Your activity: 45 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Prescription drug misuse: Epidemiology, prevention, identification, and management

Prescription drug misuse: Epidemiology, prevention, identification, and management
Authors:
William C Becker, MD
Joanna L Starrels, MD, MS
Section Editor:
Andrew J Saxon, MD
Deputy Editor:
Michael Friedman, MD
Literature review current through: Nov 2022. | This topic last updated: Nov 07, 2022.

INTRODUCTION — Opioid analgesics, benzodiazepines, other sedatives and tranquilizers, and stimulants have important medical uses, but they also stimulate the reward center of the brain. In susceptible individuals, this can lead to misuse, substance use disorders/addiction, and other serious consequences. It has led to the development of an illicit market for these medications.

Despite government regulation of these medications, prescription drug misuse and its consequences have persisted. Clinicians who prescribe these medications have an important role in preventing, identifying, and managing problems related to prescription drug misuse.

This topic reviews the epidemiology, prevention, identification, and management of prescription drug misuse. The epidemiology, pathogenesis, clinical manifestations, course, assessment, diagnosis, and treatment of opioid use disorder, benzodiazepine use disorder, and stimulant use disorder are discussed separately.

(See "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis".)

(See "Medication for opioid use disorder".)

(See "Benzodiazepine use disorder".)

(See "Methamphetamine use disorder: Epidemiology, clinical features, and diagnosis".)

(See "Cocaine use disorder in adults: Epidemiology, clinical features, and diagnosis".)

(See "Psychosocial interventions for stimulant use disorder in adults".)

(See "Pharmacotherapy for stimulant use disorders in adults".)

TERMINOLOGY

Controlled substances — Because of their potential for misuse, addiction, and illicit diversion and sale, opioid analgesics, stimulants, and benzodiazepines and other sedatives/hypnotics are regulated, restricting whether and how they can be prescribed. In the United States, these drugs are referred to as "controlled substances" and subject to federal regulations (table 1).

Prescription drug misuse — Any use of a prescription medication that is outside of the manner and intent for which it was prescribed; this includes overuse, use to get high, diversion (sharing or selling to others), having multiple prescribers or nonprescribed sources of the medication, and concurrent use of alcohol, illicit substances, or nonprescribed controlled medications. Misuse is a necessary but not sufficient criterion for a substance use disorder.

Nonmedical use — Initially defined by the National Survey on Drug Use and Health (NSDUH), as use of a medication that was not prescribed to the individual, or use "only for the feeling or experience it caused” [1]. In 2015, NSDUH eliminated the term in favor of “misuse,” which the survey defines as use in any way not directed by a doctor, including use without a prescription of one’s own; use in greater amounts, more often, or longer than told to take a drug; or use in any other way not directed by a doctor.

Prescription drug use disorder — Misuse of a prescription drug meeting the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria as a substance use disorder, which can be specified as mild, moderate, or severe [2]. Substance use disorder replaced the terms substance abuse and substance dependence from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). (See "Benzodiazepine use disorder" and "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis".)

EPIDEMIOLOGY — Misuse of prescription drugs has generally increased concurrently with greater prescribing of medication for therapeutic use. This is particularly true of opioid analgesics prescribed for patients with chronic pain, stimulants prescribed for individuals with attention deficit hyperactivity disorder (ADHD) and benzodiazepines prescribed for anxiety/insomnia; prescribing for each increased markedly between 2000 and 2010 [3-5]. After decades of increasing prescription opioid use, 2016 data indicate a decline in opioid prescribing [6] and in nonmedical opioid use by adolescents since approximately 2013 [7].

Opioid analgesics were prescribed approximately twice as often as stimulants or benzodiazepines in a 2015 study of controlled substance prescribing patterns in eight states in the United States [8]. A small proportion of prescribers were responsible for a large proportion of prescriptions. In the two states with the highest rates of long-acting opioid analgesic prescriptions, 13 and 25 percent of the medications were prescribed by 1 percent of prescribers.

Opioid analgesics

Misuse — Estimates of the prevalence of opioid misuse among patients who are prescribed opioid analgesics vary widely, from 12 to 78 percent [9-16], reflecting differences in the sample populations and definitions of opioid misuse among studies.

As an example, the 2016 to 2017 National Survey on Drug Use and Health (NSDUH) in the United States estimated that among approximately 76 million United States adults prescribed opioid drugs in the prior year, 12 percent reported prescription opioid misuse [16]. Compared with individuals who used prescribed opioids and did not report misuse, those reporting misuse of prescription opioids reported higher rates of other substance use, including cannabis, heroin, and benzodiazepine use, and were more likely to be depressed.

Motives for prescription opioid misuse tend to differ by age group. Among 5800 individuals with prescription opioid misuse who participated in the 2015 to 2016 NSDUH, a greater proportion of adults 50 years or older misused opioids solely for the purpose of pain relief compared with young adults aged 18 to 25 (65 versus 35 percent) [17]. Other motives for prescription opioid misuse included for relaxation, experimentation, and sleep. Prescription opioid misuse for motives other than pain relief was associated with greater odds of benzodiazepine misuse, substance use disorder, and suicidal ideation in the prior year.

A 2017 National Institute on Drug Abuse-funded survey of over 45,000 public and private high school students found a marked decline in past-year misuse of prescription opioids among high school seniors over the previous six years: from 8.7 to 4.2 percent [18].

A 2019 study reported an association between nonmedical prescription opioid misuse and subsequent initiation of heroin use in adolescents [19].

Disorder — In a systematic review, the incidence of opioid use disorder among patients prescribed opioids for chronic pain was estimated to be 8 to 12 percent [20]. Cross-sectional studies have reported the prevalence of DSM-IV opioid abuse and dependence among patients prescribed long-term opioids for chronic pain to range from 3 to 26 percent [9,21,22]:

26 percent of patients within a large United States health system who were prescribed long-term opioids met criteria for DSM-IV opioid dependence in the past year [21].

19.7 percent of urban primary care patients prescribed long-term opioids met criteria specifically for prescription drug abuse or dependence in the past year [22].

3 percent of primary care patients prescribed long-term opioids met criteria for current opioid dependence using a more conservative 30-day measure [9].

The prevalence of opioid use disorder involving prescription opioids has risen markedly among the United States general population. The proportion of United States individuals seeking substance use disorder treatment who reported non-heroin opioids as the primary substance used increased from 1.0 to 9.3 percent between 1995 and 2013 [23]; 88 percent of these individuals were White [23,24]. From 1995 to 2010, individuals in rural counties were more likely than those in urban counties to report non-heroin opioids as the primary substance (10.6 versus 4.0 percent) [25].

Morbidity and mortality — Concurrent with increased use of opioid analgesics for pain management since the 1990s, associated morbidity and mortality have risen markedly. There were over 63,600 deaths in the United States in 2016 due to drug overdose; approximately 42,000 (66 percent) involved opioids [26]. Of overdose deaths involving opioids, approximately 30 percent additionally involved benzodiazepines [27], which compound the sedating and respiratory-depression effects of opioids and increase overdose risk. The majority of decedents from drug overdose were males between 1999 and 2014; however, overdose deaths involving opioid analgesics increased 516 percent among females and 300 percent among males [28]. The pathway from prescription opioid use disorder to heroin has been increasingly recognized [29], and the Centers for Disease Control and Prevention identified three waves of the overdose epidemic: prescription opioids, heroin, and most recently, ultra-potent illegally manufactured fentanyl [26]. The epidemiology of opioid overdose and prevention of lethal opioid overdose is discussed in greater detail separately. (See "Prevention of lethal opioid overdose in the community".)

Risk factors — Patient factors associated with increased risk for opioid analgesic misuse when prescribed the medication for chronic pain include:

Substance use disorder, including tobacco use disorder, is consistently identified as a risk factor [10-12,22,30,31].

Family history of a substance use disorder [22,32].

Mental health disorder, including depression, posttraumatic stress disorder, and anxiety disorders [9,21,22,30,32-34].

History of legal problems or incarceration [15,16,22].

White race (compared with Black race) [22], despite studies that have identified greater clinician concern and closer monitoring for Black patients [35,36].

Age less than 40 to 45 years old, in most studies [9,10,15,30,37].

Studies are most robust for misuse, but these are also generally considered to be risk factors for developing opioid use disorder and for overdose. (See "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis", section on 'Risk factors'.)

Stimulants

Misuse — Stimulant prescribing for ADHD increased in the 1990s and 2000s [3]. Focusing on pharmaceutical stimulants only, data from the NSDUH from 2016 found that the general population past-year prevalence of prescription stimulant use (eg, methylphenidate or amphetamine products) was 6.4 percent and prevalence of misuse was 2.1 percent in the United States [38,39]. Prevalence of prescription stimulant misuse was highest among 18 to 25 year olds. Several studies have focused exclusively on younger populations; the reported prevalence of past-year pharmaceutical stimulant misuse was 5 to 9 percent [40], and past-year methylphenidate use was 2 to 5 percent [41] among high school students. For college students, studies reported past-year pharmaceutical stimulant misuse prevalence rates of 5 to 6 percent, and lifetime prevalence rates of 5 to 43 percent [38].

Disorder — Among individuals 12 or older who sought substance use treatment in the past year, 3.4 percent were for stimulant use disorder, according to the 2016 NSDUH [39]. However, robust estimates of the prevalence of pharmaceutical stimulant use disorders are lacking.

Morbidity and mortality — In 2016, over 7500 individuals in the United States died of overdose death involving pharmaceutical stimulants. This corresponds to a 33 percent increase in age-adjusted rate of overdose death from 2015 to 2016, with the highest increase among males aged 15 to 24 [42]. The number of emergency department visits involving ADHD stimulant medications increased 134 percent between 2005 and 2010, from 13,379 to 31,244 visits [43].

Stimulants may:

Increase blood pressure

Increase heart rate

Increase body temperature

Decrease sleep

Decrease appetite

Cause agitation

Cause anxiety

Cause paranoia

These symptoms are all more likely to occur when higher-than-prescribed doses are taken.

The overdose toxidrome may include [44]:

Mydriasis

Tremor

Agitation

Hyperreflexia

Combative behavior

Confusion

Hallucinations

Delirium

Anxiety

Paranoia

Seizures

Movement disorders

Risk factors — Studies of risk factors for pharmaceutical stimulant misuse have been predominantly among youths and young adults ages 12 to 25, especially college students. Reported risk factors for stimulant misuse include [38,45]:

White race

Involvement in a fraternity or sorority

Grade point average below 3.5

At least one episode of binge drinking in the past two weeks

Past-month cannabis use

Presence of conduct disorder

Sedatives-hypnotics

Misuse — Surveys of a nationally representative sample of United States residents aged 12 and older found a fairly stable prevalence of past-month nonmedical use of sedatives (0.1 to 0.2 percent of respondents) and tranquilizers (0.7 to 0.9 percent of respondents) from 2002 to 2014 [46]. In 2015, prevalence of past-year tranquilizer misuse among United States residents aged 12 and older was 2.3 percent [47]. Benzodiazepine misuse accounted for the vast majority (89 percent) of tranquilizer misuse, and alprazolam products were the most commonly misused benzodiazepines.

Disorder — Estimates of the prevalence of past-year DSM-IV sedative and tranquilizer abuse or dependence were stable from 2003 to 2011, at 78,000 and 400,000 individuals, respectively [1]. In 2015, though survey methods by the NSDUH had been revised, estimates of sedative and tranquilizer use disorder were up to 154,000 and 688,000 individuals, respectively [47]. Combined opioid abuse/dependence and benzodiazepine abuse/dependence increased dramatically; an analysis of substance use disorder treatment admissions showed a 569.7 percent increase in substance abuse treatment admissions with both benzodiazepine and prescription opioid abuse from 2000 to 2010 [48]. Specific substance use disorders are described separately. (See "Benzodiazepine use disorder" and "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis".)

Morbidity and mortality — Sedatives and tranquilizers have potent, dose-dependent central nervous system depressant effects. In the United States, overdose death involving benzodiazepines increased more than fourfold from 2002 to 2015 [28]. Co-ingestion of sedatives and tranquilizers with alcohol or opioids is an increasingly recognized and prevalent cause of overdose death [5,49-51]. From 2002 to 2015, there was a fivefold increase in overdose deaths involving both benzodiazepines and opioids [28].

Risk factors — A study of three years of United States survey data identified risk factors for past year nonmedical use of sedatives or tranquilizers [52]:

White race

Female sex

Uninsured

Unemployed

Panic symptoms

Other psychiatric symptoms

Alcohol abuse or dependence

Cigarette use

Illicit drug use

History of IV drug use

PREVENTION — Principal strategies for clinicians to prevent prescription drug misuse and its consequences are optimizing alternative treatments, including avoiding prescribing controlled substances in situations where alternative treatments are likely to be safe and effective; patient risk assessment; establishing a treatment plan that includes clear communication with the patient; and limiting dose and early refills.

Optimize alternative treatments — The first principle in prevention is to avoid prescribing controlled substances when safer alternatives are available and are likely to be effective. Clinical indications for prescribing controlled substances, such as pain, anxiety, and attention deficit hyperactivity disorder, each have evidenced-based treatment modalities that can replace or complement use of controlled substances. These include nonpharmacologic treatment with self-management strategies, behavioral treatments, physical therapy, as well as noncontrolled pharmacotherapy. (See 'Controlled substances' above and "Approach to the management of chronic non-cancer pain in adults" and "Management of attention deficit hyperactivity disorder in adults" and "Generalized anxiety disorder in adults: Management".)

Patient risk assessment — Consensus-based guidelines recommend that clinicians initiate or chose to continue controlled substances only in patients for whom the likely benefits will outweigh the risks [53,54]. Contraindications to treatment with controlled substances include patients with [53]:

Current untreated substance use disorder

Poorly controlled psychiatric illness

Erratic follow-up

There are scant data on predicting likelihood of benefit and harm in controlled substance prescribing. Tools have been developed to help predict risk of developing misuse [55-57], but none have been shown to impact outcomes, and few have been validated in primary care, where most controlled substances are prescribed.

To assess risk for prescription drug misuse, it is generally necessary to collect both patient-reported data and collateral data from other providers and objective sources. Patient-reported data include a thorough substance use history, mental health history, family and social history, as well as physical examination to assess for signs of substance use (eg, track marks and stigmata of chronic liver disease). It is also helpful to review medical records, speak with previous or current providers, check the state prescription monitoring program, and conduct drug testing. (See 'Urine drug testing' below.)

The risk profile that emerges from assessment should help to inform decisions about whether to prescribe controlled substances, and, if the clinician chooses to prescribe them, will help to inform the intensity of monitoring and determine which adjuvant treatments (eg, behavioral health) are indicated.

Establishing a treatment plan — Clinicians should discuss the potential risks, benefits, and treatment alternatives with a patient before starting a controlled substance [54]. Clinicians should also discuss the strategies that will be used to monitor for and respond to risks of potential misuse that arise in the course of treatment, including defining conditions in which a safe discontinuation of controlled substances and/or transition to substance use disorder treatment would be indicated. Clear communication is critical; patients need to know what is and is not considered safe use of controlled substances. We recommend this be done in a nonjudgmental, nonstigmatizing way that promotes patients’ understanding and comfort in asking questions.

Written documents such as informed consents, agreements on terms of treatment, or treatment plans can be useful to document this information/agreement between patients and prescribers. Though evidence for a treatment agreement's effectiveness in reducing misuse of controlled substances is not robust [58], most experts promote its role in documenting shared decision-making, treatment goal-setting, informed consent, and defining the monitoring plan [53].

Limiting exposure — Limiting exposure to controlled substances can help prevent prescription drug misuse. This includes choosing alternate treatments when possible and when controlled substances are prescribed, limiting the dose, duration, or number of prescriptions. The most rigorous data to support these strategies are for opioid prescribing. Greater daily opioid doses and greater numbers of prescriptions per month are associated with a higher risk of overdose death [59-61]. Based on these findings, the Centers for Disease Control and Prevention [54] recommends that clinicians avoid increasing the dose of prescribed opioids for chronic pain beyond 90 morphine milligram equivalents per day. Prescribing quantities of controlled substances that exceed what the patient consumes can contribute to hoarding of medication and increase the risk of diversion and misuse.

Each patient’s daily dose should be limited to the lowest effective dose. When a patient’s symptoms are controlled, it is prudent in many cases to offer and attempt dose reductions as tolerated to minimize exposure and risk. Other ways to limit the amount dispensed are to maintain a fixed dosing schedule and, except in unusual circumstances, avoid early refills.

IDENTIFICATION AND MANAGEMENT — Clinicians have a clinical responsibility to monitor patients to whom they prescribe controlled substances on an ongoing basis for misuse of these medications [53,54,62]. Practitioners should adhere to policies of their state boards in the United States, and medical regulatory authorities in other countries, which may include specific actions not discussed here. Experts recommend a "universal precautions" [63] approach incorporating a standard prescribing and monitoring framework for all patients prescribed the medications that includes:

Establishing a clear clinician-patient relationship, as with any patient.

Documenting in the patient’s medical record [53,64]:

A medical history, including substance use and mental health

Physical examination

Medical decision-making, including assessment of benefit and harm

Plan of care

Regular follow-up with standardized monitoring for benefit and harm. (See 'Regular follow-up' below.)

Drug testing. (See 'Urine drug testing' below.)

Use of prescription monitoring programs where available. (See 'Prescription monitoring programs' below.)

Discussing all planned monitoring strategies in the treatment agreement. (See 'Establishing a treatment plan' above.)

Regular follow-up — Frequent in-person follow-up with patients on controlled substances is recommended to monitor for and document benefits and harms of treatment, including concerning behaviors that may indicate misuse or a use disorder. Guidelines vary, but visits should generally occur at least every three months and more frequently in higher risk circumstances, such as during periods of dose adjustment [54].

For follow-up assessment of risks and benefits in patients who are prescribed opioids for chronic pain, the "Five A's" provides a useful framework:

Analgesia

Activities of daily living (ie, assessment of functional status)

Addiction

Adverse effects

Adherence to the treatment plan

Physical examination is essential and can provide evidence of intoxication, oversedation, withdrawal, or findings indicative of drug injection or intranasal use. Involving a patient's family member or friend can be useful for obtaining collateral history about a patient's functioning and use of the medications.

Urine drug testing — Urine drug testing provides objective data to confirm that patients have taken the prescribed medication, and to help identify use of nonprescribed substances that could interfere with the safety or effectiveness of treatment [53]. Random drug testing, as opposed to scheduled testing, may be more likely to detect surreptitious drug use. While evidence that routine urine drug testing decreases controlled substance misuse is lacking [58], urine drug testing is effective at identifying illicit and nonprescribed drug use [65-68]; it has been shown to be better than clinician assessment alone [9,66,69]. As an example, among patients whose clinicians believed were not at risk for medication misuse, 60 percent had urine drug tests showing the presence of an illicit drug or the absence of a prescribed medication [70].

Urine is the most commonly tested bodily fluid for drugs in clinical care because the window of detection is longer than for blood, and because oral fluid testing is susceptible to false negatives, particularly in smokers. Clinicians must be aware of the limitations (ie, false-positive and false-negative results) of the drug test assays that they use. Misinterpretation of results is common and could negatively affect patient care [71-73]. (See "Testing for drugs of abuse (DOAs)" and "Urine drug testing for patients with chronic pain".)

Prescription monitoring programs — Prescription monitoring programs (PMP) provide an online database listing all prescriptions of controlled substances dispensed for each patient by pharmacies in the covered region. All states in the United States have operational PMPs; other countries have similar programs. Where possible, and in accordance with state policies, prescribers should query the PMP before prescribing controlled substances to a patient, to check for undisclosed prescriptions for controlled substances. Receiving undisclosed controlled substances from other prescribers is a type of prescription drug misuse, could indicate substance use disorder or diversion, and elevates the risk for drug-drug interactions and overdose. Reviewing PMP data also helps the clinician determine when prescriptions were filled, to more accurately assess expected end date and avoid unintentional early refills.

Clinicians making use of PMP data should be aware that PMP databases may not include all medical sources. As an example, PMP data in the United States usually does not include information on methadone dispensed for the treatment of opioid use disorder from opiate treatment programs. Access to dispensing data from neighboring states is variable and increasing. Occasionally, reporting errors from pharmacies occur and calling a pharmacy directly may be necessary to confirm an unexpected finding in the PMP.

Clinician education — An epidemic of lethal opioid overdoses in the United States has prompted numerous initiatives to educate clinicians about appropriate opioid use and influencing their prescribing practices [74-76]. As an example, practice guidelines have been disseminated by a variety of organizations targeting various clinician populations and clinical settings, in some cases with follow-up measurement of their impact.

As an example, dissemination of a practice guideline aimed at reducing inappropriate opioid prescribing by emergency clinicians in Ohio was associated with a 12 percent reduction (95% CI 17.7 to -6.3) in prescriptions per month statewide [77]. The guideline encouraged emergency clinicians, when considering an opioid prescription, to review the patient’s recent prescription history in the state’s prescription drug monitoring database; limit the quantity provided; refer the patient for further evaluation, treatment, and monitoring; and provide education about opioid risks and limited benefits. (See 'Prescription monitoring programs' above.)

Addressing misuse — Before starting treatment with a controlled substance, providers should have a well thought-out plan for how to respond to evidence of prescription drug misuse. An approach that is communicated with patients as part of a treatment agreement and, whenever possible, standardized across a practice, improves time efficiency and fairness. Prescription drug misuse occurs along a spectrum of severity, from less severe behaviors (eg, a single episode of a patient taking more than prescribed) to more severe behaviors (eg, undisclosed prescription sources). The clinician's response should be commensurate with the severity and the pattern of the behaviors. As an example, a response to a single minor deviation from the patient’s treatment agreement may be to provide counseling and intensify monitoring; a response to more severe or persistent misuse may be to discontinue controlled substances safely and initiate treatment for substance use disorder if present.

In most cases of prescription drug misuse, it is appropriate to taper rather than abruptly discontinuing the medication to avoid precipitating a severe withdrawal syndrome [78,79].

If a patient is suspected of having a substance use disorder, tapering is insufficient and offering or referring for addiction treatment is essential. Many effective treatment options are available [54].

Treatment of substance use disorder is discussed in detail elsewhere.

(See "Approach to treating opioid use disorder" and "Medication for opioid use disorder" and "Psychosocial interventions for opioid use disorder".)

(See "Benzodiazepine use disorder", section on 'Treatment'.)

(See "Approach to treatment of stimulant use disorder in adults" and "Pharmacotherapy for stimulant use disorders in adults" and "Psychosocial interventions for stimulant use disorder in adults".)

(See "Cocaine use disorder in adults: Epidemiology, clinical features, and diagnosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cannabis use disorder and withdrawal" and "Society guideline links: Opioid use disorder and withdrawal" and "Society guideline links: Stimulant use disorder and withdrawal" and "Society guideline links: Benzodiazepine use disorder and withdrawal".)

SUMMARY AND RECOMMENDATIONS

Prescription drug misuse is defined as use of a prescription medication that is outside of the manner and intent for which it was prescribed; this includes overuse, use to get high, diversion (sharing or selling to others), having multiple prescribers or nonprescribed sources of the medication, and concurrent use of alcohol, illicit substances, or nonprescribed controlled medications. Misuse is a necessary but not sufficient criterion for a substance use disorder. (See 'Prescription drug misuse' above.)

Because of their potential for misuse, addiction, and illicit diversion and sale, opioid analgesics, stimulants, and benzodiazepines and other sedatives/hypnotics are regulated, restricting whether and how they can be prescribed. In the United States, these drugs are referred to as "controlled substances" and subject to Federal regulations (table 1). (See 'Controlled substances' above.)

Misuse of prescription drugs has generally increased concurrently with greater prescribing of medication for therapeutic use. This is particularly true of opioid analgesics prescribed for patients with chronic pain, stimulants prescribed for individuals with attention deficit hyperactivity disorder, and benzodiazepines prescribed for patients with anxiety; prescribing for each increased markedly between 2000 and 2015. (See 'Epidemiology' above.)

Use of opioid analgesics for pain management has increased since the 1990s, concurrent with marked increases in associated morbidity and mortality from use and/or misuse of these drugs. Rates of overdose deaths involving prescription opioids have plateaued since approximately 2011; however, opioid-related deaths overall have continued to grow, driven by illicit opioids. Higher daily dosages of prescribed opioids are associated with a greater risk of overdose for the patient they were prescribed to. (See 'Morbidity and mortality' above and "Prevention of lethal opioid overdose in the community", section on 'Epidemiology'.)

Principal strategies for clinicians to prevent prescription drug misuse and its consequences are optimization of alternative treatments, patient risk assessment, use of a treatment agreement, and limiting dose and early refills. Patient risk assessment should include a history, physical examination, and consideration of the presence of contraindications to prescribing controlled substances (see 'Prevention' above):

Current untreated substance use disorder

Poorly controlled psychiatric illness

Erratic follow-up

Monitoring patients who are prescribed a controlled substance should include regular follow-up, drug testing, and use of prescription monitoring programs or other information sources about patients who receive these medications from multiple prescribers. Monitoring should include documentation of benefits and harms of treatment, including assessment of functional status to assure that function is stable or improving on the current regimen, and evaluation for concerning behaviors that may indicate misuse or a substance use disorder. (See 'Identification and management' above.)

Prescription drug misuse occurs along a spectrum of severity, from less severe behaviors (eg, a single episode of a patient taking more than prescribed) to more severe behaviors (eg, undisclosed prescription sources). The clinician's response should be commensurate with the severity and the pattern of the behaviors. Patients suspected of having a substance use disorder should be assessed by an addiction specialist. (See 'Addressing misuse' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Theodore Parran, MD, Bonnie Wilford, MS, and Robert DuPont, MD, who contributed to an earlier version of this topic review.

  1. Substance Abuse and Mental Health Services Administration. Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings, in NSDUH Series H-44, HHS 2012. Rockville, MD 2012.
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  3. Castle L, Aubert RE, Verbrugge RR, et al. Trends in medication treatment for ADHD. J Atten Disord 2007; 10:335.
  4. Kuehn BM. Opioid prescriptions soar: increase in legitimate use as well as abuse. JAMA 2007; 297:249.
  5. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996-2013. Am J Public Health 2016; 106:686.
  6. Von Korff M, Dublin S, Walker RL, et al. The Impact of Opioid Risk Reduction Initiatives on High-Dose Opioid Prescribing for Patients on Chronic Opioid Therapy. J Pain 2016; 17:101.
  7. McCabe SE, West BT, Veliz P, et al. Trends in Medical and Nonmedical Use of Prescription Opioids Among US Adolescents: 1976-2015. Pediatrics 2017.
  8. Paulozzi LJ, Strickler GK, Kreiner PW, et al. Controlled Substance Prescribing Patterns--Prescription Behavior Surveillance System, Eight States, 2013. MMWR Surveill Summ 2015; 64:1.
  9. Fleming MF, Balousek SL, Klessig CL, et al. Substance use disorders in a primary care sample receiving daily opioid therapy. J Pain 2007; 8:573.
  10. Ives TJ, Chelminski PR, Hammett-Stabler CA, et al. Predictors of opioid misuse in patients with chronic pain: a prospective cohort study. BMC Health Serv Res 2006; 6:46.
  11. Reid MC, Engles-Horton LL, Weber MB, et al. Use of opioid medications for chronic noncancer pain syndromes in primary care. J Gen Intern Med 2002; 17:173.
  12. Morasco BJ, Dobscha SK. Prescription medication misuse and substance use disorder in VA primary care patients with chronic pain. Gen Hosp Psychiatry 2008; 30:93.
  13. Banta-Green CJ, Merrill JO, Doyle SR, et al. Measurement of opioid problems among chronic pain patients in a general medical population. Drug Alcohol Depend 2009; 104:43.
  14. Polatin PB, Kinney RK, Gatchel RJ, et al. Psychiatric illness and chronic low-back pain. The mind and the spine--which goes first? Spine (Phila Pa 1976) 1993; 18:66.
  15. Michna E, Ross EL, Hynes WL, et al. Predicting aberrant drug behavior in patients treated for chronic pain: importance of abuse history. J Pain Symptom Manage 2004; 28:250.
  16. Griesler PC, Hu MC, Wall MM, Kandel DB. Medical Use and Misuse of Prescription Opioids in the US Adult Population: 2016-2017. Am J Public Health 2019; 109:1258.
  17. Schepis TS, Wastila L, Ammerman B, et al. Prescription Opioid Misuse Motives in US Older Adults. Pain Med 2020; 21:2237.
  18. https://www.drugabuse.gov/trends-statistics/monitoring-future/monitoring-future-study-trends-in-prevalence-various-drugs (Accessed on May 31, 2018).
  19. Kelley-Quon LI, Cho J, Strong DR, et al. Association of Nonmedical Prescription Opioid Use With Subsequent Heroin Use Initiation in Adolescents. JAMA Pediatr 2019; 173:e191750.
  20. Vowles KE, McEntee ML, Julnes PS, et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 2015; 156:569.
  21. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction 2010; 105:1776.
  22. Liebschutz JM, Saitz R, Weiss RD, et al. Clinical factors associated with prescription drug use disorder in urban primary care patients with chronic pain. J Pain 2010; 11:1047.
  23. Substance Abuse Treatment Admissions by Primary Substance of Abuse, According to Sex, Age Group, Race, and Ethnicity, 2013. http://wwwdasis.samhsa.gov/webt/quicklink/US13.htm (Accessed on June 02, 2016).
  24. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. The TEDS Report: 2001-2011 National Admissions to Substance Abuse Treatment Services. 2013; Rockville, MD.
  25. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. The TEDS Report: A Comparison of Rural and Urban Substance Abuse Treatment Admissions. Rockville, MD July 31, 2012.
  26. https://www.cdc.gov/drugoverdose/epidemic/index.html (Accessed on April 14, 2018).
  27. Kandel DB, Hu MC, Griesler P, Wall M. Increases from 2002 to 2015 in prescription opioid overdose deaths in combination with other substances. Drug Alcohol Depend 2017; 178:501.
  28. https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates (Accessed on June 02, 2016).
  29. Carlson RG, Nahhas RW, Martins SS, Daniulaityte R. Predictors of transition to heroin use among initially non-opioid dependent illicit pharmaceutical opioid users: A natural history study. Drug Alcohol Depend 2016; 160:127.
  30. Edlund MJ, Steffick D, Hudson T, et al. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain 2007; 129:355.
  31. Riva JJ, Noor ST, Wang L, et al. Predictors of Prolonged Opioid Use After Initial Prescription for Acute Musculoskeletal Injuries in Adults : A Systematic Review and Meta-analysis of Observational Studies. Ann Intern Med 2020; 173:721.
  32. Griesler PC, Hu MC, Wall MM, Kandel DB. Assessment of Prescription Opioid Medical Use and Misuse Among Parents and Their Adolescent Offspring in the US. JAMA Netw Open 2021; 4:e2031073.
  33. Wasan AD, Butler SF, Budman SH, et al. Psychiatric history and psychologic adjustment as risk factors for aberrant drug-related behavior among patients with chronic pain. Clin J Pain 2007; 23:307.
  34. LaRowe LR, Powers JM, Garey L, et al. Pain-related anxiety, sex, and co-use of alcohol and prescription opioids among adults with chronic low back pain. Drug Alcohol Depend 2020; 214:108171.
  35. Becker WC, Starrels JL, Heo M, et al. Racial differences in primary care opioid risk reduction strategies. Ann Fam Med 2011; 9:219.
  36. Vijayaraghavan M, Penko J, Guzman D, et al. Primary care providers’ judgments of opioid analgesic misuse in a community-based cohort of HIV-infected indigent adults. J Gen Intern Med 2011; 26:412.
  37. Chabal C, Erjavec MK, Jacobson L, et al. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence, and predictors. Clin J Pain 1997; 13:150.
  38. Kaye S, Darke S. The diversion and misuse of pharmaceutical stimulants: what do we know and why should we care? Addiction 2012; 107:467.
  39. SAMHSA, Center for Behavioral Health Statistics and Quality, National Survey on Drug Use and Health, 2015 and 2016. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.htm#tab1-51B.
  40. Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008; 47:21.
  41. Bogle KE, Smith BH. Illicit methylphenidate use: a review of prevalence, availability, pharmacology, and consequences. Curr Drug Abuse Rev 2009; 2:157.
  42. Seth P, Scholl L, Rudd RA, Bacon S. Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016. MMWR Morb Mortal Wkly Rep 2018; 67:349.
  43. Substance Abuse and Mental Health Services Administration. The DAWN Report: Emergency Department Visits Involving Attention Deficit/Hyperactivity Disorder Stimulant Medications. Rockville, MD.
  44. Spiller HA, Hays HL, Aleguas A Jr. Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. CNS Drugs 2013; 27:531.
  45. Looby A, De Young KP, Earleywine M. Challenging expectancies to prevent nonmedical prescription stimulant use: a randomized, controlled trial. Drug Alcohol Depend 2013; 132:362.
  46. Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. SAMHSA; Department of Health and Human Services, Rockville, MD 2015.
  47. https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR2-2015/NSDUH-FFR2-2015.htm.
  48. Substance Abuse and Mental Health Services Administration. The TEDS Report: Admissions Reporting Benzodiazepine and Narcotic PainReliever Abuse at Treatment Entry. Rockville, MD 2012.
  49. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA 2008; 300:2613.
  50. Park TW, Saitz R, Ganoczy D, et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ 2015; 350:h2698.
  51. Weisberg DF, Gordon KS, Barry DT, et al. Long-term Prescription of Opioids and/or Benzodiazepines and Mortality Among HIV-Infected and Uninfected Patients. J Acquir Immune Defic Syndr 2015; 69:223.
  52. Becker WC, Fiellin DA, Desai RA. Non-medical use, abuse and dependence on sedatives and tranquilizers among U.S. adults: psychiatric and socio-demographic correlates. Drug Alcohol Depend 2007; 90:280.
  53. Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009; 10:113.
  54. Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep 2022; 71:1.
  55. Butler SF, Budman SH, Fernandez K, Jamison RN. Validation of a screener and opioid assessment measure for patients with chronic pain. Pain 2004; 112:65.
  56. Compton PA, Wu SM, Schieffer B, et al. Introduction of a self-report version of the Prescription Drug Use Questionnaire and relationship to medication agreement noncompliance. J Pain Symptom Manage 2008; 36:383.
  57. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med 2005; 6:432.
  58. Starrels JL, Becker WC, Alford DP, et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Intern Med 2010; 152:712.
  59. Paulozzi LJ, Kilbourne EM, Shah NG, et al. A history of being prescribed controlled substances and risk of drug overdose death. Pain Med 2012; 13:87.
  60. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med 2010; 152:85.
  61. Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 2011; 305:1315.
  62. Federation of State Medical Boards. Model Policy on the Use of Opioid Analgesics in the Treatment of Chronic Pain. 2013.
  63. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med 2005; 6:107.
  64. Federation of State Medical Boards. Model policy for the use of controlled substances for the treatment of pain. 2004.
  65. Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Validity of self-reported drug use in chronic pain patients. Clin J Pain 1999; 15:184.
  66. Katz NP, Sherburne S, Beach M, et al. Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesth Analg 2003; 97:1097.
  67. Schuckman H, Hazelett S, Powell C, Steer S. A validation of self-reported substance use with biochemical testing among patients presenting to the emergency department seeking treatment for backache, headache, and toothache. Subst Use Misuse 2008; 43:589.
  68. Robinson-Papp J, Elliott K, Simpson DM, et al. Problematic prescription opioid use in an HIV-infected cohort: the importance of universal toxicology testing. J Acquir Immune Defic Syndr 2012; 61:187.
  69. Michna E, Jamison RN, Pham LD, et al. Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings. Clin J Pain 2007; 23:173.
  70. Bronstein K PS, Munitz L, Leider H. Can clinicians accurately predict which patients are misusing their medications?. American Pain Society 30th Annual Scientific Meeting 2011; Austin, TX.
  71. Reisfield GM, Bertholf R, Barkin RL, et al. Urine drug test interpretation: what do physicians know? J Opioid Manag 2007; 3:80.
  72. Reisfield GM, Webb FJ, Bertholf RL, et al. Family physicians' proficiency in urine drug test interpretation. J Opioid Manag 2007; 3:333.
  73. Starrels JL, Fox AD, Kunins HV, Cunningham CO. They don't know what they don't know: internal medicine residents' knowledge and confidence in urine drug test interpretation for patients with chronic pain. J Gen Intern Med 2012; 27:1521.
  74. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA 2016; 315:1624.
  75. del Portal DA, Healy ME, Satz WA, McNamara RM. Impact of an Opioid Prescribing Guideline in the Acute Care Setting. J Emerg Med 2016; 50:21.
  76. Reid DBC, Shah KN, Shapiro BH, et al. Mandatory Prescription Limits and Opioid Utilization Following Orthopaedic Surgery. J Bone Joint Surg Am 2019; 101:e43.
  77. Weiner SG, Baker O, Poon SJ, et al. The Effect of Opioid Prescribing Guidelines on Prescriptions by Emergency Physicians in Ohio. Ann Emerg Med 2017; 70:799.
  78. Tannenbaum C, Martin P, Tamblyn R, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med 2014; 174:890.
  79. Frank JW, Lovejoy TI, Becker WC, et al. Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review. Ann Intern Med 2017; 167:181.
Topic 15236 Version 41.0

References