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

y briefly due to a high risk of tolerance, dependence, and addiction (NIDA, 2020). Prescribers should be particularly cautious when considering the potential risks and benefits of concurrent use of BZDs and opioid pain medications due to the additive sedating effects of these two groups of medications (Dowell et al., 2022). 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. They are still used in seizure disorders and during surgical procedures. All CNS depressants can 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, 2020).

Prescription stimulants such as dextroamphetamine (Dexedrine, Adderall) and methylphenidate (Ritalin, Concerta) 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 by enhancing the effects of norepinephrine and dopamine in the brain. Adverse effects include tachycardia, hypertension, and tachypnea. Previously, stimulants were used for several other conditions, but their use was reduced as the risk for addiction became evident. The effects of norepinephrine include hypertension, tachycardia, constriction of blood vessels, increased blood glucose, and bronchodilation. The public perception of these medications' relative safety and benign nature has likely contributed to their misuse in the last two decades. When augmented, dopamine enhancement can result in a feeling of euphoria. 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 these medications' risks, they are classified as Schedule II. A similar stimulant used to treat narcolepsy and extreme fatigue in MS, modafinil (Provigil), works to block dopamine reuptake. Therefore, it has a slightly safer profile and is categorized as Schedule IV (NIDA, 2018b, 2020; Via, 2019).

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

The NIDA (2020) and CDC (2021) define 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; it is due to the brain's ability to adapt to its environment physically. Tolerance is not limited to pain management or illicit drugs but is also seen in other specialties (e.g., some antihypertensives lose their potency over time) 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 withdrawal symptoms 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 ingesting or utilizing 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 SUD. This may refer to an addiction to nicotine, alcohol, prescription medications, or illicit drugs. 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 medication ingestion becomes associated with alleviating 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 (CDC, 2021; Horn et al., 2023; NIDA, 2020).

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, misuse, and potential drug interactions are significant. Frequently, most graduate nursing programs have limited formal pain management education. The consistent and diligent review of best practices and the most recent evidence in the field of pharmacology are necessary components of a safe and effective medical practice (Hudspeth, 2016).

 

Before 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 and 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 corroborate the patient’s history. Additional history components should include family history, a social history, a drug and alcohol use history, depression screening (i.e., the Patient Health Questionnaire-4 or -9), and any history of emotional/physical/sexual abuse. Family history should include substance use/misuse or psychiatric diagnoses specifically. The review of systems should consist of 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, COLDERAS, SOCRATES, OPQRST, etc.). Pain severity should be self-reported consistently 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 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. Additional options include the Pediatric Pain Questionnaire, the Adolescent and Pediatric Pain Tool, the revised Face, Legs, Activity, Cry, Consolability (r-FLACC) tool, and the individualized numeric rating scale (INRS). The provider should also assess the impact of the pain on the patient’s quality of life (QOL) and daily function, as well as the effectiveness of any current or prior pain management interventions. The Pain, Enjoyment, General Activity (PEG) tool and/or the Brief Pain Inventory (BPI) may standardize this portion of the assessment (Horn et al., 2023).

The Pain Assessment and Management Initiative (PAMI, 2020) also recommends a family dynamic checkpoint (step 3), evaluating who is caring for the patient at home (if applicable) and the overall family dynamics. Social history should include socioeconomic status, employment status, housing situation, family support, and leisure activities. Drug and alcohol use history should include questions detailing past or present use of tobacco, alcohol, illicit drugs, and the misuse of any OTC or prescription medications in the past, including details such as timing, duration, their drug of choice, treatment obtained, pending legal decisions, etc. (Horn et al., 2023). SAMHSA (2022) estimates that 19.4 million adults over 18 have SUD in combination with another mental illness, which may be depression, anxiety, ADHD, or various other psychological disorders. They found that SUD is more common in those with other mental health disorders (SAMHSA, 2022). In addition, patients with chronic pain have a higher rate of depression than the general public, making their pain management more challenging for the APRN if left untreated. The Beck Depression Inventory (BDI), the 9-Item Patient Health Questionnaire Depression Module (PHQ-9), and the Minnesota Multiphasic Personality Inventory-II (MMPI-2) are effective in screening for depression, while the General Anxiety Disorder-7 (GAD7) can be used if anxiety is suspected. The Mental Health Screening tool is a five-item assessment of feelings like calmness, happiness, peacefulness, or nervousness in the last 30 days (Horn et al., 2023). 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%; it generates a score that indicates mild (score of 5-9) to severe depression (score over 20; Beebe & Utley, 2018).

 

Anxiety/Insomnia Treatment

Sleep hygiene should be reviewed with all patients describing insomnia symptoms to attempt nonpharmacological correction of poor sleep habits. Cognitive behavioral therapy (CBT) is an effective therapy for chronic insomnia. To offer similar but safer alternatives to BZDs 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 BZDs, 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 misuse potential than BZDs. They commonly cause drowsiness, headaches, dizziness, and nightmares. Rarely, they can cause sleepwalking, abnormal thoughts/behavior, amnesia (memory loss), and anxiety. There exist significantly safer options for insomnia that should be considered before BZDs. Dual orexin receptor antagonists (DORAs) such as lemborexant (Dayvigo) and daridorexant (Quviviq) are categorized as Schedule IV by the FDA. Ramelteon (Rozerem) is a synthetic melatonin antagonist, binding to MT1 and MT2 receptors, helping to induce sleep without any misuse or addiction potential. These options are safer than BZDs, which are not considered first-line treatment for insomnia. Melatonin is an OTC option for sleep that boosts the body's sleep hormone levels (Neubauer, 2023; NIDA, 2020; National Institute of Mental Health [NIMH], 2022).

CBT is considered first-line therapy for anxiety treatment if nonpharmacological therapy is preferred. There are also medications available to treat anxiety that are not controlled substances and, therefore, less risky. First-line pharmacotherapy for GAD includes selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Alternatives include hydroxyzine (Vistaril, an antihistamine with anticholinergic side effects) and buspirone (Buspar), a partial serotonin and dopamine D2 receptor agonist. Buspirone (Buspar) can be used as an adjunct treatment for individuals that do not experience a complete response to treatment with an SNRI or SSRI and CBT. The initial dose is 10 mg/day, increasing by 10 mg every 1 to 2 weeks based on patient response, up to a maximum dose of 60 mg/day. Buspirone (Buspar) must be taken daily as it is ineffective when used as needed. Treatment should be continued for at least 4 to 6 weeks before determining its effectiveness. Adverse effects of buspirone (Buspar) include dizziness, headache, nausea, nervousness, lightheadedness, excitement, and insomnia (Craske & Bystritsky, 2021; FDA, 2022; Garakani et al., 2021; Neubauer, 2023; NIDA, 2020; NIMH, 2022).

 

ADHD Treatment

Instead of stimulants, non-stimulants are also highly effective in reducing ADHD symptoms but generally take longer to start working. Non-stimulants are often used in patients with 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 misuse potential. Atomoxetine (Strattera) has a slower onset, taking up to four weeks for the full effects of the medication to occur (FDA, 2022; NIMH, 2022).

 

Acute Pain Management

To alleviate pain and suffering has been 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 3 months) and chronic (longer than 3 months). Their care differs greatly. Acute pain is often self-limiting, and if nonpharmacological treatments can be used effectively, they are recommended over medications. Safer alternatives should always be explored/attempted before initiating a controlled substance if those alternatives exist. Nonpharmacological therapy should be optimized first. Nonpharmacological treatments such as heat, ice, elevation, rest, massage, acupuncture/pressure, or spinal manipulation have low to moderate-quality evidence but negligible risk. Heat therapy is likely effective for low back pain, and massage is typically effective for postoperative pain. Episodic migraine will probably respond to remote electrical neuromodulation (Dowell et al., 2022; HHS, 2019b; PAMI, 2020).

Mild to moderate non-neuropathic, noncancer pain likely does not warrant an opioid. Nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen (Tylenol) should be trialed first if pharmacological treatment is required. Another alternative is skeletal muscle relaxants (e.g., carisoprodol [Soma], cyclobenzaprine [Flexeril]). Topical and systemic NSAIDs were found to have the best benefit-to-harm ratio for acute musculoskeletal injuries, such as strains/sprains and whiplash. The American College of Physicians recommends NSAIDs or muscle relaxants for low back pain. For migraines, triptans, NSAIDs, antiemetics, dihydroergotamine (Migranal), and Lasmiditan (Reyvow) can improve pain and function with only mild side effects. Even the American Dental Association recommends NSAIDs as the first-line treatment for acute dental pain. NSAIDs are as effective for pain related to kidney stones as opioids (Dowell et al., 2022; HHS, 2019b; PAMI, 2020).

NSAIDs are associated with cardiovascular, GI, and renal risks, so these must be considered. Regarding the GI and renal risks of NSAIDs, celecoxib (Celebrex) and other COX-2 inhibitors are 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 regarding the increased risk of gastroduodenal ulcers and acute kidney injury, but studies have not reached statistical significance. Etodolac (Lodine) and diclofenac (Voltaren) have less renal excretion and may be more appropriate for older patients with impaired renal function. All NSAIDs carry similar cardiovascular risk, although selective COX-2 inhibitors may be associated with a slightly higher risk and naproxen (Naprosyn), ibuprofen (Advil, Motrin), and meloxicam (Mobic) somewhat less risk. All NSAIDs appear to increase blood pressure (BP; i.e., 5 mmHg on average) and the risk of hospital admission related to congestive heart failure (Ribeiro et al., 2022; Wongrakpanich et al., 2018).

 

Chronic Pain Management

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 described above. Nonopioid therapies for subacute and chronic pain are preferred. Other than those listed above, nonpharmacological treatments often used successfully for chronic back or neck pain include CBT and other psychotherapies, exercise therapy (i.e., for back pain, osteoarthritis pain in the hips or knees, and fibromyalgia), yoga, and physical therapy (i.e., manual techniques for hip osteoarthritis). Many of these techniques are also effective for fibromyalgia. Spinal manipulation may be effective for tension headaches. These treatments should be tried first or incorporated with any pharmacological treatment that is deemed appropriate. Unfortunately, these treatments often have an associated cost and may not be covered fully by traditional health insurance. An effective strategy to decrease medical costs and drug use and improve wellness for large portions of the population would be enhanced insurance coverage and access to these treatment options (Dowell et al., 2022).

Topical NSAIDs can relieve pain due to isolated (or limited) osteoarthritis. Those with neuropathic pain may find topical capsaicin or lidocaine patches effective. Systemic NSAIDs can be added for arthritis-related chronic pain, low back pain, and fibromyalgia. Additional nonopioid medications, such as neuropathics (antiepileptic drugs, AEDs), gabapentin (Neurontin) and pregabalin (Lyrica), or antidepressants such as venlafaxine (Effexor), duloxetine (Cymbalta), or tricyclic antidepressants should also be considered. These are especially helpful in patients with neuropathic pain, fibromyalgia, or chronic pain with concurrent depression or anxiety. Opioids are not first-line options for subacute or chronic pain. Opioid treatment should only be added when these treatments are deemed inadequate and the potential benefits of opioids outweigh the risks. Studies indicate minimal improvement in pain or function when opioids were used to manage chronic pain at short-term follow-up versus placebo and no improvement in pain or function versus nonopioid treatment (Dowell et al., 2022; PAMI, 2020).

Systemic corticosteroids are not recommended for chronic pain due to substantial adverse effects, especially in patients with diabetes. Intra-articular and arthrocentesis procedures using injectable glucocorticoids provide pain relief and improve joint function to improve participation in physical therapy or exercise. Similarly, epidural steroid injections may relieve lumbar radicular pain (Dowell et al., 2022; HHS, 2019b).

In New York, APRNs, physician assistants (PAs), and physicians can certify patients for medical marijuana. Patients must meet certification qualifications with a listed qualifying diagnosis, such as severe chronic pain, opioid use disorder (OUD), or as a replacement for opioids. Prescribers must have a valid state license and 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. Then they must register with the New York State Department of Health to obtain a registry ID card to purchase medical marijuana products. This pain control option may help limit the use of opioids, even in patients with acute or postoperative pain (New York State Office of Cannabis Management, n.d.).

An 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 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-Revised (SOAPP-R) assesses for prior substance misuse, mood, stress, and other risk factors to identify the level of risk for the patient
• Diagnosis, Intractability, Risk, and Efficacy (DIRE) is a questionnaire that aims to determine suitability for long-term opioid use by predicting compliance (Becker & Starrels, 2022; Horn et al., 2023; NIDA, 2023a)

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 is trained properly in its execution and interpretation. Ultimately, a patient’s risk should be considered amongst the other data collected to make the best decision regarding appropriate treatment. A high-risk score may indicate the need for a referral to a pain management clinic with additional experience and expertise in treating pain in more complex, higher-risk patients. Risk factors for opioid misuse include White race (this is also true for stimulants and CNS depressants), younger age (<40), a personal or family history of SUD, a current psychological condition such as depression or anxiety disorder, a history of legal issues or incarceration. Risk factors for stimulant misuse include young adults 18-25, especially those within Greek social organizations (fraternities and sororities), a grade point average below 3.5, a history of binge drinking or cannabis use, and a history of conduct disorder. Identified risk factors for CNS depressant misuse is female sex, patients that are uninsured and/or unemployed, those with panic attacks or other psychiatric symptoms, a history of alcohol misuse, tobacco or illicit drug use, especially intravenous drug use (Becker & Starrels, 2022; Horn et al., 2023; NIDA, 2023a).

UDT can be useful for baseline and periodic testing but is imperfect, as false positives can occur. 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 is not taking the drug, is not taking the correct dose, or the results are inaccurate. A positive result for an unexpected drug could mean the patient took it illicitly, it is a metabolite of a prescribed drug, or the results are inaccurate. For example, hydrocodone has been detected in patients using codeine (Tylenol #3), and hydromorphone has been seen in the results of patients using hydrocodone (Vicodin) as these drugs are metabolites. The cost of UDT should also be considered, discussed with the patient, and included in the initial treatment plan or patient-provider agreement (PPA). 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 before testing. Providers should also consider screening for pregnancy concurrently via a single urine sample/specimen in female patients. The CDC recommends baseline UDT and annual repeat testing (at least) for patients with chronic pain who are on opioids. The frequency can be adjusted based on risk level (every 3-12 months based on an assessed risk level of low to high; Becker & Starrels, 2022; Dowell et al., 2022; Horn et al., 2023).

The use of electronic databases to track controlled substance prescriptions (PDMPs) has become widespread (now available in 49 states, Washington DC, and Guam). They aim to improve opioid prescribing, inform clinical practice, and protect at-risk patients. States arrange individual systems to track and monitor prescriptions, but the details about use, access, and 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 (PMP Interconnect). Currently, Missouri is the only state without a statewide PDMP. However, St Louis County has developed its own PDMP, and other counties can utilize it. The key to all PDMP systems is mandated real-time reporting by pharmacies and a mandate that all providers check the system before prescribing controlled substances to a patient. Differences exist between the states regarding how frequently providers should monitor this system 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). The use of PDMPs has decreased the occurrence of multiple prescribers (doctor shopping), provided data for regulatory boards and law enforcement, reduced opioid prescribing, and encouraged communication and collaboration between prescribers and pharmacists. The CDC recommends interrogating the PDMP database initially (before issuing a controlled substance prescription) and at least every 3 months for all patients receiving opioid prescriptions (CDC, 2022; Dowell et al., 2022; D’Souza et al., 2022; Horn et al., 2023).

Finally, a complete physical exam should be performed and documented appropriately before any prescriptions are granted and periodically throughout the treatment course (Dowell et al., 2022). The state of New York specifies this requirement in its prescriptive rules and regulations (Title 10, 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 5-day supply of a 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 prescribers 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 verbally to the patient during the initial visit (often referred to as the informed discussion) before prescribing. It should include the patient’s diagnosis, the specific treatment being prescribed, risks, benefits, and desired outcomes/goals of treatment. Those goals should be collaborative. It should also cover alternatives (including no treatment) with their associated risks and benefits. At a minimum, risks should include the possibility of side effects (i.e., respiratory depression, cognitive effects), addiction, overdose, development of physical or psychological dependence or tolerance, drug interactions, hyperalgesia, inadvertent ingestion by children or others, and drug misuse by the patient/household contacts/friends. If female, the risk of neonatal opioid withdrawal syndrome (NOWS)/neonatal abstinence syndrome (NAS) if the patient becomes pregnant, should also be included. Prescribing policies regarding refills and lost or stolen medications or prescriptions should also be included. This document should be updated whenever medications are changed (Horn et al., 2023).

The PPA (also referred to as a narcotic contract, an opioid contract, or a physician treatment agreement) is a separate document signed by both the prescriber and the patient. It should incite a discussion regarding expectations, adherence, and treatment goals. While specific contracts vary, they may cover both parties' responsibilities/expected behaviors, the goals and potential risks of controlled substance use, and the consequences for noncompliance or lack of adherence. If UDTs or pill counts are to be performed periodically to assess compliance, this is typically 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. PPAs may 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., BZDs, testosterone, stimulants for ADHD/attention deficit disorder [ADD]) This tool should also include the provider’s responsibilities regarding treatment and follow-up care. The PPA can initiate conversations and provide valuable information (HHS, 2019b; Horn et al., 2023). While PPAs are recommended, there is limited scientific evidence clarifying whether or not they actively deter misuse, and many find them time-consuming (Laks et al., 2021).

 

Acute Pain

As with any new prescription medication, all current medications should be reviewed for potential interactions, and any medication allergies/sensitivities reviewed. Due to the increased risk of overdose and adverse effects, opioids should not be combined with BZDs. 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 acute severe pain (e.g., burns, crush injuries, post-operative invasive surgery) 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 (Methadose) should not be used as initial options due to their dosing challenges. They should only be prescribed by providers very familiar and comfortable with these products. Immediate-release (IR) medications with a half-life of 2-4 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 2-3 days, but patients who are being seen outpatient for short-term acute pain that are opioid-naïve will likely not require a dosage adjustment. If the dose increases, the patient should be monitored closely for respiratory depression. Controlled substances should be given at the lowest effective dose possible and for the minimum duration required. If opioids are to be used for acute pain, all prescription quantities should be individualized to the clinical scenario, but the prescription should be limited to the expected duration. For most acute, nontraumatic/nonsurgical pain, a quantity to last a few days or less is typically adequate. 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 they prefer and commonly prescribe to familiarize themselves with the details of those particular drugs extensively and avoid prescribing different or unfamiliar medications when possible (Dowell et al., 2022; Horn et al., 2023; PAMI, 2020).

Documentation is key when prescribing controlled substances for safety and legal reasons. Patients’ visit notes should be clear and 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 office staff should carefully document any phone calls made or received. Every time PDMP reports are reviewed, this should be documented along with any concerning findings. A decision to terminate care needs to be documented thoroughly. The Pain Assessment and Documentation Tool (PADT) is a tool to consider. This two-sided chart progress note provides the framework for a follow-up visit to reassess pain control and the current pain management regimen (Horn et al., 2023).

 

Chronic Pain 

Opioids are not first-line options for subacute or chronic pain. Opioid treatment should only be added when these treatments are deemed inadequate and the potential benefits of opioids outweigh the risks. Studies indicate minimal improvement in pain or function when opioids were used to manage chronic pain at short-term follow-up versus placebo and no improvement in pain or function versus nonopioid treatment (Dowell et al., 2022; PAMI, 2020).

Functional, concrete, and measurable goals should be agreed upon before 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 communicated (and included in the informed consent and PPA paperwork, if applicable) so that they can be reviewed periodically whenever necessary (Dowell et al., 2022).

As mentioned above, the lowest effective dose of IR opioids should be used initially, avoiding ER or LA options until a stable dose has been established. The HHS (2019b) suggests the acronym as low as reasonably achievable (ALARA). The CDC (Dowell et al., 2022) no longer recommends that primary care providers reassess the risks and benefits of treatment when prescribing more than a certain amount of morphine milligram equivalents (MME) daily. Instead, the guidelines suggest simply prescribing the lowest effective dose of opioids and carefully considering the potential risks and benefits before any dosage adjustments (up or down). The CDC recommends using product labeling as a starting point for dosage. This dosage can be adjusted based on patient-specific factors such as pain severity and known hepatic or renal insufficiency. Alternatively, the CDC suggests starting patients who are opioid-naïve on 5-10 MME per dose or 20-30 MME/day. They also remind prescribers that most do not see an improvement in pain or function when given 50 MME/day or more despite an increase in known risk (Dowell et al., 2022). The PAMI guide provides a starting dose for adults and children for most commonly prescribed opioids (and nonopioid analgesics), along with equivalency doses, onset, and duration information. They recommend that fentanyl transdermal (Duragesic) not be used in patients who are opioid-naïve and that methadone (Dolophine, Methadose) only be used in children for severe chronic pain (see Table 2; PAMI, 2020).

 

Table 2

PAMI Recommended Starting Doses for Commonly Prescribed Opioids

Opioid	PO Doses for Adults	IV Doses for Adults	PO Doses for Children > 6 months	IV Doses for Children > 6 months
Codeine (Tylenol #3)	5-10 mg q4h	2-4 mg q2-4h	0.3 mg/kg q4h	0.1 mg/kg q2-4h
Fentanyl (Duragesic, Sublimaze) in mcg/hr	Transdermal not to be used in patients who are opioid-naïve	50 mcg q1-2h	Transdermal not to be used in patients who are opioid-naïve	1-2 mcg/kg q1-2h (max 50 mcg/dose)
Hydrocodone (Vicodin)	5-10 mg q6h	NA	>2 yo: 0.1-0.15 mg/kg q4-6h	NA
Hydromorphone (Dilaudid)	2-4 mg q4h	0.2-1 mg q2-3h	0.06 mg/kg q4-6h	0.015 mg/kg q2-4h
Methadone (Methadose)	2-5 mg q8-12h	NA	0.7 mg/kg/day PO/SC/IV/IM divided q 4-6 hours for severe chronic pain
Oxycodone (Percocet)	5-10 mg q6h	NA	0.05-0.15 mg/kg q4-6h	NA
Tapentadol (Nucynta)	50 mg q4-6h	NA	NA	NA
Tramadol (Ultram)	50-100 mg q6h (max 400 mg/day)	NA	NA	NA

(PAMI, 2020)

The CDC guidelines provide a calculator to accurately determine a patient’s current MME and suggest using this formula during any medication dosage changes and for transitions between different medications to establish equivalent dosages (see Table 3; Dowell et al., 2022). Several similar calculators exist online, including the Centers for Medicare & Medicaid Services (HHS, 2020). 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 of incidental overdose or underdose. When initiating or increasing the dose of opioids for subacute or chronic pain, follow-up within 1-4 weeks is recommended to assess benefits and any harms; once stable, follow-up at least every 3 months is suggested (Dowell et al., 2022).

Table 3

MME Conversion Factors for Commonly Prescribed Opioids per the CDC

Opioid	Conversion Factor
Codeine (Tylenol #3)	0.15
Tramadol (Ultram)	0.2
Tapentadol (Nucynta)	0.4
Morphine (Roxanol, MS Contin), Hydrocodone (Vicodin)	1.0
Oxycodone (Percocet)	1.5
Fentanyl transdermal (Durgesic) in mcg/hr	2.4
Oxymorphone (Opana)	3.0
Methadone (Methadose)	4.7
Hydromorphone (Dilaudid)	5.0

(Dowell et al., 2022)

Opioids commonly cause significant side effects, which should be explained and discussed with the patient before prescribing. The most common are constipation, dry mouth, nausea, vomiting, confusion, and drowsiness. Constipation can be prevented with a bowel regimen that includes increased fluid intake, oral fiber intake, and physical activity. A stimulant laxative (e.g., sennosides [Senokot]) may be given prophylactically with a stool softener. Over time, patients taking opioids are at risk of developing tolerance and physical dependence. If stopped abruptly, patients are at risk of withdrawal (Dowell et al., 2022).

Extreme caution should be used when prescribing methadone (Dolophine, Methadose), which is challenging to dose and carries drug interaction concerns related to its complex CYP450 metabolism. Its MME conversion is also difficult, as it is dose-dependent (FDA Center for Drug Evaluation and Research, 2022). Methadone (Methadose) also acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, activating the norepinephrine and serotonin descending pathways. The half-life of methadone (Methadose) is significantly longer than morphine (8-60 hours, avg 24 hours), with lipophilic storage, so great care should be taken with this drug to treat pain safely. However, the low cost and ease of availability often make methadone (Methadose) an attractive option if used carefully by a skilled and experienced prescriber, especially regarding cancer and EOL pain. It should not be the first choice for a LA/ER opioid due to its characteristic challenges. It can also prolong QTc, so cardiovascular monitoring may be beneficial. Follow-up visits to assess patients after starting or with dose increases of methadone (Methadose) may need to be as frequent as 2-3 days initially (HHS, 2019b). Similarly, tapentadol (Nucynta) is a centrally acting analgesic (synthetic opioid agonist) with an added mechanism of norepinephrine reuptake inhibition in addition to its mu-receptor agonism (FDA Center for Drug Evaluation and Research, 2022).

 

Stimulants

Stimulants generally contain different types of methylphenidate and amphetamines and produce a calming effect on hyperactivity by increasing brain dopamine levels. The most common stimulants used for ADHD are methylphenidate (Ritalin, Concerta, Aptensio, Jornay PM), dextroamphetamine (Dexedrine), and dextroamphetamine/amphetamine (Adderall). They are available as IR formulas (lasting about 4 hours), LA formulas (ranging from 6 to 12 hours), and ER preparations (lasting up to 24 hours). Many caregivers and patients prefer LA or ER formulations, as these may reduce the "ups and downs" experienced throughout the day and eliminate the need to dose medication at school or work (Children and Adults with Attention-Deficit/Hyperactivity Disorder [CHADD], n.d.; Wolraich et al., 2019). Proton pump inhibitors (PPIs) such as omeprazole (Prilosec) and esomeprazole (Nexium) can interfere with the absorption of methylphenidate (Ritalin, Concerta, Aptensio, Jornay PM), and there is a rare risk of sudden death in patients with a cardiac history. Dextroamphetamine/ amphetamine (Adderall) can be administered with or without food but should be taken in the morning to avoid insomnia. Patients taking the ER formulation should swallow capsules whole, or the contents can be sprinkled on a bite of food that does not require chewing (e.g., applesauce or pudding; Wolraich et al., 2019; Woods, 2023). Dextroamphetamine (Dexedrine) should not be administered in the late evening due to the risk of insomnia. This medication interacts with antihypertensives (diminishes effects), monoamine oxidase inhibitors (MAOIs; may cause severe hypertension), and acidic foods or fruit juices due to delayed absorption and decreased effectiveness. It should be used cautiously in patients experiencing agitation, motor or phonic tics, or Tourette syndrome (Woods, 2023).

Lisdexamfetamine (Vyvanse) is a LA preparation and differs from other medications in this class due to its pharmacokinetics. It is considered a prodrug, which means it must undergo chemical conversion by metabolic processes before becoming an active agent. It does not convert to its active formulation until it reaches the GI tract; its effects take 60 to 90 minutes. The drug has less misuse potential than dextroamphetamine/amphetamine (Adderall), as it cannot be absorbed intravenously or transmucosally. Dosing must be adjusted for patients with severe renal impairment. For patients with a glomerular filtration rate (GFR) of 15-30 mL/min/m², the maximum dose is 50 mg/day. For those with end-stage renal disease (ESRD) or a GFR below 15 mL/min/m², the maximum dose is 30 mg/day. Lisdexamfetamine (Vyvanse) should be taken in the morning with or without food to prevent insomnia (Wolraich et al., 2019; Woods, 2023). Drug interactions with methylphenidate (Ritalin, Concerta) include antacids (i.e., H2 blockers, PPIs) and MAOIs. Because methylphenidate (Concerta) does not dissolve after ingestion, it is contraindicated in patients with a history of peritonitis or conditions that cause GI tract narrowing (e.g., short-gut syndrome, cystic fibrosis, or small-bowel inflammatory disease). These medications should be used cautiously in patients with a history of bipolar disorder, electroencephalogram (EEG) abnormalities, psychosis, or emotional disorders (Woods, 2023).

The side effects of stimulants include hypertension, tachycardia, anxiety, decreased appetite, sleep problems, personality changes, tics, stomach pain, and headaches. Less commonly reported side effects include allergic reactions, fever, arthralgia, psychosis, and depression. Sudden death is a rare adverse effect in patients with preexisting cardiac conditions. These drugs should be used cautiously in patients with hypertension, seizures, a history of myocardial infarction, stroke, liver disease, kidney disease, or anxiety disorders. Stimulants are contraindicated for patients with advanced arteriosclerosis, hyperthyroidism, symptomatic cardiovascular disease, structural cardiac abnormalities, cardiomyopathy, serious arrhythmia, or glaucoma. APRNs should counsel patients on strategies to manage insomnia, including taking the medication before noon, limiting or avoiding caffeine, and maintaining healthy sleep hygiene. When insomnia requires pharmacological management, melatonin is encouraged as the initial intervention, as it naturally occurs in the body and is non-addicting. Some patients may require adjunctive prescriptive sleep aids, such as clonidine (Catapres, Kapvay) or trazodone (Desyrel), which may be used in children and adults. Medications such as eszopiclone (Lunesta) and zolpidem (Ambien) should only be prescribed for adults and should be taken 30 to 60 minutes before bedtime (NIMH, 2022; Tarraza, 2023; Woods, 2023).

Stimulants carry a risk for diversion (i.e., when legitimate stimulant prescriptions for ADHD are diverted and used for reasons other than treating ADHD). When taken at doses and via routes other than those prescribed, stimulants can increase dopamine levels in the brain in a rapid and highly amplified manner (similar to other drugs commonly misused, such as opioids), thereby disrupting communication between brain cells and producing euphoria. As a result, these biochemical processes and subsequent euphoric effects increase the risk of addiction. Therefore, before prescribing these medications, providers must assess each patient's risk for diversion and continue to reassess at each follow-up visit while continuing treatment. Following drug selection, providers are advised to "start low and go slow" when prescribing these agents, initially prescribing the lowest dose possible and gradually titrating the dose upward to minimize side effects. Most side effects of stimulants can be eliminated or decreased with this medication initiation plan. Some people describe a stimulant rebound during the period between dosing as the medication is wearing off, in which they can experience a negative mood, fatigue, or hyperactivity. These symptoms can be managed by changing the dose or schedule of IR formulas or switching to an LA formula if possible (CHADD, n.d.; Wolraich et al., 2019).

 

CNS Depressants

BZDs are known to improve anxiety and insomnia symptoms but are no longer recommended as first-line therapy due to their side effect profile and the risk of tolerance, dependence, or misuse. For patients with severe anxiety without a history of substance misuse, a BZD may be initiated to manage symptoms until the first-line treatment reaches therapeutic levels. They are also frequently used for short-term anxiety management during minor medical procedures (e.g., dental work) or as pre-sedation. BZDs enhance the effects of GABA in the brain. They promote relaxation and alleviate muscular tension and other physical symptoms of anxiety. The most commonly used BZDs include clonazepam (Klonopin), alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan). Of these, diazepam (Valium) and clonazepam (Klonopin) are the most widely used for anxiety due to their rapid onset and long half-life, which can decrease the risk of withdrawal symptoms when discontinued. Adverse effects of BZDs include drowsiness or tiredness, dizziness, nausea, blurred vision, headache, confusion, and nightmares (Craske & Bystritsky, 2021; Garakani et al., 2021). Before prescribing a BZD, patients should be screened for risk factors of BZD use disorder, including severe insomnia, concurrent use of antidepressants, and a lower level of education. The duration of treatment and increased doses also correlate with increased risk for BZD use disorder (Park, 2022).

 

Special Populations: Older Adults or Pregnant Patients

Special consideration should be taken when prescribing for older adults (over age 65) or pregnant patients. Pain is more common in older adults, and aging causes physiological changes that affect medication absorption, metabolism, and excretion. For these reasons, medications should be started at the lowest possible dose and gradually increased only as needed (start low and go slow). When prescribing opioids, a bowel program to prevent constipation may be advised, as described above. The American Geriatric Society Beers Criteria (BC, 2023) of potentially inappropriate medication use in older adults outlines medications that should be avoided. Included in the most recent version are the following recommendations (The American Geriatrics Society Beers Criteria Update Expert Panel, 2023):

• Barbiturates (e.g., butalbital, phenobarbital) should be avoided due to the high rate of physical dependence, tolerance, and overdose.
• BZDs should be avoided for insomnia, agitation, or delirium due to fall risk, delirium, fractures, and motor vehicle crashes, especially longer-acting versions. There is a risk of misuse and addiction. Especially when combined with opioids, they can lead to respiratory depression, sedation, coma, and death.
• Non-benzodiazepine, benzodiazepine receptor agonist hypnotics (eszopiclone [Lunesta], zaleplon [Sonata], zolpidem [Ambien]) should be avoided due to the risk of falls, delirium, fractures, and motor vehicle crashes.
• Avoid meperidine (Demerol) as it is ineffective and carries an increased risk of neurotoxicity compared to other opioids.
• Opioids should be avoided in those with a history of falls or fractures; they also increase delirium risk.
• Combining BZDs and opioids increases the risk of overdose and adverse events.
• Combining opioids and AEDs such as pregabalin (Lyrica) and gabapentin (Neurontin) increases the risk of sedation, respiratory depression, and death.
• Combining three or more CNS depressants increases the risk of falls and 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 the increased risk of stroke, cognitive decline, and mortality in older adults with dementia and olanzapine (Zyprexa) syncope.
• Tricyclic antidepressants should be avoided/used with caution secondary to anticholinergic effects.
• Avoid using indomethacin [Indocin] and ketorolac [Toradol] due to the increased risk of GI bleeding, peptic ulcer disease, and acute kidney injury.
• Avoid scheduled or chronic use of the other non-selective NSAIDs (i.e., aspirin [ASA], diclofenac [Voltaren], diflunisal [Dolobid], etodolac [Lodine], flurbiprofen [Ansaid], ibuprofen [Motrin, Advil], meloxicam [Mobic], nabumetone [Relafen], naproxen [Naprosyn], oxaprozin [Daypro], piroxicam [Feldene], and sulindac [Clinoril]) due to the risk of GI bleeding and peptic ulcer disease in those at increased risk (over 75, on corticosteroids, anticoagulants, or antiplatelet agents) as well as increased BP and kidney injury; this risk may be reduced (not eliminated) with a PPI or misoprostol.
• Skeletal muscle relaxants (i.e., carisoprodol [Soma], chlorzoxazone [Lorzone], cyclobenzaprine [Flexeril], methocarbamol [Robaxin]) commonly used for musculoskeletal symptoms are poorly tolerated due to anticholinergic effects, sedation, and fracture risk and should be avoided in older adults.

In 2014, the FDA removed the older system of ranking medications for pregnant patients (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 potentially fatal NOWS, lower birth weight, and premature birth; animal studies have shown no evidence of teratogenicity. Opioids are excreted in breast milk, increasing 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 before issuing any opioid or controlled substance prescriptions. Acetaminophen (Tylenol) can be used safely during pregnancy and while breastfeeding. Due to an increased risk of bleeding and premature ductal closure, pregnant patients should avoid NSAIDs, especially during the first trimester and after 30 weeks of gestation. NSAIDs appear safe to use during breastfeeding. BZDs 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 breast milk. They have been shown to increase the risk of congenital abnormalities, especially if used in the first trimester. Other dangers of BZD use during pregnancy include postnatal withdrawal symptoms, neonatal flaccidity, respiratory and feeding difficulties, and hypothermia. Due to insufficient evidence, Zolpidem (Ambien) was category C in the old system. 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 breast milk, and caution should be advised. Stimulants, such as methylphenidate (Ritalin, Concerta), were a category C and are not well studied in pregnancy but were shown to cause congenital abnormalities at very high doses in animal studies. It is unknown if methylphenidate (Ritalin, Concerta) is excreted in breast milk, but amphetamines are (FDA Center for Drug Evaluation and Research, 2022).

Buprenorphine (Sublocade) and methadone (Methadose) appear safe and effective for treating OUD in pregnant patients. Studies indicate that methadone (Methadose) is associated with improved treatment retention in pregnant patients and is 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 (Sublocade) 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 (Methadose; NIDA, 2021a; SAMHSA 2023b).

 

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. Pain management in patients who are terminally ill does not typically conform to the aforementioned standard regulations. Within the care of these patients, there is less concern for misuse 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 EOL. 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 the potential risks of increased opioid doses. Still, if the patient and family prioritize pain relief over the length of life, the care team should accept and respect that decision. It is generally accepted that clinicians should never withhold needed pain medication from patients who are terminally ill for fear of hastening death if they have received informed consent from the patient. Loss of consciousness may not be directly caused by high doses of opioids in the patients who are dying 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 & O’Neill, 2021). There is no legal protection for assisted suicide or euthanasia in New York. Still, 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 patients who are terminally ill 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 SUD

The prevention of misuse 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 with the best evidence possible to limit risk to patients and society. An honest dialogue with the patient regarding risks, benefits, treatment goals, treatment alternatives, and expectations of both parties before prescribing can help prevent misuse of potentially dangerous medications. This includes using the 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 (Becker & Starrels, 2022; Dowell et al., 2022; Horn et al., 2023; NIDA, 2020, 2023b). Regarding stimulant misuse, studies indicate that the prompt, appropriate, and long-term treatment for ADHD benefits the patient’s mental well-being and decreases the risk of substance misuse rather than increasing it, as their mental health needs are being adequately met. The Coalition to Prevent ADHD Medication Misuse is an online resource launched in 2016 to provide healthcare providers and others with information on discussing and preventing prescription stimulants' misuse and diversion (Via, 2019).

For patients, misuse can best be prevented by taking their medications (and only their medications) exactly as prescribed, discussing any changes with the prescriber before adjusting the 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 (Duragesic) patches and other medication can be flushed down the toilet if necessary (Becker & Starrels, 2022; Dowell et al., 2022; Horn et al., 2023; NIDA, 2020, 2023b).

Medication manufacturers are studying and trialing various methods to make medications less vulnerable to 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 release long-acting medication over time slowly, or new molecular entities/prodrugs that renders a drug inactive unless it is taken orally. From an administrative or regulatory perspective, additional regulation may prevent misuse. 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 (FDA, 2021). Valid and reliable screening tools for drug abuse/misuse include:

• Current Opioid Misuse Measure (COMM), a 17-item questionnaire for current opioid users which assesses for signs and symptoms of misuse, 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 (APA’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; NIDA, 2023a)

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 may also be an important aspect of screening for misuse. Also, the prescriber should talk with the patient about their pain, treatment plan, and current medication usage. An invitation for any questions and concerns using open-ended questions and nonjudgmental language cannot be understated (Becker & Starrels, 2022; Horn et al., 2023).

Some red flags exist that patients 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 know the common pitfall of assuming a well-liked or well-known patient is at a lower risk for 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. Data support the prescribing or offering 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 (Horn et al., 2023).

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

• increased agitation or irritability
• personality changes
• lack of energy or motivation
• changes in behavior (sudden insistence on privacy, being secretive, different friends)
• doing immoral/illegal/unethical things to obtain the substance
• conjunctival irritation (red or bloodshot eyes)
• dilated or constricted pupils
• abrupt changes in weight
• sudden change in appearance and hygiene (lack of interest in clothes, grooming)
• slurred speech, tremors, impaired coordination
• 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
• dropping grades (adolescents) or poor performance at work (adults)
• engaging in high-risk behavior while under the influence of the substance, such as driving (American Addiction Centers, 2023; NIDA, 2021b)

 

Overdose Management

Naloxone (Narcan) is an opioid antagonist that blocks 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 2-5 minutes and can be repeated if no response is seen. First responders, emergency medical providers, and bystanders can administer it. 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 (Ultram), alcohol, CNS depressants, or stimulants. If ineffective after two doses, other explanations for the patient’s symptoms should be explored and considered, including BZD 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, chronic opioids (greater than 3 months), concurrent opioids and BZDs, current ongoing treatment for SUD, 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, and pale, clammy skin that may be blue or grey. 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 breast milk (NIDA, 2022; SAMHSA, 2023c; City of New York Department of Health, n.d.). In the case of BZD overdose, there exists a benzodiazepine antagonist, flumazenil (Romazicon), that can be administered via an IV by emergency medical personnel (Park, 2022).

 

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 (Dowell et al., 2022). As with treating any medical condition, the goal is to restore health and resume pre-illness activities of daily living; the same is true for the termination of chronic opioid therapy. Termination is an intentional process that occurs when a patient has achieved most of the treatment goals and/or when therapy must end for other reasons. According to the HHS Working Group on Patient-Centered Reduction or Discontinuation of Long-term Opioid Analgesics (2019a), the prescriber should continue tapering and/or discontinuing opioid therapy if the following conditions are met:

• the patient’s pain (or targeted symptom) has improved
• the patient desires to reduce their dose or wean off of the medication
• the goals of treatment (less pain, enhanced function) have NOT been met, despite adherence to treatment and/or escalating doses
• the risk-benefit ratio is no longer favorable to continue treatment (should be reassessed quarterly)
• there is evidence of substance misuse or diversion, or other nonadherence to treatment agreements
• the side effects related to the medication are intolerable (i.e., decreased QOL or worsened function)
• the patient has indications of impending overdose (i.e., sedation, confusion, speech changes)
• the patient experiences an overdose resulting in medication reversal or hospitalization
• the patient has new risk factors that increase their potential for an adverse effect (i.e., a medical condition such as sleep apnea or liver/kidney dysfunction, a new prescription for another CNS depressant)

Studies indicate that most patients who voluntarily reduce their long-term opioid use experience better function, mood, sleep, anxiety, and no change in pain levels. This should not be encouraged if the benefits of therapy continue to outweigh the potential harms (HHS, 2019a). A 2017 systematic review found that opioid tapering was associated with improved pain, function, and QOL based on available low-quality evidence (Frank et al., 2017). The VA Health System (2019) collected evidence regarding the harms and potential benefits of long-term opioid therapy in patients with chronic pain. They found that the evidence available was of low overall quality. They determined that when opioid tapering was voluntary and a component of an intensive pain management interventional plan, patients reported improved pain severity and function. Those who tapered opioids with less intensive co-interventions reported unchanged pain and function (Mackey et al., 2019). Dosages above the reported benefit level for most patients do not have to be reduced in all patients simply because they are high. The risks of continued long-term substance use should be clearly outlined with the patient and family to promote shared decision-making. Comorbid mental health conditions must be treated to enhance the likelihood of success when tapering controlled substances, so patients should be screened before initiating a taper. Patients with risk factors or red flags for SUD should be formally screened. The provider should directly address their concerns with the patient, allowing them the time and space to mirror or further discuss their own concerns. If the screening tool indicates OUD/SUD, treatment should be offered and initiated (HHS, 2019a; Pisansky et al., 2023).

The following strategies for collaborative tapering of controlled substances may be helpful:

• open, honest communication and dialogue with the patient from the point of the initial consultation
• an informed consent and PPA that include a discussion of the goals of treatment and the process to reduce/taper or discontinue treatment if and when appropriate
• realistic, measurable goals for treatment that reflect the patient’s objectives
• allow the patient to participate in shared decision-making regarding a taper- which medications, which dosages, and a targeted timeline
• 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, as this can lead to severe psychological distress and suicidal thoughts/intent
• provide support (reassurance and encouragement) and information about other available resources (i.e., community resources, support groups, nonpharmacological pain modalities), and document that resources have been provided (Mackey, 2019)

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 (5-20%) every 4 weeks. A patient who has been on opioid medications for a year or more may require a 10% (or less) reduction every month to avoid withdrawal symptoms. Some patients can tolerate a faster taper (10% every 1-2 weeks until 30% of the original dose remains, followed by 10% weekly). Once the patient is taking the smallest dose available, the interval between doses can be extended. Once the patient is taking the substance less than once a day, the substance can be safely stopped. A temporary hold (or pause) during a taper may allow extra time for a patient to adjust to a new dose and ease symptoms. In the case of a serious adverse event (e.g., overdose), some patients may need to be tapered over 2-3 weeks to limit the risk of continued substance use. Weekly or monthly follow-up visits during a substance taper are typically beneficial. The patient may not need to discontinue the substance completely but reduce their dose until the benefits of therapy again outweigh the potential harm. The taper's goals (and how success will be measured) should be agreed upon before tapering in collaboration with the patient, just as before initiating therapy with the controlled substance (HHS, 2019a; Pisansky et al., 2023).

A slow, gradual taper will limit withdrawal symptoms. The patient should be fully educated regarding potential symptoms and management or coping techniques to avoid concern or worry. Early symptoms (yawning, restlessness/anxiety, muscle aches, sweating, abdominal cramping/diarrhea) typically subside within 5-10 days. Symptoms such as irritability, insomnia, and dysphoria may take weeks or months to resolve. Sweating, tachycardia, and other autonomic symptoms can be managed with a₂-adrenergic agonists such as tizanidine (Zanaflex), clonidine (Catapres), or lofexidine (Lucemyra). Other signs of withdrawal can be managed symptomatically (trazodone [Desyrel] for insomnia, NSAIDs or acetaminophen [Tylenol] for muscle aches, loperamide [Imodium] or bismuth subsalicylate for diarrhea; HHS, 2019a). An alternative is to transition the patient to a partial agonist, such as buprenorphine (Sublocade), or referral to a provider with specialized training and/or certification to prescribe for OUD. An interdisciplinary rehabilitation program will typically include pain management as one of its many components. Other than a long history of opioid or other substance use, the patient characteristics that increase the risk for an unsuccessful or challenging taper include high pain scores before taper, anxiety over possible withdrawal, psychiatric disorder, female sex, and older age (Pisansky et al., 2023).

In addition to the risks of continued substance use, the patient should be counseled on the potential dangers of tapering or discontinuing the substance. The risks associated with a rapid or abrupt tapering of controlled substances vary by substance. Opioid withdrawal, increased pain, insomnia, anxiety/depression, and thoughts of suicide may result due to an opioid taper. Pregnant patients are at risk for spontaneous abortion (miscarriage) and premature (preterm) labor. Anxiety, hallucinations, seizures, and death may characterize BZD withdrawal. The risk of overdose increases within a week of tapering or discontinuing any substance due to a rapid loss of tolerance. If the patient were to resume their original dose, they might overdose quickly and easily without intention. Patients tapering or discontinuing their medications should be counseled extensively regarding this risk and the signs/symptoms of overdose. A prescription for naloxone (Narcan) should be considered in these patients (HHS, 2019a; Pisansky et al., 2023).

 

Diagnosis and Treatment of SUD and Addiction

The diagnosis of SUD is a clinical one based primarily on thorough patient history. The APA’s Diagnostic and Statistical Manual (5^th Edition, Text Revision) lists eleven different criteria for the diagnosis of SUD. Mild SUD is diagnosed when a patient has two to three criteria met, moderate SUD is diagnosed when four to five are met, and severe SUD is diagnosed when six or more are met (APA, 2022). SUD is defined as a destructive repetition or habit of ingesting/administering an intoxicating substance that causes substantial anguish or drastically affects the patient’s ability to function professionally, socially, or otherwise. These effects are evidenced by two or more of the conditions listed here within one year:

• ineffective attempts to reduce the use of the substance or a wish to do so
• an intense need or impulse to use the substance
• a persistent ingestion/administration of the substance even though they have experienced repeated relational challenges (i.e., with surrounding friends and family members) related to its use
• a persistent ingestion/administration of the substance in environments where it is unsafe
• the development of tolerance, which is a gradual reduction in the physical impact/effect of a given substance when administered at a consistent dose or amount, requiring an increase in dose or amount to achieve the prior effect
• a persistent ingestion/administration of the substance for a longer time and at a higher dose or amount than planned
• a considerable investment of time related to the substance, procuring it, ingesting/administering it, or recuperating from the consequences of its use
• a persistent ingestion/administration of the substance, interfering with significant responsibilities and commitments (i.e., academic, professional, or familial)
• a decrease in attendance or participation in significant events at work, at home, or with friends/family due to the use of the substance
• a persistent ingestion/administration of the substance even though they are aware of a significant challenge directly related to the substance use
• the development of withdrawal as evidenced by the signs and symptoms of withdrawal syndrome for that particular substance or the use of the substance to prevent these symptoms (APA, 2022)

The disorder may be considered in early (3 or more months) or sustained (12 or more months) remission when all of the above symptoms have resolved, except for an intense need or impulse to use the substance. This may also be qualified in a controlled environment if the patient currently lacks access to the substance (APA, 2022).

Brief intervention (BI) is an appropriate engagement for 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 method:

• Feedback of risk,
• Encouraging responsibility for change,
• Advice,
• A menu of options,
• Therapeutic empathy,
• Enhancing self-efficacy (Pearson & Duff, 2019)

BI is a component of screening, brief intervention, and referral to treatment (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 a substance misuse 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 explore 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 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 and dignity and reassessed later. 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 misuse), 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, consisting of some combination of sessions with an addiction counselor, behavior therapies, group therapies, psychotherapy, and social services (Pearson & Duff, 2019).

For the treatment of most SUDs, 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 and the family or occur in a group setting. The goal is to improve relationships and functionality at work, home, and community. Motivational incentives (contingency management) designed to use positive reinforcement to encourage abstinence may also be used. In 2017, 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 marijuana or stimulants, including cocaine. Opioid addiction was added to the platform in 2018 (reSET-O), designed to be used along with buprenorphine (Sublocade) as a remote adjunct to CBT. The company recently announced bankruptcy proceedings, so the program's future is unknown (NIDA, 2020, 2021a, 2023b).

Medication options for OUD treatment include buprenorphine (Sublocade), methadone (Methadose), and naltrexone (Vivitrol, Revia). Buprenorphine (Sublocade) is a partial opioid agonist, methadone (Methadose) is a full agonist, and naltrexone is an antagonist. Buprenorphine (Sublocade) and methadone (Methadose) have stronger evidence for better outcomes, including reduced overdose deaths and all-cause deaths. They also do not require abstinence (see the naltrexone section for abstinence recommendations) and are more commonly used than naltrexone (HHS, 2019b). Most individuals do not divert buprenorphine (Sublocade) or methadone (Methadose). Illicit buprenorphine (Sublocade) use is typically related to reducing withdrawal symptoms and cravings. The blunted effects of buprenorphine (Sublocade) limit its attractiveness as a drug of misuse. Those that divert methadone (Methadose) are typically prescribed the medication for pain, not for OUD treatment. Most treatment programs have strict diversion control plans and heavy monitoring in place. The primary reason cited for methadone (Methadose) diversion is the giving away of doses to others suffering from substance misuse and withdrawal who do not have access to treatment themselves. Studies indicate that buprenorphine (Sublocade) and methadone (Methadose) are equally effective at medium to high doses. A direct comparison of naltrexone ER (Vivitrol) and buprenorphine/naloxone (Suboxone) showed the two are similarly effective once detoxification is complete and treatment has been initiated (NIDA, 2021a).

Buprenorphine (Sublocade) is a semi-synthetic partial opioid agonist (binds to receptors but only partially activates) that reduces cravings. A specialty waiver is no longer required to prescribe buprenorphine (Sublocade) for OUD treatment. An 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 misuse 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, buprenorphine/naloxone (Zubsolv and generic) sublingual tablets, buprenorphine sublingual tablets (Subutex). 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 (Sublocade) 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 mixing other medications or diverting/selling their prescription and not taking it at all. Consistent use of available PDMPs will also help the prescriber recognize patients obtaining prescriptions elsewhere. Overdoses are rare, and some studies indicate that buprenorphine (Sublocade) is six times safer than methadone (Methadose). Concerning 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 early stages (12-24 hours) of 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. Common side effects include GI symptoms (e.g., nausea, vomiting, constipation), headache, dizziness, drowsiness, dry mouth, tooth decay, muscle aches/cramps, insomnia, fever, visual changes (e.g., blurry or dilated pupils), tremors, palpitations, and lack of attention. Serious side effects may include overdose with respiratory depression/distress, adrenal insufficiency, dependence, withdrawal, and NOWS/NAS in infants. The implant may cause pain, itching, and edema at the implant site, and the injection may cause injection site reactions/pain (Moore, 2019; SAMHSA, 2023a).

Methadone (Methadose) is only administered in SAMSHA-approved opioid treatment programs (OTPs) when used for OUD (FDA Center for Drug Evaluation and Research, 2022). It is a synthetic opioid agonist that has been used for over 40 years to help limit symptoms of withdrawal/cravings. Its half-life may vary from 8-60 hours, and steady-state plasma levels may take 3-5 days to achieve. Patients with hepatic disease may have delayed clearance and subsequently increased plasma levels. Unfortunately, methadone (Methadose) is also highly addictive and 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 SAMHSA's Center for Substance Abuse division. It is available as a diskette, liquid, or powder form. Patients with a history of opioid misuse 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 treatment with methadone (Methadose; SAMHSA, 2023b; NIDA, 2021a).

Common side effects include nausea/vomiting, constipation, hyperhidrosis (increased sweating), restlessness, bradypnea, and urticaria. Serious risks include respiratory depression, overdose, anaphylaxis, angina, tachycardia, hallucinations, and QTc prolongation. Cardiovascular monitoring during long-term use may be beneficial. The initial dose of methadone (Methadose) should be supervised by medical personnel and not exceed 40 mg. Maintenance dosing will vary from patient to patient, typically 60-120 mg. Research indicates that doses over 100 mg lead to greater success rates in avoiding relapse. Methadone (Methadose) is relatively safe during pregnancy and breastfeeding. OUD treatment with methadone (Methadose) should continue for at least 12 months (SAMHSA, 2023b; NIDA, 2021a).

Naltrexone (Vivitrol) is an opioid antagonist (prevents opioids from 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 misuse/diversion potential than the other two options above (SAMHSA, 2023b). Before starting naltrexone (Vivitrol), the patient should be opioid-free for seven to ten days before beginning the medication to prevent opioid withdrawal syndrome, which is a treatment initiation challenge. It is available as a long-acting injection every four weeks. Despite this convenient delivery method and the fact that any licensed prescriber can prescribe it, it is used less commonly than methadone (Methadose) and buprenorphine (Sublocade) for the treatment of OUD (Moore, 2019; Theriot et al., 2023). Naltrexone (Vivitrol) has not been evaluated in patients with OUD and comorbid pain. Still, it has comparable effectiveness to buprenorphine (Sublocade) in preventing a relapse of drug use in patients who can complete the recommended withdrawal period. Naltrexone (Vivitrol) is also used to treat alcohol use disorder (AUD; HHS, 2019b; SAMHSA, 2023b).

Studies regarding the best methodology continue, including the administration of LA buprenorphine (Sublocade) in emergency departments to patients who have overdosed and the application of comprehensive programs for people who are incarcerated. In 2016, the opportunity to undergo the required training for a prescribing waiver for buprenorphine (Sublocade) 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 SAMHSA website provides a search engine for OTPs by state. Alternatively, 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 therapy (City of New York Department of Health, n.d.; SAMHSA, 2023a, 2023b).

The Mainstreaming Addiction Treatment (MAT) ACT was passed in 2022 to expand the treatment opportunities for OUD. This legislation removed the DATA Waiver that was previously required to prescribe buprenorphine (Sublocade). Any prescriber registered with the DEA to prescribe at least schedule III medications can now prescribe buprenorphine (Sublocade). The MAT Act also removed the previous limits that capped the number of OUD patients a single prescriber could manage (Theriot et al., 2023).

For those with BZD or barbiturate use disorder, great care must 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 (NIDA, 2020). Withdrawal from benzodiazepines can cause cravings, tremors, anxiety, agitation, insomnia, hallucinations, hyperactive reflexes, tachycardia, hypertension, elevated body temperature, and seizures. Patients should be screened for comorbid mental health conditions, as described previously, and treatment for these conditions should be optimized to increase the potential success rate of any SUD treatment. A gradual taper of medication (25-50% every week or two) can typically be done over 6-10 weeks, depending on the dosage and the duration of current use, with weekly follow-up during this time. During the taper, patients may be switched to a longer-acting agent, such as diazepam (Valium) or chlordiazepoxide (Librium). The taper may be paused or slowed down if symptoms increase. Withdrawal symptoms can be formally assessed using a tool like the Clinical Institute Withdrawal Assessment-Benzodiazepines. Flumazenil (Romazicon) and phenobarbital (Sezaby) may limit acute withdrawal symptoms in inpatient settings. However, the safety of flumazenil (Romazicon) for this purpose has not been fully investigated, and phenobarbital (Sezaby) has a narrow therapeutic index and significant safety concerns (anaphylactic and allergic reactions, sedation, respiratory depression, suicidality). Melatonin can be used for reported insomnia. Behavioral therapies like CBT are recommended for patients recovering from CNS depressant addiction (NIDA, 2018a; Park, 2022).

Stimulant withdrawal can be uncomfortable, although less dangerous than CNS depressant withdrawal, and stimulant medications should be tapered to ease withdrawal symptoms (NIDA, 2020). Withdrawal from stimulants may result in fatigue, sleep disturbances, and a depressed or poor mood. As with most controlled substances, experts cite the importance of consulting and regularly monitoring the state’s PDMP (CDC, 2022; NIDA, 2018b). Behavioral therapies (e.g., CBT) and contingency management (motivational incentives to recognize and reinforce positive behavioral change) effectively treat stimulant misuse. Still, there are no FDA-approved medications for treating stimulant addiction (NIDA, 2018b, 2020). Studies are currently ongoing regarding possible pharmacological adjuncts. One such product, N-acetylcysteine (NAC or Acetadote, a glutamatergic agent), may help treat SUD by regulating glutamate, especially stimulants. NAC is currently FDA-approved for the treatment of acetaminophen (Tylenol) overdose and pulmonary complications of cystic fibrosis. Although not FDA-approved for the treatment of SUD, preclinical research on rodents found that NAC diminished drug-seeking behavior in rats/mice with alcohol, cannabis, and nicotine use disorder. Clinical research has found favorable effects in those with cocaine, heroin, and tobacco addiction. A recent meta-analysis of RCTs found that patients treated with NAC reported significantly fewer cravings, withdrawal, and depressive symptoms than the control group. Advocates highlight NAC’s broad applicability (adolescent and adult patients), favorable adverse-effect profile, accessibility, and low cost. It appears to be most effective as an anti-relapse agent in those already abstaining from stimulants when they start treatment. It may also be an effective adjunct (with contingency management) in cannabis use disorder treatment. Early studies also show effectiveness in tobacco use disorder, and more research is needed to determine if it is effective in AUD treatment (Chang et al., 2021; Tomko et al., 2018; Smaga et al., 2021).

 

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:

• Physicians and other authorized practitioners, in the course of their professional practice, may dispense, administer, or prescribe controlled substances for legitimate medical purposes or treatment other than treatment for addiction to controlled substances, when the practitioner regulates the dosage and prescribes or administers a quantity of such drugs no greater than that ordinarily recognized by members of their profession as sufficient for proper treatment in a given case. Such practitioners shall maintain a written patient record of administering, dispensing, and prescribing all controlled substances. The patient record shall contain sufficient information to justify the diagnosis and warrant the treatment. The record shall include at least the following information: patient identification data; chief complaint; present illness; physical examination as indicated; diagnosis; other data which support the diagnosis or treatment; and the regimen, including the amount, strength, and directions for the use of the controlled substance. This subdivision shall not be construed to require a record distinct from the patient's medical record (NYSDoH, n.d., Section 80.62).
• The use of preprinted prescriptions that indicate the controlled substance or the strength, dosage, and/or quantity of the controlled substance is prohibited. Such prohibition shall not apply to printed prescriptions generated using a computer or an electronic medical record system, provided such printed prescriptions are generated when a practitioner prescribes a controlled substance for a patient (NYSDoH, n.d., Section 80.63).
• No such prescription shall be made for a quantity of substances exceeding a 30-day supply if the substance were used per the directions for use specified on the prescription. A practitioner may issue no additional prescriptions for a controlled substance to an ultimate user within 30 days of the date of any prescription previously issued unless and until the ultimate user has exhausted all but a seven days' supply of that controlled substance provided by any previously issued prescription. A practitioner may issue a prescription for up to a three-month supply of a controlled substance, including chorionic gonadotropin, or up to a six-month supply of an anabolic steroid if used per the directions for use, provided that the prescription has been issued for the treatment of:
  • panic disorders (code A)
  • attention deficit disorder (code B)
  • chronic debilitating neurological conditions characterized as a movement disorder or exhibiting seizure, convulsive, or spasm activity (code C)
  • relief of pain in patients suffering from conditions or diseases known to be chronic or incurable (code D)
  • narcolepsy (code E)
  • hormone deficiency states in males, gynecologic conditions that are responsive to treatment with anabolic steroids or chorionic gonadotropin, metastatic breast cancer in women, anemia, and angioedema (code F; NYSDoH, n.d., Section 80.67)
• No refills are allowed on Schedule II medications or BZDs, and no more than five refills are 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 BZDs 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 BZDs) medications, this limit is a 30-day supply, or quantity #100, whichever is less (NYSDoH, n.d., Section 80.68 and 80.70).
• Before 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 to review 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 before the practitioner prescribes or dispenses 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 why such consultation was not performed (NYSDoH, n.d., Section 80.63).
• A practitioner (or any prescriber) is prohibited from providing any prescriptions of controlled substances to an addict or habitual user not in the course of professional treatment but to provide 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).
• According to New York State Public Health Law section 3331, a seven-day supply limit exists 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, per existing rules and regulations, any appropriate renewal, refill, or new prescription for an opioid (New York State Senate, n.d.).
• 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, WalMart, Stop and Shop, and Walgreens, amongst many others; NYSDoH, 2023).

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.

For additional training on the management of anxiety, please see the NursingCE activity titled Anxiety Disorders for APRNs

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