Prescribing Controlled Substances and Drug Diversion, Best Practices - 3 hr

Prescription opioid abuse takes a heavy toll on the patient, healthcare provider and society. Abuse and misuse of controlled substances occur for multiple reasons, including self-medication, use for reward, diversion, and for-profit and compulsive use. Opioid use has recently increased, leading to increased abuse and opioid overdoses. Proper screening lowers the risk of iatrogenic addiction. Unfortunately, no currently available screening method accurately predicts who is at high risk of abuse or misuse opiates (Sehgal et al., 2012).

Using prescribed medications not as directed describes potentially aberrant drug-taking behaviors. In a study of 202 patients, only 44.1% were screened for potential aberrant drug-taking behaviors. It was concluded that screening for abuse or misuse of opioids does not frequently occur in large family medicine training programs. More training and set policies for risk evaluation and monitoring of opioid abuse are needed (Colburn et al., 2012).

Health care providers tend to under-assess patients at risk for opioid-related aberrant behaviors. One study showed that providers assessed the risk of misuse, abuse or diversion at less than 2% when in reality, 10.4% of patients had prior illicit drug use, 23.4% had abnormal urine drug tests, and almost 11% reported crushing or chewing opioids in the past and 60% of patients self-reported abuse, misuse or diversion (Setnik et al., 2017).

Prescribers' lack of training and inexperience can profoundly impact the misuse of medications. One study showed that resident physicians (when compared to attending physicians) more often prescribed opioids for more than three months, were more likely to have their patients report that their prescriptions were lost/stolen, and were more likely to have patients who exhibited substance misuse and were more likely to have their patients get opioids prescribed by a different prescriber in addition to them (Colburn et al., 2012).

Prescribers receive little training in prescribing scheduled substances, screening for substance abuse, and referring patients who need treatment. Proper continuing education is one way to address this problem (Brown et al., 2012).

Many known risk factors for opioid misuse, diversion, addiction, and overdoses (Webster, 2017). Evaluating these risk factors is an important aspect of evaluating a patient. Factors that increase the risk of problematic opioid use include:

• A prior history of misuse or abuse
• Younger age
• Untreated psychiatric disorder
• Living in a social or family environment that encourages misuse
• Genetics
• Physical, sexual or emotional abuse
• Using nicotine, alcohol or other drugs at an early age
• Substance use/abuse in the family or among friends
• Stress
• Access to addictive substances
• Highly impulsive personality
• Family or personal history of drug/alcohol abuse and mental health issues, including depression, anxiety, eating disorders, or personality disorders
• History of legal trouble/incarceration
• White race

How do Drug Abusers Get Drugs?

Removing prescription medications from legitimate channels is drug diversion and can occur in many ways.

• Slightly more than 40 percent of patients who abuse prescription pain medication got it from a relative or friend without having to pay for the drugs.
• 36.4 percent of abusers of prescription medications got them through their health care provider either by prescription or by stealing.
• Ten percent stole drugs from a relative or friend.
• Some patients get drugs through doctor shopping, but most patients receive their drugs through one doctor.
• Fraudulent prescriptions are another method of obtaining prescription drugs. This fraudulence can occur in many ways. Methods include: altering an already written prescription, stealing a prescription pad, or creating falsified computer prescriptions (Dixon, 2018).

Health care professionals are also known to divert, misuse or abuse drugs. Health care providers abusing drugs may be irritable, defensive or isolated. Other signs or symptoms of prescription drug abuse or misuse include frequent bathroom trips, coming into the office when not scheduled, working overtime, multiple medication errors, incorrect counts of controlled substances, poor judgment, neglect of patients, long sleeves in warm weather, and strange behavior.

• In 2016, 48.5 million individuals in the United States misused prescription or illicit drugs. Sixty-six percent of the 630,000 drug overdose deaths were due to illicit or prescription opioids. The number of opioid overdoses in the emergency department increased by 30 percent from July 2016 to September 2017 (CDC, 2016).
• Opioid misuse affects 34.2 million Americans over 12 (SAMHSA, 2011). According to the Center for Disease Control and Prevention (CDC), 46 people die each day in the United States from an overdose of prescription painkillers.
• In 2012, healthcare providers wrote 259 million prescriptions for painkillers (CDC, 2014). Two times as many painkiller prescriptions are written in the United States as in Canada.
• Overdoses from synthetic opioids increased from 3.1 per 100,000 people in 2015 to 6.2 per 100,000 in 2016 (Hedegaard et al., 2019).
• Between 1999 and 2015, drug overdose deaths tripled (Manchikanti et al., 2017).
• Of US veterans treated in primary care settings, 4.8% reported opioid analgesic misuse (Becker et al., 2009).
• 12.2% of 12th graders reported abusing opioids, and 7.9% reported past-year use (Merikangas & McClair, 2012).
• Of those prescribed opioids, dependence may be as high as 26% (Boscarino et al., 2010).
• The number of individuals who sought treatment for non-heroin opioid substance abuse increased from 1.0% in 1995 to 8.7% in 2010 (SMASHA, 2013).
• Research shows that white individuals account for 88% of those who reported non-heroin opioid substance abuse, most of whom lived in rural settings. (SMASHA, 2013).
• Of overdose deaths from opioid analgesia, 30% also involved benzodiazepines (Jones et al., 2010).

Opioid dependence costs the United States health care system one billion dollars annually (NCDP, n.s.). In addition, opioid dependence leads to decreased work productivity, increased legal costs and lasting psychological effects experienced by the victims of the crimes caused by opioid abuse. In addition, opioid misuse may lead to other diseases such as HIV, hepatitis and sexually transmitted diseases.

Chris T. is a 58-year-old widowed male. He presents to the Emergency Department upon being found on the couch by his son in an unresponsive state. His son was able to wake him, but his speech was incoherent.

Mr. T's past medical history is positive for hypertension, hyperlipidemia, Stage III CKD, anxiety/depression, osteoarthritis of his knees, and low back pain. He is currently on a daily aspirin, amlodipine, citalopram, atorvastatin and hydrocodone/acetaminophen.

Mr. T. has been taking hydrocodone /acetaminophen 1 - 2 times daily for over three years. About three months ago, he presented to the Emergency Department with a similar presentation and was discharged after six hours with no definitive diagnosis but was given a prescription for more hydrocodone /acetaminophen for pain.

Mr. T's son reports that Mr. T. has not been coming to as many social events over the last month because his pain level has increased. The Emergency Department nurse practitioner notes that the vital signs (including oxygen saturation) are stable, but the patient is somnolent. He does wake when stimulated and answers only yes/no questions. His blood work, including liver/kidney function tests, glucose, and metabolic profile, are negative, except he is shown to have Stage III CKD (but at baseline for the patient). His drug screen is positive for opioids.

Mr. T. is admitted to the hospital and is back to his baseline the next day. He does report that his pain has been worse and that he has been taking more than his prescribed dose of oxycodone/acetaminophen.

The patient's symptoms are thought to be caused by sedation due to the opioids and impaired kidney function, leading to a buildup of metabolites. He is discharged from the hospital and is seen by his primary care provider the next day.

His primary care provider recognizes that his pain is poorly controlled, leading to him overdosing on opioids. Due to his CKD, NSAIDs are not an appropriate option. Managing his depression/anxiety along with closely monitored opioid therapy, with extensive counseling on safe use, is implemented.

The patient is given a treatment plan that includes:

• A list of goals:
  • Improved pain and increased function
  • Improved anxiety and depression
  • Eventual cessation of opioid therapy
  • Regular exercise program
• Physical therapy
• The addition of mirtazapine to his citalopram

After two weeks, the patient returns to his primary care provider and reports that he has started therapy, is sleeping better and is only using one hydrocodone/acetaminophen daily – typically after exercise. After four more weeks, he reports using about 3 - 4 doses of hydrocodone/acetaminophen per week, feels less anxious and depressed and is sleeping "just fine." After another four weeks, he says he no longer uses his opioid medication, has gotten a part-time job and is regularly exercising.

Chronic pain affects approximately 76.2 million Americans.18 Pain is a common problem seen in primary care, with about 20% of outpatient visits being for pain issues (Alford et al., 2009). Chronic pain affects about one in two long-term care residents (AMDA, 2012).

Persistent pain is often associated with anxiety, depression, functional impairment, sleep disturbances, disability and impairment in activities of daily living. Every year, chronic pain leads to more than 50 million lost workdays in the United States and costs the American taxpayer over 100 billion dollars (Stewart, 2003).

Chronic pain is defined as pain lasting more than 3 months and may affect any body part. Chronic pain is most frequently caused by back pain (10%), leg/foot pain (7%), arm/hand pain (4.1%), headache (3.5%), and widespread pain (3.6%). Many individuals affected by chronic pain have more than one type of pain (Hardt et al., 2008).

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (Merskey & Bogduk, 1994).

Acute pain is defined as pain that has an abrupt onset and offers a warning of a disease process or a threat to the body (Merskey & Bogduk, 1994).

Chronic pain is "Pain that lasts beyond the usual duration of time that an insult or injury to the body needs to heal. (Merskey & Bogduk, 1994). Chronic pain can also be viewed as pain without apparent biologic value that has lasted beyond the usual tissue healing time (typically at least three months). Some define chronic pain as pain that continues for at least six months (APA, 2013).

Opioids are indicated for pain conditions. An expert panel concluded that chronic opioid therapy might be effective for some individuals with chronic noncancer pain that have been thoughtfully selected (Chou et al., 2009). When deciding to prescribe opioids, the risks versus benefits must be considered.

The use of high-dose long-acting opioids is used only in specific circumstances with severe, intractable pain that has not responded to short-acting or moderate doses of long-acting opioids. No evidence exists of who responds better between long-acting and short-acting opioids in relation to effects and side effects (Manchikanti et al., 2012).

A recent survey showed that individuals would go to extreme lengths to obtain certain prescription medications. Opioids were the most commonly obtained medications, followed by sedative-hypnotics and amphetamines. Individuals seeking these medications are more likely to use more than one physician and one pharmacy. This survey showed that seventy-five patients feigned symptoms to get prescriptions, two of thirty-six used falsified MRI images, three patients paid the prescribers, and three harmed themselves to get the prescriptions (Bouland et al., 2015).

A comprehensive medical history is the first step in the workup of an individual experiencing chronic pain. Many healthcare providers believe pain is the fifth vital sign. A thorough medical history should include an evaluation of the patient's medical and surgical history and a medication list review.

The comprehensive medical history must include a detailed description of the pain. The pneumonic: OLD CARTS is sometimes used to evaluate pain.

• Onset:
  • When did the pain start?
  • Describe the mechanism of injury?
  • What was the causative factor?
• Location
  • Where is the pain?
• Duration
  • How long has the pain persisted?
  • Is the pain intermittent or constant?
• Characteristics
  • Describe the pain (dull, sharp, lancing, burning, throbbing or squeezing).
• Associated symptoms
  • Are other symptoms associated with the pain, such as spasms, reduced range of motion, edema, diaphoresis, weakness, or changes in skin, nails or hair?
• Radiation
  • Does the pain radiate? If so, where?
• Temporal
  • What are the aggravating/causative factors?
  • What factors alleviate or diminish pain?
• Severity
  • Rate the severity of the pain?

Document the impact the pain has on the patient's quality of life. Ask:

• Does the pain affect activities of daily living or instrumental activities of daily living?
• Does the pain limit exercise or activity?
• Does the pain affect your mood?
• Is there a reduction in your energy?
• Does the pain lead to a strain on relationships?
• Does the pain affect your sleep?
• Does the pain lead to mood alterations?
• Does the pain affect your social life?

Measuring pain intensity is often done on scales and is meant to compare the intensity of the patient's pain at different points, not to compare one person's pain to another. The use of pain scales helps the prescriber assess the effectiveness of pain treatment.

The best scales are brief, valid, require minimal training, and use both behavioral and descriptive measures of pain.20 A scale commonly used rates pain from 0 to 10. Another scale allows the patient to rate their pain as no, mild, moderate, severe, or unbearable. Other scales have the patient select the degree of pain on a pictorial scale with facial expressions. Pain maps are helpful in individuals who have a difficult time speaking. Pain maps have a front and rear view of the body on a piece of paper, and the patient marks the pain's location and rates the pain's severity.

The patient's perception of the pain should be reviewed:

• What are the patient's treatment goals?
• Why does the patient think they have persistent pain?
• Does the patient feel there was sufficient workup done on their condition?

Psychological factors that contribute to the pain should also be assessed. Patients need to have reasonable expectations about the pain and its management.

All patients with chronic pain should have a complete physical examination. It is important to have a baseline physical examination, so ensuing evaluations will permit the healthcare team to establish progress in how well the pain is being managed.

Other key features that should be assessed prior to treatment include:

• Current and past treatments
• History of substance abuse
• Underlying conditions

The physical examination should include:

• Hygiene, dress and appearance - those in severe pain will often have poor hygiene and be unkempt
• A detailed neurological examination
• Assessment of skin and joints for redness, swelling or deformities, which may help determine the location and etiology of pain
• Assessing for joint range of motion
• Inspecting for any splinting
• Any signs of chronic liver disease
• An abdominal examination for any tenderness, mass or distention
• A skin examination that looks for any track marks
• Any signs of acute intoxication, withdrawal signs, or oversedation

Diagnostic testing is often part of the workup of painful conditions. It is important to realize that an abnormal diagnostic test does not necessarily diagnose the source of the pain. Blood tests may be helpful in certain diseases that cause pain. For example, an elevated C-reactive protein or erythrocyte sedimentation rate is often present in individuals with polymyalgia rheumatica, infection or rheumatoid arthritis.

Imaging can be useful in some cases of chronic pain. X-rays, computed tomography and magnetic resonance imaging, can help determine the cause of the pain. Remember, diagnostic testing needs to be interpreted carefully as some abnormalities may be incidental and not the source of the pain.

Caution should be used when evaluating patients as overuse of imaging, or other diagnostic modalities may lead to increased use of opioids, activity restriction, and increased fear.

An electromyogram (EMG) or a nerve condition study (NCS) assesses the cause of pain. The EMG measures the electrical activity of the muscle and can help find damaged muscle, nerves or neuromuscular abnormalities such as a herniated disc or myasthenia gravis. The NCS measures the capacity of the nerves to transmit electrical signals and assists in diagnosing multiple types of neuropathies.

An important role of the practitioner is prescribing controlled substances. Establishing treatment goals is an important aspect of opioid therapy. Goals should focus on pain relief and improvement in function. Controlled substances are laced with risks, and the prescriber needs to realize that a primary goal of prescribing opioids should be to maintain patient safety. A responsible prescriber should follow multiple steps to assure safe and effective care of their patient.

Therapeutic goals should be established regarding pain control and improvement in function. Pain goals typically involve a reduction in pain, not necessarily an elimination of pain. Functional goals may include improved sleep, improved ability to perform activities of daily living, progress in physical therapy, increased social interactions, returning to work, and improved regular exercise. In addition, goals should also include limiting side effects and minimizing adverse drug events.

The health care industry should shoulder some of the burdens of the opioid epidemic. The 1990s were a time when pharmaceutical companies aggressively marketed pain medications. Healthcare providers, encouraged by the Joint Commission, were encouraged to assess pain and manage it appropriately. The combination of intense assessment and pharmaceutical companies marketing pain medication were partially responsible for the increased use of opioid pain medications. In addition, support was given to multiple medical organizations, including the American Pain Society, the Federation of State Medical Boards and the American Academy of Pain Medicine that lobbied for aggressive identification and management of pain (Lopez, 2018).

Research from 2015 showed that six times more opioids were dispensed in counties with high prescribing rates versus counties with low prescribing rates. Certain characteristics make prescribing controlled substances more likely. The CDC reported risk factors for counties at higher risk for prescribing a more controlled substance that include: a higher percentage of white people, more patients with diabetes, arthritis, or disability, when a higher percentage of people were unemployed or uninsured, counties with more dentists or primary care physicians, and counties with small cities or large towns (CDC, 2017).

In 2018, the Joint Commission changed its standards in the management and assessment of pain (TJC, 2018). Some of their modifications included:

• Identify patients at high risk of misusing opioids
• Encouraged the use of nonpharmacological pain management techniques
• Identify a leadership team to help manage pain
• Focus on function
• Educate patients about the misuse and medication disposal and storage
• Set realistic goals with the help of the patient
• Use the prescription drug monitoring program
• Refer addicted patients to treatment programs
• Engage in improvement activities regarding pain management

Opioid medications are associated with multiple side effects, including constipation, nausea, vomiting, pruritus, abdominal cramping, sedation and mental status changes. Multiple interventions are available to reduce or eliminate the side effects of opioids.

• Constipation is a common issue for those who use opioids. Risk factors for constipation include those with intra-abdominal pathology and those who eat a low-fiber diet. Patients on opiates should be encouraged to increase fiber intake, drink plenty of fluids and exercise. Stool softeners (e.g., docusate sodium) and stimulants (e.g., bisacodyl) may be needed to manage constipation. An osmotic laxative such as polyethylene glycol or lactulose may also be considered and added to stool softeners/stimulants for resistant constipation.
• Antiemetic medications can help treat nausea.
• Antihistamines can relieve or lessen pruritus.
• Opioids are associated with somnolence and other mental status changes. Patients do develop tolerance to these symptoms over weeks. Reducing the dose of opioids may lessen the mental status changes. An adjunctive medication may be added to the lower dose of opioids to help manage the pain. Rarely the use of a stimulant can be used to manage the sedation due to opioid use.
• Respiratory depression may occur, but it is uncommon to use the medication carefully. Starting with a low dose and slowly titrating the dose higher will reduce the risk of respiratory depression. Problems arise with rapid titration, the addition of another drug that may depress the respiratory drive (benzodiazepines, alcohol or a barbiturate) or the patient overdoses. Sedation precedes respiratory depression, so when starting a patient on opioid therapy, the patient should be encouraged to take the first dose in the office to be monitored or in the presence of a responsible adult who can help monitor the patient. The level of consciousness should be assessed at least every 30-60 minutes after the opioid is given. The next dose should be held, and the prescriber should be contacted immediately if a reduced level of consciousness occurs, hypoxia develops, or the respiratory rate is less than 10 per minute.

Drug interactions can lead to significant health concerns in those taking opioids. Many individuals with chronic pain have co-morbid conditions that necessitate using other medications. A study showed that drug-to-drug interactions in those with chronic low back pain on long-term opioid analgesics were 27% (Pergolizzi et al., 2018).

Drug-to-drug interactions are variable among products. Medications that depress the central nervous system, such as alcohol, benzodiazepines and tricyclic antidepressants, may potentiate the respiratory depression and sedative effects of opioids. Some extended-release formulations of opioids may rapidly release the opioids when given with alcohol. Methadone and buprenorphine may prolong the QT interval.

Many medications can affect various cytochrome P450 enzymes. Codeine, oxycodone, hydrocodone and tramadol levels may be increased when given with selective serotonin reuptake inhibitors (SSRIs), protease inhibitors, diltiazem, verapamil, diazepam, clarithromycin, fluoroquinolones and diphenhydramine. Levels may be decreased with carbamazepine and phenytoin. Fentanyl levels may be increased by SSRIs, protease inhibitors, diltiazem, verapamil, diazepam and clarithromycin. Some opioids used with anticholinergic medications may increase the risk of constipation and urinary retention.

Grapefruit juice can potentially increase levels of multiple opioids such as fentanyl, codeine, hydrocodone and methadone. Ginkgo Biloba, Valerian Root and St. John's Wort can potentially reduce levels of multiple opioids. Some individuals have an allelic variant in CYP-2D6, making them inefficient at converting codeine to its active metabolite morphine, thus resulting in a less analgesic effect to codeine.

Not all patients on chronic opioid therapy need to have a referral, but some do. Consider a referral to psychology, psychiatry or an addiction expert for those at high risk or those who engage in aberrant drug-related behaviors. Those with a substance abuse disorder are also candidates for referral. A pain management consultation may be helpful for those on high-dose opioids.

The management of pain may include medications, behavioral interventions, physical medicine, neuromodulation, medical interventions or surgery. A multidisciplinary approach is typically used in the management of chronic pain.

Current treatments in managing chronic pain result in approximately a 30% reduction in pain (Turk et al., 2010). One of the problems encountered is that general practitioners have limited training in managing chronic pain (Institute of Medicine, 2011). A pain management specialist is often needed to manage pain properly.

The treatment plan should be established prior to initiating treatment. In this plan, the patient and the provider should discuss the benefits, risks and alternatives before starting treatment. In addition, the clinician needs to discuss how the patient will be monitored, including how the patient will be evaluated for potential misuse of the prescribed medication. The use of written documents is often included in the plan. This documentation may include agreements, treatment plans, and informed consent. It is important that the clinician document that decision-making was implemented, including informed consent, goal setting was discussed, and a monitoring plan was defined (Chou et al., 2009).

High doses of opioid prescriptions are given increase the risk of overdose death. Therefore, the clinician must discuss and limit the amount of opioids prescribed. The CDC recommends that providers prescribe no more than 90 morphine milliequivalents per day (Dowell et al., 2016).

The World Health Organization (WHO) analgesic ladder was created to manage cancer pain and published in the 1980s (WHO, 2019). Key points of the analgesic ladder include:

1. Medications are given through the most comfortable route (preferably orally).
2. A stepwise approach should be followed, starting with non-opioid medications with or without adjuvant medications.
3. Managing mild to moderate enduring or progressive pain with opioids, with or without adjuvant medications, with or without non-opioids.
4. Considering the use of more potent opioids such as morphine with or without adjuvant medications with or without non-opioids for persistent pain or pain that is increasing, notwithstanding the previous step 3 above.
5. Administering analgesic pain medication used for moderate to severe chronic pain on a fixed schedule (not as needed).

This approach is 80-90% effective.

Adjunctive medications enhance the analgesic effect, reduce side effects and assist with co-existent symptoms. Different patients will respond distinctively to different treatments regarding efficacy and side effects. Trial and error are often used in the treatment of chronic pain.

When starting therapy, the dose should be initiated at a low dose and titrated to obtain pain control and minimize side effects. Tolerance often develops as a patient gets used to the medication.

Treatment is typically started with a short-acting medication, and the medication is then titrated upwards to control pain while side effects are monitored. After determining the dose of the medication required to provide adequate pain relief with minimal side effects, the medication can be converted to a sustained release form and administered once or twice a day. When a long-acting medication is used, breakthrough medication can be given.

A periodic review of the patient's pain and clinical status is important to assure that opioids need to be continued or should be discontinued. Any change in the patient's state of health, degree or nature of pain, mental health, and overall function should be noted. The clinician and patient should review the proper dosage and schedule of medication. Decisions on benefits of pain management should focus on previously decided upon goals. Positive response to treatment can include a reduction in pain, improvement in the quality of life, or improved function.

An important role of the practitioner is prescribing controlled substances. Controlled substances have inherent risks, so the prescriber needs to realize that a primary goal of prescribing opioids should be to maintain patient safety. A responsible prescriber should follow multiple steps to assure safe and effective care of the patient.

Steps a prescriber can take include:

1. Assessment and documentation of a comprehensive history, including medical history, substance abuse history, current medications including dosages, route and time (including opioids), and psychiatric and psychosocial history.
2. Establish a physical and psychological diagnosis and medical necessity before starting or maintaining opioid therapy. Those with mental illness are at higher risk of abusing medications.
3. Screening for substance abuse history because substance abusers are at increased risk of misusing controlled substances.
4. Establishing goals in therapy regarding pain control and functional goals.
5. Using prescription monitoring programs to help determine prescription use patterns and reduce abuse of medications. These state-run databases track controlled substance prescriptions and help find issues with overprescribing and misuse patterns.
6. Urine drug testing can be used to identify non-compliance or aberrant drug use.
7. Consider contraindications prior to prescribing opioids such as acute psychiatric instability, uncontrolled suicide risk, opioid allergy, respiratory instability, history or current abuse of substances or alcohol, current use of benzodiazepines, current use of heavy doses of other central nervous system depressants, current use of other medications that have severe drug interactions or those who practice diversion of controlled substances.
8. Judicious utilization of imaging tests and other evaluations as some testing may increase fear, foster activity restriction, encourage maladaptive behaviors and encourage requests for more opioids.
9. A written agreement between prescriber and patient (see Table 1) when opioids are used reduces the risk of abuse, diversion, misuse and overuse.
10. Discuss the risks and benefits of the medications.
11. Obtaining informed consent prior to prescribing controlled substances.
12. In general, starting opioid therapy at low doses with short-acting medications.
13. Long-acting opioids in high doses only for severe, intractable pain cannot be adequately managed with short-acting opioids or moderate doses of long-acting opioids.
14. Use caution when titrating with long-acting opioids and consider the potential for overdose and misuse.
15. Considering consultation for those who require high-dose opioid therapy.
16. Being the only prescriber of all opioids for a given patient.
17. Monitoring for and managing constipation.
18. Prescribing the lowest effective dose and the smallest quantity needed based on the expected length of the pain.
19. Periodically reviewing the treatment plan, including any new information about the patient, their condition, their pain, and progress toward their goals.
20. Keeping accurate records.
21. Being compliant with all laws and regulations related to controlled substances.
22. Individualizing treatment based on the patient's prior exposure to opioids, response to treatment and adverse events.
23. Monitoring for aberrant drug-related behaviors.
24. Discontinuing chronic opioid therapy in those who repeatedly engage in aberrant drug-related behaviors, do not progress toward established goals, or experience significant side effects. Patients taking the opioid for an extended time should have the medication tapered slowly. A 10% taper per week will minimize the symptoms of withdrawal. Some recommend a faster taper, such as 20 – 50% per week for those who are not addicted (Manchikanti et al., 2012).

• Have an upper dosing threshold. The risk of accidental overdose increases with higher doses of opioids. Prescribers should generally avoid doses of morphine or morphine equivalents more than 90 - 200 mg/day (Nuckols et al., 2014).
• Use caution with certain medications. For example, methadone should only be used by a prescriber who is extremely comfortable with the medication. Fentanyl is another medication that requires extreme caution as there is unpredictable absorption – especially with the patch.
• With opioid use, respiratory depression is more likely in the older population and those who are cachectic or debilitated. Patients at high risk should be monitored more closely, and opioids should not be given in combination with other respiratory depressants. The dose of opioids should be started at one-third to one-half the typical starting dose in at-risk patients. Titration should be done carefully. Constipation is more likely, and a bowel regime should be prescribed when opioids are used.
• When starting, opioid therapy should be initially started as a therapeutic trial that may last from several weeks to several months. The decision to continue the therapy must be carefully considered based on the trial's outcomes, such as progress toward meeting goals, side effects, changes in the underlying condition causing pain and any concern for medication misuse or addiction.
• The greatest risk of opioid use is respiratory arrest and death, which is greatest when therapy is started, or the dose is increased. Opioid-induced respiratory depression is manifested by the reduced desire to breathe and reduced respiratory rates. The patient will be breathing shallowly, and CO₂ retention can exacerbate the sedating effects of opioids. If this is noted, the family should call 911.
• Opioids should not be used in those with respiratory depression. Titration must be done slowly, and when changing formulations, do not overestimate the converting dosage.
• Opioid rotation – changing from one opioid regime to another to reduce adverse events and improve therapeutic outcomes - may be considered. Tolerance to one opioid can lessen the analgesic effects, and using a different opioid may result in an improved analgesic effect and less adverse effects.
• When opioid rotation is done, the prescriber must determine the approximate equianalgesic dose. This dose is the ratio used to get about the equivalent analgesic effect. When switching from one opioid to another, the dose should be reduced by 25 – 50% to prevent adverse effects. Multiple computer programs or applications for mobile devices are available to help with this conversion.
• Avoid combinations of opioids and benzodiazepines. When these two classes are combined, particularly if more than 100 mg of morphine or morphine equivalents per day are used, the risk of accidental overdose is high.
• Pay attention to drug-to-drug and drug-to-disease interactions.

To prevent prescription drug abuse, the prescriber needs to ensure:

• Patients are assessed and reassessed
• Treatment agreements are used
• Prescription monitoring occurs
• Safe prescription methods are practiced
• Informed consent is used

Patient risks should be assessed, and contraindications should be immediately identified. Contraindications to opioid treatment include those who have an erratic follow-up, suffer from current untreated addiction or have poorly controlled mental illness (Chou et al., 2009).

Informed consent provides written documentation regarding the therapy's benefits and risks and discusses the patient's and prescriber's legal responsibilities. Informed consent improves adherence, improves the effectiveness of a treatment plan, reduces the risk of inadvertent drug misuse, lays out the potential adverse effects, including side effects and addiction, discusses how refills will happen as well as the policy of early refills and lost prescriptions/medications and discuss reasons for discontinuing therapy.

When taking a patient history, document the opioid currently prescribed, its dose, frequency, and duration of use. It is important to query the state prescription drug monitoring program (PDMP) to confirm the patient's report of prescription use. In addition, it is important to contact past providers to obtain medical records.

Before controlled substances are prescribed, a history of illegal substance use, alcohol use, tobacco use, prescription drug use, family history of substance abuse and psychiatric disorders, history of sexual abuse, legal trouble history, behavioral problems, employment history, marital history, social network and cultural background should be assessed. History of substance abuse does not prohibit treatment with opioids but may necessitate more intensive monitoring or referral to an addiction specialist.

Multiple tools to evaluate opioid risk are available. The Opioid Risk Tool is a tool that is used in primary care to screen adults for the risk of aberrant behaviors when they are prescribed opioids for chronic pain. It is a copyrighted tool, encompasses five questions and takes about one minute to administer. It classifies a patient as low, moderate or high risk for opioid abuse. Those at high risk have a higher likelihood of aberrant drug-related behavior. This tool is not validated in individuals without pain. The five questions include family and personal history of substance abuse (alcohol, prescription drugs or illegal drugs), age (risk is 16 - 45 years old), psychological disease and a history of preadolescence sexual abuse. The questions are scored with different points assigned for each question, which is variable between men and women, and a total score is tallied. The patient is placed at low, moderate or high risk.

Over the last few years, educating clinicians has been a primary focus of the medical community. This focus has led to increased awareness and safer prescribing of controlled substances. Practice guidelines disseminated among the emergency providers in Ohio were linked to a 12% reduction in opioid prescriptions per month (Weiner et al., 2017). This guideline included multiple positive steps, including assuring the clinician reviewed the prescription drug monitoring database, the patient was referred for further evaluation, reduced quantities of medication were prescribed, and education was provided about the risks versus benefits of the opioid.

Regular follow-up is important and should occur at a minimum of every 3 months and more frequently in individuals at high risk for abuse or during periods of medication adjustment (Dowell et al., 2016). Baseline evaluation of the nature and intensity of the pain and the underlying effects pain is having on a patient's physical and psychological function will help assess the treatment's effectiveness.

When assessing the patient experiencing pain, the six A's should be assessed: analgesia, addiction, activities of daily living, adherence, aberrant behaviors and adverse effects. Part of follow-up should be urine drug testing which can be used to detect medication adherence, as well as illicit and non-prescription drug use. The prescriber should adequately document any interactions with patients, assessments, results of testing and treatment plans.

Documentation should include the amount of pain relief experienced as indicated by the patient's improved ability to function physically or psychologically. It should include recommended goals (e.g., improved level of function and improved quality of life). It should also include the plan of care and methods to help patients meet their goals.

Treatment should not be continued if the patient is not making adequate progress toward their goals. In this case, modification of treatment should be considered.

Written treatment agreements between prescribers and patients when controlled substances are used help guide the conversation between patient and prescriber. It discusses expectations, the risks and the monitoring that will occur to limit the complications of controlled substances (Table 1).

Prescription monitoring programs are available in 49 states. They provide an online database that lists all prescriptions of controlled substances dispensed to each patient by pharmacies. The prescriber should check the database before prescribing controlled substances. A patient with an undisclosed prescription for controlled substances can be considered prescription drug misuse.

When abuse/misuse is detected, how should the clinician respond? If it is a single, minor deviation, then counseling and more intensive monitoring may be all that is needed. Tapering controlled substances to reduce the risk of withdrawal is appropriate in more severe or persistent cases of misuse. When diversion is the cause of misuse, immediate prescription removal is likely the best course. A referral to an addiction specialist is recommended if a substance abuse disorder is suspected.

Non-steroidal anti-inflammatory drugs (NSAIDs) are laced with risks, and some patients cannot tolerate NSAIDs due to side effects and pre-existing co-morbid conditions. The risks associated with NSAIDs are one reason many prescribers choose an opioid to manage pain. Opioid therapy effectively manages many chronic conditions, including cancer, osteoarthritis, low back pain, neuropathic pain, and postherpetic neuralgia.

Recently, opioid therapy has fallen out of favor as a commonly prescribed medication. In the distant past, it was only used for severe acute and cancer pain. In the early 2000s, opioids were one of the most commonly prescribed medications, but now only hydrocodone with acetaminophen falls in the top ten prescribed medications (Fuentes et al., 2018).

A position paper from the American Academy of Neurology suggested that there is evidence for good short-term pain relief with opioids. However, no good evidence exists for continuing pain relief or improved function for extended periods without sustaining serious risks of dependence, overdose, or addiction (Franklin, 2014).

When non-opioid therapy is ineffective, or there is severe nociceptive pain, opioid therapy is often used. In chronic back pain, opioids do not improve pain scores more than non-opioid therapy (Martell et al., 2007). Opioid therapy is often used to manage neuropathic pain but is commonly thought to be the second line to antidepressants and anticonvulsants.

In 2011, the White House Office of National Drug Control Policy was introduced to address prescription drug abuse. It supported states in expanding prescription drug monitoring programs, worked to eliminate "pill mills," and educated healthcare providers and patients.

In West Virginia, multiple bills were passed regarding substance abuse and controlled substances. This bill was likely in response, at least partly, to the 550% increase in death rates from unintentional poisoning between 1999 and 2004 (CDC, 2007). State Bill 437 required providers who dispense, prescribe or administer controlled substances to have an education. State Bill 365 provided all pharmacies online access to a controlled substance database. State Bill 362 provided more legislation prohibiting patients from obtaining prescriptions by providing false information. State Bill 81 required prescriptions to be written on tamper-proof pads.

Hospitals and pharmacies are important players in assuring the safe use of controlled substances. The Food and Drug Administration (FDA) is responsible for assuring the safety of the drug supply in the United States. They require the pharmacy to confirm that prescribers and organizations they work with are licensed and registered with the FDA. Under the FDA, the hospital must investigate and handle suspicious or known illegitimate prescriptions.

The Drug Enforcement Agency (DEA) regulates the distribution of controlled substances. The DEA is responsible for enforcing laws and regulations related to controlled substances. They also have the authority to bring about criminal or civil charges to individuals or organizations involved in illicit traffic of controlled substances.

The Environmental Protection Agency (EPA) helps assure that there is proper disposal of pharmaceutical waste to help assure that there is little pharmaceutical waste in the environment, such as in the ground and drinking water. The EPA has regulations that the pharmacy must follow (Modern HealthCare, 2018).

Patient education is important as it will reduce the risks associated with these medications and improve pain management. Patients need education in the safe use, storage and disposal of opioid medications. Safe use of opioids requires the patient to know about adverse events and risks of abuse, misuse and addiction.

An overdose occurs when someone takes a higher dose than the body can tolerate leading to a significant adverse effect. Respiratory depression is the primary risk. This risk is highest in those who are not tolerant to opioids, take other respiratory depressants, have multiple health conditions, have debilitated health, or have impaired respiratory function.

Medications associated with a high risk of respiratory depression are schedule II opioids. Fentanyl, a synthetic opioid pain reliever, is 50 to 100 times more potent than morphine and has been implicated in many cases of overdose death. Medications that are altered for administration also increase the risk of overdose. Snorting, injecting, inhaling, chewing, or dissolving medications that should be swallowed whole (particularly extended-release opioids) increases the risk. Other methods that may lead to overdose include rapid titration of opioids and overestimating the dose when converting from one opioid to another. Overdoses also occur when the medication is taken by someone it was not prescribed, especially children. Therefore, safe storage and disposal are critical.

Information on abuse should be taught to the patient. Many patients, who end up abusing opioid medications, usually get a valid initial prescription. Most patients who abuse medications get them - either by buying or stealing - from an acquaintance (typically a friend or relative) (CDC, 2014).

Patients should also be taught about misuse. Many patients will misuse medications because they seek to improve function, have uncontrolled pain or are using them to manage stress or mental disease. Aberrant behavior may be seen in those who are undertreated for pain. In the absence of addiction, these behaviors cease when pain is adequately controlled.

Patients should also be taught that drug diversion will not be tolerated. It will immediately terminate the prescription with referral to a substance abuse program and possible legal action.

Patients should be taught about addiction. Addiction is a chronic disease with psychological, social, genetic, and environmental factors influencing its presentation and development. Addiction presents with a drug craving, compulsive use, impaired control, and continued use despite harm.

Drug Take-Back Programs provide a convenient way for patients to dispose of unneeded, expired, or unused controlled substances. If no program is available, the patient must use extreme caution when disposing of controlled substances. Improper disposal may lead to environmental complications or drug diversion. Controlled substances can be mixed with cat litter or coffee grounds and then sealed in a non-leaking container.

Key points in patient education include:

• Goals of treatment.
• Alternative treatment options.
• Patients should be encouraged to read their medication guide or package insert every time they get a new prescription.
• Teach about abuse, addiction, misuse and diversion.
• Risks of overdose or death if the dose is not taken exactly as prescribed or if someone else takes the medication.
• Pain medications may impair breathing.
• Do not give the medication to anyone else.
• If anyone else takes the mediation, emergency services should be contacted.
• Swallow whole pills meant to be swallowed – do not crush, snort, chew, inhale or take any other means other than the method prescribed.
• Maintain contact with the prescriber for monitoring and titration.
• Teach about drug-to-drug interactions. Medications that should be avoided in combination with opioids include alcohol or medication that has not been prescribed. Medications that should only be taken after a careful review and counseling by a prescriber include sedatives, hypnotics, anxiolytics, antidepressants and antihistamines.
• Opioids may lead to cognitive impairment and affect driving ability or safety at work, especially when operating heavy equipment.
• Opioids should be stored safely and away from family members, acquaintances, and friends.
• Medications should be locked up in a drawer, cabinet or safe – so no one else will get them.
• Educate patients that giving away or selling their medications to others is illegal and dangerous.
• Patients should keep track of the number of pills, capsules, etc. - so it can be determined if any are missing.
• Do not store them in a pill reminder container.
• Teach about common side effects: sedation, drowsiness, respiratory problems, dizziness, mental status changes, nausea, vomiting, constipation, anxiety, tremors and diaphoresis.
• Monitoring will take place in the form of pill counts, urine drug screens and the use of the prescription drug monitoring program. Unfavorable results may lead to termination of treatment or alteration in the treatment plan.

Discontinuation of opioid therapy may be considered if problematic patterns are noticed, opioid therapy is ineffective, or goals are not achieved. The prescriber and patient must agreed-upon reasons to terminate therapy before initially prescribing the medications. This plan should be part of the initial agreement.

The clinician should have a method for addressing prescription drug misuse. Minor infractions may result in patient counseling and intensifying monitoring activities. More severe behaviors may require the clinician to discontinue prescribing controlled substances. If patients are found to be diverting prescription medication, immediate cessation of the prescriptions is appropriate. In most other cases, it is appropriate to taper the controlled substances to reduce the risk of inducing a withdrawal syndrome.

When stopping the medication, the patient and prescriber must agree. For patients who decide to continue treatment with another prescriber, the prescriber may consider maintaining the current dose for 4 weeks.

When appropriate, a tapering schedule should be implemented to avoid withdrawal. A reduction of 10% every 7 to 14 days until the patient gets to a lower dose may be made at a 5% reduction every 2-4 weeks.

Individuals who have shown aberrant behavior should be offered other non-opioid options. Patients who have engaged in criminal activity (such as diverting drugs or altering prescriptions) should be referred to a substance abuse treatment program and discharged from the practice.

West Virginia has a controlled substance monitoring act that records and retains information about the prescribing, consuming and dispensing controlled substances. This monitoring is established in West Virginia Code, Chapter 60A, Article 9. This Chapter/Article discusses access to the West Virginia Controlled Substance Monitoring Program database.

The database must be registered for and accessed when a pain-relieving controlled substance is prescribed to manage chronic, nonmalignant pain in individuals not suffering from a terminal illness. The database should be evaluated for undisclosed prescriptions of controlled substances, which is a sign of misuse or may indicate diversion or addiction. In addition, at least annually, the prescriber who continues to treat the patient should access the database for information regarding the patients they are treating with controlled substances for nonmalignant pain. The information obtained from the database should be documented in the patient's medical record. It can also confirm controlled substance prescriptions when a patient presents in an acute care setting.

The program's goal is to keep the prescribers/dispensers informed, allowing them to evaluate patients better and identify patients who may be abusing, misusing, or diverting controlled substances.

The data is secure and can only be accessed by prescribers and dispensers who have been credentialed, and they must agree to maintain confidentiality to use the information. Misuse of the site may lead to civil penalties and disciplinary action.

Prescribers in West Virginia must register at www.csappwv.com.

Drug diversion is the use of legal drugs for illegal purposes or the use of prescription drugs for recreational purposes and is a key concern in the use of controlled substances.

Drugs can be diverted through multiple methods. Diversion may occur on any level from the patient, prescriber, other healthcare providers or pharmacist.

Patients' methods to obtain medication for illicit use include: influencing or forcing prescribers to write the prescription, changing the prescription, getting multiple prescriptions for the same drug, or writing their prescription.

Healthcare professionals may also be the source of diversion. The prescriber can be engaged in drug trafficking or selling medications for money or sexual favors. The prescriber may also steal the drugs, make poor decisions or may not recognize diversion.

The pharmacist may be the source of diversion. The pharmacist may dispense medications based on incomplete information on the prescription, not catch obvious fraudulent attempts by the patient or not check the accuracy of the physician's DEA number.

Other methods of diversion include theft, losses during transportation or internet pharmacies.

Methods to obtain drugs illegally include:

• Burglary/robbery
• Stealing prescription pads and writing prescriptions
• Faking injuries
• Doctor shopping
• Prescription forgery – photocopying, changing numbers on the prescription
• Fraudulently phoned in prescriptions

Techniques to reduce drug diversion are:

• Write in ink
• Writing out numbers makes it difficult to modify numbers on prescriptions
• Use electronic prescribing
• Mark the number of refills – mark through the unused portions
• Lock up the prescription pad

It is very difficult to deal with a patient with a chief complaint of severe pain who wants opioid therapy. It is important to understand the motivations of patients who seek drugs. Do the patients have pain or are they looking for controlled substances for nonmedical purposes?

Prescribers often want to trust their patients, or they do not want to confront the patient about their medication habits. Prescribers want their patients to be happy. In addition, time is often a factor and taking time to assess the patient, including their physical, psychological and social state, takes much more time than just writing a prescription.

Good communication is important to help deal with drug-seeking patients. Prescribers must be empathetic and acknowledge that the patient is suffering. Providers must maintain confidentiality and privacy to assure that the patient is comfortable.

When communicating with the patient, confidently present information. Question patients using open-ended questions to promote honesty and document well, including the patient's assessment and agreements.

Having firm office policies is important in managing patients being prescribed opioids. Generally, prescribing opioids at the first visit should be avoided. The policies should include the frequency and timing of refills. It should be documented that patients are aware of these policies.

The use of a pain management contract should be utilized. Providing the patient with an understanding of how long the medication will be prescribed should be done. This understanding is particularly true for an acute injury or a surgical procedure where pain typically improves.

Prescribers must be aware of problematic behaviors. Behaviors highly suggestive of a substance abuse disorder include legal problems, using medications not as prescribed, getting medications through nonmedical channels, reduced function at work or home and concurrent abuse of other drugs or alcohol. Behaviors that may suggest addiction include: requesting specific medications, increased dosage needs, missed appointments and requesting more medications.

Sara is a 42-year-old physical therapy assistant with chronic back pain due to a herniated disc and spinal stenosis, first diagnosed after lifting a patient four years ago. She currently rates the severity of her back pain as an 8/10 and has been unable to work due to her pain. The pain is described as dull and constant with occasional sharp exacerbation in the low back, with the pain increasing with bending, prolonged standing and walking. The patient denies any loss or change of bowel/bladder control, history of IV drug use, recent infection, progressive neurological complaints, night pain, night sweats, weight loss or fever. The pain occasionally radiates into the right buttock. The patient can do all her ADLs but reports poor sleep at night.

She has no significant past medical or surgical history.

She has had multiple rounds of physical therapy, chiropractic treatment and numerous medications. She tried to control the back pain on acetaminophen, naproxen, ibuprofen, the lidocaine patch and topical NSAIDs without relief. The patient experienced a possible seizure while on tramadol. Epidural injections did not help. Surgery was discussed, but the patient refused this option.

Sara is single, and now that she is not working, she has limited financial means. She reports having a problem with drinking in her twenties but has not had a drink in three years. She currently smokes. She denies any history of substance abuse and has no family history of alcohol or substance abuse.

Physical examination showed a patient with a slow, deliberate gait and a limited range of motion in the spine with no obvious deformity, swelling or erythema. There is mild tenderness on the right side of the spine from L4 to S1 and tenderness in the right sacroiliac joint. Normal reflexes, sensation, strength, and no atrophy are noted in the lower extremities. The straight leg raise test is normal.

An MRI was done one year ago that was significant for a herniated disc at the L5/S1 level and mild spinal stenosis.

The Opioid Risk Tool was administered and determined that the patient is at low risk for opioid abuse. She signed a written opioid treatment agreement that outlines the conditions of opioid therapy. The state prescription drug monitoring program was queried and showed no suspicious activity.

The patient is prescribed hydrocodone/acetaminophen 5 mg/500 mg; two tablets every six hours as needed (56 tablets) for 1 week.

Five days later, she calls for an early refill and reports that the medication is not helping her pain, and she just lies around all day.

She comes back into the office for re-evaluation and reports she needed to take more pain medication than prescribed. It was reviewed with the patient that she violated the opioid agreement. A urine sample showed no illicit substances or medications that would not be expected in the urine. The prescription drug monitoring program did not show that she got any other prescriptions in the interim.

She was referred to a psychiatrist and a pain specialist. She was agreeable to both. She was able to get into the psychiatrist within one week, but the specialist pain appointment was three weeks out. The patient saw the psychiatrist, and he diagnosed the patient with depression and started her on duloxetine (which may also help with pain). The psychiatrist was unable to make an assessment related to opioid abuse.

With the help of the pain specialist, oxymorphone ER 5 mg was ordered every 12 hours. The patient was told to follow up in one week to assess effectiveness. After one week, the patient reports she is more functional but still in a lot of pain. The dose of oxymorphone ER was increased to 10 mg every 12 hours. After one more week, she was given oxymorphone IR 5 mg to be used one hour before exercise. This prescription allowed the patient to function well and participate in an exercise program. The patient was ordered a bowel stimulant (Senna) with a stool softener (Colace) to prevent constipation.

The patient was prescribed fourteen pills of oxymorphone ER 10 mg (to be taken twice a day) and seven pills of oxymorphone IR 5 mg (to be taken once a day before exercise) once a week.

The use of controlled substances is laced with risks for the prescriber and the patient. Abuse, misuse, drug diversion and overdose are all potential complications of opioid use.

Prescribers must be knowledgeable in pain assessment, knowledge of addiction and the appropriate management of pain. Multiple techniques are important to implement to reduce the risks associated with opioid therapy, including informed consent, controlled substance agreements, screening for drug abuse, patient education, teaching patients about proper storage and disposal of medications and monitoring patients using controlled substance monitoring programs.

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