Opioid Management: Initiating, Monitoring and Tapering

Synopsis

Numerous guidelines targeting the safe use of opioids for chronic pain have been published but substantial challenges persist in the clinical application of best practice recommendations. The purpose of this article is to describe a pragmatic approach to the clinical care of adults with chronic pain receiving long-term opioid therapy. Three key components of care will emphasized including (1) the medical and mental health assessment prior to initiating opioid therapy; (2) clinical surveillance during the course of long-term opioid therapy; and (3) clinical considerations and strategies governing opioid tapering. The pragmatic approaches set forth in this review could be one small step toward operationalizing best practice recommendations for implementation in daily clinical practice. However, a pressing need exists for ongoing research to further clarify the optimal role that long-term opioid therapy has in the treatment of chronic pain.

INTRODUCTION

In recent years, numerous guidelines targeting the safe use of opioids for chronic pain have been published. The most influential guideline published to data is the Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain.¹ However, substantial challenges persist in the clinical application of best practice recommendations provided by the CDC and other guidelines.² Therefore, the purpose of this article is to describe a pragmatic approach to the clinical care of adults with chronic pain receiving long-term opioid therapy. This article is comprised of three sections. The first section focuses on key components of the clinical evaluation prior to initiating long-term opioid therapy. The second section highlights (1) the importance of identifying individual patient characteristics that should be considered when initiating opioid therapy; and (2) provides a simple acronym for organizing and documenting the clinical surveillance of long-term opioid therapy. The final section outlines several approaches to discontinuing opioid therapy including the potential risks and benefits of this aspect of patient care.

This review is not intended to supplant previously published guidelines, specifically, the CDC guidelines. Rather, this review is intended to build on current knowledge to drive the clinical implementation of previously established best practice recommendations for the care of adults receiving long-term opioid therapy.

CLINICAL EVALUATION PRIOR TO INITIATING OPIOID THERAPY

Pain Pathways

A constellation of spinal cord and brain regions are activated by pain stimuli. This is important because receptors for endogenous opioids are located in the periphery, the dorsal root ganglion, the spinal cord and the brain. A growing body of research suggests that pain stimuli are processed by a three-tiered neural network that encompasses the initial encoding of pain stimuli and extends to include the conscious modulation and memory formation of the pain experience (Figure 1).^{3, 4} Peripheral nociceptors are activated by noxious stimuli. These stimuli are transmitted by primary afferents to the dorsal root ganglion and then on to the dorsal horn of the spinal cord. In the dorsal horn, the spinothalamic tract is activated and pain stimuli are transmitted to the posterior thalamus. Pain stimuli undergo further processing in the anterior cingulate cortex, insula, prefrontal cortex and posterior parietal cortex. As a result, pain stimuli are consciously perceived, subjected to cognitive modulation and transformed into somatic responses. In a related group of neural structures, pain perception is further modulated by the emotional context of the stimuli and individualized by psychological factors that influence memory formation. These cortical regions interact with descending spinal cord tracts to either inhibit or facilitate modulation of incoming pain stimuli.

Figure 1.

Schematic representation of 3-tiered pain matrix (pTHAL,posterior thalamus;PFC, prefrontal cortex; pPAR, posterior parietal cortex; ACC, anterior cingulatecortex; INS, insula; ORB-F, orbitofrontal; PGN, perigenual ACC;AL-PFC,anteriolateralprefrontal cortex). From Hooten WH. Chronic pain and mental health disorders: shared neural mechanisms, epidemiology, and treatment. Mayo Clinic Proceedings. 2016; 91(7):955–970; with permission.

Opioid Pharmacology

Opioids bind a 7-transmembrane G-protein coupled receptor in the central nervous system and results in hyperpolarization of the cell membrane, inhibition of adenylate cyclase, decreased intracellular cAMP, and reductions in the release of neurotransmitters associated with nociception.⁵ Three receptors with distinct pharmacologic effects have been identified including the mu-, delta, and keppa-opioid receptor (Table 1).⁶ Agonist activity at these receptors results in hyperpolarization of the membrane, inhibition of adenylate cyclase, and decreased intracellular cAMP. This cascade of intracellular reactions reduces the release of neurotransmitters (e.g., substance P, GABA, dopamine, acetylcholine and norepinephrine) that play key roles in nociception.

Table 1.

Opioid receptor class and effects.

Receptor Class	Effects
Mu	Analgesia, euphoria, addiction potential, confusion, dizziness nausea, respiratory depression, miosis, urinary retention, constipation, physical dependence
Delta	Analgesia, cardiovascular depression, constipation, respiratory depression
Keppa	Analgesia, dysphoria, hallucinations, delusions, sedation

History and Physical Examination

Prior to initiating opioid therapy, a complete history and physical examination should be performed. One of the key aspects of the initial examination is to establish the primary pain diagnosis that will be the indication for opioid therapy which will facilitate a targeted assessment of pain intensity. Clearly identifying the primary pain diagnosis also allows the clinician to fully optimize evidence-supported non-opioid pharmacotherapy and non-pharmacological therapies prior to initiating opioids. Other important components of the initial history and physical examination include identification of comorbid medical problems that could alter drug metabolism and potentially increase the risk of adverse effects. For example, baseline serologic measures of renal and hepatic function should be assessed in patients with known or suspected renal insufficiency or hepatic dysfunction. Similarly, individuals with pulmonary disease or sleep-disordered breathing should be carefully assessed to ensure the respiratory depressant effects of opioids do not worsen pulmonary function or sleep-related problems. Finally, use of concurrent medications should be carefully assessed to mitigate the risk of adverse drug-drug interactions. Due to the risk of accidental overdose associated with concurrent use of benzodiazepines and opioids,⁷ use of benzodiazepines should be thoroughly assessed including review of prescription monitoring databases. Although the CDC guidelines clearly discourage co-prescribing of opioids and benzodiazepines, prescribing patterns have only been modestly impacted since publication of the guidelines.⁸ A urine toxicology screen should be considered if the current status of benzodiazepine use remains indeterminate.

Pain and Functional Assessment

An assessment of pain and functioning should be obtained prior to initiating opioid therapy. A functional assessment generally implies determining the capacity of an individual to perform physical activities. Critical domains of physical functioning that should be assessed prior to initiating opioid therapy include the capacity to perform routine activities of daily living, the capacity to perform work-related activities, and the ability to engage in leisure activities. Other domains of function include the capacity to engage in social and family activities. Functional impairments related to fixed anatomical or neurological problems can be further confounded by pain interference which is defined as the extent to which pain limits engagement in activities. Although opioid therapy would not be expected to alter fixed anatomical or neurological deficits, effective treatment should attenuate functional impairments attributed to pain interference. Although numerous questionnaires are available to assess pain and functioning, the Brief Pain Inventory (BPI) incorporates both of these clinical parameters. The BPI is a validated, self-administered questionnaire that takes less than 5 minutes to complete.⁹ Responses to all items are completed using 10-point visual analogue scales. In addition to assessing pain intensity, the BPI assesses the impact of pain interference on general activity, walking ability, work-related activities, social activities and life enjoyment. A 3-item short-form of the BPI has been developed. The PEG (P – pain intensity; E – pain interference with life enjoyment; G – pain interference with general activity) has demonstrated construct validity comparable to the BPI and it can be used to detect changes in pain and function over time.¹⁰

Mental Health Evaluation

A mental health assessment should be performed to identify potential problems that increase the risk for problematic opioid use or opioid use disorder. Due to the paucity of mental health services in the ambulatory care setting, several key factors can be readily assessed by the non-mental health professional. For example, a mental health history should be obtained from the patient and medical record should be carefully reviewed. Important aspects of this history include previous diagnosis of a psychiatric disorder, prior psychiatric hospitalization, prior admissions for alcohol or other substance detoxification, and previous suicide attempts. In addition, a review of current and previously prescribed psychotropic medications could also provide important information about prior episodes of psychiatric care.

When a psychiatric disorder is suspected in the absence of a past history of mental health care, several of screening instruments are available to assess for depression, anxiety and substance use disorders (Table 2).³ Two very brief screening questionnaires that are widely used in the primary care setting are the 2-item Patient Health Questionnaire¹¹ (PHQ-2), which is used to screen for depression, and the 2-item Generalized Anxiety Disorder¹² (GAD-2) questionnaire. The PHQ-2 and the GAD-2 use the same lead question: “Over the past 2 weeks, how often have you been bothered by the following problems?” Responses to the following 2 questions are used to score the PHQ-2: (1) “Little interest or pleasure in doing things” and (2) “Feeling down, depressed or hopeless.” Each question is scored from zero, indicating “Not at all,” to 3 indicating “Nearly every day.” A score ≥ 3 has a sensitivity and specificity of 83% and 90%, respectively, for major depressive disorder and a sensitivity and specificity of 62% and 95%, respectively, for any depressive disorder.¹¹ Similar to the PHQ-2, responses to the following 2 questions are used to score the GAD-2: (1) “Feeling nervous, anxious or on edge” and (2) “Not being able to stop or control worrying.” The GAD-2 and the PHQ-2 use the same scoring scheme. A score ≥ 3 has a sensitivity and specificity of 86% and 83%, respectively, for generalized anxiety disorder and a sensitivity and specificity of 65% and 88%, respectively, for any anxiety disorder.¹²

Table 2.

Sensitivities and specificities of screening questionnaire cutoff scores for depression, anxiety and substance use disorders.

Depression	Cutoff score	Sensitivity	Specificity
Beck Depression Inventory	15	77%	61%
Hamilton Rating Scale for	17	81%	65%
Depression
Center for Epidemiologic Studies	27	82%	68%
Depression Scale
Patient Health Questionnaire	10	79%	60%
Depression (PHQ-9)
Anxiety
Hospital Anxiety and Depression	8	88%	81%
Scale-Anxiety
Beck Anxiety Inventory	5.5	76%	77%
Patient Health Questionnaire	10	89%	82%
Anxiety (GAD-7)
Substance Use Disorders
Alcohol Use Identification Test (AUDIT)	8	88%	77%
CAGE (alcohol)	2	71%	90%
Drug Abuse Screening Test (DAST)	2	85%	78%
Current Opioid Misuse Measure (COMM)	10	84%	82%

Modified from Hooten WH. Chronic pain and mental health disorders: shared neural mechanisms, epidemiology, and treatment. Mayo Clinic Proceedings. 2016; 91(7):955–970; with permission.

If clinically suspected, patients should also be screened for substance use disorders. Although numerous screening instruments are available (Table 2), the majority only screen for a single substance. The Tobacco, Alcohol, Prescription Medication, and other Substance use (TAPS) tool screens for multiple substances and provides a substance-specific risk assessment for positive screen results.¹³ The TAPS is supported by the National Institute on Drug Abuse, and clinician and patient versions are available online.¹⁴ A score ≥ 1 on the self-administered TAPS has a sensitivity and specificity of 77% for problem alcohol use, a sensitivity and specificity of 61% and 98% for problem opioid use, and a sensitivity and specificity of 82% and 75% for any substance use problem.¹³ A urine toxicology screen should be considered if the substance use status is indeterminate or if relapse to substance use is clinically suspected.

Screening Tools to Predict Problematic Opioid Use

Screening for psychiatric disorders, including substance use disorders, that are associated with problematic opioid use should be distinguished from screening tools specifically designed to assess, or predict, the risk of developing opioid use-related problems. In general, the operating characteristics of these targeted screening tools are poor and this was acknowledged in the CDC guidelines:

“Previous guidelines have recommended screening or risk assessment tools to identify patients at higher risk for misuse or abuse of opioids. However, the clinical evidence review found that currently available risk-stratification tools (e.g., Opioid Risk Tool, Screener and Opioid Assessment for Patients with Pain Version 1, SOAPP-R, and Brief Risk Interview) show insufficient accuracy for classification of patients as at low or high risk for abuse or misuse.”^{1 (page 29)}

For example, the sensitivity and specificity of the Opioid Risk Tool for predicting development of opioid use-related problems is 25% and 85%, respecitvely.¹⁵ Furthermore, the positive predictive value (PPV) is 10% and the positive likelihood ratio (LR) is 1.5.¹⁵ The operating characteristics of the Screener and Opioid Assessment for Patients with Pain Version 1 (SOAPP-R) are similarly poor: sensitivity 59%; specificity 48%; PPV 8%; and positive LR 1.2.¹⁶ Consistent with the content of the CDC guidelines, these type of measures should be used with caution.

Establishing Goals of Opioid Therapy

Prior to initiating a trial of opioid therapy, realistic expectations for pain relief, functional improvements, and potential adverse medication effects should be openly discussed including the risks of an accidental overdose, death, and development of opioid use disorder. This encounter should also include a discussion about the initial duration of therapy and plans to discontinue opioids if the goals of treatment are not met. Many ambulatory care clinics and healthcare delivery systems use opioid contracts which are non-legally binding agreements signed by the patient and clinician. In general, opioid contracts outline the responsibilities of the patient and clinician, and provide documentation that the goals, risks and benefits, and duration of therapy have been discussed. The potential benefits of opioid contracts in deterring aberrant drug-related behaviors has been brought into question by the results of a recently published systematic review.¹⁷

INITIATION AND SURVEILLANCE OF OPIOID THERAPY

Imitation of Opioid Therapy

The least potent drug prescribed at the lowest effective dose should be the general aim of treatment. Because the clinical problem is chronic pain and not acute pain, a patient’s desire for prompt analgesia should be carefully assessed in order to avoid the risks associated with a rapid dose titration including respiratory depression. The initial dose should be prescribed when the patient does not have any scheduled activities due to the potential occurrence of an acute adverse effect (e.g., nausea or sedation). Comorbid medical conditions should guide selection of the most appropriate medication and long-acting agents should be strictly avoided in opioid naïve patients (Table 3). For tramadol and tapentadol, an initial dose of 50 milligram (mg) followed by a second 50 mg dose 12 hours later is a reasonable regimen especially for adults greater than 65 years of age. Although any dose titration should be individualized, the dose of each drug could then be increased by 50 mg every 3 to 4 days. For hydrocodone and immediate release oxycodone, an initial dose of 5 mg followed by a second 5 mg dose 12 hours later is a safe initial dosing regimen that would not be expected to have any significant respiratory depressant effects. The dose of each drug could then be increased by 5 mg every 3 to 4 days. A follow-up evaluation should be scheduled 10 to 14 days following initiation of therapy or sooner if clinically indicated.

Table 3.

Properties of commonly prescribed shorting-acting opioids.

Opioid	Description	Morphine Equivalency	Half-Life	Metabolites	Safety Considerations
Hydrocodone	Oral, semisynthetic, 36% protein-bound	1:1	3–4 hrs	Norhydrocodone (CYP3A4) Hydromorphone (CYP2D6)	Mainly renal excretion.
Hydromorphone	Semisynthetic; multiple formulations available.	1:5	2–3 hrs	H3G (direct conjugation)	High potency restricts use as first line agent.
Morphine	Derived from the poppy seed; multiple formulations available.	Not applicable	2.5 to 4 hrs	M3G, M6G (direct conjugation) Normorphine (CYP3A4)	M6G more potent and longer acting than parent compound.
Oxycodone	Oral, semisynthetic, 45% protein bound	1:1.1	3.2 hrs	Noroxycodone (CYP3A4) Noroxymorphone (CYP2D6, CYP3A4) Oxymorphone (CYP2D6)	Improved toxicity in patients with impaired renal or hepatic function.
Tapentadol	Oral, synthetic, mu-receptor agonist and NE reuptake inhibition	4:1	4 hrs (IR)	Inactive metabolites via direct conjugation, CYP2C9, CYP2C19, CYP2D6	Weak muscarinic and 5-HT3 antagonist. No effect on cP450 enzymes.
Tramadol	Oral, synthetic codeine analog, 20% protein bound; mu-receptor agonist and NE reuptake inhibition	5:1	6.0–7.5 hrs	Single active metabolite Ml, derived from 0-methylation mediated by CYP2D6	Caution with impaired CYP2D6 activity.

H3G, hydromorphine-3-glucuronide; M3G, morphine-3-glucuronide; M6G, morphine-6-glucuronide; 5HT3, serotonin; NE, norepinephrine.

Clinical Surveillance During Long-Term Opioid Therapy

Key components of the CDC guidelines center around best practices for maintaining long-term opioid therapy. Maintenance of best practices provides the framework for identifying potential complications including opioid misuse and opioid use disorder. Application of the CDC guidelines in daily clinical practice is often difficult to operationalize but the CAREFUL acronym (Box 1) provides a summary of many key components of clinical surveillance recommended in the CDC guidelines.¹⁸

BOX 1. The CAREFUL acronym for the clinical surveillance of long-term opioid therapy.

C	Contract for opioid use
A	Addiction risk
R	Rx monitoring programs
E	Effective lowest dose
F	Functionality
U	Urine drug screen
L	Longitudinal follow-up

From Hooten WH. CAREFUL: a practical guide for improving the clinical surveillance of long-term opioid therapy. Mayo Clinic Proceedings. 2018; 93(8):1149; with permission.

Although use of opioid contracts (C in CAREFUL acronym) has been previously discussed, it should be emphasized that these agreements specify shared responsibilities between the patient and clinician. This is important because the responsibilities of clinicians are often overlooked.

Despite assessing for addiction (A in CAREFUL) before initiation of opioid therapy, all patients should be assessed during the course of therapy to identify early signs and symptoms of opioid misuse or OUD. One important surveillance method that provides objective data about controlled substance use are prescription drug monitoring programs (R_x in CAREFUL) which are now available in all 50 states and the District of Columbia. These online databases of dispensed controlled substances should be checked whenever an opioid prescription renewal is issued.

The opioid dose should be regularly assessed to ensure the effective (E in CAREFUL) lowest dose is being prescribed. Although dosing regimens are typically individualized, doses greater than 50 morphine milligram equivalents have been associated accidental overdoses. An important determinant of the effective lowest dose is functionality (F in CAREFUL) including pain intensity. As discussed earlier, the 3-item PEG questionnaire is sensitivity to changes in pain and pain interference over time.

Similar to prescription drug monitoring programs, urine drug screens (U in CAREFUL) provide an objective measure of medication compliance including the use of other controlled and illicit substances. Aberrant urine drug screen results during the course of therapy could help identify an emerging substance use problem including OUD. Although the CDC guidelines recommend at least 1 urine drug screen annually, obtaining a screen every 3 to 4 months could enhance early detection of an evolving problem.

Finally, longitudinal follow-up (L in CAREFUL) is the cornerstone of clinical surveillance because all other surveillance interventions are dependent on face-to-face encounters with the patient. The frequency of follow-up was not specified in the CDC guidelines, but regularly scheduled appointments every 1 to 3 months should provide ample opportunities to document an accurate account of the patient’s clinical course. Thus, the CAREFUL acronym is a pragmatic tool that can be used in daily clinical practice to guide the assessment and documentation of many key recommendations of clinical surveillance recommended in the CDC guidelines.

Monitoring Endocrine Function During Opioid Therapy

Opioid use is associated with a broad range of endocrinopathies. Opioids inhibit the entire hypothalamic-pituitary-gonadal axis by binding to opioid receptors in the hypothalamus which decreases the secretion of gonado-tropin-releasing hormone.¹⁹ Commonly occurring signs of hypogonadism including diminished libido and sexual functioning, infertility, fatigue, and loss of muscle mass and strength. Opioids also inhibit the hypothalamic-pituitary-adrenal axis by (1) directly suppressing adrenal function; and (2) suppressing the production of corticotripin-releasing hormone and adrenocorticotropic hormone.^{19, 20} Commonly occurring signs of adrenal insufficiency include fatigue, weight loss, dizziness and diffuse myalgia. Many of the signs and symptoms of hypogonadism and adrenal insufficiency overlap with symptoms that are frequently associated with chronic pain. Thus, serologic monitoring for hypogonadism¹⁹ (e.g., total and free testosterone in men, estradiol in women) and adrenal insufficiency²⁰ (e.g., cortisol, corticotropin, and corticotropin stimulation test) should be considered if clinically indicated. However, due to the diurnal variation hormone levels and complexities associated with accurately interpreting the test results, referral to an endocrinologist may be warranted.

TERMINATION OF LONG-TERM OPIOID THERAPY

Indications for Opioid Tapering

Widely accepted indications for tapering long-term opioid therapy have not been fully established, aside from a patient’s request to discontinue therapy. However, the indications for tapering can be loosely grouped into three categories.^{21, 22} The first category is comprised of clinical factors indicating that the goals of treatment were not met. For example, inadequate pain reduction in the context of diminishing analgesia, lack of functional improvement, and progression of pain interference in physical, emotional and social functioning. The second category is comprised of changes in patient’s medical status that increases the risk of potential opioid-related adverse effects. For example, deterioration of renal or hepatic function may necessitate dose reductions or tapering to reduce the risk of toxicity due to high serum drug levels. Similarly, the diagnosis of a central nervous system disease (i.e., Parkinson’s Disease, stroke, Alzheimer’s Disease) may necessitate dose reductions or tapering to reduce the risk of delirium or other adverse neurological effects. The third category is comprised of signs and symptoms indicative of opioid misuse, OUD or identification of drug diversion. A pocket guide for opioid tapering is available online from the CDC.²²

Risks of Tapering Long-Term Opioids

A chief determinant of risk in long-term opioid tapering is patient consent. Consensual tapering, defined as mutual agreement between the patient and clinician to taper opioids, is generally safe and effective. Non-consensual tapering, defined as lack of patient consent or agreement to taper opioids, has been associated with a broad array of adverse effects including failure to complete the taper, termination of care, overdose, suicidal ideation, worsening depression and anxiety, and increased utilization of hospital and emergency department services.^23–25 However, patient-related factors (e.g., OUD, opioid misuse) that precipitated opioid discontinuation may play an independent causal role in the harms associated with tapering.

Other factors associated with unsuccessful tapering include fear of acute opioid withdrawal and increased pain following opioid discontinuation. Although acute opioid withdrawal in ambulatory patients is a non-lethal withdrawal state, signs and symptoms of withdrawal should be carefully followed in order to reduce the risk of patient dropout during the taper. Commonly encounter physical symptoms include restlessness, sleep disruption, diaphoresis, rhinorrhea, yawning, nausea, loose stool, pupillary dilation, piloerection, and elevated blood pressure and heart rate. Affective distress, characterized by acute dysphoria and anxiety, are often observed. Finally, due to activation of descending pain facilitatory tracts during opioid tapering, patients may report diffuse arthalgia and myalgia with or without acute exacerbation of baseline pain symptoms.

Opioid Taper Schedules and Treatment of Acute Withdrawal

Evidence-supported opioid tapering schedules do not currently exist. However, several approaches based on percent dose reduction are used in the outpatient setting. In general, these approaches suggest reducing the baseline dose by 5% to 10% followed by similar dose reductions based, in part, on the indication for opioid tapering.^{22, 26, 27} When the indication for tapering requires rapid dose reduction (i.e., acute change in the patient’s medical status, patient safety at risk due to unsafe opioid use), dose reductions of 5% to 10% may occur every 2 to 3 days to every week. Rapid tapering intended to protect patient safety is generally non-consensual and occurs in the context of opioid misuse, OUD, or following an accidental overdose. If the indication for tapering is consensual dose reductions of 5% to 10% my occur every week, bi-weekly or every month. In these clinical scenarios where the duration of the taper is not time sensitive, the frequency of dose reductions should be carefully discussed and planned with the patient. This will enhance patient trust, reduce anticipatory anxiety about the taper, and provide adequate opportunities to provide other non-opioid based treatments for pain as clinically indicated.

In the context of consensual tapering, slow dose reductions should mitigate the risk of acute opioid withdrawal. In these clinical scenarios, acute opioid withdrawal can be easily treated by (1) temporarily providing additional small doses of opioid until the symptoms abate; (2) temporarily increasing the dose; or (3) increasing the frequency of further dose reductions. In the context of a rapid taper, several adjunct medications are available. Alpha-2 agonists reduce symptoms of acute opioid withdrawal by, in part, reducing the activity of the sympathetic nervous system.²⁸ Oral clonidine at doses of 0.05 mg to 0.1 mg every 6 to 12 hours is widely used but the drug should be carefully titrated due to adverse effects including hypotension and bradycardia. These adverse effects may be accentuated in the context of acute withdrawal which can be associated with hypovolemia due to the gastrointestinal effects of the withdrawal state. Another alpha-2 agonist is lofexidine, which is widely used in Europe and was recently approved by the Food and Drug Administration for acute opioid withdrawal.²⁹ Lofexidine is typically dosed at 0.54 mg every 6 hours. Similar to clonidine, commonly occurring adverse effects include hypotension, bradycardia and dizziness. Other medications of varying mechanisms have been used to treat acute withdrawal including gabapentin,³⁰ trazodone,³¹ low dose naltrexone combined with clonidine,³² and loperamide but use of this drug at higher doses can cause arrhythmias.³³

In addition to the pharmacologic management of acute opioid withdrawal, non-pharmacological interventions should be considered including supportive therapy, cognitive behavioral therapy, use of stress reduction techniques, meditation, pain and withdrawal-related psychoeducation and graded exercise.³⁴

Clinical Outcomes of Opioid Tapering

Recently, interest in the long-term of opioid tapering has grown. In a systematic review that involved 67 studies focusing on opioid reduction and discontinuation, significant improvements in pain severity (8 of 8 studies), function (5 of 5 studies) and quality of life (3 of 3 studies) were observed.³⁵ The quality of evidence supporting these clinical observations was assessed as fair. In a separate systematic review, it was hypothesized that pain improves or does not change following opioid tapering.³⁶ This review included 20 studies that involved a total of 2109 patients. Study inclusion included reporting pre- and post-taper pain scores and exclusion criteria included use of opioid substitution. Sixteen studies reported improved pain post-tapering, 3 studies reported that pain was unchanged post-tapering, and a single study reported that pain was unchanged or improved in 97% of patients and worse in 3% of patients. In summary, these systematic reviews suggest that opioid tapering is associated with longer-term improvements in pain and functionality.

Conclusions

As the national crisis of opioid-related morbidity and mortality persists, approaches to increase the uptake of best practice recommendations are needed. The pragmatic approaches set forth in this review could be one small step toward operationalizing these recommendations for implementation in daily clinical practice. However, a pressing need exists for ongoing research to further clarify the optimal role that long-term opioid therapy has in the treatment of chronic pain.

Key Points.

• A detailed medical and mental health evaluation prior to initiating long-term opioid therapy is needed to determine the patient’s candidacy for long-term opioid therapy.

• The least potent drug prescribed at the lowest effective dose should be the general aim of treatment.

• The CAREFUL acronym is a pragmatic tool that can be used in daily clinical practice to guide the assessment and documentation of many key recommendations of clinical surveillance recommended in the CDC guidelines.

• Consensual tapering, defined as mutual agreement between the patient and clinician to taper opioids, is generally safe and effective. Non-consensual tapering, defined as lack of patient consent or agreement to taper opioids, has been associated with a broad array of adverse effects including suicide.