Opioid Addiction and Overdose

Opioid use, abuse, and associated deaths have skyrocketed in the United States over the past decade. Since 1999, the number of opioid-related deaths has quadrupled. In 2015, the CDC reported 33,091 deaths from opioids, which included prescription pain medications and heroin.¹ About 12.5 million people misused prescription opioids in 2015, and 2 million received a diagnosis of opioid-use disorder.²

The severity of this epidemic has become a public health crisis and spurred a federal response, including an initiative by the secretary of Health and Human Services and other government entities. Collaborative efforts emphasize evidence-based methods to improve prescribing practices, the deployment of naloxone to reverse overdoses, and improved access to medication-assisted treatment for opioid-use disorders.³The FDA is also expanding the use of its advisory committees, working with drug manufacturers to develop better safety labeling, updating risk evaluation and management strategies, and strengthening post-marketing requirements.⁴

The public health consequences of the opioid epidemic include deaths from drug overdose, legal problems, higher crime rates, newborn withdrawal syndrome, contribution to accidents, and the spread of infectious diseases such as hepatitis C and HIV.

Opioid-Use Disorder

In the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition, the psychiatric diagnoses of opioid abuse and opioid dependence have been replaced by opioid-use disorder. Opioid-use disorder is defined as a problematic pattern of opioid use that leads to clinically significant distress or impairment.⁵The diagnosis centers on the repeated occurrence of 2 of the 11 criteria, including taking larger amounts of the drug or for a longer period than prescribed, the presence of craving and/or tolerance, and continued use, despite interpersonal or social problems over a 12-month period.⁵

Risk factors for misuse include a prior history of substance abuse, increasingly severe pain, co-occurring mental disorders, and certain demographic factors. For example, females are more likely to use prescription painkillers, but males are more likely to abuse them. Studies have shown that illicit use often first begins in late adolescence to early adulthood. Other risk factors can be individual, family, peer, social, and environmental. For instance, impulsivity and novelty-seeking behaviors are related to a person’s temperament but may be genetically determined.⁵

Pharmacology

Opioids are prescribed for the management of severe acute and chronic pain. An opioid is a natural or synthetic substance that acts on one of the main opioid receptor systems (mu, kappa, delta) in the central nervous system (CNS) and to a lesser extent in the periphery.⁶Activation of mu endogenous opioid receptors results in many of the prototypical effects we associate with opioids: reward, withdrawal, and analgesia. Mu receptor activation in the CNS is also responsible for respiratory depression, euphoria, and miosis.⁶

Tolerance to opioids happens in response to long-term exposure to exogenous opioids. Increased opioid levels and increased opioid potency are needed to generate the same effect.

Treatment of Overdose

Opioid intoxication usually presents as symptoms of apathy, attention impairment, dysphoria, euphoria, miosis, motor retardation, sedation, and/or slurred speech. Overdose symptoms include respiratory depression, a depressed level of consciousness, coma, and miosis.⁶

Overdose can be treated with an opioid antagonist that inhibits opioid action at the receptor site, such as naloxone. Naloxone is available as an injectable solution, an intramuscular (IM)/subcutaneous autoinjector, and a nasal spray. In overdose, an initial dose of 0.4 mg to 2.0 mg IM/intravenous should be given, and a response should occur within 1 to 2 minutes.⁶The dose can be repeated every 2 to 3 minutes up to 10 mg. If the nasal spray is used, 1 spray should be administered intranasally into 1 nostril. If repeat doses of the nasal spray are needed, alternating nostrils is recommended. The effects of naloxone wear off after 2 to 3 hours, so individuals must seek emergency treatment and continue to be monitored for up to 72 hours, especially if the overdose is the result of using longer-acting drugs, such as methadone.

As part of the public health response, naloxone (Narcan) nasal spray has been made available as an OTC drug in pharmacies in many states. Emergency first responders are also carrying naloxone.

Long-Term Management

Guidelines for opioid addiction set by the American Psychiatric Association recommend combining pharmacological treatment with psychosocial treatment, such as cognitive-behavioral therapy, psychodynamic therapy, and group and family therapy.⁷

Pharmacological treatment strategies for the management of opioid dependence and withdrawal include:⁷

• Opioid substitution with methadone or buprenorphine, followed by a gradual taper
• Abrupt opioid cessation, with the use of clonidine
• Clonidine—naltrexone detoxification

Symptoms of withdrawal are generally the opposite of the acute effects of the drug and include 3 of the following over the course of minutes to several days (depending on the drug consumed): dysphoric mood, nausea or vomiting, muscle aches, lacrimation or rhinorrhea, pupillary dilation, piloerection, sweating, diarrhea, yawning, fever, insomnia, and a mild elevation in body temperature, respiratory rate, and blood pressure.^6,8

Methadone is a long-acting synthetic opioid agonist that has been the maintenance treatment gold standard for years. Methadone can be dosed once daily and replaces the need for multiple daily heroin injections. Methadone maintenance therapy (MMT) must be administered in a specialty program under the supervision of a physician with special training.^6,8

The opioid partial agonist buprenorphine and an opioid partial agonist/antagonist buprenorphine/naloxone are also good choices for maintenance therapy. Because buprenorphine can only partially activate the mu receptor, the user does not generally feel the intense rush or high that they would with other opioids. The mechanism of action of buprenorphine also prevents craving and withdrawal symptoms. Because it tightly binds to the mu receptor, users are not able to get high from other drugs when taking buprenorphine.^6,8

In 2016, the FDA approved the buprenorphine implant Probuphine for opioid dependence. Probuphine provides a constant, low-level dose for 6 months.⁸Historically, l-alpha-acetylmethadol has been used for opioid dependence. However, it is associated with a prolonged QT interval and, in severe cases, cardiac arrhythmias and death and is therefore rarely used anymore.

Although there is a need for larger multicenter, randomized trials, several Cochrane Reviews have been conducted to look at maintenance treatments. Results from the reviews have shown that patients who took methadone were 4 times more likely to stay in treatment compared with placebo, patients who took buprenorphine significantly decreased their number of opioid-positive drug tests, and positive outcomes significantly increased when maintenance therapy was combined with counseling.⁹The reviewsalso found that high-dose MMT was more effective than low-dose MMT, low-dose MMT was less effective than buprenorphine, and high-dose MMT was more effective than buprenorphine maintenance treatment.^8,9

The Pharmacist’s Role

Pharmacists can play a key role in the dissipation of the opioid epidemic. Whether they are screening in clinics, assisting in the treatment of intoxication or withdrawal in emergency departments, or dispensing naloxone, they are instrumental in the education of both patients and providers. Many states also use online prescription drug monitoring programs that allow pharmacists to proactively work with providers when prescribing and dispensing opioids. Opioid abuse and overdose remain big problems in the United States. However, drug manufacturers, government agencies, and health care providers are working together to find solutions to the crisis.

Joanna Lewis, PharmD, MBA, is clinical pharmacist who is passionate about medication safety, clinical quality, leadership development, and regulatory affairs. She received her pharmacy degree from the Medical University of South Carolina and is an active member of the American Society of Health-System Pharmacists. She has worked in a variety of practice settings, most recently as a coordinator at Duke University Hospital in Durham, North Carolina.

1.CDC. Opioid overdose-understanding the epidemic. cdc.gov/drugoverdose/epidemic/index.html. Updated August 30, 2017. Accessed December 2, 2017.

2. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(5051):1445-1452. doi: 10.15585/mmwr.mm655051e1.

3. National Institute on Drug Abuse. Opioid overdose crisis. drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis. Updated June 2017. Accessed December 4, 2017.

4. FDA. FDA opioid action plan. fda.gov/drugs/drugsafety/informationbydrugclass/ucm484714.htm. Updated July 11, 2017. Accessed December 4, 2017.

5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.Washington, DC: American Psychiatric Association; 2013:541-546.

6. Dixon DW, Peirson RP. Opioid abuse. Medscape. emedicine.medscape.com/article/287790-overview#a1. Updated November 15, 2017. Accessed December 4, 2017.

7. American Psychiatric Association. Practice guideline for the treatment of substance use disorders.In: American Psychiatric Association Practice Guidelines for Psychiatric Disorders: Compendium 2006.2nd ed. Arlington, VA: American Psychiatric Association, 2006:291-563.

8. Schuckit MA. Treatment of opioid-use disorders.N Eng J Med. 2016;375(4):357-68. doi: 10.1056/NEJMra1604339.

9. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009;8;(3):CD002209. doi: 10.1002/14651858.CD002209.pub2.