.^14,37 Generally, patients with OUD and acute pain should be managed with nonopioid pharmacologic agents (eg, NSAIDs or acetaminophen) when possible. There is not a consensus regarding use of opioids for treatment of pain in patients with OUD; however, potential strategies are available. Patients with active OUD who are not currently receiving treatment with MAT (ie, not receiving methadone, buprenorphine, or naltrexone for OUD) can potentially receive short-acting opioids or methadone with short-acting opioids for pain with increased monitoring for adverse events.³⁶ In patients with OUD who are receiving MAT and require pain management with opioids, recommendations for further analgesia differ based on the specific MAT (methadone, buprenorphine, or naltrexone). Both methadone and buprenorphine have a shorter duration of analgesic action compared to their duration of effect on withdrawal.³⁶ Patients receiving methadone should continue receiving methadone, and additional opioids may be required to treat moderate-to-severe acute pain.^14,36 Patients should be monitored closely. Because of the shorter analgesic effect of methadone, some clinicians may divide the methadone daily dose; however, available evidence is lacking.³⁶

Treatment of pain in patients receiving buprenorphine may be difficult due to its high affinity for the opioid mu receptor.³⁶ Proposed strategies for treatment of pain in patients receiving buprenorphine for OUD include: 1) Increase the buprenorphine dose; 2) Add short-acting opioids while continuing buprenorphine therapy; 3) Divide the buprenorphine daily dose into multiple doses 3 to 4 times per day; or 4) Discontinue buprenorphine and initiate a high-potency opioid (monitor closely as serum concentrations of buprenorphine will decrease, requiring a reduction in the high-potency opioid dose after 24 to 72 hours).^14,36,37 Additionally, if pain is anticipated (eg, elective surgery), discontinuation of buprenorphine should be considered and completed 24 to 36 hours prior to the procedure.¹⁴

Because naltrexone is an opioid antagonist, treatment of pain with opioids is challenging. NSAIDs, ketorolac, or regional anesthesia may be analgesic options.^14,37 Some clinicians may use high doses of opioids to overwhelm the antagonistic effects of naltrexone and treat severe pain; monitoring for signs and symptoms of opioid overdose is necessary.^36,37 In a situation where pain is anticipated (eg, a planned surgery), oral naltrexone and extended-release injectable naltrexone should be stopped 72 hours and 30 days prior, respectively.

Conclusion

Opioid use disorder and opioid overdose are a significant cause of mortality. Pharmacists are well poised to identify patients at risk for OUD and reduce risk by screening patients using PDMP, performing medication reconciliation and MTM, participating in opioid exit plans and discharge planning, interpreting urine drug screening tests, and educating patients on proper opioid disposal. Further, pharmacists may dispense naloxone and counsel patients on its important role in averting opioid overdose. Finally, pharmacists can educate health care providers and support the care of patients on MAT (methadone, buprenorphine, and naltrexone) for OUD.

References

1. Centers for Disease Control and Prevention. Understanding the epidemic. Centers for Disease Control and Prevention website. https://www.cdc.gov/drugoverdose/epidemic/index.html. Updated March 19, 2020. Accessed April 29, 2020.
2. Wilson N, Kariisa M, Seth P, Smith H 4th, Davis NL. Drug and opioid-involved overdose deaths - United States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020;69(11):290-297.
3. Centers for Disease Control and Prevention. Drug overdose deaths. Centers for Disease Control and Prevention website. https://www.cdc.gov/drugoverdose/data/statedeaths.html. Reviewed March 19, 2020. Accessed April 29, 2020.
4. Chisholm-Burns MA, Spivey CA, Sherwin E, Wheeler J, Hohmeier K. The opioid crisis: Origins, trends, policies, and the roles of pharmacists. Am J Health Syst Pharm. 2019;76(7):424-435.
5. US Department of Health and Human Services - Office of the Surgeon General. Surgeon General Priority: Opioids and Addiction. US Department of Health and Human Services website. https://www.hhs.gov/surgeongeneral/priorities/opioids-and-addiction/index.html. Reviewed May 14, 2019. Accessed April 29, 2020.
6. Volkow ND, Jones EB, Einstein EB, Wargo EM. Prevention and treatment of opioid misuse and addiction: a review. JAMA Psychiatry. 2019;76(2):208-216.
7. Dowell D, Haegerich T, Chou R. CDC guideline for prescribing opioids for chronic pain – United States, 2016. MMWR Early Release. 2016;65(1):1-49.
8. American Psychiatric Association. Substance-related and addictive disorders. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
9. Centers for Disease Control and Prevention. Commonly used terms. Centers for Disease Control and Prevention website. https://www.cdc.gov/drugoverdose/opioids/terms.html. Reviewed February 12, 2019. Accessed April 29, 2020.
10. Blanco C, Volkow ND. Management of opioid use disorder in the USA: present status and future directions. Lancet. 2019;393(10182):1760-1772.
11. National Institutes of Health - National Institute on Drug Abuse. Screening and assessment tools chart. NIH - National Institute on Drug Abuse website. https://www.drugabuse.gov/nidamed-medical-health-professionals/screening-tools-resources/chart-screening-tools. Revised June 2018. Accessed April 29, 2020.
12. Opioid Risk Tool. NIH - National Institute on Drug Abuse website. https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/opioidrisktool.pdf. Accessed March 16, 2020.
13. Centers for Disease Control and Prevention. What health care providers need to know about PDMPs. Centers for Disease Control and Prevention website. https://www.cdc.gov/drugoverdose/pdmp/providers.html. Reviewed July 12, 2019. Accessed April 29, 2020.
14. Kampman K, Jarvix M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med. 2015;9(5):358-367.
15. Genord C, Frost T, Eid D. Opioid exit plan: A pharmacist's role in managing acute postoperative pain. J Am Pharm Assoc (2003). 2017;57(2S):S92-S98.
16. Food and Drug Administration. Safe opioid disposal - Remove the Risk outreach toolkit. Food and Drug Administration website. https://www.fda.gov/drugs/ensuring-safe-use-medicine/safe-opioid-disposal-remove-risk-outreach-toolkit?utm_source=other&utm_medium=content-text&utm_campaign=RemoveTheRisk. Updated March 5, 2020. Accessed April 29, 2020.
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