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Last Updated: 12/10/2013  

Pain

Screening
  • Screen older patients and those with cancer or other chronic conditions for pain at every visit.

Diagnosis
  • Use the patient's self-report of pain as the primary source of assessment and use a standard pain scale (such as a visual analog scale, numerical scale, or verbal rating scale) to quantify pain intensity.

  • Obtain a detailed history and perform a physical exam in patients with pain. Assess functional capacity.

  • Identify comorbid medical conditions that may affect the pain or its management through appropriate testing, including testing for kidney and liver disease, baseline ECG, and toxicology screen in appropriate patients.

Therapy
  • Choose initial drug therapy based on pain intensity and patient-specific pathophysiology, risks, and drug interactions. Begin therapy with acetaminophen or NSAIDs in most patients with mild pain and with opioids in most patients with severe pain.

  • Use opioids alone or in combination with non-opioids (as in multimodal therapy) for patients with severe pain or pain despite maximal non-opioid therapy, and for patients who cannot tolerate non-opioids or for whom the harms outweigh the benefits.

  • Consider adjuvant analgesics for specific types of pain including tricyclic antidepressants or gabapentin for neuropathic or chronic pain.

  • Consider cutaneous techniques such as the application of ice and heat, especially for pain associated with muscle spasm or tension.

  • Use a multimodal approach including drug therapy and other therapeutic interventions such as acupuncture, ablative techniques, and blocks in patients with chronic pain.

  • Predict, recognize, and treat side effects of opioids, including nausea, constipation, somnolence, ataxia, and pruritus.

  • Realize that psychological dependence (addiction) may occur in patients who receive opioids for pain control.

  • Understand “drug seeking” behavior, drug abuse, misuse, or diversion, and doctor shopping; concepts of tolerance and psychological dependence (addiction); and monitor for each regularly.

Screen populations at increased risk for chronic pain and acute pain on a regular basis. 
  • Screen regularly for pain in all patients, especially those with:

    • Osteoarthritis

    • Rheumatoid arthritis, bursitis, tendonitis, cephalalgia

    • Other arthritides (e.g., gout, ankylosing spondylitis)

    • Other musculoskeletal disorders (e.g., systemic lupus erythematosus, scleroderma)

    • History of trauma

    • Known neuropathy or conditions predisposing to neuropathy

    • HIV

    • Status post procedures (e.g., phantom limb pain syndrome)

    • Sickle cell disease

    • Fibromyalgia syndrome

    • Low back pain

    • Neurologic disorders (migraine, multiple sclerosis, cephalalgia)

    • Malignancy

    • Treatment-induced pain

    • Postoperative pain

    • Visceral pain

    • Ischemic pain

    • Dental pain

  • Ask appropriate initial screening questions (in patient's primary language and at an appropriate academic level), including:

    • Do you have any ongoing pain problems or did you have discomfort in the past?

    • Do you have pain or discomfort now?

    • Have you had pain or discomfort recently?

    • Have you experienced pain or discomfort with your current problems or any of your other medical, surgical, or psychiatric conditions?

    • Does the pain cause depression, anxiety, sadness, guilt, insomnia, or other changes in emotion or mood?

    • Does the pain disrupt your function or impair your activities of daily living?

    • Does the medication you are prescribed for pain satisfy your immediate needs?

    • Do any of your medications cause side effects which limit their usefulness?

  • Note that certain patient populations have been identified as being at high risk for undertreated or untreated pain and warrant particular attention, including:

    • Residents of nursing homes, extended care facilities, and assisted living facilities

    • Minorities and non-English-speaking patients

    • Hospitalized patients

    • Seniors living alone

    • Patients with Alzheimer's disease and others cognitively impaired

Evidence
  • A 2009 guideline from the American Geriatrics Society recommended routine screening for pain of all older patients (1).

  • A 2008 guideline from the American College of Physicians recommended that physicians regularly ask patients at the end of life about pain and other symptoms (2).

  • A 2005 guideline from the American Pain Society recommended screening all patients for pain (3).The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) showed a high incidence of uncontrolled moderate-to-severe pain in seriously ill and dying hospitalized adults (4).

  • A study of over 5000 general medical inpatients showed significant levels of pain (5).

  • The Hospitalized Elderly Longitudinal Project (HELP) investigators found a large pain burden among hospitalized elderly patients (6).

  • A survey documented undertreatment of pain and barriers to pain management in HIV patients (7; 8; 9).

  • A large, retrospective, cross-sectional study looked at the prevalence of daily pain in 13,625 elderly and minority nursing home residents with cancer and found that more than 25% of patients reported daily pain, and 25% of those reporting daily pain did not receive any analgesic agents (10). See also the accompanying editorial (11).

Rationale
  • Patients with various risk factors have a greater likelihood of experiencing significant episodes or flares of chronic pain.

  • Some patients are reluctant to report pain and deny having pain; therefore, screening is essential.

Comments
  • Joint Commission standards require that patients be asked about pain.

Screen patients presenting with acute problems or acute exacerbations of chronic illness for pain. 
  • Ask about the intensity, location, exacerbations and flares, and quality of pain or discomfort when a patient presents with acute complaints or with acute concerns related to an exacerbation of a chronic illness.

  • Examples of pain related to acute illness include:

    • Pain related to infectious processes such as diverticulitis, cellulitis, and primary or recurrent herpes simplex and herpes zoster

    • Pain related to vascular diseases such as deep venous thrombosis, claudication, venous stasis, and ischemia

    • Pain related to trauma, from minor to life-threatening, or surgery

    • Neuropathic pain from diabetes, multiple sclerosis, postprocedure, complex regional pain syndrome, fibromyalgia, nerve trauma, postcerebrovascular accident pain, central thalamic pain syndrome, alcohol- and drug-induced neuropathy, dental pain, and migraine

    • Other somatic complaints that are secondary to a major depressive disorder or generalized anxiety disorder, or other psychopathologies

Evidence
  • A 2000 review of acute pain in an emergency department setting highlighted deficits in identifying and treating acute pain (12).

  • Several randomized, controlled trials have shown that opioid analgesics can be safely administered to patients with acute abdominal pain, achieving effective pain relief without altering the ability of clinicians to accurately evaluate, diagnose, and treat these patients (13; 14; 15).

  • A survey of emergency medicine physicians revealed that whereas most (85%) acknowledged that pain medication would not alter their ability to evaluate the patient, 76% still would not give an opioid analgesic until the patient was evaluated by a surgeon (16).

Rationale
  • Many acute medical problems or illnesses have pain as an associated symptom.

  • Patients may not report associated pain unless asked.

  • Clinicians often attend to the treatment of the underlying process while directing less attention to treating the associated pain and psychosocial issues.

Screen older patients for the presence of chronic pain or discomfort at initial evaluation. 
  • Ask patients if they have any persistent or recurrent pain or discomfort.

  • Use terms synonymous with pain (burning, discomfort, soreness, tightness, stiffness) when screening older patients for pain.

  • Rely on nonverbal pain behavior (moaning, crying, guarding, agitated behavior, or sequestered activity) or the report of caregivers in patients with cognitive or language deficits.

Evidence
  • A 2009 guideline from the American Geriatrics Society recommended routine screening for pain of all older patients (1).

  • A retrospective, cross-sectional study of elderly nursing home residents with cancer revealed that between 25% to 40% of patients experienced daily pain, and the prevalence increased with age (10).

Rationale
  • Chronic pain is common in both community-dwelling elderly and nursing home residents.

  • Older patients often suffer from chronic medical conditions that predispose to pain yet will deny the existence of pain, as it is perceived as a sign of weakness.

Comments
  • Consequences of untreated pain in older persons include impaired ambulation, depression, anxiety, sleep disturbance, geographical constriction, and social isolation. Additional consequences include self-treatment with OTC medications, old prescriptions, shared medication, phytopharmaceuticals, or alcohol.

  • Elderly patients may be lonely or bored and may resist pharmacologic interventions due to past experience with side effects by self or others, inadequate therapeutic outcomes, or financial burdens.

Screen all patients with cancer for the presence of pain or discomfort at each visit and at predetermined intervals between visits. 
  • Ask patients with cancer to describe the characteristics, intensity, and duration of each type and site of pain.

  • Rely on nonverbal pain behavior or the report of caregivers in patients with cognitive or language deficits.

  • If pain is disclosed, complete a comprehensive pain assessment.

  • Screen patients for predictable comorbid conditions, such as alcoholism, tobacco use, social recreational drug use, depression, anxiety, and somatization.

Evidence
  • A 2012 guideline from the European Society for Medical Oncology recommended routinely assessing pain in patients with cancer, and recommended particular screening tools (17).

  • A 1994 guideline for the management of cancer pain from AHCPR reviewed the extensive evidence that cancer pain is common, undertreated, and controllable with simple measures (18).

  • A large, retrospective study of older patients with cancer found that uncontrolled pain was common. Many patients reported daily pain, including 38% of those aged 65 to 74, 29% of those aged 75 to 84, and 24% of those over 85 (10).

Rationale
  • Patients with cancer often have more than one type of pain, even at a given site.

  • Pain is common in patients with cancer; their pain is frequently undertreated, and they are often reluctant to report it; depression and anxiety may be comorbid with the diagnosis of cancer.

  • Unrelieved pain affects a patient's normal function, quality of life, and ability to fight the underlying disease, and it can diminish the patient's desire to live.

  • Cancer pain can be controlled with relatively simple measures in over 90% of patients.

Comments
  • The NCCN has issued guidelines for the management of pain, which are available for clinical use on their web site.

Screen patients approaching the end of life for, and ask their caregivers and family members about, pain and discomfort as well as other physical and psychosocial symptoms. 
  • Ask patients with life-limiting illnesses about pain and other symptoms at each evaluation.

  • Consider using a standardized symptom assessment scale (e.g., Edmonton Symptom Assessment Scale, Memorial Symptom Assessment Scale) to screen for pain in patients near the end of life.

  • Be aware that many physical and psychosocial symptoms are common near the end of life and can exacerbate the patient's experience of physical pain and suffering.

  • Rely on and consider the report of caregivers and family or on the patient's appearance if patient is unable or refuses to describe symptoms.

Evidence
  • A 2008 guideline from the American College of Physicians recommended that physicians regularly ask patients at the end of life about pain and other symptoms (2).

  • A 2008 systematic review of end of life palliative care found strong evidence in support of various pain control interventions (19).

  • A 2006 AHRQ systematic reviewon cancer care quality measures regarding symptoms and end-of-life care reviewed the evidence in support of available quality measures (20).

  • The SUPPORT study showed a high incidence of uncontrolled moderate-to-severe pain in seriously ill and dying hospitalized adults with both cancer and noncancer diagnoses (4).

  • A survey of 100 patients admitted to a palliative care unit revealed pain as a prominent symptom in 49% of patients (21).

  • A retrospective chart review of patients dying in the hospital with any diagnosis suggested that 47% of patients experienced pain in the last 48 hours of life (22). Other physical and psychosocial symptoms were equally prevalent in these two studies.

Rationale
  • Careful screening for the presence of bothersome symptoms represents the first step in management.

  • Prompt attention to these symptoms is particularly important in end-of-life care given the limited life expectancy of these patients.

Comments
  • Use perception, recognition, and identification of pain-mediated events that are not readily disclosed by the patient, caregivers, or family.

Use the patient's self-report of pain as the primary source of assessment. 
  • Rely on timely patient self-report whenever possible.

  • Accept the patient's subjective report coupled with physiologic (sympathetic, adrenergic) or behavioral signs.

  • For patients with cognitive or language impairment, rely on nonverbal pain behavior, reports of caregivers, and change in level of functioning or ability to perform activities of daily living.

Evidence
  • A 2012 guideline from the European Society for Medical Oncology recommended routinely assessing pain in patients with cancer, and recommended a visual analog scale, numerical scale, and verbal rating scale (17).

  • A 2009 guideline from the American Geriatrics Society recommended routine screening for pain of all older patients and stated that the patient's own report is the most reliable source of information (1).

  • A 2008 Institute of Aging in Canada expert consensus document on the assessment of pain in older persons recommended a detailed pain history, a history of comorbid conditions and medications, an exploration of functional status, and a detailed physical exam including a general exam, musculoskeletal exam, neurological exam, and mental status exam (23).

  • Observational studies in patients with and without cancer confirm that clinicians often believe that patients exaggerate their pain (24; 25).

Rationale
  • No objective biologic markers can confirm the presence of pain.

  • Vital signs and behavior are not reliable measures of pain intensity and cannot be used reliably to confirm the presence of pain, but the autonomic sympathetic indices (xerostomia, mydriasis, diaphoresis, or increases in pulse, blood pressure or respiration) may reflect unmanaged painful events.

  • Discordance between a patient's self-report and observed behaviors may reflect stoicism, chronic pain with resultant learned coping skills, or family dysfunction, and requires further assessment.

Comments
  • As cited in The American Journal of Nursing, Joint Commission standards establish the patient's self-report as the primary source for assessing the presence of pain (26).

  • The NCCN has issued guidelines for the management of pain, which are available for clinical use on their web site.

Obtain a detailed history and perform a physical exam in patients with pain. 
  • Ask about pain intensity, character (e.g., aching, burning, throbbing, shooting, cramping, knife-like), frequency, duration, location, radiation, precipitating and alleviating factors, current and past treatments, treatment successes and unsuccessful interventions, treatment side effects, and adverse events.

  • Examine the sites of pain and likely referral patterns, and complete a focused neurologic exam.

  • Use a comprehensive initial pain assessment tool or a brief pain inventory form, especially for patients with new or difficult to control pain.

Evidence
  • A 2008 Institute of Aging in Canada expert consensus document on the assessment of pain in older persons recommended a detailed pain history, a history of comorbid conditions and medications, an exploration of functional status, and a detailed physical exam including a general exam, musculoskeletal exam, neurological exam, and mental status exam (23).

  • Joint Commission standards outline the key history elements for a complete pain assessment across all care settings (26).

Rationale
  • A careful history guides the appropriate prescribing of drug and non-drug therapies.

  • Pain may represent the first sign of significant underlying pathology warranting prompt further evaluation.

  • Treatments directed at the underlying etiology of the pain are often most effective in managing the pain.

Use a standard pain rating scale to quantify pain intensity. 
  • Use a standard pain scale such as:

    • A visual analog scale

    • A numerical scale

    • A verbal rating scale

  • Ask patients to rate their pain now, at its worst, and at its best.

  • Ask patients to identify a pain level that would be tolerable or acceptable as a mutually agreeable target endpoint.

  • Use scales tailored for patients with cognitive, academic, or language barriers.

  • Encourage patients with chronic pain to keep a pain diary documenting pain intensity at regular intervals.

  • Understand that a lower score on the pain scale does not necessarily translate to lower doses of pain medication.

  • See Pain Distress Scales.

Evidence
  • A 2012 guideline from the European Society for Medical Oncology recommended routinely assessing pain in patients with cancer, and recommended a visual analog scale, numerical scale, and verbal rating scale (17).

  • Joint Commission standards require the use of standard pain intensity scales for appropriate patients in all health care systems (26).

  • A 2003 review of the validity of pain measures in patients with cancer included 164 articles. Visual analog scales and numerical rating scales were found to be valid, and a verbal rating scale was somewhat less stable over short periods of time (27).

  • A review of six different scales (visual analog, numerical rating, verbal rating, and others) found that all scales had similar predictive validity (28).

  • Evaluations of specific scales, including the Faces Pain Scale for use with the elderly (29) and a verbally administered pain scale (30), found them to be valid.

Rationale
  • Quantitative pain-intensity scales have been shown to be valid and reliable when presented with adequate description.

  • Modified scales are available for almost all patients with special needs.

  • Scales are unidimensional measures of a multidimensional syndrome.

Complete an assessment of psychosocial and physical functioning. 
  • Assess ability to perform patient-specific activities of daily living.

  • Assess ability to participate in vocational, avocational, and recreational activities.

  • Assess patients' typical coping style and how they are currently coping.

  • Assess the effect of pain on mood, affect, relationships, sleep, concentration, and appetite.

  • Screen patients with chronic or persistent pain for comorbid depression, anxiety, insomnia, and polysubstance abuse or misuse (using assessment tools coupled with diagnostics).

Evidence
  • Joint Commission standards require a psychosocial and physical function assessment as part of any pain evaluation (26).

  • A 2008 Institute of Aging in Canada expert consensus document on the assessment of pain in older persons recommended a detailed pain history, a history of comorbid conditions and medications, an exploration of functional status, and a detailed physical exam including a general exam, musculoskeletal exam, neurological exam, and mental status exam (23).

Rationale
  • Untreated pain affects all levels of the patient's physical and psychosocial functioning and adversely affects quality of life and relationships.

  • Depression is often associated with chronic, persistent pain (maldynia), especially in older patients.

Identify the type of pain in an effort to clarify etiology, optimize therapy, and minimize morbidity. 
  • Distinguish neuropathic pain (from injury to peripheral or CNS) from nociceptive pain (from stimulation of pain receptors in visceral or somatic tissues).

  • Note that neuropathic pain is often described as burning, lancinating, stabbing, stinging, shooting, sharp, electric shock-like, numbing, and pins and needles; examples include:

    • Postherpetic neuralgia

    • Trigeminal neuralgia

    • Diabetic and other peripheral neuropathies

    • Nerve trauma

    • Phantom limb pain, sciatica, complex regional pain syndrome

  • Note that somatic (nociceptive) pain is often well localized and described as dull, aching, or throbbing; examples include:

    • Skin and mucosal ulcerations

    • Myalgias

    • Arthropathies

    • Bone metastases

  • Note that visceral (nociceptive) pain is often more difficult to localize and describe but may be described as deep, squeezing, or pressure-like; examples include:

    • Pancreatitis

    • Peptic ulcer disease

    • Myocardial infarction

Evidence
  • A 2008 Institute of Aging in Canada expert consensus document on the assessment of pain in older persons described various types of pain and recommended appropriate approaches (23).

  • A 2010 narrative review described therapies for neuropathic pain (31).

Rationale
  • Classifying pain in pathophysiologic terms can help the clinician select appropriate therapy and determine prognosis.

  • Treatment strategies targeted specifically to underlying pain mechanism are likely to be most effective.

Recognize common pain syndromes and consider specific underlying causes of pain and clinical settings when planning management strategy. 
  • Recognize specific common pain problems that often warrant more specific treatments, such as:

    • Osteoarthritis

    • Rheumatoid arthritis

    • Fibromyalgia syndrome

    • Burns

    • Pain related to sickle cell disease (vasoocclusive crisis)

    • Low back pain

    • Migraine, cluster headache

  • Recognize specific cancer pain syndromes, including:

    • Bone metastases

    • Spinal cord compression

    • Mucositis

    • Plexopathies or peripheral neuropathies

  • Recognize evidence of and inquire about domestic violence in both genders, especially in patients with recurrent episodes of trauma or in emergency room or urgent care settings.

Evidence
  • Systematic reviews of treatment modalities for osteoarthritis (32; 33), rheumatoid arthritis (34; 35; 36; 37), fibromyalgia (38), and low back pain (39; 40; 41) confirm that each of these specific pain syndromes responds to specific treatment modalities and that accurate diagnosis is important to guide optimal pain management.

Rationale
  • Multiple treatment strategies targeted specifically to underlying pain mechanisms are likely to be most effective.

Use lab and diagnostic studies if indicated to identify causes of pain. 
  • Review any previous studies that may help to identify the underlying cause of the pain.

  • Order relevant diagnostic tests as dictated by the history and physical exam to determine the etiology of the pain.

Evidence
  • Consensus.

Rationale
  • Specific pains often respond to specific therapies.

  • Using multimodal therapies can be helpful.

  • Treating the underlying process causing the pain often produces the most effective pain relief.

Assess for comorbid conditions which may influence pain treatment. 
  • Begin treating the pain immediately, even if a diagnostic work-up is ongoing.

  • Discuss adequately with the patient and family the treatment plan, rationale, and specific medications selected, including medication harms vs. benefits, side effects, warnings and precautions, monitoring, time intervals of dosing, and pregnancy category (if relevant).

  • Identify comorbid medical conditions that may affect the pain or its management. Consider the following in appropriate patients:

    • Lab testing including a complete metabolic profile, including creatinine clearance, albumin, and liver function tests in patients with known or suspected comorbid conditions

    • A baseline ECG to determine any conduction defects (QTc changes) in patients with a history of cardiac disease and in those on medications which prolong the QTc

    • Consider testing for genetic polymorphism of the CYP450 system if the patient is on other medications which are metabolized by the CYP450 system

  • Obtain signed informed consent to perform initial and periodic clinical urine drug testing for controlled substances and alcohol as part of a pain contract.

Evidence
  • Consensus.

Rationale
  • Initiation of pain treatment should not be delayed while a diagnostic work-up is completed, as uncontrolled pain has significant adverse effects on quality of life, functioning, vocation, avocation, and mood.

Comments
  • Mood.

Consult appropriate specialists based on the initial pain assessment. 
  • Consult a specialist to assist with diagnosis if the etiology of the pain remains unclear or requires further evaluation.

  • Choose the appropriate specialist based on the most likely diagnosis suggested by the initial pain assessment.

Evidence
  • Consensus.

Rationale
  • Pain may be the first sign of the presence of underlying disease and usually warrants evaluation to determine its etiology, including specialist input when indicated.

  • If an underlying cause of pain can be identified, treatment can often be directed at the underlying cause rather than only at managing the symptoms.

Consult pain specialists for patients with pain unrelieved by standard drug and non-drug measures and those with multiorgan dysfunction, extensive pharmacologic therapies, or who have shown noncompliance or substance abuse or for patients requiring invasive procedures. 
  • Consider referring patients for invasive procedures for pain relief when noninvasive measures provide inadequate relief or result in intolerable side effects.

  • Recognize the specific pain syndromes that may respond best to invasive measures, including:

    • Head and neck pain

    • Upper extremity pain

    • Thoracic pain

    • Lower extremities

    • Complex regional pain syndrome (reflex sympathetic dystrophy, causalgia)

  • Consider as invasive measures:

    • Peripheral nerve blocks

    • Radiation

    • Epidural/spinal catheter for drug delivery (implant pump)

    • Spinal cord stimulation

    • Ablative techniques, including radiofrequency ablation

    • Surgical interventions

    • Joint infections

Evidence
  • A 2010 guideline for chronic pain management from the American Society of Anesthesiologists and the American Society of Regional Anesthesia and Pain Management recommended multimodal treatment for chronic pain including drug therapy, ablative techniques, acupuncture, electrical nerve stimulation and blocks, many of which require specialist involvement (42).

  • Practice guidelines for cancer pain published in 1996 by the American Society of Anesthesiologists, and a 1999 review of interventional pain management for chronic pain, highlighted the evidence supporting the role of pain specialists and invasive procedures in pain management (43; 44).

Rationale
  • Most pain can be modulated with noninvasive measures.

  • Invasive procedures should be reserved for difficult-to-control pain or for specific pain syndromes likely to respond best to invasive measures.

Refer patients with difficult-to-manage chronic pain syndromes to multidisciplinary, comprehensive pain treatment programs. 
  • Refer patients with chronic pain causing disability in various aspects of their lives (vocational, emotional, physical, interpersonal) to a multidisciplinary, comprehensive pain treatment program including:

    • Psychologists

    • Rehabilitation specialists (physical therapists, occupational therapists, physiatrists, physical medicine and rehabilitation specialists)

    • Physicians, such as anesthesiologists and neurologists

    • Clinical pharmacologists focused on pain and pain-related issues

    • Nursing specialists

    • Case managers

    • Social workers

    • Stress-management and vocational counselors

  • Engage the patient's outpatient pharmacist for information about prescriptions the patient uses, especially if there is suspected drug misuse.

  • Use multidisciplinary programs to help patients cope better with chronic pain rather than focusing on complete pain relief; specific goals may include:

    • Improved physical and psychological functioning

    • Learning to cope more adaptively with chronic pain

    • Reducing the use of the health care system

    • Returning to work if possible and increasing avocational pursuits

  • Use multidisciplinary programs to reassess chronic opioid use and consider alternative pharmacologic and nonpharmacologic regimens for chronic pain. Recognize complementary/alternative medicine.

Evidence
  • A 1992 meta-analysis of 65 studies of multidisciplinary treatment for chronic back pain found that multidisciplinary treatment was superior to no treatment and to single-discipline treatments in terms of pain, mood, return to work, and use of the health care system (45).

  • An observational study of the impact of a comprehensive pain management program reported clinical outcomes after 6 months. Participants reported significantly less pain and distress after the program (46).

  • A cohort study evaluated patients with back pain who received multidisciplinary treatment. After a follow-up time of 13 years, the investigators interviewed 26 of 45 participants and found that patients maintained treatment gains and had similar overall health to the general population despite persistent pain (47).

Rationale
  • Multidisciplinary pain programs work with these patients to shift the focus from total pain relief to how they can negotiate life more effectively and function better with chronic pain.

Consult a psychiatrist or psychologist for patients with significant underlying psychiatric conditions. 
  • Consider psychiatric consult for patients with:

    • Psychiatric complications from living with chronic pain

    • Worsening of chronic pain related to underlying comorbid psychiatric issues

Evidence
  • A 2007 meta-analysis of psychological interventions for low back pain included 22 studies with a variety of control interventions. Overall, psychological interventions were associated with improved pain and functioning, fewer physician visits, and less medication use. Cognitive-behavioral and self-regulatory approaches were effective (48).

  • A 2007 narrative review discussed comorbid psychiatric disorders in patients with chronic pain (49).

Rationale
  • Psychiatric and psychosocial issues can negatively contribute to chronic pain in various ways.

  • Consultation may be important in addressing these issues.

Consult specialists with expertise in both pain and addiction management for patients with current or past history of substance abuse or addiction. 
  • Identify patients with previous or current history of substance abuse.

  • Identify patients currently abusing legal or illicit substances.

  • Recognize that prescribing opioids is not contraindicated in patients with history of substance abuse, but discuss the risks and benefits with each patient.

  • Identify drug, nicotine, and alcohol addictions as treatable conditions and treat with specialized and careful management.

  • Utilize clinical comprehensive confirmatory urine drug testing.

  • Utilize a state patient prescription monitoring program where available.

Evidence
  • A study of risk factors for medication misuse was performed in a cohort of 196 patients in an academic pain-management program who were treated with opioids for chronic non-cancer pain. Nearly one third of patients (32%) committed opioid misuse, most commonly due to the use of illicit drugs (40% of misusers). In the multivariate analysis, younger age, past cocaine abuse (OR, 4.3), history of conviction for driving under the influence (OR, 2.6), and past alcohol use (OR, 2.6), were independent predictors of opioid misuse (50).

  • A 2008 structured review of the prevalence of medication abuse and addiction among patients receiving chronic opioid therapy included 67 studies. The pooled rate of abuse/addiction was 3.27% and the rate of aberrant drug-related behaviors was 11.5% (51).

  • A 2011 Canadian guideline on the use of opioids for chronic pain in primary care discussed the management of patients at high risk for misuse and addiction (52).

Rationale
  • Patients with current or past substance abuse often experience chronic pain.

  • Clinicians managing pain in these patients require a comfort level and expertise in dealing with both pain and substance abuse.

  • Unique management issues often arise in controlling pain in these patients.

Hospitalize patients with intolerable pain or pain that limits safe and independent functioning despite maximal outpatient management. 
  • Hospitalize patients if they cannot function safely in an outpatient setting either due to the pain itself, their comorbidities, or consequences from side effects of the analgesic regimen.

Evidence
  • A 2010 practice guideline for the management of chronic pain from the American Society of Anesthesiologists and the American Society of Regional Anesthesia and Pain Medicine recommends therapies, some of which may require hospitalization (42).

Rationale
  • If a patient cannot care for himself or herself as an outpatient, admission into an acute or subacute setting may be necessary until a safe home environment can be arranged.

Hospitalize patients for evaluation of the underlying etiology if prompt work-up is needed or if patient is at risk for significant morbidity from the underlying disease. 
  • Hospitalize patients if the pain suggests significant underlying pathology that requires inpatient evaluation, observation, or treatment to prevent an adverse outcome; for example, new back pain in a patient with cancer may signal spinal cord compression or bony metastasis.

Evidence
  • A 2000 review of pitfalls in the diagnosis of subarachnoid hemorrhage highlights the role of pain assessment in diagnosis (53).

  • A 1999 review of back pain in patients seen in an emergency department discusses significant underlying pathology that may be signaled by pain (54).

Rationale
  • Pain may signal significant underlying pathology that requires prompt evaluation and treatment to prevent morbidity.

  • Hospitalization may be warranted to facilitate a prompt work-up and diagnosis to prevent associated morbidity (e.g., paralysis or neurologic compromise).

Hospitalize patients based on activity of underlying disease. 
  • Hospitalize patient if increased or uncontrolled pain suggests exacerbation of underlying disease with risk for significant morbidity, noncompliance with the treatment plan, inadequate analgesic outcomes, or emergent severe iatrogenic events.

Evidence
  • Consensus.

Rationale
  • Worsening or uncontrollable pain may signal inadequate analgesia, patient noncompliance, exacerbation or worsening of specific underlying conditions, or new complications that indicate the need for hospitalization.

Comments
  • Maintain vigilance for patients with an agenda (drug route, dose of their choice), or requests for multiple tests to be repeated as an attempt to validate their “pain complaints” or for patients who may have psychiatric illness.

Choose initial drug therapy based on pain intensity and patient-specific pathophysiology, risks, and drug interactions. 
  • Classify pain as mild, moderate, or severe.

  • In patients with mild pain:

    • Use acetaminophen first (up to 3000 mg/d), especially in patients at risk for side effects from NSAIDs or aspirin, and in patients who will be using analgesics for chronic pain.

    • Consider aspirin or NSAIDs in well-selected patients.

    • Consider the use of topical NSAIDs (e.g., diclofenac gel) in patients with chronic need for analgesics.

  • In patients with moderate to severe pain:

    • Begin with opioid therapy in most patients, choosing lower potency opioids for patients with moderate pain and higher potency opioids for patients with severe pain.

    • Treat pain that is persisting with increasing opioid potency, higher dosages, or multimodal pharmacotherapy.

  • If pain persists or increases, consider initially adding a low-dose opioid to non-opioid therapy.

  • Consider adding adjuvant agents at any step to:

    • Enhance analgesic efficacy

    • Treat exacerbating symptoms

    • Provide independent analgesic activity for specific types of pain

    • Counteract side effects of specific analgesics

    • Utilize additional pain pathways (spinal, supraspinal)

    • Engage transduction, transmission, conduction, modulation, and pain perception.

  • Consider using the WHO three-step pain relief ladder developed only for cancer pain management that depicts a stepped approach to pharmacologic pain therapy, and modify the steps for noncancer pain, focusing on multimodal treatment plans.

  • Consider a time-specific treatment plan based on effectiveness, duration, and mechanism of action, which may be beneficial in a multimodal therapy plan.

  • See table Drug Treatment for Pain.

Evidence
  • The 2013 practice guidelines from the American College of Critical Care Medicine for management of pain, agitation, and delirium in adult ICU patients provided detailed recommendations regarding assessment and treatment of pain in this population at high risk for pain (55).

  • A 2010 guideline for chronic pain management from the American Society of Anesthesiologists and the American Society of Regional Anesthesia and Pain Medicine recommended multimodal treatment for chronic pain including drug therapy, ablative techniques, acupuncture, electrical nerve stimulation, and blocks. The guideline recommended specific medications based on the type of chronic pain (42).

  • A 2009 guideline on the management of chronic pain in older persons from the American Geriatrics Society recommended acetaminophen as the first-line medication in most patients, NSAIDs for inflammatory pain, and weighing the potential benefits and harms before initiating opioid therapy (56).

  • A 2005 guideline from the American Pain Society recommended multimodal therapy, treatment of postoperative and cancer pain with both scheduled and as-needed medications, and frequent reassessment of pain (3).

  • The WHO three-step pain relief ladder (WHO, 1996) is a well-validated method for assuring the rational progression of pain therapy in cancer patients but has been applied to other populations of patients with pain.

  • Limited randomized, controlled data exist regarding the pharmacologic management of pain. Much of it relates to NSAID use compared with placebo in specific patient populations, including patients with osteoarthritis (33), low back pain (57), and renal colic (58).

Rationale
  • The severity and type of pain provide insights regarding initial drug therapy.

  • A rational approach to drug selection and titration, as outlined by the WHO ladder, has been shown to be effective in relieving pain in 90% of patients with cancer, but its efficacy is not proven in patients with noncancer pain.

Comments
  • Duloxetine, an SNRI, is FDA-approved for treatment of diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain. Another SNRI, milnacipran, is FDA-approved for management of fibromyalgia.

  • Patients with advanced cancer may require Schedule II opioids as first-line therapy for their pain.

Use non-opioid analgesics alone for mild pain or in combination with opioid analgesics for moderately severe pain. 
  • Begin treatment with acetaminophen (up to 300 mg/d) for mild-to-moderate musculoskeletal pain, especially in elderly patients, in patients at risk for side effects of NSAIDs, and for chronic pain. Avoid use in patients with glutathione deficits.

  • Use NSAIDs for various types of acute and chronic pain from an inflammatory process, but use them with caution in the elderly and other patients at higher risk for side effects (i.e., patients with liver or renal dysfunction and patients at risk for cardiovascular disease or stroke).

  • Prescribe analgesics around-the-clock for persistent, chronic pain rather than as needed.

  • Include a non-opioid drug in most pain regimens unless contraindicated or not tolerated.

  • Consider topical NSAID (diclofenac gel 1%) two to four times daily for joint-specific therapy in selected patients with osteoarthritis due to a low incidence of systemic adverse drug reactions.

  • Be aware that NSAIDs and acetaminophen have a ceiling analgesic effect, and therefore maximum recommended doses should not be exceeded:

    • Acetaminophen, up to 3000 mg/d, acute use; 2000 to 2600 mg for chronic use

    • OTC NSAIDs are agent dependent and include:

      • Ibuprofen, 2400 mg/d

      • Naproxen, 1250 mg/d

    • Monitor carefully, especially in elderly patients, for side effects and toxicities, such as:

      • Risk factors of stroke or myocardial infarction

      • ASA/NSAID allergy (i.e., bronchoconstriction)

      • Renal compromise (including acute tubular necrosis, acute ischemic renal injury, and glomerular injury)

      • Myocardial infarction

      • Stroke

      • Bleeding

      • Gastric ulceration

      • Hepatic dysfunction

      • Sulfonamide allergy (if taking celecoxib)

  • Fully explain NSAID use to the patient. Advise that only one NSAID should be used and that NSAIDs should be used only under supervision of a physician regardless of where it is OTC or prescription.

  • See module Drug Prescribing in the Older Patient.

  • See table Drug Treatment for Pain.

Evidence
  • A 2009 guideline on the management of chronic pain in older persons from the American Geriatrics Society recommended acetaminophen as the first-line medication in most patients, NSAIDs for inflammatory pain, and weighing the potential benefits and harms before initiating opioid therapy (56).

  • A 2005 Cochrane review of NSAIDs for cancer pain included 42 randomized trials with 3084 participants. Overall, NSAIDs were superior to placebo, and most studies comparing the combination of an NSAID and an opioid to either agent alone found no difference (59).

  • A 2006 Cochrane review of acetaminophen for osteoarthritis included 15 studies with 5986 participants. Acetaminophen reduced pain compared to placebo, with a difference of 4 points on a 100-point scale, but was less effective than NSAIDs. Adverse events, including GI events, were less common among patients taking acetaminophen than among those taking NSAIDs (13% vs. 195) (60).

  • A small, randomized, placebo-controlled trial of the addition of acetaminophen to a strong opioid regimen suggested that patients preferred the combined regimen (61).

  • A 2009 narrative review discussed the pharmacology, clinical efficacy, and safety profiles of diclofenac sodium 1% gel, salicylates, and capsaicin for treatment of hand and knee osteoarthritis (62).

  • A pooled analysis of the safety of diclofenac gel compared to placebo with short-term therapy found the dyspepsia (7.7%) and dry skin (33%) were common in patients receiving diclofenac, but that rates of hypertension, renal toxicity, and liver toxicity did not differ between diclofenac and placebo (63).

Rationale
  • The concurrent use of opioids, NSAIDs, and acetaminophen often provides more analgesia than does either drug class alone.

  • The addition of NSAIDs or acetaminophen to opioid analgesics may achieve a dose-sparing effect.

Comments
  • Medication dosing in elderly patients may require special attention.

Use opioids alone or in combination with non-opioids (as in multimodal therapy) for patients with severe pain or pain despite maximal non-opioid therapy, for more severe pain at onset, and for patients who cannot tolerate non-opioids or for whom the harms outweigh the benefits. 
  • Begin therapy with opioids in patients with severe pain.

  • Choose specific drugs based on the clinical situation:

    • For patients with mild to moderate pain which is poorly controlled on other agents, begin with codeine or tramadol for breakthrough pain.

    • For patients with severe pain, begin with morphine in most patients.

  • Consider the patient's previous experience with specific medications, and the patient's pharmacokinetics and pharmacodynamics, including CYP450 pathway effects and mechanisms of action of the specific opioid.

  • Cautiously use equianalgesic dosing tables when changing to a new opioid or a different route:

    • See table Conversion to Transdermal Fentanyl (Duragesic)

    • See table Oral and Parenteral Narcotic Analgesics

    • Consider incomplete opioid cross-tolerance when switching between different opioids by decreasing the calculated dose of the new opioid by one third or one half in opioid-tolerant patients.

    • Be aware that tables are designed to guide unidirectional and not bidirectional drug changes; use tables to convert doses only in the direction for which they were designed.

    • Be aware of the populations for whom each table was created.

  • Be aware that most opioids do not have an analgesic efficacy ceiling and can be titrated upward as needed until limiting side effects appear, except for codeine, buprenorphine, meperidine, tapentadol, and tramadol, which all have a maximum dose.

  • See table Drug Treatment for Pain.

Evidence
  • A 2010 Canadian practice guideline on the use of opioids for chronic non-cancer pain recommended specific agents. For patients with mild to moderate pain, the guideline recommended codeine and tramadol as first-line agents and morphine, oxycodone, and hydromorphone as second-line agents. For patients with severe pain, the guideline recommended morphine, oxycodone, and hydromorphone as first-line agents, fentanyl as a second-line agent, and methadone as a third-line agent (64).

  • A 2005 guideline from the American Pain Society recommended multimodal therapy, treatment of postoperative and cancer pain with both scheduled and as-needed medications, and frequent reassessment of pain (3).

  • A 2010 guideline for chronic pain management from the American Society of Anesthesiologists and the American Society of Regional Anesthesia and Pain Medicine recommended multimodal treatment for chronic pain including drug therapy, ablative techniques, acupuncture, electrical nerve stimulation, and blocks. The guideline recommended specific medications based on the type of chronic pain, noting that opioids are effective (42).

  • A 2009 guideline on the management of chronic pain in older persons from the American Geriatrics Society recommended that all patients with severe pain be considered for opioid therapy. The guideline also recommended clarifying therapeutic goals (56).

  • A 2008 consensus statement on opioid use in the elderly discussed many aspects of opioid prescribing and stated that buprenorphine is likely the preferred agent in the elderly (65).

  • The 2013 practice guidelines for management of pain, agitation, and delirium in adult ICU patients provided detailed recommendations regarding assessment and treatment of pain in this population at high risk for pain (55).

  • A 2005 systematic review of the effect of opioids for neuropathic pain included 22 trials. Studies with intermediate-term follow-up found that opioids were more effective than placebo with average pain scores 14 units lower on a scale of 0 to 100. Adverse events were common, including nausea (NNH, 4), constipation (NNH, 5), vomiting (NNH, 6), and dizziness (NNH, 7) (66).

  • A 2007 Cochrane review of oral morphine for cancer pain included 54 studies with 3749 participants. Different preparations of oral morphine were effective with few apparent differences (67).

  • A 2002 Cochrane review of hydromorphone for acute and chronic pain included 43 studies with 2725 participants. Many studies were small or of poor quality, but overall hydromorphone appeared similar to morphine (68).

  • A 2006 meta-analysis suggested that oxycodone and morphine are similar in terms of efficacy and tolerability for cancer pain (69).

  • A 2006 Cochrane review of opioids for breakthrough pain in cancer patients showed limited evidence but suggested that oral transmucosal fentanyl citrate is effective (70).

  • A 2007 Cochrane review of methadone for cancer pain included nine randomized trials and found that efficacy and side effects were generally similar between morphine and methadone (71).

Rationale
  • Opioids are the major class of analgesics used in the management of moderate to severe pain because of their effectiveness, ease of titration, and favorable harm-to-benefit ratio.

Comments
  • Methadone has a potential role in chronic and cancer pain management, but its complex and highly individual pharmacokinetics, drug interactions, and QTc prolongation require that highly experienced clinicians and compliant patients initiate therapy at doses of 2.5 mg and titrate slowly (start low and go slowly) while closely monitoring its use and nontherapeutic consequences (e.g., QTc prolongation).

Consider adjuvant analgesics for specific types of pain including tricyclic antidepressants or gabapentin for neuropathic or chronic pain. 
  • Use specific drugs for neuropathic pain including:

    • Tricyclic antidepressants (such as amitriptyline)

    • Gabapentin or pregabalin

    • SNRIs (such as duloxetine)

    • Topic anesthetics

  • Consider, in selected patients, the use of corticosteroids for cautious, brief periods, for their anti-inflammatory effects, mood elevation, and appetite elevation, especially in patients with cancer pain; however, be aware of side effects of chronic steroid use, including insomnia, weight gain, and avascular necrosis of the hip, as well as ocular, dermatologic, CNS, and endocrine/metabolic side effects.

  • Consider the use of pain relievers such as tramadol or tapentadol for acute relief but avoid chronic use.

  • Consider bisphosphonates or radiopharmaceuticals for cancer patients with pain related to bone metastases.

    • Administer pamidronate or zoledronate to patients with known osteolytic bone lesions, every 3 to 4 weeks to reduce pain

    • Radiopharmaceuticals, such as strontium, are useful for metastatic bone pain from osteoblastic lesions, but timing and degree of response cannot always be predicted; monitor for joint necrosis

  • Consider ketamine for acute postoperative pain in the first 24 hours or as an adjunct to opioid therapy in patients with poorly controlled cancer pain.

  • Consider lamotrigine for HIV-related neuropathic pain.

  • Consider psychostimulants such as methylphenidate, modafinil, or dextroamphetamine to counteract opioid-induced, persistent sedation despite decreasing dose.

  • Consider opioid dose manipulation for variations in opioid peak effects.

  • See table Drug Treatment for Pain.

Evidence
  • A 2013 NICE guideline on the management of neuropathic pain recommended amitriptyline, duloxetine, gabapentin, or pregabalin for the initial management of neuropathic pain other than pain from trigeminal neuralgia. The guideline recommended tramadol only as an acute rescue therapy, recommended considering capsaicin cream for patients with localized pain who wish to avoid systemic therapy, and recommended against the use of other antiepileptic medications. For trigeminal neuralgia, the guideline recommended carbamazepine as initial therapy.

  • A 2005 guideline from the American Pain Society recommended anticonvulsants for neuropathic pain, tricyclic antidepressants and SNRIs for chronic pain, and SSRIs for diabetic neuropathy (3).

  • A 2007 Cochrane review of antidepressants for neuropathic pain included 61 randomized trials. Tricyclic antidepressants provided at least moderate pain relief with overall NNT, 3.6 (CI, 3 to 4.5). Tricyclic antidepressants were effective for diabetic neuropathy (NNT, 1.3) and postherpetic neuralgia (NNT, 2.7); many studies used amitriptyline. Amitriptyline caused major adverse events (NNT, 28). Data were limited for other agents (72).

  • A 2009 Cochrane review of pregabalin for acute and chronic pain in adults found that pregabalin was effective for postherpetic neuralgia, diabetic neuropathy, and fibromyalgia (73).

  • A 2011 Cochrane review of gabapentin for neuropathic pain and fibromyalgia included 29 studies with 3571 participants. Overall, gabapentin was superior to placebo in moderate pain improvement (NNT, 5.8 [CI, 4.8 to 7.2]). Many patients had adverse events (66%) and 12% withdrew due to adverse events (74).

  • A 2009 Cochrane review of duloxetine for neuropathic or chronic pain included six trials with 2220 participants. Duloxetine was effective for pain reduction in diabetic neuropathy (NNT, 6 [CI, 5 to 10]) and in fibromyalgia (NNT, 8 [CI, 5 to 17). Adverse events were common; 16% of patients receiving duloxetine withdrew due to side effects (75).

  • A 2006 Cochrane review of tramadol for neuropathic pain included six trials. Tramadol reduced pain (NNT, 3.8 [CI, 2.8 to 6.3]) for at least 50% pain reduction compared to placebo (76]).

  • A randomized, controlled trial of venlafaxine extended release for painful diabetic neuropathy compared to placebo was effective at 6 weeks (NNT, 4.5) (77).

  • A randomized, controlled trial of lamotrigine for HIV-associated painful sensory neuropathy suggested that it was well tolerated and effective in patients on neurotoxic antiretroviral therapy (78).

  • Clinical trials have demonstrated a benefit of decreased pain over time in patients with osteolytic lesions with breast cancer (79) and multiple myeloma (80) treated with bisphosphonates.

  • A 2012 Cochrane review of ketamine for cancer pain as an adjuvant to opioids found only two small studies, both of which showed that ketamine improved pain (81).

  • A 2011 Cochrane review of radioisotopes for metastatic bone pain included 15 studies. Radioisotopes lead to complete pain relief compared with placebo (NNT, 5) but caused leukopenia and thrombocytopenia (NNH, 13) (82).

  • A 2006 Cochrane review of ketamine for acute postoperative pain included 37 trials with 2240 participants. Ketamine reduced pain or opioid requirements and reduced nausea and vomiting in the 24 hours after surgery (83).

Rationale
  • Adjuvant analgesics provide independent analgesia for specific types of pain, enhance the analgesic efficacy of opioids, and treat concurrent symptoms or side effects that exacerbate pain.

Consider cutaneous stimulation techniques such as the application of ice and heat, especially for pain associated with muscle spasm or tension. 
  • Apply heat to the site of pain using:

    • A hot pack

    • A hot water bottle

    • A moisture-proof electric heating pad

    • A moist, hot compress

    • Immersion in water

  • Take care to prevent burns (safe range, 40°C to 45°C [104°F to 113°F]) and tissue damage.

  • Apply cold to the site of pain using:

    • Waterproof container (plastic bag, frozen vegetable bag)

    • Frozen or cold contents

    • Cold gel pack

    • Cold moist towel (temperature range around 15°C [59°F])

  • Note that heat and cold can be used interchangeably for many situations because:

    • Cold is often preferred for acute pain from trauma, bleeding, swelling, inflammation

    • Cold may relieve pain faster, longer, and more effectively than heat

  • Apply vibration to the site of pain:

    • Various hand-held vibrating devices are available

    • Vibration may benefit patients with muscle pain or spasm, pruritus, and chronic neuropathic and nonmalignant pain

    • Vibration should not be used if patient is predisposed to bruising or does not have intact skin

Evidence
  • A 2006 Cochrane review of superficial heat or cold for low back pain found limited supportive evidence, although heat wrap therapy provided some pain relief (84).

  • A randomized trial compared cold gel to placebo in 74 patients with sports-related musculoskeletal injuries. Pain scores, patient satisfaction, and functional ability were all significantly better in the cold gel group (85).

Rationale
  • Cutaneous stimulation techniques (TENS, others) have been shown to have benefits including making pain more tolerable, as well as actual reduction of pain.

  • The mechanism of action is not well understood.

Comments
  • These interventions often warrant consideration despite the limited controlled data supporting their efficacy, given the low cost, minimal morbidity, and potential benefits.

Encourage patients to remain active, participate in self-care, and perform prescribed exercise to whatever extent possible. 
  • Tailor exercise to the needs and preferences of the individual patient in consultation with the primary clinician.

  • Note that initial training may involve a trial of physical and occupational therapy.

  • Limit exercise during episodes of acute pain.

Evidence
  • A 2005 Cochrane review of bed rest compared with advice to stay active for low back pain found one study showing that patients with low back pain who were advised to rest had more pain and disability than those advised to stay active. For patients with sciatica bed rest and activity resulted in equivalent levels of pain and disability (86).

  • A 2005 Cochrane review of exercise therapy for nonspecific low back pain included 61 randomized trials with 6390 participants. Exercise improved pain and function in patients with chronic pain, but did not improve symptoms in acute pain (87).

  • A 2010 Cochrane review of physical conditioning for work-related back pain included 23 randomized trials. In workers with chronic low back pain, conditioning programs slightly reduced the number of sick days but there was no effect in workers with acute low back pain (88).

  • A randomized, controlled trial of 101 adults with chronic low back pain found yoga to be more effective than conventional therapeutic exercise or a self-care book in terms of functional status and pain (89).

  • A study in patients with chronic neck pain showed improved posture when using a regimen aimed at training craniocervical flexor muscles (90).

  • In a 2012 prospective study, 272 adults with nonspecific neck pain were randomly assigned to one of three arms, either spinal manipulation therapy, home exercise with advice, or medications. Patient-rated pain was assessed at 2, 4, 8, 12, 26, and 52 weeks. Spinal manipulation therapy was significantly more effective than medication therapy at both short-term and long-term follow-up. Home exercise with advice with just a few instructional sessions had similar results to spinal manipulation but did not differ significantly from medication therapy (91).

Rationale
  • Exercise strengthens muscles, mobilizes stiff joints, and restores coordination or balance in patients with subacute or chronic pain.

Introduce psychosocial interventions early in combination with pharmacotherapy interventions. 
  • Use distraction for mild-to-moderate pain of relatively brief duration in patients who are open to this technique, which includes active and passive strategies, such as:

    • Listening to desirable music

    • Singing a familiar song

    • Performing mental arithmetic

    • Looking at pictures

  • Note that relaxation or imagery may benefit interested patients with almost any type of pain (see module Mind-Body Medicine) and includes:

    • Simple focused-breathing exercises

    • Progressive muscle relaxation

    • Meditation

  • Offer psychotherapy to patients with:

    • Difficult-to-manage chronic pain

    • History of depression

    • History of substance abuse or misuse

    • Other psychiatric conditions

Evidence
  • A 2006 systematic review of relaxation techniques for pain included 15 studies of various techniques. Many studies were of poor quality, and there was little evidence in support of most specific methodologies (92).

  • Randomized, controlled trials of various relaxation techniques (structured attention, self-hypnosis, relaxation training, music) and psychotherapy as adjuncts for pain control in specific patient populations—those undergoing invasive procedures (93; 94; 95), postoperative patients (96), patients with rheumatoid arthritis (97), and patients with chronic temporomandibular disorder pain (98)—have shown reductions in pain levels as well as other beneficial outcomes.

Rationale
  • Beneficial effects of psychosocial interventions are variable but may include decreased pain intensity, increased pain tolerance, or improved mood.

Use a multimodal approach which includes drug therapy and other therapeutic interventions in patients with chronic pain. 
  • Consider interventions in patients with chronic pain including:

    • Acupuncture

    • TENS

    • Ablative techniques

    • Nerve and joint blocks

  • Consider interventions that may benefit some individuals in certain patient groups, including:

    • Vitamin C, 500 mg/d for 7 weeks, in patients with wrist fracture to prevent CRPS

    • Acupuncture or TENS in patients with phantom limb pain, myofascial pain, headache, or CRPS

    • Physical/exercise therapy for chronic low back pain

    • Therapeutic massage for chronic low back pain

    • Chiropractic care for neck pain, low back pain, and other musculoskeletal pain

  • Note that these interventions should be performed only by licensed trained professionals.

  • Advise patients to report incremental or decremental changes in their pain and continue to undergo regular assessments by the primary clinician.

Evidence
  • A 2010 guideline for chronic pain management from the American Society of Anesthesiologists and the American Society of Regional Anesthesia and Pain Medicine recommended multimodal treatment for chronic pain including drug therapy, ablative techniques, acupuncture, electrical nerve stimulation, and blocks (42).

  • A 2012 guideline from the Ottawa panel recommended therapeutic massage for chronic low back pain, stating that it could improve both pain and functional status (99).

  • A 2008 Cochrane review of TENS for chronic pain included 25 randomized trials with 1281 patients. Studies were generally of poor quality. Among 22 studies with inactive controls, 13 found that TENS improved pain control (100).

  • A 2009 Cochrane review of TENS for acute pain included 12 randomized trials with 919 participants, but inconsistencies in the data precluded firm conclusions (101).

  • A 2008 Cochrane review of TENS compared to placebo for chronic low back pain included four randomized trials. The evidence on pain was inconsistent but TENS did not have an impact on functional status (102).

  • A multicenter randomized trial of patients with wrist fractures compared vitamin C (200 mg, 500 mg, or 1500 mg daily) to placebo for 50 days. Overall, fewer patients receiving vitamin C had CRPS after 50 days (2.4% vs. 10.1%, P=0.002). The 200-mg dose was not significantly different than placebo but the 500- and 1500-mg doses were equivalent (103).

  • A 2005 Cochrane review of acupuncture and dry needling for low back pain included 35 randomized trials in multiple languages. No conclusions could be drawn regarding acute low back pain, but in patients with chronic low back pain acupuncture led to improved pain and functional status (104).

  • A 2005 systematic review and meta-analysis of acupuncture for low back pain included 33 randomized trials. In patients with chronic low back pain, acupuncture was more effective than sham treatment (SD, 0.54 [CI, 0.35 to 0.73]) and no treatment (SD, 0.69 [CI, 0.40 to 0.98]) for short-term relief. There was no conclusive evidence regarding acupuncture for acute low back pain (105).

  • A 2010 systematic review of exercise therapy for nonspecific low back pain included 37 randomized trials. Compared to usual care, exercise therapy improved pain, disability levels, and functional status (106).

  • A 2010 Cochrane review of chiropractic care for low back pain included 12 studies with 2887 participants. For acute low back pain, chiropractic care improved short-term and medium-term, but not long-term, low back pain and improved disability in the short term (107).

  • A 2008 Cochrane review on injection therapies for low back pain included 18 trials involving a variety of approaches and several medications including corticosteroids, local anesthetics, and others. Pooling of results was not possible, and overall the studies did not support any particular type of injection therapy (108).

  • In a 2012 prospective study, 272 adults with nonspecific neck pain were randomly assigned to one of three arms, either spinal manipulation therapy, home exercise with advice, or medications. Patient-rated pain was assessed at 2, 4, 8, 12, 26, and 52 weeks. Spinal manipulation therapy was significantly more effective than medication therapy at both short-term and long-term follow-up. Home exercise with advice with just a few instructional sessions had similar results to spinal manipulation but did not differ significantly from medication therapy (91).

Rationale
  • Using multiple therapeutic approaches can optimize pain control.

Use a standardized approach when treating chronic nonmalignant pain with opioids. 
  • Follow these steps when initiating opioid therapy for chronic nonmalignant pain:

    • Establish that non-opioid therapy has not adequately controlled pain

    • Explain the potential benefits and pitfalls of long-term opioid therapy

    • Establish agreed-on goals for treatment

    • Ensure patient and family are well-informed

    • Ensure comprehensive, periodic follow-up including possible documentation of medication adherence through testing of urine and/or blood.

  • Document the therapeutic regimen, goals of care, visit frequency, and other expectations in a controlled substance agreement (or opioid contract).

  • Use adjuvant pharmacologic and nonpharmacologic therapies whenever possible.

  • Monitor carefully for signs of opioid abuse, misuse, or diversion using comprehensive clinical evaluation, confirmatory urine drug testing, and state prescription-monitoring sites.

  • Consider weaning and/or discontinuing opioid therapy if treatment goals are not met or discontinue if there is evidence of addiction, abuse, misuse, diversion, or noncompliance.

  • See table Drug Treatment for Pain.

Evidence
  • A 2004 public policy statement from the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine states that physicians prescribing opioids should follow patients closely to document adherence to therapy and to look for side effects or signs of abuse (109).

  • A retrospective study of opioid contracts in primary care patients receiving opioids for chronic pain noted that 63% of patients adhered to their contracts over 22 months (110).

Rationale
  • Opioids can provide safe and effective relief of chronic pain but they can have side effects and there is abuse potential.

Avoid the use of meperidine and codeine for repeated dosing or for chronic pain management. 
  • Avoid meperidine except for very short courses (less than 48 hours) in otherwise healthy patients.

  • Avoid codeine for long-tem treatment.

  • Note that naloxone does not reverse the CNS toxicity from the non-opioid metabolite normeperidine and may actually increase neuro-excitability.

  • Do not consider meperidine the first-choice opioid in patients with biliary disease, pancreatic disease, or other comorbidities.

Evidence
  • A study of meperidine used for postoperative or chronic pain found a high incidence of neuroexcitatory effects including nervousness, twitches, myoclonus, and seizures, as well as adverse mood alterations in patients with and without renal dysfunction. (111)

  • A study of biliary sphincter spasm associated with opioids found that all opioids, including meperidine, can cause sphincter spasm with a similar incidence (112).

  • Mainly consensus.

Rationale
  • Meperidine has a neurotoxic metabolite, normeperidine, which accumulates with repeated dosing, especially in patients with renal dysfunction and the elderly who receive daily repeated dosing.

  • Accumulation of normeperidine can result in CNS toxicity, with tremors, confusion, seizures, hyperreflexia, and myoclonus.

  • Codeine is a short-acting drug; longer acting alternatives are more appropriate for the treatment of chronic pain.

Comments
  • Meperidine can precipitate a serotonin syndrome with SSRIs.

  • Propoxyphene (no longer available in the U.S.) has poor analgesia, multiple drug interactions, and caused arrhythmias and pulmonary edema; it was banned in the UK for many years before U.S. withdrawal of the product. Codeine is a prodrug for morphine, has a ceiling dose, and requires renal dosing. Avoid use with CYP450 2D6 deficit or ultra-rapid metabolizers.

  • Evidence does not support the old, commonly quoted notion that meperidine causes less contraction of the sphincter of Oddi than other opioids; therefore, meperidine should not be considered as a preferred opioid in patients with pain and biliary disease.

Individualize the route, dosage, and schedule of medications. 
  • Use the least-invasive route of administration possible (usually oral); avoid intramuscular injections by using intravenous or subcutaneous administration.

  • Consider intravenous or epidural patient-controlled analgesia for hospitalized patients if oral analgesics are not possible or are ineffective.

    • Patient-controlled analgesia can be used for acute pain or for acute exacerbations of chronic pain

    • When used for acute pain, a loading dose may be given if necessary when starting the patient-controlled analgesia to ensure adequate analgesia

    • A cautious, continuous infusion of opioid may be given along with the patient-controlled analgesia bolus dosing in well-selected patients with chronic pain exacerbations

  • Consider using continuous epidural analgesia for pain after intra-abdominal surgery and selected neurosurgery and/or orthopedic surgeries.

  • Use a multimodal analgesic regimen for postoperative pain management.

  • Cautiously use the equianalgesic dosing tables Conversion to Transdermal Fentanyl (Duragesic) and Oral and Parenteral Narcotic Analgesics, also found in published package inserts, to convert between different routes and different opioids employing incomplete opioid cross-tolerance in the process.

  • Prescribe fast-onset, short-acting analgesics for episodic pain and episodes of breakthrough pain on an as-needed basis.

  • Use around-the-clock dosing or long-acting analgesics for pain that is more continuous or present most of the day.

  • Provide fast-onset, short-acting preparations for episodes of breakthrough pain in most patients receiving long-acting opioids.

  • Titrate analgesics carefully based on persistent need and use of medications for breakthrough pain and on the pharmacodynamics of specific drugs and the pharmacokinetics of the patient and their respective medications.

  • See table Drug Treatment for Pain.

Evidence
  • A 2005 guideline from the American Pain Society recommended multimodal therapy, treatment of postoperative and cancer pain with both scheduled and as-needed medications, and frequent reassessment of pain (3).

  • A 2005 Cochrane review of patient-controlled analgesia compared to continuous medication after abdominal surgery included nine studies with 711 participants. Overall, patients receiving continuous epidural analgesia had less pain than those receiving patient-controlled opioids; length of stay did not differ between the groups (113).

  • A study of patients' perceptions of pain from injections found that intramuscular injections were more painful than intravenous insertion or spinal injections (114).

  • Randomized, controlled trials and critical reviews of multimodal analgesia after total knee arthroplasty, laparoscopic cholecystectomy, and midline laparotomy showed that they improved analgesia (115; 116; 117).

Rationale
  • Oral administration maximizes convenience and flexibility and produces consistent blood levels when administered at controlled times of each day in long-acting dosage forms once steady state is achieved.

  • Intramuscular administration of drugs should be avoided because this route can be painful and absorption is not reliable.

  • Patient-controlled analgesia may achieve better analgesia effect often by using less medication compared with as-needed dosing.

  • Regular, controlled, long-acting dosage forms, and timed dosing of analgesics for patients with persistent pain maintains a constant level of drug in the body and helps prevent a recurrence of pain with less peak and trough levels than seen with immediate-release dosage forms.

  • Combining multiple modes of analgesia (multimodal) can optimize pain control and minimize side effects in postoperative patients.

Minimize patient discomfort by avoiding intramuscular injections and anticipating other painful events. 
  • Anticipate possible painful episodes or events such as physical therapy sessions.

  • Avoid intramuscular injections, especially in patients with intravenous access.

  • Use appropriate patient-specific analgesics and anesthetics before and after all potentially painful procedures.

  • Minimize “routine” medical procedures (venipuncture, capillary glucose measurements, arterial blood gas) that cause pain unless they will provide essential information or alter the clinical course or management.

Evidence
  • Mainly consensus.

  • Topical anesthetics have been evaluated for use for procedural pain in adults with somewhat inconsistent results; they have shown some benefit in arterial cannulation (118) and treatment of genital human papillomavirus lesions (119), but have shown a limited role in peripheral intravenous placement (120).

Rationale
  • Many routine medical procedures cause pain that can be avoided or minimized with appropriate attention to analgesia and anesthesia.

  • Painful procedures that do not alter the clinical course or plan may be more burdensome than beneficial; evaluate the risk of procedures vs. the benefit of test or procedure outcome.

Predict, recognize, and treat side effects of opioids, including nausea, constipation, somnolence, ataxia, and pruritus. 
  • Be aware and make patients aware of the more common side effects of opioids, including constipation, somnolence, mental clouding, sedation, ataxia, nausea, and itching; tolerance develops to each of these side effects except constipation but they often reappear with dose escalation.

    • Consider opioid rotation as a method that may reduce side effects

    • Prevent constipation with a comprehensive prophylactic bowel regimen and close follow-up

      • Include a stimulant laxative in the bowel regimen in addition to a stool softener, titrated to maintain regular bowel movements at least every other day, and increase fluid intake when possible

    • Consider treatment of resistant opioid-induced constipation with subcutaneous methylnaltrexone (a peripherally acting μ-opioid receptor antagonist)

    • Anticipate sedation and give appropriate warnings (driving cautions, avoid ethanol, monitor for falls and more profound sedation)

      • Consider low-dose psychostimulants (methylphenidate, dextroamphetamine, modafinil) in combating persistent opioid-induced sedation; or consider dosing changes to minimize side effects

    • Use antiemetics for nausea on a short-term basis until nausea resolves

    • Manage pruritus with nonsedating antihistamines, if needed and if efficacious

  • Monitor patients on long-term NSAIDs for GI blood loss, hepatic insufficiency, renal insufficiency, electrolyte abnormalities, and drug-drug and drug-disease interactions.

  • Monitor patients for opioid-induced hyperalgesia, which may be delayed or diminished by adjuvant drug therapies, opioid rotation, NMDA antagonist therapy, or a trial of decremental changes in opioid treatment.

Evidence
  • A 2005 systematic review of the effect of opioids for neuropathic pain included 22 trials. Studies with intermediate-term follow-up found that opioids were more effective than placebo, with average pain scores 14 units lower on a scale of 0 to 100. Adverse events were common, including nausea (NNH, 4), constipation (NNH, 5), vomiting (NNH, 6), and dizziness (NNH, 7) (66).

  • A 2003 systematic review of management of opioid side effects in cancer-related and chronic noncancer pain found little evidence to guide management of opioid side effects (121).

  • A 1994 review of psychostimulants as adjuvant analgesics confirmed their role for counteracting opioid-induced, persistent sedation and cognitive impairment (122).

  • A randomized, placebo-controlled study in patients with advanced illness and opioid-induced constipation showed that methylnaltrexone rapidly induced laxation without affecting central analgesia (123).

Rationale
  • Many side effects of analgesics can be anticipated and managed prophylactically or promptly.

  • Advance discussion of side effects with patients and caregivers may allow earlier identification of problems and improved use of medications.

Understand “drug seeking” behavior, drug abuse, misuse, or diversion, and doctor shopping; concepts of tolerance and psychological dependence (addiction); and monitor for each regularly. 
  • Watch for the development of tolerance and treat appropriately.

    • Tolerance may be defined as the need for increasing amount of drug to achieve the same analgesic effect.

    • Treatment may include increasing the dose of the current opioid, switching to a different opioid, and/or adding a non-opioid to the current opioid regimen.

  • Be aware of the development of physical dependence and prevent withdrawal.

    • Physical dependence is a physiologic state manifest by the development of opioid withdrawal symptoms when opioids are discontinued abruptly or when opioid antagonists are administered.

    • Withdrawal can be prevented by slowly tapering chronically used opioids, and by avoiding opioid antagonists and mixed agonists-antagonists in patients on chronic opioid therapy.

  • Be aware that psychological dependence (addiction) can occur in patients receiving opioids for pain control.

    • Psychological dependence is an abnormal behavioral condition in which a person develops an overwhelming involvement in the acquisition and use of a drug despite adverse social, psychosocial, or physical consequences.

    • Monitor patients on long-term opioid therapy periodically for inappropriate, dangerous, or nonprescribed drug-use patterns.

    • Addiction is a primary chronic neurologic and biologic disease with contributing factors from genetic, environmental, and psychosocial elements, characterized by impaired compulsive drug use control, despite a resulting harm to self and subject to relapse.

    • Watch for signs of drug-seeking behavior, doctor shopping, abuse, misuse, or diversion.

Evidence
  • A 2004 public policy statement from the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine states that physicians prescribing opioids should follow patients closely to document adherence to therapy and to look for side effects of signs of abuse (109).

  • A study of risk factors for medication misuse was done in a cohort of 196 patients in an academic pain-management program, who were treated with opioids for chronic non-cancer pain. Nearly one third of patients (32%) committed opioid misuse, most commonly due to the use of illicit drugs (40% of misusers). In the multivariate analysis, younger age, past cocaine abuse (OR, 4.3), history of conviction for driving under the influence (OR, 2.6), and past alcohol use (OR, 2.6), were independent predictors of opioid misuse (50).

  • A 2008 structured review of the prevalence of medication abuse and addiction among patients receiving chronic opioid therapy included 67 studies. The pooled rate of abuse/addiction was 3.27% and the rate of aberrant drug-related behaviors was 11.5% (51).

Rationale
  • There are many misconceptions regarding tolerance, physical dependence, and addiction.

  • Optimal pain management requires awareness and understanding of these phenomena to guide appropriate practice.

Realize that psychological dependence (addiction) may occur in patients who receive opioids for pain control. 
  • Do not confuse physical dependence and tolerance (expected with long-term opioid treatment) with addiction.

  • Counsel patients and their families about the rarity of addiction when opioids are prescribed for legitimate medical indications, but explain that physical dependence and tolerance do develop with prolonged daily use.

Evidence
  • A study of more than 500 patients in England taking oral heroin for chronic pain relief found no cases of addiction (124).

  • A prospective study of 11,882 hospitalized medical patients found that only 4 patients were documented as becoming addicted as a result of receiving opioid analgesics (125).

  • A review of the literature on addiction resulting from taking opioid analgesics found that only 7 of 24,000 patients studied had become addicted as a result of receiving opioids for pain control (126).

  • A 2003 narrative review noted that the risk of addiction is low (127).

Rationale
  • Fear of addiction represents a significant barrier both in physicians prescribing opioids and in patients using opioids as prescribed; the risk for addiction requires vigilance.

  • Awareness of the rarity of addiction when opioids are prescribed for pain is essential for the appropriate prescribing and use of chronic opioids.

Comments
  • The 6-keto opioids (hydrocodone, hydromorphone, oxycodone) appear to provide prominent recreational abuse characteristics due to activity on the dopamine pathway producing euphoria.

  • Engage in a collaborative open dialogue arrangement with the patient's pharmacists for prescription-related issues.

Correct misconceptions, concerns, and myths about pain management. 
  • Explore common patient and caregiver barriers to effective pain management:

    • Patient reluctance to report pain (not wanting to complain, expecting to have pain based on age or underlying disorders, concern about distracting from treatment of underlying condition)

    • Fear of addiction or of being thought of as an addict

    • Worries about unmanageable side effects

    • Concern about becoming tolerant to pain medications

  • Explain concepts of addiction, tolerance, and physical dependence clearly to patients.

  • Re-address these barriers at each follow-up visit.

Evidence
  • Joint Commission standards for pain management in all health care settings require specific education to overcome common patient barriers to pain relief (26).

  • Studies in AIDS and cancer patients have confirmed these patient barriers (9; 128).

Rationale
  • Common misconceptions about pain management prevent some patients from pursuing maximal pain relief.

  • Correcting misconceptions proactively may improve assessment and management of pain in some patients.

  • Efforts to inform patients about their treatment plan need to be repeated over time to be most effective.

Comments
  • Patients and their families often will not take pain medication because of fear of addiction or concern that they may need to reserve pain medication for when their disease worsens. These fears have been documented to inhibit good pain control and need to be specifically addressed.

  • Manage patient expectations about “no pain” vs. pain relief (anesthesia vs. analgesia).

Provide verbal and written information about pain assessment and management to actively involve patients and families in treatment program. 
  • Provide general information about pain assessment and management, such as:

    • Pain can be diminished in most cases but not always eliminated

    • How to assess pain by using a pain rating scale

    • Use of a pain diary

    • How and when to contact a clinician about unrelieved pain and pain management

    • How to use a preventive approach to pain management

  • Provide specific information about drug management, such as:

    • Optimal use of long-acting medications to maximize efficacy, safety, and dosing intervals, and short-acting faster onset agents for acute painful flares, breakthrough pain, or incident pain

    • Addressing fears of addiction and tolerance

    • Prevention and control of side effects

  • Provide information about available or recommended non-drug interventions.

  • Review the potential risks and benefits of all treatments with patients.

  • Actively involve the patient's family and caregivers in treatment plan information.

  • Encourage patients to participate actively with prescribers, pharmacists, and nurses in setting, reviewing, and evaluating pain management goals.

  • Instruct the patient, family, and caregivers not to use OTC analgesics or phytopharmaceuticals unless medically supervised, and not to use discontinued prescription or nonprescription medications.

Evidence
  • Joint Commission standards require that patients receive education about pain management as part of their treatment (26).

  • A randomized, controlled trial of a nurse-administered educational intervention for cancer pain management improved patients' perceived control over pain and self-reported pain knowledge (129).

Rationale
  • Pain management requires active patient participation, and adherence to a time-contingent pain regimen is improved when patients are active participants in their care.

  • Individual patients and families may have different goals and expectations for pain management that will influence the treatment plan.

  • Informing patients and their families is an important step in a well-designed pain treatment plan.

Reassess pain and interventions within days to weeks after initiating the treatment plan, with each new pain complaint, and after any change in treatment. 
  • Base frequency of follow-up on pain severity, and pharmacotherapy and nonpharmacotherapy interventions.

  • See or speak with patients frequently during periods of medication adjustment (within days or weeks).

  • See patients on stable therapy for chronic pain at least every few months.

  • Re-address the key elements of the history and physical exam at each visit.

    • Ask about characteristics of pain.

    • Examine site of pain and related areas.

  • Assess and document quantitative pain level at each visit.

  • Use clinical urine drug testing (confirmatory)

  • Routinely use state prescription monitoring program.

Evidence
  • A 2010 Canadian practice guideline on the use of opioids for chronic non-cancer pain recommended monitoring patients closely for pain control, adverse events, and aberrant drug-related behavior (64).

  • A 2009 guideline on the management of chronic pain in older persons from the American Geriatrics Society recommended routine reassessment of patients receiving pain medication, particularly NSAIDs or opioids (56).

  • Joint Commission standards require all institutions to incorporate follow-up into their pain management protocols (26).

Rationale
  • Pain associated with many conditions changes over time as the underlying disease progresses or remits.

  • Maintaining pain control over time requires close monitoring and compliance/adherence.

Comments
  • Limited, controlled data exist for determining the appropriate follow-up for patients with pain.

Assess adherence and symptom control at each visit. 
  • Ask how patients have been administering their medications to assess compliance, and create a time-contingent treatment plan.

  • Review pain diary if appropriate for specific patients.

  • Ask about effectiveness of and adherence with non-drug interventions.

  • Use informed consent coupled with a controlled substance agreement.

  • Ask about barriers to pain management such as cost, copays, concerns about addiction, and diversion of medications.

Evidence
  • A 2010 Canadian practice guideline on the use of opioids for chronic non-cancer pain recommended monitoring patients closely for pain control, adverse events, and aberrant drug-related behavior (64).

  • A 2009 guideline on the management of chronic pain in older persons from the American Geriatrics Society recommended routine reassessment of patients receiving pain medication, particularly NSAIDs or opioids to look for potential toxicity (56).

Rationale
  • Management of pain requires close monitoring of all interventions to control pain.

Monitor for side effects and complications of the treatment plan at each visit. 
  • Screen for any complications of the pain management regimen.

  • Specifically assess for the potential side effects of commonly used analgesics, such as:

    • NSAIDs: GI symptoms, bleeding, renal or hepatic dysfunction, hematoma

    • Opioids: constipation, sedation, nausea, pruritus, cognition

Evidence
  • A 2009 guideline on the management of chronic pain in older persons from the American Geriatrics Society recommended routine reassessment of patients receiving pain medication, particularly NSAIDs or opioids to look for potential toxicity (56).

Rationale
  • Side effects from analgesics are common but often preventable and treatable.

  • Frequently and routinely monitoring for side effects and complications ensures prompt management.

Assess periodically for inappropriate or dangerous drug-use patterns in patients on chronic opioid therapy. 
  • Assess the patient's reliability with the treatment plan, including:

    • Adherence to prescribed drugs, using clinical comprehensive confirmatory urine drug testing

    • Follow-up with clinic visits to obtain pharmacotherapy

    • Recommended consultations and follow-up if needed

  • Assess current or past history of drug abuse, misuse, or diversion.

  • Assess for adverse life consequences related to medication use, such as:

    • Loss of vocation

    • Relationships

    • Legal or medical problems due to drugs

  • Assess for drug-seeking behaviors, including:

    • Prescriptions from several prescribers for same or similar medications

    • Filling prescriptions at several different pharmacies and different chain pharmacies

    • “Lost”, stolen, or misplaced medications or prescriptions

    • Multiple emergency room visits for refills of pain medications

    • Premature refills

    • Invalid “call in” or written prescription for controlled substances

  • Assess for abuse of other drugs, such as:

    • Euphorigenic drugs

    • Alcohol

    • Tobacco

    • Cocaine

    • Benzodiazepines

    • Heroin

    • Phencyclidine

    • Amphetamines

    • Hallucinogens

    • Cannabis

  • Consider using written informed consent with a treatment plan (“controlled substance agreement”) that specifies the physician and patient responsibilities with respect to chronic prescribing of opioids.

  • Be aware that undertreatment of chronic pain can result in behaviors resembling addiction which resolve when the patient's pain is treated with an adequate dose of analgesics given at an appropriate dosing interval.

  • Recognize addiction drug-seeking behaviors:

    • Requesting prescriptions prematurely

    • Visiting emergency room

    • Misusing drugs for nonmedical purposes

    • Overwhelming involvement in the acquisition of specific pain medications (e.g., hydrocodone, hydromorphone, oxycodone) and other controlled or euphorigenic drugs

    • Displaying aberrant behaviors

    • Be aware of the “excuse-driven patient” (one with an increased excuse pattern for the above behavior)

Evidence
  • A 2010 Canadian practice guideline on the use of opioids for chronic non-cancer pain recommended monitoring patients closely for pain control, adverse events, and aberrant drug-related behavior (64).

  • A 2008 structured review of the prevalence of medication abuse and addiction among patients receiving chronic opioid therapy included 67 studies. The pooled rate of abuse/addiction was 3.27% and the rate of aberrant drug-related behaviors was 11.5% (51).

  • A prospective study of 11,882 hospitalized medical patients found that only 4 patients were documented as becoming addicted as a result of receiving opioid analgesics (125).

  • A 1990 review of literature on addiction resulting from the use of opioid analgesics for pain control found that only 7 of 24,000 patients studied had become addicted (126).

  • A 1999 review of the opioid contract in the management of chronic pain analyzed contracts from 39 academic pain centers and identified common themes while acknowledging that their efficacy is not yet well established (130).

  • A 2006 review of opioid contracts examined the limited empirical evidence for their use (131).

Rationale
  • Addiction is not common in patients prescribed opioids for pain, but evidence of inappropriate drug use should be periodically monitored and reconciled on all patients prescribed controlled substances for pain.

Table Grahic Jump Location
 Drug Treatment for Pain

Swipe to view table

Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
Mild-Moderate Pain
FirstLineIconblackboxiconAcetaminophen (Tylenol)500-1000 mg q4-6hr. Maximum total daily dose: 4000 mg for acute pain, 2600 mg for chronic pain. Available in oral or rectal formulationsblackboxicon Hepatotoxicity. Avoid alcohol. Avoid chronic use with CKD. Caution with salicylate hypersensitivityCan combine with opioids for severe pain. Use caution to avoid exceeding the maximum daily dose; use maximum daily dose of 3g in patients with hepatic disease.
blackboxiconOral nonsteroidal anti-inflammatory drugsNephrotoxicity, hepatotoxicity, platelet dysfunction, anemia, nausea, dyspepsia, tinnitus, headache, dizzinessblackboxicon CV risk and GI risk. Avoid with: aspirin-sensitive asthma, severe CKD, third trimester pregnancy. Decrease dose with hepatic disease, CKD. Caution with: CV disease, elderly. Drug interactions with CYP2C9 inhibitors or inducersCan combine with other agents in chronic pain. Watch for GI and renal toxicity with chronic use.
blackboxiconCelecoxib (Celebrex)200 mg qd or 100 mg bidHypersensitivity reactionsAvoid with: severe hepatic disease, sulfonamide hypersensitivity. Use half dose with CYP2C9 poor metabolizers. Caution with black patientsCOX-2 inhibitor. Use if GI side effects from other NSAIDS.
blackboxiconDiclofenac (Cataflam, Zipsor, Flector patch)Immediate-release (Zipsor): 25 mg qid. (Cataflam): 50 mg tid. Topical patch: 1 patch bidAllergic reactions, dermatologic reactions
blackboxiconEtodolac200-400 mg q6-8hr
blackboxiconIbuprofen (Advil, Motrin) Ibuprofen IV (Caldolor)PO: 400-800 mg q4-8hr. Maximum total daily dose 2400 mg. IV: 400-800 mg q6hr. Maximum total daily dose 3200 mg
blackboxiconKetoprofenImmediate-release: 25-50 mg q6-8hr. Maximum total daily dose 300 mgDecrease dose with: elderly, CrCl<90
blackboxiconNaproxen (Naprosyn, Naprelan, Anaprox)Immediate-release: Initially, 500-550 mg, then 250-275 mg q6-8hr. Maximum total daily dose 1250 mg. Controlled-release (Naprelan): 1000 mg qdAvoid if CrCl<30
Nonacetylated salicylatesMinor-severe GI side effects, tinnitus, hearing loss, hepatotoxicity. Uncommon: Dermatologic reactions, renal toxicity, hematologic reactionsAvoid with: third-trimester pregnancy, OTC salicylates, long-term acetaminophen. Caution with: CV disease, hepatic disease, CKD, GI disease, gout, elderly. Monitor plasma salicylic acid if taken long-term
Choline magnesium trisalicylate2-3 g total daily dose, dosed bid-tidMay decrease absorption of quinolones or tetracyclines. Use 750 mg tid if elderly
blackboxicon Diflunisal500 mg q8-12hrblackboxicon CV risk and GI risk. Decrease dose by half with: elderly, CrCl<50
Aspirin325-650 mg q4hr, or 1000 mg q6hr. Maximum total daily dose 4000 mg. Available in oral or rectal formulationsGI side effects, GI bleeding, tinnitus, hearing loss, hypersensitivity reactions, hepatotoxicity, platelet dysfunction. Uncommon: dermatologic reactionsAvoid with severe hepatic disease or severe CKD. Caution with: asthma, GI disease, elderly
Moderate-severe pain
Opioid agonist/ norepinephrine and serotonin reuptake inhibitorsCNS depression, GI side effects, CV adverse reactions, pruritus, dependence, tolerance, serotonin syndromeAvoid with: MAOI therapy, severe pulmonary disease. Avoid: abrupt withdrawal, use of alcohol or other CNS depressants Caution with: GI motility disorders, seizure disorder, elderly
blackboxiconTapentadol immediate-release (Nucynta), Tapentadol extended-release (Nucynta ER)Immediate-release: 50-100 mg q4-6hr. Maximum total daily dose 600 mg. Extended-release: 50 mg q12hr, up to 250 mg q12hrRespiratory depressionblackboxicon (Extended-release): Potential for abuse, proper patient selection, not for prn use or for acute pain. Avoid alcohol, including in medications. Avoid with: severe hepatic disease, severe CKD. Decrease dose with moderate hepatic disease. CYP metabolism is minor
Tramadol immediate-release (Ultram, Rybix ODT), Tramadol extended-release (Ultram ER, Ryzolt, ConZip)Immediate-release: 50-100 mg q4-6hr. Maximum total daily dose 400 mg. Extended-release: 100-300 mg qdVertigo, asthenia, diaphoresis, xerostomia, CNS stimulation, headacheAvoid with: opioid hypersensitivity, depression, alcohol abuse. Caution with CKD. Decrease dose with: hepatic disease, CrCl<30. If elderly, maximum total daily dose 300 mg. Substrate for CYPs 2D6, 3A4, 2B6Less respiratory depression than morphine
OpioidsControlled- and extended-release preparations must be swallowed wholeRespiratory and CNS depression, hypotension, nausea, vomiting, constipation, biliary spasm, pruritus, urinary retention, CV adverse reactions, toleranceRisk of abuse. Avoid with severe pulmonary disease. Avoid: abrupt withdrawal, use of alcohol or other CNS depressants. Caution with: GI motility disorders, seizure disorder, elderly. If <50 kg, may require lower doseDo not give extended-release preparations to opioid-naïve patients
Codeine15-60 mg q4hr. Maximum total daily dose 360 mgCaution with hepatic disease. Substrate for CYPs 2D6 and 3A4Not for chronic pain
blackboxiconFentanylAnticholinergic effectsblackboxicon Abuse potential and risk of overdose. For opioid tolerant patients only. Potential for serious adverse events and death. Interacts with CYP3A4 inhibitors. Caution when converting between opioids or fentanyl formulations. Use lowest possible dose with hepatic disease or CKD.For opioid tolerant patients only
blackboxiconFentanyl injection (Sublimaze)50-100 mcg IM or slow IV over 1-2 min.Chest wall rigidity with IVFor hospitalized patients
blackboxiconFentanyl transdermal (Duragesic)Patients must be opioid tolerant. Start with 25 mcg/ hourApplication site reactionsblackboxicon High concentration opioid. Avoid heat sources. Remove patch before MRI
blackboxiconFentanyl transmucosal troche/lozenge (Actiq), Fentanyl buccal tablet (Fentora), Fentanyl buccal film (Onsolis), Fentanyl sublingual tablet (Abstral), Fentanyl sublingual spray (Subsys), Fentanyl nasal spray (Lazanda)For breakthrough pain.
Actiq: Initially, 200 mcg. May receive additional dose 15 min after finishing first. Then, may repeat in 4 hr.
Fentora, Abstral, Subsys: Initially, 100 mcg. May receive additional dose 30 min after starting first. Then, may repeat in 2 hr (Abstral) or 4 hr (Fentora, Subsys).
Onsolis: Initially, 200 mcg. May repeat in 2 hr.
Lazanda: Initially, 1 spray of 100 mcg in 1 nostril. May repeat in 2 hr
blackboxicon Only available through restricted distribution program. Only indicated for breakthrough pain in opioid tolerant cancer patients under care of a skilled HCP. Keep away from childrenFor breakthrough pain in opioid tolerant cancer patients
Hydrocodone5-10 mg q4-6hrSubstrate of CYPs 2D6 and 3A4
blackboxiconHydromorphone immediate-release (Dilaudid, Dilaudid-HP) extended-release (Exalgo)PO (immediate-release): 2-4 mg q4-6hr. Extended-release (Exalgo): convert from patient's immediate-release dose. SC, IM or IV: 1-2 mg q4-6hrblackboxicon Respiratory depression, potential for abuse and medication errors, drug interactions with other CNS depressants and alcohol. Decrease initial dose with: moderate-severe hepatic disease, CrCl<60
LevorphanolPO: 2-4 mg q6-8hrDecrease dose with CKD
Meperidine (Demerol)50-150 mg PO, SC, IV or IM q3-4hrLess biliary spasm than morphineAvoid with SSRIs. Caution with: hepatic disease, CKD, elderly due to accumulation of neurotoxic metaboliteNot for chronic pain
blackboxiconMethadone (Dolophine)PO, SC, IM or IV: 2.5-10 mg q8-12hrQT prolongation and TdPblackboxicon Cardiac and respiratory deaths, respiratory depression, cardiac complications. Substrate of CYPs 2C19, 3A4, 2B6 and P-gp
blackboxiconMorphine immediate-release
, Morphine extended-release (MS Contin, Kadian)
Injectable morphine (Astramorph PF, Duramorph PF, Infumorph)
Immediate-release: 10-30 mg q3-4hr. Extended-release: 15-30 mg q12hr. Kadian: 10 mg bid or 20 mg qd.
SC, IM or IV: 2.5-15 mg q2-6hr
Miosisblackboxicon (controlled-release, extended-release): Abuse liability, not for prn use, life-threatening respiratory depression, accidental exposure. Substrate for P-gpUsed for treatment of chronic severe pain
blackboxiconMorphine immediate-release and Morphine extended-release (Avinza)Initially, 30 mg qd. Maximum total daily dose 1600 mg. Must swallow intact or sprinkle on applesauceBeads contain fumaric acid that can cause renal toxicity if maximum total daily dose exceededblackboxicon Interaction with alcohol. Avoid alcohol, including in food and medicationCapsules contain immediate- and extended-release beads of morphine
blackboxiconMorphine ER/Naltrexone (Embeda)20/0.8 mg q12hr or qd. Must swallow intact or sprinkle on applesauceblackboxicon Interaction with alcohol. Avoid alcohol, including in food and medicationContains pellets of morphine with a sequestered core of naltrexone, to prevent abuse
blackboxiconOxycodone immediate-release (Roxicodone, Oxecta) Oxycodone controlled-release (Oxycontin)Immediate-release: 5-15 mg q4-6hr, up to 10-30 mg q4hr. Controlled-release: initially, 10 mg q12hrAsthenia, diaphoresisblackboxicon (Controlled-release): Abuse potential, requires proper patient selection and proper administration, drug interactions with CYP3A4 inhibitors. Decrease dose with hepatic disease or CKD. Substrate of CYPs 2D6, 3A4Controlled release oxycodone has high abuse potential and street value.
blackboxiconOxymorphone immediate-release (Opana) Oxymorphone extended-release (Opana ER)Immediate-release: 5-20 mg PO q4-6hr. Extended-release: 5 mg PO q12hr on an empty stomach. SC or IM: 1-1.5 mg q4-6hr. IV: Initially, 0.5 mgFever, miosisblackboxicon (Extended-release): Abuse, misuse potential. Avoid with moderate-severe hepatic disease. Caution with mild hepatic disease. Decrease dose if CrCl<50
Partial opioid agonist
blackboxiconBuprenorphine (Buprenex, Butrans)0.3 mg IM or slow IV push q6-8hr. Transdermal: Initially 5 mcg/hr, applied once weeklyRespiratory and CNS depression, QT prolongation, hypotension, nausea, vomiting, constipation, biliary spasm, pruritus, CV adverse reactions, tolerance, dependenceblackboxicon (transdermal): Potential for abuse, requires proper patient selection, do not exceed 20 mcg/hr, do not expose application site to heat. Avoid: abrupt withdrawal, use of alcohol or other CNS depressants Avoid with: severe hepatic disease, severe pulmonary disease. Decrease dose by half if elderly. Caution with severe CKD, GI motility disorders, seizure disorderSublingual formulation is used to treat opioid addiction; other formulations used to treat pain
Mixed opioid agonist/antagonistsCNS depression, hypotension, nausea, vomiting, constipation, xerostomia, pruritus, dependence, less tolerance than morphineAvoid: abrupt withdrawal, use of alcohol or other CNS depressants. Caution with: GI motility disorders, cardiac disease, seizure disorder, pulmonary disease, elderlyLower abuse potential than pure opioid agonists. Generally prescribed by pain specialists
Butorphanol (Stadol)IM: 1-4 mg q3-4hr. IV: 0.5-2 mg q3-4hr. Intranasal: 1 mg (1 spray) in 1 nostril. After 60-90 min, may repeat in other nostril. May repeat sequence in 3-4 hrRespiratory depression is less likely than with morphine, but it is serious. Intranasal: nasal congestion, dyspnea, epistaxisDecrease dose and extend dosing interval with: hepatic disease, CKD, elderlyFor post-operative pain
NalbuphineSC, IM, IV: 10 mg q3-6hrBiliary spasm. Ceiling effect to respiratory depression, but it is serious when it occursConsider decreased dose with: CKD, hepatic impairment
Pentazocine (Talwin)PO: 50-100 mg q3-4hr. Maximum total daily dose 600 mg. SC, IM, IV: 30 mg q3-4hr. Avoid >30 mg IV or >60 mg SC/IM. Maximum total daily dose 360 mg. Use SC route only when necessaryChills, diaphoresis, paresthesias, urinary retention, biliary spasm, injection site reactions. Dysphoria and psychotomimetic effects at high doses. Rare respiratory depressionDecrease dose with: hepatic disease, CrCl<50. Not recommended in elderlyNot commonly used due to dysphoria
N-type calcium channel blocker
blackboxiconZiconotide (Prialt)Intrathecal: Initially, 0.1 mcg/hr intrathecal infusion. Maximum 0.8 mcg/hrDizziness, nausea, vomiting, somnolence, confusion, memory impairment, asthenia, headache, diarrhea, ataxia, aphasia, elevated creatine kinaseblackboxicon Severe psychiatric symptoms and neurological impairment may occur. Monitor frequently. Can discontinue abruptly if needed. Avoid with cardiac disease. Decrease initial dose if elderlyFor patients with chronic severe pain requiring intrathecal therapy who cannot take other agents
Adjuvant therapy
Tricyclic antidepressantsDue to sedation, bedtime dosing may be preferredDrowsiness and other CNS side effects, anticholinergic side effects, orthostatic hypotension, ECG abnormalities, tremor, nausea, weight gain, sexual dysfunctionblackboxicon Suicidality, particularly in young adults. Avoid: abrupt discontinuation, MAOI therapy. Decrease dose with: hepatic disease, elderly. Caution with: GI dysmotility, cardiac disease, glaucoma, BPH, urinary retention, seizure disorderEffective for neuropathic pain
blackboxiconAmitriptyline10-50 mg qhsMost anticholinergic effects
blackboxiconImipramine (Tofranil)10-50 mg qhs
blackboxiconNortriptyline (Pamelor)10-50 mg qhsPreferred agent for postherpetic neuralgia. Fewer anticholinergic effects
blackboxiconSerotonin-norepinephrine reuptake inhibitorsPlatelet dysfunction, nausea, constipation, anorexia, weight loss, xerostomia, insomnia, anxiety, asthenia, dizziness, drowsiness, headache, hypertension, tachycardia, hyperhidrosis, sexual dysfunction, hyponatremia, serotonin syndrome, rare NMSblackboxicon Suicidality, particularly in young adults. Avoid: abrupt withdrawal, other serotonergic drugs, MAOI therapy
blackboxiconDuloxetine (Cymbalta)60 mg qdUrinary retention, hepatotoxicity, musculoskeletal pain, muscle spasms. May increase blood pressureAvoid with: hepatic disease, severe CKD, closed-angle glaucoma. Substrate and moderate inhibitor of CYP2D6. Caution with diabeticsMay be useful for peripheral neuropathy, fibromyalgia, chronic musculoskeletal pain
blackboxiconMilnacipran (Savella)50 mg bid. Maximum total daily dose 200 mgHepatotoxicityAvoid with CrCl<5. If CrCl 5-29, decrease dose by half. Caution with: severe hepatic disease, closed-angle glaucomaFDA-approved for fibromyalgia
blackboxiconVenlafaxine (Effexor, Effexor XR)Initially, 37.5- 75 mg qd. Maximum total daily dose: Immediate-release: 75 mg bid. Extended-release: 150 mg qdHigh rate of nausea and vomiting. May increase heart rate and blood pressureDecrease initial dose by at least 50% with moderate-severe hepatic disease. Decrease dose by 25-50% if CrCl<70. Caution with CYP2D6 inhibitorsAvoid abrupt withdrawal. Effective in neuropathic pain
AnticonvulsantsCNS side effects (drowsiness, dizziness, headache, insomnia, anxiety, asthenia, tremor, others), hypersensitivity reactions, nausea, vomiting, depressionAvoid abrupt withdrawal. Caution with: elderly, pregnancy. Monitor for depression
blackboxiconCarbamazepine (Carbatrol, Tegretol, Tegretol-XR, Epitol)Regular-release: 100 mg bid-300 mg tid. Extended-release: 100-600 mg bid. Monitor serum concentrationsHepatic, CV and ocular adverse events, hyponatremiablackboxicon Serious hematologic and dermatologic reactions. Caution with Asian patients. Consider dose reduction with hepatic disease. Caution with: cardiac disease, glaucoma, sunlight. Complex drug interactionsFor neuropathic pain though long term data are lacking
Oxcarbazepine (Trileptal)Initially, 300 mg bid. Usual dose 450-1200 mg bidHyponatremia, visual impairmentCaution with severe hepatic disease. If CrCl<30, decrease dose by half. Inhibitor of CYP2C19, inducer of CYP3A4Newer agent; less evidence of efficacy
Gabapentin immediate-release (Neurontin)Immediate-release: Initially, 300 mg on day 1. Titrate as needed to 600 mg tidPeripheral edema, weight gain, diplopia, blurred vision, myoclonusDecrease dose if CrCl<60. Does not interact with other anticonvulsantsFor neuropathic pain
Pregabalin (Lyrica)50-100 mg tid. Daily dose of 300 mg or higher generally neededPeripheral neuropathy, amnesia, peripheral edema, weight gain, angioedema, diplopia, thrombocytopenia, dependence, creatine kinase elevationDecrease dose if CrCl<60. Few drug interactions. Caution with HFFor neuropathic pain; high rates of adverse events
Topiramate (Topamax)Initially, 12.5-25 mg total daily dose, dosed qd-bid. Maximum 50-100 mg bidParesthesias, language problems, impaired memory and concentration, hypoesthesia, anxiety, nausea, diarrhea, oligohidrosisCaution with: hepatic disease, ocular disease. If CrCl<70, decrease dose by half. CYP3A4 inducer and CYP2C19 inhibitor. Caution with CYP3A4 inducersFor neuropathic pain; little long-term data
Combination agents
Codeine/Acetaminophen (Tylenol with codeine #3, Tylenol with codeine #4)15/300 mg, 30/300-650 mg, 60/300-650 mg; dosed 1-2 tablets q4hrAcetaminophen maximum total daily dose: 4000 mg for acute pain, 2600 mg for chronic pain
Hydrocodone/ Acetaminophen (Vicodin, Lortab, Norco, Anexsia, Zydone)5/300-750 mg, 7.5/300-750 mg, 10/300-750 mg; dosed 1-2 capsules or tablets q4-6hrAcetaminophen maximum total daily dose: 4000 mg for acute pain, 2600 mg for chronic pain
Hydrocodone/Ibuprofen (Vicoprofen, Reprexain)2.5/200 mg, 5/200 mg, 7.5/200 mg, 10/200 mg; dosed 1 tablet q4-6hr
Oxycodone/ Acetaminophen (Percocet, Tylox, Roxilox, Oxycet, Roxicet)2.5/300-400 mg, 5/300-500 mg, 7.5/300-500 mg, 10/300-650 mg; dosed 1-2 tablets or capsules q6hrAcetaminophen maximum total daily dose: 4000 mg for acute pain, 2600 mg for chronic pain
Oxycodone/Aspirin (Percodan)4.8355/325 mg; dosed 1 tablet q6hr
Oxycodone/Ibuprofen5/400 mg; dosed 1 tablet q6hr. Do not exceed 7 days of therapy
Tramadol/ Acetaminophen (Ultracet)37.5/325 mg, dosed 2 tablets q4-6hr. Maximum 8 tablets dailyAcetaminophen maximum total daily dose: 4000 mg for acute pain, 2600 mg for chronic pain

FirstLineIcon = first-line agent; blackboxicon = black box warning; AM = morning; bid = twice daily; BPH = benign prostatic hypertrophy; CABG = coronary artery bypass graft; CKD = chronic kidney disease; CNS = central nervous system; COX-2 = cyclooxygenase-2; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P450 isoenzyme; ECG = electrocardiogram; FDA = Food and Drug Administration; GI = gastrointestinal; HCP = healthcare professional; HF = heart failure; IM = intramuscular; IV = intravenous; MAOI = monoamine oxidase inhibitor; MRI = magnetic resonance imaging; NMS = neuroleptic malignant syndrome; NSAID = nonsteroidal anti-inflammatory drug; OTC = over-the-counter (nonprescription); P-gp = P-glycoprotein; PO = oral; PM = evening; prn = as needed; q12hr = every 12 hours; q4-6hr = every 4 to 6 hours; qd = once daily; qhs = every day at bedtime; qid = four times daily; SC = subcutaneous; SCr = serum creatinine; SSRI = selective serotonin reuptake inhibitor; TdP = torsade de pointes; tid = three times daily

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Table Grahic Jump Location
 Conversion to Transdermal Fentanyl (Duragesic)

Swipe to view table

Parenteral Morphine (mg/24h)Duragesic Equivalent (mcg/h)
8-2225
23-3750
38-5275
53-67100
68-92125
83-97150
Table Grahic Jump Location
 Oral and Parenteral Narcotic Analgesics

Swipe to view table

DrugRouteEquianalgesic Dose (mg)Duration (h)Plasma Half-life (h)
Morphine
im1042-3.5
po30-604
Codeine
im13043
po3004
Oxycodone
im
po203-4
Hydromorphone
im1.542-3
po7.54
Meperidine
im754 (2?)3-4
po3004 (2?)Normeperidine
Methadone
imVariable*6-8†12-24
poVariable*6-8†
Fentanyl
iv0.1
Hydrocodone
im
po20-303-4
Oxymorphone extended release
po20-30129-11
Oxymorphone immediate release
po104-67-9
iv1

* The equianalgesic dose of methadone compared to other opioids is extremely variable with chronic dosing. Initiate dose 2.5 mg orally, slow titration necessary.

† Risk of CNS depression with repeated use; accumulation in elderly or persons with impaired renal function with regular dosing. Monitor for patient variability in duration of efficacy. Be aware of QTc prolongation; be aware of any coprescribing with other QTc-prolonging pharmacotherapies. Be aware of any comorbid or premorbid cardiac abnormalities. Read methadone package insert (prescribing information) before prescribing.

im = intramuscular; iv = intravenous; po = oral.

Adapted from 132.

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AIDS

acquired immunodeficiency syndrome

ASA

acetylsalicylic acid

bid

twice daily

CNS

central nervous system

CrCl

creatinine clearance

CRPS

complex regional pain syndrome

CYP450

cytochrome P450

ECG

electrocardiogram

ESR

erythrocyte sedimentation rate

FDA

Food and Drug Administration

GI

gastrointestinal

HIV

human immunodeficiency virus

im

intramuscular

iv

intravenous

NMDA

N-methyl-d-aspartic acid

NNH

number needed to harm

NNT

number needed to treat

NSAID

nonsteroidal anti-inflammatory drug

OTC

over the counter

po

oral

PT

physical therapy

qd

once daily

qhs

every night

qid

four times daily

QTc

QT corrected for heart rate

sc

subcutaneous

SNRI

serotonin and noradrenaline reuptake inhibitor

SSRI

selective serotonin reuptake inhibitor

TENS

transcutaneous electrical nerve stimulation

tid

three times daily

WHO

World Health Organization


Guidelines

Neuropathic pain - pharmacological management

Pharmacological management of persistent pain in older persons

Practice guidelines for chronic pain management: an updated report by the American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine

Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians

Evidence for improving palliative care at the end of life: a systematic review

Management of cancer pain: ESMO Clinical Practice Guidelines

American Pain Society recommendations for improving the quality of acute and cancer pain management: American Pain Society Quality of Care Task Force

Control of pain in adults with cancer: summary of SIGN guidelines

Opioids for chronic noncancer pain: a new Canadian practice guideline

Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit

Ottawa Panel evidence-based clinical practice guidelines on therapeutic massage for low back pain

Pharmacological management of persistent pain in older persons

Acupuncture

Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain

Pharmacological management of persistent pain in older persons

Systematic Reviews

Evidence for improving palliative care at the end of life: a systematic review

Meta-analysis: acuncture for low back pain

Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction

Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain

Systematic review of topical capsaicin for the treatment of chronic pain

Factors predisposing women to chronic pelvic pain: systematic review

Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups

Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials

Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review

Efficacy of postoperative epidural analgesia: a meta-analysis

The cochrane review of advice to stay active as a single treatment for low back pain and sciatica

Massage for low-back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group

DOI: 10.7326/d325
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Author(s) and Disclosures:
Linda King, MD has nothing to disclose. Rowena Schwartz, PharmD has nothing to disclose. Bob Arnold, MD has nothing to disclose. Robert L. Barkin, MBA, PharmD, FCP received honoraria and consultancies.

One or more of the present or past ACP Smart Medicine physician editors worked on this module and had nothing to disclose: Davoren Chick, MD, FACP; Deborah Korenstein, MD, FACP; Marjorie Lazoff, MD; Richard Lynn, MD, FACP.

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