Safe and Effective Prescribing of Controlled Substances for APRNs Nursing CE Course

3.5 ANCC Contact Hours 3.5 ANCC Pharmacology Contact Hour(s) AACN Category A

Disclosure Form

The purpose of this course is to discuss and introduce the basic tenets of safety that must be observed by advanced practice registered nurses (APRNs) who are actively treating patients with prescribed controlled substances.

By the end of this module, the APRN should be able to:

  • Describe the epidemiology of substance use disorder, the three different classes of controlled substances most commonly misused: indications, risks, benefits, common adverse effects, and alternatives for opioids, central nervous system (CNS) depressants, and stimulants.
  • Define medication tolerance, dependence, and addiction.
  • Discuss general guidelines for safe prescribing practices.
  • Discuss pain management, including both acute and chronic pain, and special considerations for controlled substance use in the elderly and pregnant populations.
  • Review the special circumstances involved in palliative medicine and end-of-life care.
  • Review the prevention, screening, and signs of potential substance use disorder and addiction.
  • Describe appropriate response to and current treatment options for substance use disorder and addiction.
  • Review the New York State and federal requirements for prescribing controlled substances.

The Epidemiology of the Misuse of Controlled Substances

According to the 2018 National Survey on Drug Use and Health conducted by the US Department of Health and Human Services Substance Abuse and Mental Health Services Administration (SAMHSA, 2019), 2.9 million people age 12 and older misused prescription pain medications in the past month, and an estimated 9.9 million people misused pain medications in the past year. While nearly 10 million seems large at first, it represents only 3.6% of the US population. The most commonly misused medications were hydrocodone products. Of those who misused pain medications in the last year, 63.6% report that they misused due to physical pain; 51% obtained the last medications they used from a relative or friend, and 36.7% acquired them through a valid prescription written by one or more provider. The number of current misusers of tranquilizers/sedatives and stimulants in 2018 was estimated at 1.8 million and 1.7 million, respectively (SAMHSA, 2019). The Centers for Disease Control and Prevention (CDC, 2020) estimates that opioid overdose killed nearly 47,000 people in the US in 2018, and 32% involved prescription opioids. According to the US Drug Enforcement Agency (DEA), nurse practitioners, nurse midwives, and physician assistants (PAs) are legally permitted to prescribe schedule II-V medications within the states of Florida and New York at this time, amongst many others (DEA, 2020).

Controlled Substances: The Basics

The three categories of controlled substances that are most commonly misused or abused include opioids, sedatives/anxiolytics, and stimulants (National Institute on Drug Abuse [NIDA], 2018b). Opioids are CNS depressants usually prescribed for pain control and function as opioid agonists, by binding to mu-opioid receptors in the central nervous system to reduce or block the pain signal to the brain.  They also affect receptors in the respiratory and gastrointestinal (GI) tract and are occasionally used to treat diarrhea and cough. Tramadol (Ultram) is a schedule IV synthetic opioid commonly used to treat mild to moderate pain. Codeine (Tylenol #3) is frequently prescribed to treat mild to moderate pain or cough, either alone or in combination with acetaminophen or as a component of cough and cold formulas.  According to the US Department of Health and Human Services (USDHHS, 2019), the most common opioid agonists prescribed for moderate or severe pain include: 

  • Hydrocodone (Vicodin, Lortab, Norco): found only in combination products, usually combined with acetaminophen; may be oral tablet formulation or liquid cough syrup;
  • Oxycodone (Roxicodone, Oxycontin): available as immediate-release (IR) or extended-release (ER) formula, fast onset, available in oral tablet or solution form;
  • Morphine sulfate (Roxanol, MS Contin): available as an IR or ER formula, as well as parenteral and oral formulations;
  • Oxymorphone (Opana, Opana ER): available as an IR or ER formula, long half-life;
  • Hydromorphone (Dilaudid, Exalgo ER): derivative of morphine, but with a faster onset; available as an oral tablet, liquid, suppository, and parenteral formulations; available as an IR or ER formula (US Department of Health and Human Services [HHS], 2019; US Food and Drug Administration [FDA] Center for Drug Evaluation and Research, 2020).

They may be naturally occurring alkaloids (derived from the opium poppy plant), synthetic (human-made), or semi-synthetic. These and other common types of opioid agonists are listed in Table 1.

Adverse reactions of opioid use include respiratory depression, drowsiness, mental confusion, nausea/vomiting, dizziness, headache, fatigue, pruritus, pinpoint pupils, urinary retention, and constipation. Since these agents can induce euphoria, especially when taken in higher doses than prescribed or ingested via snorting or injection, they pose a high risk for abuse and addiction. Long-term use of these drugs can also carry the added risk of drug tolerance and hyperalgesia, which is an increased sensitivity to pain caused by damage to nociceptors or peripheral nerves (FDA Center for Drug Evaluation and Research, 2020). 

Tranquilizers, sedatives, and hypnotics are CNS depressants that are used to treat anxiety and sleep disorders by increasing the inhibitory activity of the neurotransmitter gamma-aminobutyric acid (GABA), inhibiting overall brain activity and producing a sedating or calming effect. This class includes benzodiazepines, such as diazepam (Valium), clonazepam (Klonopin), alprazolam (Xanax), triazolam (Halcion), and estazolam (ProSom). They are typically categorized as schedule IV medications and used to treat general anxiety as well as panic attacks, acute stress reactions, and occasionally muscle spasms (diazepam), seizure disorders (clonazepam [Klonopin]), or sleep disorders (triazolam [Halcion] or estazolam [Prosom]). In general, this group of medications should be used with great caution and only short-term due to a very high risk of tolerance, dependence, and addiction. Concurrent use of benzodiazepines and opioid pain medications should be avoided due to the additive sedating risks of these two groups of medications. Barbiturates, such as mephobarbital (Mebaral), phenobarbital (Luminal), and pentobarbital (Nembutal), are less commonly used medications for anxiety and sleep disorders due to their high risk of potential addiction or overdose but are still used in seizure disorders and during surgical procedures. All CNS depressants commonly cause drowsiness, confusion, and poor coordination. CNS depressants should never be stopped abruptly, but tapered off slowly, due to the risk of withdrawal symptoms, seizures, or other harmful effects. Barbiturate withdrawal can be especially dangerous and potentially life-threatening (NIDA, 2018b).

Prescription stimulants may be used to treat conditions such as attention-deficit hyperactivity disorder (ADHD), narcolepsy (a sleep disorder), severe depression, and chronic diseases that cause fatigue, such as multiple sclerosis (MS). They help improve alertness, attention, and energy level. Adverse effects include tachycardia, hypertension, and tachypnea. Previously, stimulants were used for a number of other conditions, but as the risk for addiction became evident, their use has been reduced. Dextroamphetamine (Dexedrine, Adderall) and methylphenidate (Ritalin, Concerta) enhance the effects of norepinephrine and dopamine in the brain. The dopamine enhancement, when augmented, can result in a feeling of euphoria. The effects of norepinephrine include hypertension, tachycardia, constriction of blood vessels, increased blood glucose, and bronchodilation. The public perception of the relative safety and benign nature of these medications has likely contributed to their misuse and abuse in the last two decades. Patients and their caregivers/parents should be adequately educated regarding the potential risks of nonprescription drug use, such as unsafe driving, unsafe sexual activities, and a progression to illicit substances. They are often used for nonmedical purposes to enhance mental performance, and within the military to combat extreme fatigue. Repeated misuse of stimulants has been linked to feelings of hostility, paranoia, and psychosis, and overdose can lead to hyperthermia, arrhythmias, cardiovascular arrest, or seizures.  Due to the seriousness of all of the risks associated with these medications, they are classified as schedule II. A similar stimulant used to treat narcolepsy and extreme fatigue in MS, modafinil (Provigil), works to block the reuptake of dopamine. It has a slightly safer profile and is therefore categorized as schedule IV (NIDA, 2018b; Via, 2019).

Tolerance, Dependence, and Addiction- What is the difference?

The National Institute on Drug Abuse (NIDA, 2018b) defines tolerance to medication as the gradual need for an increased dose of a particular medication over time to obtain a similar effect. The development of tolerance varies significantly from individual to individual and from medication to medication and is due to the brain's ability to adapt to its environment physically. It is a phenomenon that is not limited to pain medication or illicit drugs but is also seen in other specialties and circumstances. Physical dependence is the physiological adaptation to a medication that develops with consistent and regular use and is a component of addiction. The medication becomes necessary for normal homeostasis and functioning. This phenomenon typically correlates with opposing symptoms of withdrawal if that medication is no longer used. Addiction is a combination of physical dependence and compulsive drug-seeking behaviors despite significant negative repercussions. Misuse of prescription drugs is the ingestion or utilization of these medications in a manner, a dose, or by an individual other than prescribed. This includes taking someone else's medication or taking pain medication to induce feelings of euphoria instead of relieving pain. The medical terms substance abuse and substance dependence have been replaced in recent years with the term substance use disorder (SUD). This may refer to an individual who has become addicted to nicotine, alcohol, prescription medications, or illicit drugs (NIDA, 2018b). Separate from these, there also exists another phenomenon called pseudoaddiction, in which the patient becomes intensely fearful of being in pain. This is common in postoperative patients and usually manifests as clock-watching, asking to be awoken to receive pain medication, and hypervigilance with documenting and monitoring pain medications. Pseudoaddiction usually resolves with effective pain management treatments and the resolution of painful stimuli (in the postoperative patient, this is the healing of the surgical site). Psychological dependence occurs when the ingestion of medication becomes associated with the alleviation of discomfort, such as pain, anxiety, depression, etc. The presence of that drug then becomes a calming and reassuring presence in the patient’s life, similar to a comfort or security object (Hudspeth, 2016a).

Guidelines for Safe Prescribing Practices

APRNs have been professionally trained to effectively and safely prescribe medications to treat and manage medical conditions as a vital component of the overall treatment plan. However, the unique risks associated with controlled substances, their use, their misuse, and potential drug interactions are significant. Oftentimes, there exists limited formal pain management education in most graduate nursing programs.  The consistent and diligent review of best practices and the most recent evidence in the field of pharmacology are necessary components to a safe and effective medical practice (Hudspeth, 2016a). We will briefly highlight general safe prescribing practices all prescribers should abide by.

Prior to Prescribing

As with most medical conditions, treatment should begin with a comprehensive history and physical, including information and assessment specific to pain.  It should include a full list of current and past medical conditions, as well as a review of all medications currently being prescribed or taken (including over-the-counter [OTC]) and how they are being taken. If possible, a copy of the patient’s records from previous providers may serve to corroborate the patient’s history.  Review of systems should include questions related to controlled substances and their use, such as nausea, constipation, cognitive changes/impairment, and a full pain assessment including pain severity rating, location, quality, duration, treatment history, and aggravating/alleviating factors. The APRN should become familiar with and use the acronym of their choice for a full and consistent pain assessment every time (OLDCART, SOCRATES, OPQRST, etc.). Pain severity should be self-reported in a consistent format at each visit to allow for trend identification.  Commonly used tools for pain severity assessment include the verbal rating scale (patients choose from three to six adjectives to describe their pain ranging from no pain to severe pain), a numerical rating scale (patients choose a number between 0 and 10), a picture scale (uses multiple facial expressions indicating increasing levels of discomfort) and a visual analog scale (requests that the patient indicates their current level of pain with a handwritten mark on a 10 cm line representing a continuum of no pain to the worst pain). The descriptor differential tool is the most reliable and consistent but quite lengthy to administer. It utilizes 12 adjectives describing pain, and the patient is asked to rate each adjective from 0 to 10.  The tool chosen for each patient should be based on individual circumstances. For example, children and those with language barriers or developmental delays may be best suited for the visual analog or picture scale, while a numerical rating may suffice in an emergent or urgent care setting where time and efficiency are a concern (Hudspeth, 2016a).  

Additional components of the history should include family history, a social history, a drug and alcohol use history, and a depression screening. Family history should include substance use/abuse or psychiatric diagnoses specifically (Hudspeth, 2016a). The Pain Assessment and Management Initiative (PAMI, 2017) also recommends a family dynamic checkpoint, assessing for who is caring for the patient at home (if applicable) and the overall family dynamics. Social history should include socioeconomic status, employment status, marital status, education level, living situation, dependents, and legal issues, past or present.  Drug and alcohol use history should include questions detailing past or present use of tobacco, alcohol, illicit drugs, and the misuse/abuse of any over the counter or prescription medications in the past, including details such as timing, duration, their drug of choice, treatment obtained, pending legal decisions, etc. (Hudspeth, 2016a).  SAMHSA (2019) estimates that 9.2 million adults and over 350,000 adolescents have SUD in combination with another mental illness, which may be depression, anxiety, attention deficit hyperactivity disorder (ADHD), or various other psychological disorders. They found SUD to be more common in those with other mental health disorders (SAMHSA, 2019). In addition, most chronic pain patients have depression as a comorbidity, which can make managing their pain more difficult for the APRN if left untreated. The Beck Depression Inventory (BDI), the 9-Item Patient Health Questionnaire Depression Module (PHQ-9), and the Profile of Mood States have been shown effective in the screening of chronic pain patients (Hudspeth, 2016a).  Depression screening is also a recommendation of the US Preventive Services Task Force as of 2016. The PHQ-9 is a self-administered tool with a sensitivity and specificity of 88% that generates a score which indicates mild (score of 5-9) to severe depression (score over 20; Beebe & Utley, 2018). 

Safer alternatives should always be explored/attempted prior to initiating a controlled substance if those alternatives exist. Mild pain likely does not warrant an opioid, but non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen (Tylenol) should be trialed first (PAMI, 2017). In order to offer similar but safer alternatives to benzodiazepines and barbiturates, the pharmacology industry developed non-benzodiazepine sleep medications, including zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata). They act on the same GABA type A receptors in the brain as traditional benzodiazepines, but with a different chemical structure, thought to result in fewer side effects and less risk of dependence. They remain classified as schedule IV, with lower abuse potential, but these are newer drugs with fewer long-term studies completed at this point. They commonly cause headaches, amnesia, dizziness, and nightmares. There exist significantly safer options for insomnia that should also be discussed and offered to patients who are at high risk or otherwise simply want to avoid taking controlled substances. Melatonin is an OTC option for sleep that boosts the levels of the body's own sleep hormone, melatonin. Ramelteon (Rozerem) is a prescription option that acts as a synthetic melatonin antagonist, binding to MT1 and MT2 receptors, helping to induce sleep without any abuse or addiction potential. For anxiety treatment, there are medications available to treat anxiety that are not controlled substances and, therefore, less risky, such as buspirone (Buspar), which binds to serotonin and dopamine D2 receptors. Buspirone (Buspar) is generally better tolerated than benzodiazepines, with less drowsiness and less abuse potential (NIDA, 2018b)

In lieu of stimulants, non-stimulants are also highly effective in reducing ADHD symptoms, but they generally take longer to start working. Non-stimulants are often used in place of stimulants in patients who had unacceptable adverse effects or inadequate results with stimulants, or in combination with stimulants to enhance effects. Non-stimulants can help improve focus and attention and decrease impulsivity. Some of the most common types of non-stimulant medications include atomoxetine (Strattera), guanfacine (Tenex), and guanfacine ER (Intuniv). Atomoxetine (Strattera) alleviates inattention and hyperactivity symptoms of ADHD by selectively inhibiting the reuptake of norepinephrine. It is not a controlled substance and is thus determined to have low abuse potential. Atomoxetine (Strattera) has a slower onset, taking up to four weeks for the full effects of the medication to occur (National Institute of Mental Health [NIMH], 2016).

An opioid use disorder (OUD) risk assessment tool, a urine drug test (UDT), and a review of the state’s prescription drug monitoring program (PDMP) should be completed to enhance the prescriber's assessment of the potential future risk of abuse/misuse before any controlled substance prescriptions are given. Some options for an OUD risk assessment tool are as follows:

  • Opioid Risk Tool (ORT): a five-question self-administered tool that assesses personal/family history; screens only for future risk of drug misuse and is designed for adult patients;
  • Screener and Opioid Assessment for Patients with Pain (SOAPP)
  • Diagnosis, Intractability, Risk, and Efficacy (DIRE) aims to determine suitability for long-term opioid use.

This list is by no means exhaustive, and the most important part of screening for future risk is that the prescriber is familiar with the tool they are using, understands how and why it was developed, and trained properly in its execution and interpretation. Ultimately, a patient’s risk should be considered amongst all of the other data collected in order to make the best decision regarding appropriate treatment moving forward. Oftentimes, a high-risk score may result in a nurse prescriber referring the patient to a pain management clinic, with additional experience and expertise treating pain in more complex, higher-risk patients. Risk factors for drug misuse/abuse include younger age (18-25), women, older adults (age 58-75), a personal or family history of alcohol or drug abuse, and current psychological condition such as depression or bipolar disorder (Hudspeth, 2016a; NIDA, 2018a; SAMHSA, 2019).

Urine drug testing (UDT) can be a useful tool for baseline and periodic testing if diversion or misuse is suspected but is certainly imperfect, as false positives can occur. Hydration, drug dose, metabolism, the patient’s body mass index (BMI), urine pH, duration of use, and individual drug pharmacokinetics can all affect the results. For example, hydrocodone has been detected in the results of patients using codeine (Tylenol #3), and hydromorphone has been detected in the results of patients using hydrocodone (Vicodin) as these drugs are metabolites.  Manufacturer impurities have also shown hydrocodone amounts to be evident in oxycodone (Percocet) products. Ingestion of poppy seeds or the herb Papaveris fructus may cause positive morphine results. A negative result for a prescribed drug may indicate that the patient was not taking the drug at all, the patient was not taking the correct dose, or the results are inaccurate. A positive result for an unexpected drug could mean the patient was taking the drug illicitly, it is a metabolite of a prescribed drug, or the results are inaccurate. The cost of UDT should also be considered, discussed with the patient, and included in the initial treatment plan or patient-provider agreement (PPA, more on this later).  How the results of a UDT will be interpreted, confirmed, and used, including its effects on the continuation of treatment, should be explained to the patient prior to testing. In female patients, providers should also consider screening for pregnancy concurrently via a single urine sample/specimen (Hudspeth, 2016a). The CDC recommends baseline UDT and repeat testing at least annually for chronic opioid pain patients (CDC, 2019). 

The use of electronic databases to track controlled substance prescriptions (PDMPs) has become widespread (now available in 49 states, Washington DC, and Guam). Their purpose is to improve opioid prescribing, inform clinical practice, and protect patients at risk. States arrange individual systems to track and monitor prescriptions, but the details about use, access, which drugs are included, and the regulations and implications for prescribers vary greatly. Most states require prescribers to consult the system, and most also have a method by which users can access patients’ records in other or neighboring states as well. Currently, Missouri is the only state without a statewide PDMP. However, St Louis County has developed its own PDMP, and other counties in the state are permitted to utilize their system, so currently, 79% of the population of Missouri is covered by the St Louis County PDMP. The key to all PDMP systems is mandated real-time reporting by pharmacies, and a mandate that all providers check the system prior to prescribing controlled substances to a patient. Differences exist between the states regarding how frequently this system should be monitored by providers, and which schedules of controlled substances are included. Also, some federal agencies are beginning to participate, including the Veterans Administration (VA) and the Indian Health Services (IHS) (CDC, 2017; National Alliance for Model State Drug Laws, n.d.). The PDMP database should be reviewed initially and at least every three months for all patients receiving opioid prescriptions (Hudspeth, 2016b).  

Finally, a complete physical exam should be performed and documented appropriately prior to any prescriptions being granted and periodically throughout the treatment course (Hudspeth, 2016a). In fact, the state of New York specifies this requirement in its prescriptive rules and regulations (section 80.63).  In the presence of a new medical condition or problem requiring a controlled substance prescription, prescribers in New York may prescribe a five-day supply of controlled substance medication to a patient without performing a physical exam only in the case of an emergency if the prescriber has a prior relationship with that patient (New York State Department of Health [NYSDoH], n.d.).

Safe and Effective Treatment

After making the critical decision to prescribe a controlled substance based on all the information gathered above, what can APRNs do to optimize safety and effectiveness? Recommendations start with two important documents: informed consent and a patient-provider agreement (PPA). The informed consent is a document signed by the patient that reiterates what should be communicated directly to the patient verbally during the initial visit, prior to prescribing. It should include the specific drug being prescribed, risks, benefits, and desired outcome/goals of treatment and should be updated when medications are changed. Those goals should be collaborative. At a minimum, risks should include possible overdose, respiratory depression, development of physical dependence or tolerance, drug interactions, inadvertent ingestion by children or others, and drug misuse or abuse by the patient/household contacts/friends. If female, the risk of neonatal withdrawal syndrome if the patient were to become pregnant should also be included (Hudspeth, 2016b).  The PPA is a separate document, signed by both the provider and the patient, that covers the responsibilities/expected behaviors of both parties, the goals and potential risks of controlled substance use, and the consequences for noncompliance.  If UDTs or pill counts are to be performed periodically to assess compliance, this should be included in the PPA, as well as how medication refills and changes should be requested and obtained by the patient and handled by the office staff and providers. This provides the prescriber with a clear exit strategy should treatment need to be discontinued.  Most PPAs specify that the patient is expected to use a single prescriber for all of their controlled substance needs; some may simply limit the patient to one prescriber for pain medicine, but allow the patient to obtain prescriptions from other providers for other controlled substances (i.e., benzodiazepines, testosterone, stimulants for ADHD/ADD) (Hudspeth, 2016b).  While PPAs are recommended, there is limited scientific evidence clarifying whether or not they actively deter misuse/abuse (Albrecht et al., 2015). Quality sample informed consent forms and PPAs can be obtained through the NIH/NIDA website (NIDA, 2017a).

As with any new prescription medication, all current medications should be reviewed for potential interactions and any medication allergies/sensitivities reviewed. Due to increased risk for overdose and adverse effects, avoid combining opioids with benzodiazepines whenever possible. Moderate pain can often be managed with weaker opioids such as codeine (Tylenol #3) or tramadol (Ultram), a synthetic analog of codeine with a low affinity for opioid receptors.  Treatment for severe pain in a patient that can swallow should be started with a stronger oral opioid such as hydrocodone (Vicodin), oxycodone (Percocet), morphine sulfate (MSIR), or hydromorphone (Dilaudid).  Fentanyl (Duragesic) and methadone (Dolophine) should not be used as initial options due to their dosing challenges. Immediate release (IR) medications with a half-life of two to four hours should be started initially with opioid-naive patients until the dose is established and stable. The initial opioid prescription should be considered a trial, with a follow-up appointment scheduled at a predetermined time to review the effectiveness of the prescribed medication and overall success based on established treatment goals. Dose adjustments may need to be made as early as every two to three days. Extended-release (ER) or long-acting (LA) formulas with a half-life of 8-12 hours in the same family are commonly added later if long-term use is required.  It is recommended that prescribers become familiar with certain medications that they prefer and commonly prescribe in order to familiarize themselves with the details of those particular drugs extensively and avoid prescribing different or unfamiliar medications when possible (CDC, 2019; Hudspeth, 2016b; PAMI, 2017; Qaseem et al., 2017).

Documentation is key when prescribing controlled substances, both for safety and legal reasons. Patients’ visit notes should be clear, concise, and include all details of dose adjustments or medication changes with associated justifications and equivalency calculations. Notes should also include the effectiveness of treatments based on consistent pain assessments repeated at each visit, and any adverse effects and associated treatments required. Documentation should also specify if the patient is adhering to treatment plans as outlined in the PPA and include the results of any UDTs or pill counts.  Any concerning or aberrant behavior should be carefully documented with as much detail as possible with a clear plan for resolution and/or future monitoring. Interviews with family members and caregivers can also be included in documentation records for these same reasons. Any letters sent to patients should be included in the patient’s electronic medical record (EMR), and any phone calls made or received should be carefully documented by office staff.  Every time PDMP reports are reviewed should be documented along with any concerning findings. A decision to terminate care, which will be discussed further in an upcoming section, needs to be documented thoroughly (Hudspeth, 2016b).

Acute versus Chronic Pain Management

To alleviate pain and suffering is one of the basic tenets of medical care since its inception. Pain can be broken down into two basic categories, acute (occurring for less than three months) and chronic (longer than three months). Their care differs greatly.

Acute pain is oftentimes self-limiting, and if nonpharmacological treatments can be used effectively, they are recommended over medications. Nonpharmacological treatments such as heat, ice, massage, acupuncture, or spinal manipulation have low to moderate-quality evidence but negligible risk. If pharmacological treatment is required, treatment should start with NSAIDs and/or skeletal muscle relaxants such as ibuprofen (Advil, Motrin), naproxen (Naprosyn), carisoprodol (Soma), and cyclobenzaprine (Flexeril; Qaseem et al., 2017).  Cardiovascular, GI, and renal risks are associated with NSAIDs, so these need to be considered as well. Regarding the gastrointestinal and renal risks of NSAIDs, celecoxib (Celebrex) and other COX-2 inhibitors have been shown to be safer, and studies have shown that adding misoprostol (Cytotec), a proton pump inhibitor, or an H2 blocker is gastroprotective. The two traditional NSAIDs with the most COX-2 selectivity, meloxicam (Mobic) and diclofenac (Voltaren), may also be slightly safer than other traditional NSAIDs in regard to the increased risk of gastroduodenal ulcers and acute kidney injury, but studies have not reached statistical significance. All NSAIDs carry similar cardiovascular risk, although naproxen (Naprosyn), ibuprofen (Advil, Motrin), and meloxicam (Mobic) seem to be the least risky options in terms of cardiovascular and stroke risk. All NSAIDs appear to increase blood pressure by 5 mmHg on average and seem to increase the risk of a hospital admission related to congestive heart failure (Wongrakpanich et al., 2018). Systemic corticosteroids do not have great evidence to support their effectiveness or use and certainly have substantial adverse effects, especially in the diabetic patient (Qaseem et al., 2017).  If opioids are to be used for acute pain, as recommended by the state of New York and the CDC, all prescription quantities should be limited to no more than seven days in duration, and most can and should be limited to three days (NYSDoH, 2017). 

Chronic pain (excluding cancer patients, palliative care, and end-of-life [EOL] care) treatment, like acute pain, should always start with and include non-pharmacologic and nonopioid treatment options as above.  Other nonpharmacological treatments often used successfully for chronic pain include cognitive-behavioral therapy (CBT), exercise therapy, and physical therapy. These treatments should be tried first or incorporated with any pharmacological treatment that is deemed appropriate. Additional nonopioid medications, such as neuropathics gabapentin (Neurontin) and pregabalin (Lyrica) or antidepressants such as venlafaxine (Effexor), duloxetine (Cymbalta), or tricyclic antidepressants should also be considered.  Opioid treatment should only be added when these treatments are deemed inadequate, and the potential benefits of opioids outweigh the risks (NIDA, 2017a; PAMI, 2017; Qaseem et al., 2017). 

Goals should be agreed upon prior to treatment initiation (see PPA section above for further details on this) as well as a plan for discontinuation of treatment if benefits do not outweigh risks, and there is no clinically meaningful improvement in pain and function.  Risks, benefits, and responsibilities of both patient and provider should be clearly communicated within the informed consent and PPA paperwork so that they can be reviewed periodically whenever necessary (Hudspeth, 2016a). As above, the lowest effective dose of IR opioids should be used initially, avoiding ER or LA versions until a stable dose has been established.  The CDC (2019) recommends that primary care providers reassess risks and benefits of treatment when prescribing more than 50 morphine milligram equivalents (MME) per day and should avoid (and carefully justify) prescribing more than 90 MME/day.  According to the CDC, the risk of overdose is increased by at least twice in patients taking 50 MME/day or more, as compared to patients taking less than 20 MME/day. 50 MME/day is about 50 mg of hydrocodone (Vicodin) or 33 mg of oxycodone (Percocet) per day.  Prescribers should become familiar with access to a calculator to regularly, quickly, and accurately determine a patient’s current MME and use this formula during any medication dosage changes, and for transitions between different medications to establish equivalent dosages (CDC, 2019).  Several exist online, including the CDC, Centers for Medicare & Medicaid Services (CMS.gov), and NYC.gov (CDC, 2019; City of New York Department of Health n.d.a).  The CDC has come under some scrutiny recently for its 2016 published opioid guidelines, being called too strongly anti-opioid.  Certainly, these calculators can have their limitations and complicated exceptions (Fudin et al., 2018). Variations and exceptions need to be made to account for variability in the pharmacologic properties of each medication and patient individuality when changing from one opioid to another, and extreme caution should be used to limit the risk for incidental overdose or underdose. When initiating or increasing the dose of opioids, follow-up within one to four weeks is recommended to assess benefits and any harms; once stable, follow-up every three months is suggested (CDC, 2019).

Extreme caution should be used when prescribing methadone (Dolophine), which is extremely complicated to dose and requires specialized training for prescribers and is only administered in opioid treatment programs (OTPs) (USFDA Center for Drug Evaluation and Research, 2020). If an APRN makes the decision to prescribe methadone, the CNP should be able to provide evidence of appropriate education to manage this drug. The half-life of methadone is significantly longer than morphine (8-59 hours), with lipophilic storage, so great care should be taken with this drug in order to treat pain safely.  However, the low cost and ease of availability often make methadone (Dolophine) an attractive option if used carefully by a skilled and experienced prescriber (Hudspeth, 2016b). Similarly, tapentadol (Nucynta) is a centrally acting analgesic with an added mechanism of norepinephrine reuptake inhibition in addition to its mu-receptor agonism (USFDA Center for Drug Evaluation and Research, 2020).

In the state of New York, APRNs, PAs, and physicians are able to certify patients for medical marijuana. Patients must meet certification qualifications with a listed qualifying diagnosis, such as severe chronic pain, OUD, or as a replacement for opioids.  Prescribers must have a valid state license, DEA registration number, complete a four-hour state-approved course in medical marijuana, and then register with the state to participate and begin certifying patients. Patients are diagnosed and certified by a registered prescriber and then must register with the New York State Department of Health to obtain a registry ID card in order to purchase medical marijuana products. This pain control option may help limit the use of opioids, even in patients with acute or postoperative pain (NYSDoH, 2020).

Special Considerations: The Older or Pregnant Patient

Special consideration should be taken when prescribing for older (over age 65) or pregnant patients. Pain is more common in the elderly, and aging causes physiological changes that affect the absorption, metabolism, and excretion of medications. For these reasons, medications should be started at the lowest possible dose and gradually increased only as needed (start low and go slow). It may also be helpful, in opioids, to initiate a bowel program to prevent constipation. The 2015 American Geriatric Society Beers Criteria (BC) of potentially inappropriate medication use in older adults publishes medications that should be avoided (Terrery & Nicoteri, 2016). Included in the most recent version are the following recommendations:

  • Benzodiazepines should be avoided for insomnia, agitation, or delirium due to fall risk and high rate of physical dependence, especially longer-acting versions.
  • Non-benzodiazepine, benzodiazepine receptor agonist hypnotics (eszopiclone [Lunesta], zaleplon [Sonata], zolpidem [Ambien]) should be avoided for insomnia regardless of duration due to fall/fracture risk and high rate of physical dependence, especially in patients with dementia/cognitive impairment.
  • Opioids should be avoided in those with a history of falls or fractures.
  • Antipsychotic drugs should be avoided as a first-line treatment for delirium unless the patient is a threat to self or others due to increased risk of stroke and mortality in the elderly with dementia and olanzapine (Zyprexa) syncope.
  • Tricyclic antidepressants and skeletal muscle relaxants (cyclobenzaprine [Flexeril], carisoprodol [Soma]) should be avoided/used with caution secondary to anticholinergic effects.
  • Indomethacin (Indocin) and ketorolac (Toradol, PO and IV) should be avoided due to risk of gastrointestinal (GI) bleeding and kidney damage, replaced instead with celecoxib (Celebrex), nabumetone (Relafen), naproxen (Naprosyn), or ibuprofen (Motrin, Advil) in combination with proton pump inhibitor for GI prophylaxis (Terrery & Nicoteri, 2016)

In 2014, the FDA removed the older system of ranking medications for pregnant women (Category A, B, C, D, and X), and now requires detailed specific information about pregnancy safety (including during labor and delivery), safety while breastfeeding, and safety for females and males of reproductive potential. Opioid use in pregnancy is not well studied, but there has been no evidence for an increased risk of minor or major fetal malformations.  The most substantial risks are that of potentially fatal neonatal withdrawal syndrome, lower birth weight, and premature birth, but animal studies have shown no evidence of teratogenicity. Opioids are excreted in breastmilk and increase the risk for CNS and respiratory depression if taken while breastfeeding. These risks can be minimized by using the lowest effective dose to achieve pain control, but the patient should be very well informed of all of these risks prior to issuing any opioid or controlled substance prescriptions.  Acetaminophen can be used in pregnancy and while breastfeeding relatively safely. NSAIDs should be avoided in pregnant patients, especially during the first trimester and after 30 weeks gestation, due to the risk of bleeding and risk of premature ductal closure. NSAIDs appear safe to use during breastfeeding, however. Benzodiazepines were a category D and should be avoided in pregnant and breastfeeding patients, as they are known to cross the placenta and are excreted in breastmilk.  They have been shown to increase the risk of congenital abnormalities, especially if used in the first trimester. Other risks of benzodiazepine use during pregnancy include postnatal withdrawal symptoms, neonatal flaccidity, respiratory and feeding difficulties, and hypothermia.  Zolpidem (Ambien) was category C in the old system due to a lack of evidence. Cases have been reported of severe neonatal respiratory depression, withdrawal, and flaccidity, but no teratogenicity has been observed, although animal studies showed issues with skeletal ossification at high doses. Zolpidem (Ambien) is excreted in breastmilk, and caution should be advised. Stimulants, such as methylphenidate (Ritalin, Concerta), were a category C and are not well studied in pregnant women but were shown to cause congenital abnormalities at very high doses in animal studies.  It is unknown if methylphenidate (Ritalin, Concerta) is excreted in breastmilk, but amphetamines are (Hudspeth, 2016b; USFDA Center for Drug Evaluation and Research, 2020).

Buprenorphine (Sublocade) and methadone (Dolophine) both appear to be safe and effective for the treatment of OUD in pregnant patients. Studies indicate that methadone (Dolophine) is associated with improved treatment retention in pregnant patients and appears to be better tolerated when divided into more frequent but smaller doses throughout the day to reduce peaks/valleys of medication in the mother's/newborn's system. By comparison, buprenorphine (Suboxone) treatment appears to result in 10% fewer symptoms of NAS, a shorter neonatal treatment time, and less morphine (Roxanol, MS Contin) required for NAS treatment as compared to methadone (Dolophine; NIDA, 2017b).

Cancer, Palliative, and End-of-Life Care

The treatment of cancer pain is extremely complex and is usually best managed by oncologists, not APRNs. The patient’s disease prognosis, concurrent medications, and individual goals of care should be considered (Hudspeth, 2016b). The treatment of pain for terminally ill patients does not typically conform to the aforementioned standard regulations. Within the care of these patients, there is less concern for misuse, abuse, or addiction, and more focus can be placed on effective pain relief.  Concerns within these populations continue to be overdose, respiratory depression, and potential loss of consciousness or hastening of end-of-life. Medications should be increased gradually and only as tolerated, with the full consent of the patient or their proxy medical decision-maker/guardian or via an intact living will or advance directive. The patient and/or caregivers should be fully informed of these potential risks of increased opioid doses, but if pain relief is prioritized by the patient and family over the length of life, that decision should be accepted and respected by the care team. It is generally accepted that clinicians should never withhold needed pain medication from terminally ill patients for fear of hastening death if they have received informed consent from the patient to do so.  Loss of consciousness should not always be assumed to be directly caused by high doses of opioid painkillers in the dying patient if those doses have been stable or slowly increasing over time, especially in chronic cancer pain.  Loss of consciousness in this population is more commonly related to metabolic encephalopathy, infection, or brain metastases (Berger et al., 2013).  There is no legal protection for assisted suicide or euthanasia in the state of New York, but the state Task Force on Life and the Law developed a report, originally published in 1994, which sheds light on the legal protections in the state of New York for the treatment of pain in the terminally ill patient as follows:

“Professional medical standards should recognize the provision of effective pain relief and palliative care, including treatment for depression or referral for treatment, as a basic obligation all physicians owe to their patients. Physicians should seek their patients' participation in decisions about withdrawing or withholding life-sustaining treatment early enough in the course of illness to give patients a meaningful opportunity to have their wishes and values respected. Health care professionals have a duty to offer effective pain relief and symptom palliation to patients when necessary, in accord with sound medical judgment and the most advanced approaches available. New York State statutes and regulations should be modified to increase the availability of medically necessary analgesic medications, including opioids. This should be done in a balanced manner that acknowledges the importance of avoiding drug diversion. Physicians, nurses, and patients must be aware that psychological dependence and physical dependence on pain medication are distinct phenomena. Contrary to a widely shared misunderstanding, psychological dependence on pain medication rarely occurs in terminally ill patients.  While physical dependence is more common, proper adjustment of medication can minimize negative effects. The provision of appropriate pain relief rarely poses a serious risk of respiratory depression.  Moreover, the provision of pain medication is ethically and professionally acceptable even when such treatment may hasten the patient's death, if the medication is intended to alleviate pain and severe discomfort, not to cause death, and is provided in accord with accepted medical practice" (New York State Task Force on Life and the Law, 2011).

Prevention, Screening, and Signs/Symptoms of Drug Abuse/Misuse

The prevention of misuse and abuse of controlled substance medications should start with the provider; specifically, experts recommend formal continuing education regarding indications, risks, and benefits of these medications and safe prescribing practices to guide medical decision-making using the best evidence possible to limit risk to the patients and society. An honest dialogue with the patient regarding risks, benefits, treatment goals, treatment alternatives, and expectations of both parties prior to prescribing can help prevent misuse of potentially dangerous medications.  This includes the use of aforementioned informed consent and PPAs, with updates and changes to these documents as treatment is adjusted over time. A good professional relationship with the network of local pharmacists who are familiar with the local prescribers can also be helpful in monitoring for altered, falsified, or otherwise suspicious looking prescriptions (Hudspeth, 2016b; NIDA, 2018b). Regarding stimulant abuse, studies indicate that the prompt, appropriate, and long-term treatment for ADHD benefits the patient’s mental wellbeing and decreases the risk of substance abuse rather than increasing it, as their mental health needs are being adequately met. The Coalition to Prevent ADHD Medication Misuse is an online resource that launched in 2016 to provide healthcare providers and others with information on how to discuss and prevent the misuse and diversion of prescription stimulants (Via, 2019).

For patients, misuse and abuse can best be prevented by taking their medications (and only their medications) exactly as prescribed, discussing any changes with the prescriber prior to enacting a change in strength or dosing frequency, and safely storing medications to avoid intentional or accidental use by anyone other than the patient for which they were prescribed. Per the FDA, any expired or unnecessary medications should be deposited at a registered take-back event or location or disposed of in the household trash (pills should be mixed with dirt, coffee grounds, or cat litter and disposed of with the household trash sealed in a plastic bag, and all empty pill bottles should be thrown away separately after blacking out all prescription detail information). If no drug take-back program is readily available, used or unwanted fentanyl patches and other medication can be flushed down the toilet if necessary (Hudspeth, 2016b; NIDA, 2018b). 

Manufacturers of medication are studying and trialing various methods to make medications less vulnerable to abuse or misuse, called abuse-deterrent formulations (ADF).  This includes physical or chemical barriers to prevent dissolving, grinding, or crushing, agonist/antagonist combinations or aversive substances added that are released if the product is manipulated or taken in a way other than directed, delivery systems that are implanted or injected to slowly release long-acting medication over time, or new molecular entities/prodrugs that renders a drug inactive unless it is taken orally. From an administrative or regulatory perspective, misuse may be prevented with additional regulation. This was the case in 2014 when hydrocodone (Vicodin) was moved to a schedule II category drug by the DEA. Additional research is ongoing regarding medications that target alternative pathways, such as the endocannabinoid system, and further research is needed on the effective treatment of chronic pain and risk factors that lead some patients to SUD (Hudspeth, 2016b; NIDA, 2018b).

Screening for drug abuse/misuse should not only include the formal screening tools mentioned above prior to starting any controlled substances but may also include:

  • Current Opioid Misuse Measure (COMM), a 17-item questionnaire for current opioid users which assesses for signs and symptoms of abuse, psychiatric disorders, evidence of willful dishonesty, provider visitation patterns, and medication noncompliance;
  • Tobacco, Alcohol, Prescription Medication, and Other Substance Use Tool (TAPS)- a self-administered tool that combines screening, and if positive, a brief assessment for adult patients;
  • NIDA Drug Use Screening Tool: Quick (NM ASSIST) is a clinician-administered tool for adult patients; the American Psychiatric Association's adapted version NIDA-modified ASSIST is a self-administered version;
  • CAGE Adapted to Include Drugs (CAGE-AID): a brief questionnaire based on the original CAGE tool utilized for alcohol;
  • Screening to Brief Intervention (S2BI) and Brief Screener for Alcohol, Tobacco and other Drugs (BSTAD) are both self-administered tools designed specifically for adolescents;
  • Prescription Drug Use Questionnaire-Patient (PDUQ-P), a patient-administered tool;
  • Pain Medication Questionnaire (PMQ), a patient-administered tool;
  • Addiction Behavior Checklist (ABC), a clinician-completed questionnaire (Cheattle, 2019; Hudspeth, 2016a; NIDA, 2018a).

As previously stated, periodic review of the state’s PDMP (and possibly neighboring states depending on proximity to the state line), pill counts, and UDTs should also be an important aspect of screening for misuse.  Also, the APRN spending a few minutes talking with the patient about their pain and treatment plan, current medication usage, along with an invitation for any questions and concerns, using open-ended questions and nonjudgmental language cannot be understated (Hudspeth, 2016a). 

There exist some red flags that a patient may be misusing or diverting controlled substances. These include rapid increases in the amount of medication needed, frequent/unscheduled refill requests, repeated dramatic stories about prescriptions or medication being lost or stolen, multiple visits with multiple providers or pharmacies, resistance to nonopioid and nonpharmacological treatments, or frequent after-hours calls to the on-call prescriber or trips to the emergency department resulting in prescriptions.  Prescribers should be aware of the common pitfall of assuming a well-liked or well-known patient is at lower risk for abuse/misuse.  Patients that repeatedly delay needed or planned surgeries and opt instead to treat with an otherwise correctable condition with medications should be monitored closely. There is data supporting the prescribing or offering of naloxone (Narcan) as a potential overdose reversal agent in high-risk patients exhibiting disturbing signs or symptoms of drug misuse that the prescriber deems aberrant. In these patients, careful consideration should be given to referring patients to a pain management or addiction specialist; if not, documentation should thoroughly and extensively describe why this was not done (Hudspeth, 2016b).

Being aware of the signs and symptoms of addiction will allow the APRN to identify patients, coworkers, or even family/friends that may be struggling with addiction. The signs and symptoms of addiction may include:

  • Lack of energy or motivation;
  • Changes in weight;
  • Conjunctival injection (red or bloodshot eyes);
  • Sudden change in appearance (lack of interest in clothes, grooming);
  • Changes in behavior (sudden insistence on privacy, being secretive, different friends);
  • A need to use the substance regularly;
  • An obsession with protecting or maintaining a steady supply of the substance;
  • Financial issues- spending large amounts of money to obtain the substance without regard for the availability of those resources, requests for money without an explanation, reports of missing cash or valuable personal items from those around the user;
  • Decrease in grades (adolescents) or performance at work (adults);
  • Doing immoral/illegal/unethical things to obtain the substance;
  • Engaging in high-risk behavior while under the influence of the substance, such as driving (Mayo Clinic, 2017).

Overdose Management

Naloxone (Narcan) is an opioid antagonist that functions by blocking opioids from binding to and activating mu-opioid receptors in the CNS and can be used as a reversal/rescue drug in the case of an opioid overdose. It can reverse the respiratory depression seen in patients who have ingested large amounts of prescription opioids or heroin within two to five minutes and can be repeated if no response is seen at that time. It can be administered by first responders and emergency medical providers as well as bystanders. It typically stays in the patient’s system for 30-90 minutes, depending on the patient’s body mass, metabolism, renal status, as well as the health and functioning of other physiological processes, and the patient may require more than one dose depending on the half-life of the opioid ingested. It is given as a nasal spray or intramuscular injection.  While it is an effective opioid antagonist, it has no reversal effect on tramadol, alcohol, CNS depressants, or stimulants.  If ineffective after two doses, other explanations for the patient’s symptoms should be explored and considered, including benzodiazepine overdose; other treatments, such as flumazenil (Romazicon, a benzodiazepine antagonist) should be attempted.  Administration of naloxone (Narcan) causes symptoms of opioid withdrawal, including sweating/chills, nausea, vomiting, agitation/anxiety, fever, rhinorrhea (runny nose), lacrimation (watery eyes), hypertension, shivering/shaking, yawning, fever, dilated pupils, piloerection (involuntary erection of body hairs) and muscle aches. Prescribers should consider this safety option in patients currently taking a high dose of opioids (above 90 MME/day), chronic opioids (greater than three months), concurrent opioids and benzodiazepines, current ongoing treatment for SUD, past history of opioid misuse or overdose, or immediate family members with a history of opioid misuse or overdose.  A naloxone (Narcan) prescription should also be considered during periods of transition from one opioid to another in case of accidental overdose.  Patients in secluded rural settings or those with chronic respiratory disease, current alcohol use, renal disease, hepatic disease, cardiac disease, HIV/AIDS, or depression/antidepressant medication use are also considered good candidates for naloxone (Narcan) rescue prescriptions. Naloxone (Narcan) prescriptions should also be granted to caregivers who request them. It is important that patients, as well as family members and caregivers, are educated on the signs/symptoms of an opioid overdose, such as snoring or choking sounds, shallow respirations, unresponsiveness, bradycardia, hypotension, pale, clammy skin that may be blue or grey in color. While naloxone (Narcan) does cross the placenta, no adverse effects were seen in animal studies, and the benefits of overdose reversal are thought to outweigh the risks. It is still unknown if it is excreted in breastmilk (Calás et al., 2016; City of New York Department of Health, n.d.b). In the case of benzodiazepine overdose, there exists a benzodiazepine antagonist, flumazenil (Romazicon), that can be administered via an IV by emergency medical personnel (NIDA, 2018b).

Termination of Chronic Opioid Therapy

If, at any point, the risks or harm outweighs the potential benefits, opioids should be tapered to a lower dose or gradually discontinued and other treatments optimized (Hudspeth, 2016b). As with the treatment of any medical condition, the goal is to restore health and resume pre-illness activities of daily living; the same is true for termination of chronic opioid therapy. Termination is an intentional process that occurs when a patient has achieved most of the goals of treatment, and/or when therapy must end for other reasons. According to the FSMB (2017), continuation, modification, or termination of opioid therapy for pain is contingent on "the clinician's evaluation of (1) evidence of the patient's progress toward treatment objectives and (2) the absence of substantial risks or adverse events, such as signs of substance use disorder and/or diversion" (Federation of State Medical Boards [FSMB], 2017, p.11).

The most common reasons for termination of long-term opioid therapy include the achievement of goals of therapy, treatment policy nonadherence, follow-up nonadherence, or concern for misuse/abuse or diversion (McDonald, 2015). Other reasons include the resolution of the underlying condition, intolerable adverse effects, inadequate analgesic effects, and a lack of improvement in the patient's quality of life (FSMB, 2017). Appropriate termination helps to avoid the betrayal of trust and abuse of power, prevents harm, and conveys caring. The PPA plays a critical role in this process, and therefore termination must be addressed comprehensively in the initial contractual agreement and updated accordingly. Termination always carries the risk of exposing the patient to severe pain and sending the wrong message to the patient (McDonald, 2015). A carefully structured taper should be given to anyone who is potentially physically dependent on their opioid to avoid withdrawal symptoms. Otherwise, a referral to an addiction specialist may be required for those on very high doses of opioids. The provider should reassure the patient that this change does not indicate the end of their treatment, which will proceed with other modalities or through another provider if necessary (FSMB, 2017).

Strategies for termination of chronic opioid therapy include the following:

  • Establish open, honest communication and dialogue with the patient from the point of the initial consultation;
  • Comprehensively address termination in the informed consent and PPA process and readdress or refer back to as necessary during the duration of therapy;
  • Set realistic, time-sensitive goals at the beginning of treatment;
  • Balance clinical judgment and individualization;
  • Incidents or events that cause concern regarding a pain agreement need to be interpreted within the context of the whole patient;
  • Safely taper opioids after a discussion with the patient/caregiver. There is no “one way” to taper a patient, yet generally, the longer the patient has been on opioids, the longer it will take for a successful taper;
  • Avoid terminating the relationship when a patient is in crisis without referral to a specialized facility and a warm handoff to the receiving provider. If a patient is terminated while in crisis, it might reasonably be considered abandonment and escalate abhorrent behaviors;
  •  As part of the termination preparation process, the patient should be given information about other available resources (i.e., community resources, support groups, nonpharmacological pain modalities), and document that resources have been provided (McDonald, 2015).

The evidence regarding best practices in tapering long-term opioid use in patients with chronic, noncancer pain is not robust. Most recommend a modest reduction in dosage (10%) every week, but a patient who has been on opioid medications for years may require a 10% reduction every month in order to avoid withdrawal symptoms. Withdrawal symptoms can be managed with a2-adrenergic agonists such as clonidine (Catapres) or tizanidine (Zanaflex). An alternative is to transition the patient to a partial agonist, such as buprenorphine (Suboxone), or a different opioid agonist, such as methadone (Dolophine), and then taper at the above-referenced rate to avoid withdrawal symptoms. However, as previously mentioned, both buprenorphine (Suboxone) and methadone (Dolophine) require specialized training and/or certification to prescribe and are not without their own associated risk (Berna et al., 2015).

Diagnosis and Treatment of Drug Abuse/Misuse and Addiction

The diagnosis of SUD is a clinical one based primarily on thorough patient history. The Diagnostic and Statistical Manual (5th Edition) lists eleven different criteria for the diagnosis of SUD. Mild SUD is diagnosed when a patient has two to three criteria met, while moderate SUD is diagnosed when four to five are met, and severe SUD is diagnosed when six or more are met. The criteria include four broad categories: lack of self-control (1-4), social impairment (5-7), personal risk (8 and 9), and pharmacological criteria (10 and 11; APA, 2013). 

Brief intervention (BI) is an appropriate engagement of most SUD patients. It encourages the patient to recognize the problem with substance use and engage them in positive change. It typically lasts 5-15 minutes and consists of brief advice via motivational interviewing techniques. The FRAMES acronym is one commonly used technique:

  1. Feedback of risk,
  2. Encouraging responsibility for change,
  3. Advice,
  4. A menu of options,
  5. Therapeutic empathy,
  6. Enhancing self-efficacy (Pearson & Duff, 2019).

BI is a component of SBIRT, an evidence-based method of screening patients and briefly providing education and/or motivation to change, with an associated referral for additional treatment. SBIRT is meant to be brief, universal, comprehensive, targeted, and performed outside of a substance abuse treatment setting. Once granted permission to discuss the drug use by the patient, SBIRT should begin with a validated screening tool to assess risk, which provides the basis for the feedback of risk (step #1 above). The brief counseling session should include an exploration of ambivalence, enhance motivation, and facilitate shared goal setting (if applicable) by first defining healthy patterns of use/behavior and then drawing a clear distinction with the patient's current use/behavior in a nonjudgmental manner. The discussion should be collaborative, with questions regarding how the patient perceives any benefits and potential risks of their substance use. Abstinence is not a goal, but a question regarding whether or not the patient is interested in and ready to change their behavior is appropriate. If the answer is yes, the provider may ask the patient to gauge their motivation using a 1-10 scale. A patient who is unwilling or not yet ready to make a behavioral change should be treated with respect, dignity, and simply reassessed at a later date. A comprehensive substance-related history should be completed if the above screening tools are positive, with questions regarding onset, duration, characteristics, precipitating factors, other substances used, and withdrawal symptoms (Albrecht et al., 2019).

Goal setting is associated with improved outcomes, as are nonpharmacological lifestyle changes such as establishing a consistent sleep schedule, exercising regularly, avoiding triggers (situations, people, or places associated with the substance of abuse), engaging in a new hobby/interest to prevent boredom and occupy time, and spending time with supportive friends and family members. Both inpatient and outpatient treatment programs should be explored/considered, both of which should consist of some combination of sessions with an addictions counselor, behavior therapies, group therapies, and psychotherapy as well as social services (Pearson & Duff, 2019). For the treatment of most SUDs, cognitive behavioral therapy (CBT) has been proven effective. CBT attempts to modify the patient's unhealthy thought and behavior patterns as well as develop strategies to manage cravings and avoid triggers. Some forms of therapy also provide incentives for abstinence. Behavioral treatments may involve the individual, the family, or take place in a group setting. The goal is to improve relationships and functionality at work, home, and in the community. Motivational incentives (contingency management) designed to use positive reinforcement to encourage abstinence may also be used. In 2018, reSET, the first mobile application designed as an adjunct for SUD outpatient treatment was approved for marketing by the FDA for patients struggling with addiction to alcohol, marijuana, and stimulants, including cocaine. Opioid addiction was added to the platform in 2018, designed to be used along with buprenorphine (Sublocade) for a remote-style MAT (NIDA, 2018b, 2019). 

Medication options for OUD treatment include buprenorphine (Sublocade), methadone (Dolophine), and naltrexone (Vivitrol, Revia). Buprenorphine (Sublocade) is a partial opioid agonist (binds to receptors but only partially activates) used to reduce cravings. Prescribers must be certified to prescribe, but implantable or once-monthly injection is available. It has a half-life of approximately 24 hours. It may cause mild euphoria in some patients but is designed with the aforementioned ceiling effect to limit the abuse potential. It may also cause respiratory depression when combined with BZDs or other CNS depressants. There are a few types of buprenorphine approved for use by the FDA, which include a monthly subcutaneous injection (Sublocade), a subdermal implant that lasts for six months (Probuphine), buprenorphine/naloxone (Bunavail, Suboxone) sublingual or buccal film, and buprenorphine/naloxone (Zubsolv) sublingual tablets. The combination products are used most often, as the addition of naloxone effectively blocks attempts at misuse. The naloxone component, an opioid antagonist, is not well absorbed through the oral mucosa. However, if the tablets/films are crushed or melted for injection or any other delivery method, the naloxone component blocks the effects of all opioids. Buprenorphine is not without risk, as some patients may divert the drug or combine it with a BZD to augment the euphoric effects, a potentially lethal combination. Random UDTs may help screen for and identify patients that are combining other medications or those that are diverting/selling their prescription and not taking it at all. Consistent use of available prescription drug monitoring programs (PDMPs) will also help the APRN identify patients that are obtaining prescriptions elsewhere. There are also reports of significant difficulty obtaining a supply of the medication, as many pharmacies do not want to consistently carry large stockpiles of the medication, in combination with a system-wide drug shortage. Overall, overdoses are rare, and some studies indicate that buprenorphine (Sublocade) is six times safer than methadone (Dolophine). With regard to dosing, it is a long-acting agent and requires only daily dosing for many patients. Due to its high affinity for the mu-opioid receptors, it should ideally be started when the patient is experiencing mild to moderate withdrawal (score of 6 to 12 on the scale). Home-based, or unobserved, treatment inductions supported by extensive patient education and preparation are possible and becoming more common (Moore, 2019; SAMHSA, 2018)

Methadone (Dolophine) is a synthetic opioid agonist that has been used for over 40 years to help limit symptoms of withdrawal/cravings. It is available only through specially licensed opioid treatment programs (OTPs; SAMHSA, 2020). Its half-life may vary from 8-59 hours, and steady-state plasma levels may take three to five days to achieve. Patients with hepatic disease may have delayed clearance and subsequently increased plasma levels. Unfortunately, methadone is also highly addictive and is therefore strictly regulated. The Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) ensures that providers are well educated and counsel and educate patients regarding the risks included in the medication guide SAMHSA oversees the accreditation and certification of OTPs and providers, who must register separately with the Center for Substance Abuse division of SAMHSA. Patients with a history of opioid abuse for at least one year, or who are currently at high risk due to pregnancy or recent release from prison or a similar institution qualify for MAT with methadone (Dolophine). Risks include respiratory depression, overdose, and QTc prolongation. The initial dose of methadone should be supervised by medical personnel and should not exceed 40 mg. Maintenance dosing will vary from patient to patient but is typically 60-120 mg. Research indicates that doses over 100 mg lead to greater success rates in avoiding relapse (Villegas & Thielet, 2020).

Naltrexone (Vivitrol, Revia) is an opioid antagonist (prevents opioids binding to/activating receptors) used for addiction treatment. It is available as a long-acting injection, can be prescribed by any licensed prescriber, and has a lower abuse/diversion potential than the other two options above (SAMHSA, 2020). Before starting naltrexone (Vivitrol, Revia), the patient should be opioid-free for seven to ten days before beginning the medication to prevent opioid withdrawal syndrome, making this option difficult for some. It is available as a long-acting injection every four weeks. Despite this convenient delivery method and the fact that it can be prescribed by any licensed prescriber, it is used less commonly than methadone (Dolophine) and buprenorphine (Sublocade) for the treatment of OUD (Moore, 2019; Theriot & Azadfard, 2019).

There continues to be a discrepancy in the estimated number of people in the US with OUD and the capacity of available OTPs and trained prescribers of buprenorphine (Sublocade), so this highly effective treatment remains difficult to access for patients that desperately need help for their addiction. Studies regarding the best methodology for MAT continue, including exploring the administration of long-acting buprenorphine (Sublocade) in emergency departments to overdose patients and the application of MAT programs in incarcerated populations. In 2016, the opportunity to undergo the required training for a prescribing waiver for buprenorphine was extended to NPs and PAs on a national level, and these numbers were extended in 2018 to expand the number of patients able to be treated by a single provider. The training consists of a 24-hour program, and additional details for interested providers can be found on the website for the Substance Abuse and Mental Health Services Administration (www.samhsa.gov). Prescribers and the public can also search for authorized prescribers by the state through the SAMHSA website. The SAMHSA website also provides a search engine for OTPs by state, or providers can reference the Office of Alcoholism and Substance Abuse Services website (www.oasas.ny.gov) and utilize their provider and program search tool. OTPs are also able to dispense buprenorphine (Sublocade) as a component of MAT (City of New York Department of Health, n.d.b; SAMHSA, 2020). 

For those with benzodiazepine or barbiturate use disorder, great care needs to be taken to avoid sudden cessation of these medications. Drug detoxification for these medications may need to be done under medical supervision, as withdrawal symptoms can be severe and potentially life-threatening. Stimulant withdrawal can be uncomfortable, although less dangerous than CNS depressant withdrawal, and stimulant medications should be tapered to ease withdrawal symptoms (NIDA, 2018b). As with the abuse of most therapeutically prescribed medications, experts cite the importance of consulting and regularly monitoring the state’s PDMP (Via, 2019). Behavioral therapies are effective for the treatment of stimulant misuse, but currently, there are no FDA-approved medications for the treatment of stimulant addiction (NIDA, 2018b). Studies are currently ongoing regarding possible pharmacological adjuncts. One such product, N-acetylcysteine (NAC or Acetadote, a glutamatergic agent), may be helpful in the treatment of cocaine addiction by helping to correct glutamate dysregulation (McClure et al., 2014).

Specific Rules and Regulations for the State of New York

All prescribers licensed under Title Eight of the Education Law in New York to treat humans and who have a DEA registration number to prescribe controlled substances, as well as medical residents who prescribe controlled substances under a facility DEA registration number, must complete at least three hours of coursework or training in pain management, palliative care, and addiction every three years. The Rules and Regulations on Controlled Substances in NYS (Part 80) specifies that:

  • Practitioners shall maintain a written record of prescriptions of all controlled substances, as well as a medical record for all patient receiving controlled substances that includes patient identification data, chief complaint, present illness, physical examination as indicated (which must be completed prior to any prescriptions being issued but may have been performed by a consulting physician or hospital and those records are available for review by the prescriber), diagnosis, data which support diagnosis or treatment, and the treatment regimen to include amount, strength, and directions for the use of any controlled substances (NYSDoH, n.d., Section 80.62).
  • Preprinted prescriptions are prohibited. As of 2016, all prescriptions, including controlled substances, must be submitted electronically (or written on an official NYS prescription, ONYSRx, with ink or printed in the event of a power outage or technical failure, or by practitioners who meet one of the exceptions listed in Article 2A - Section 281 or Title 10 Part 80 Section 80.6 and include a handwritten signature of the prescriber) containing the date as well as the patient's name, sex, address and age; the prescribers name, telephone number, address, and DEA registration number; the drug's name, strength, quantity in both numerical and written word form and the directions for use, including dose, frequency, and maximum daily dose (NYSDoH, n.d., Section 80.63).
  • There are no refills allowed on Schedule II medications or benzodiazepines, and no more than five refills allowed on Schedule III-V (NYSDoH, n.d., Section 80.67 and 80.69).
  • Emergency prescriptions may be called into pharmacies by prescribers for schedule II or III medications or benzodiazepines for no more than a five-day supply, as long as the official written or electronic prescription is delivered to the pharmacist within 72 hours. For schedule IV (except benzodiazepines) medications, this limit is a 30-day supply, or quantity #100, whichever is less (NYSDoH, n.d., Section 80.68).
  • A new prescriber may prescribe a controlled substance to a patient as part of a continuing treatment plan in the temporary absence of the initial prescriber as long as the new prescriber has access to that patient’s record, including a physical exam completed prior to the initial controlled substance being prescribed, or with the approval from the original prescriber via direct consultation (NYSDoH, n.d., Section 80.63).
  • In the presence of a new medical condition or problem requiring a controlled substance prescription, prescribers in New York may prescribe a five-day supply of controlled substance medication to a patient without performing a physical exam only in the case of an emergency if the prescriber has a prior relationship with that patient (NYSDoH, n.d., Section 80.63).
  • Prior to prescribing for or dispensing to a patient any controlled substance listed on schedule II, III, or IV of section 3306 of the public health law, every practitioner shall consult the prescription monitoring program registry for the purpose of reviewing that patient's controlled substance history. The patient's controlled substance history shall be obtained from the prescription monitoring program registry no more than 24 hours prior to the practitioner prescribing or dispensing any controlled substance to that patient. A practitioner shall document such consultation in the patient's medical chart or, if the practitioner does not consult the prescription monitoring program registry, the practitioner shall document in the patient's medical chart the reason such consultation was not performed (NYSDoH, n.d., Section 80.63).
  • A practitioner (or any prescriber) will be held legally liable for providing any prescriptions of controlled substances to an addict or habitual user not in the course of professional treatment but for the purpose of providing the user with medication sufficient to keep them comfortable by maintaining their customary use, unless that patient has a known incurable disease, such as cancer or advanced tuberculosis, or addicts who are aged and infirm and withdrawal would be dangerous to life (NYSDoH, n.d., Section 80.85).
  • No prescriptions exceeding a 30-day supply of schedule II drugs are permitted, and additional prescriptions may not be issued for at least 23 days (NYSDoH, n.d., Section 80.67).
  • According to New York State Public Health Law section 3331, effective July 22, 2016, there exists a seven-day supply limit for any opioid prescriptions at an initial consultation or treatment for acute pain. Upon any subsequent consultations for the same pain, the practitioner may issue, in accordance with existing rules and regulations, any appropriate renewal, refill, or a new prescription for an opioid (New York State Senate, n.d.).
  • Chorionic gonadotropin may be prescribed for up to three months, and anabolic steroids for up to six months, in the treatment of panic disorders, attention deficit disorder (ADD), chronic debilitating neurological conditions characterized as a movement disorder or exhibiting seizure, relief of pain in conditions known to be chronic or incurable, narcolepsy, hormone deficiency states in males, gynecological conditions or metastatic breast cancer, anemia, or angioedema (NYSDoH, n.d., Section 80.67).
  • Within the state of New York, naloxone (Narcan) can be accessed without a doctor’s prescription, and sometimes with reduced or no out-of-pocket cost to the patient, via an authorized opioid overdose program or at a participating pharmacy via the voluntary standing order program (currently includes CVS, Duane Reade, Rite Aid, and Walgreens, amongst others) (NYSDoH, 2019).  

For additional training on addiction, please see the NursingCE.com activity titled Substance Abuse and Addiction (for APRNs).

For additional training on the effective management of pain, please see the NursingCE.com three-part series titled Pain Management (for APRNs).

For additional training on palliative care, please see the NursingCE.com activity titled Palliative Care (for APRNs).

For additional training on care at the end of life, please see the NursingCE.com activity titled Ethical Issues in End-of-Life Care.


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