REVIEW
A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain: Tailoring Therapy to Meet Patient Needs

https://doi.org/10.4065/84.7.602Get rights and content

Management of chronic noncancer pain (CNCP) requires a comprehensive assessment of the patient, the institution of a structured treatment regimen, an ongoing reassessment of the painful condition and its response to therapy, and a continual appraisal of the patient's adherence to treatment. For many patients with CNCP, the analgesic regimen will include opioids. Physicians should consider the available evidence of efficacy, the routes of administration, and the pharmacokinetics and pharmacodynamics of the various formulations as they relate to the temporal characteristics of the patient's pain. When making initial decisions, physicians should decide whether to prescribe a short-acting opioid (SAO) with a relatively quick onset of action and short duration of analgesic activity, a long-acting opioid (LAO) with a longer duration of analgesic action but a potentially longer onset of action, or both. Studies suggest that SAOs and LAOs are both effective for most types of CNCP. A review of published studies found no data to suggest that either SAOs or LAOs are generally more efficacious for treating any particular CNCP condition. The LAOs may provide more stable analgesia with less frequent dosing; however, opioid therapy should be tailored to the pain state and the individual patient, and SAOs may be appropriate for some patients with CNCP. MEDLINE and PubMed searches were conducted to locate relevant studies published from January 1975 to April 2008 using the following search terms: opioids, short-acting opioids, long-acting opioids, chronic pain, chronic pain AND opioids, and narcotics. English-only randomized controlled trials and nonrandomized studies were considered.

Section snippets

PHARMACOKINETICS AND PHARMACODYNAMICS OF LAOs AND SAOs

Few studies directly compare the pharmacokinetic and pharmacodynamic properties of SAOs and LAOs.37, 38, 39, 40, 41 Compared with SAOs, LAOs are associated with fewer peak-trough fluctuations and thus provide more stable drug plasma concentrations, which may lead to fewer periods of inadequate pain control.42 However, the analgesic effects of short- and long-acting formulations of the same opioid were similar when dosed consistently in several trials.37, 43

Comparisons of similar opioid

ANALGESIC EFFICACY OF LAOs AND SAOs IN COMMON CNCP CONDITIONS

The use of opioids for the treatment of CNCP is supported by a number of professional organizations, including the American Academy of Pain Medicine and the American Pain Society.16 However, few studies have compared SAOs with LAOs head to head; most data concerning the efficacy of opioids are based on comparisons of the active study drug with a placebo control. Therefore, little evidence shows that either SAOs or LAOs are superior for the treatment of CNCP.48, 49, 50, 51

OSTEOARTHRITIS

Osteoarthritis, the most common rheumatologic disorder and a primary cause of disability, is associated with structural malfunction of the synovial joints.52 Osteoarthritis affects approximately half the population 65 years and older and currently affects 1 in 5 Americans overall.53 The number of Americans 65 years and older is expected to double by 2030; therefore, the social burden of osteoarthritis will likely increase.53 The American College of Rheumatology recommends opioid analgesics if

LOW BACK PAIN

Chronic LBP occurs in 28.3% of adults 18 years or older61 and is the fifth most common reason that Americans consult with a physician.62 Opioid therapy, as part of a multimodal approach to pain management, may prove beneficial for some people with chronic LBP. The American College of Physicians and the American Pain Society consensus guidelines for the treatment of chronic LBP state that opioids are a treatment option for severe, disabling pain not controlled by acetaminophen or NSAIDs.15

The

NEUROPATHIC PAIN

Neuropathic pain, resulting from a lesion or dysfunction in the peripheral and/or central nervous system, is associated with such conditions as diabetic neuropathy (DN), postherpetic neuralgia (PHN), and phantom limb pain.2 The most recently published evidence-based guidelines call for the initial treatment of neuropathic pain with TCAs, the α2δ ligands gabapentin and pregabalin, or selective SNRIs, alone or in combination.19, 20 These guidelines recommend that opioid analgesics be used when

QUALITY OF LIFE

Pain is a complex experience for patients, encompassing psychological and emotional aspects that can be difficult to fully articulate. Pain affects the physical, mental, and social functions that allow patients to take part in ADLs. Conventional numeric pain scales ranging from 0 to 10 do not distinguish between the physical and emotional pain components. Learning how pain affects QOL may help to improve function, a critical goal of pain therapy. To aid the physician in identifying baseline and

SLEEP

Comorbid pain-related sleep disturbances are reported by 88.9% of patients with chronic pain.79 The pain-sleep relationship is such that pain may exacerbate sleep disturbances, which, in turn, may further intensify physical and mental symptoms, such as pain, disability, impaired daily functioning, and depression.4, 79 Therefore, providing effective analgesia may relieve pain-related sleep disorders (Figure).80

The LAO formulations may effectively improve sleep in some patients with chronic pain.

ADVERSE EFFECTS

Patients being treated for CNCP should be monitored for AEs, which may influence the decision to continue, adjust, or discontinue a pharmacological regimen. Moreover, because of response variability to treatment, AE profiles for medications or classes of agents may differ.85 With opioid therapy, common AEs include constipation, nausea, vomiting, dry mouth, and sedation.86 In several studies comparing SAOs and LAOs, no definitive evidence linked the pharmacokinetic profile of the formulation and

APPROACHES TO RISK ASSESSMENT AND MANAGEMENT WITH SAOs AND LAOs

Opioid therapy is associated with risks for misuse and abuse. In recent years, an increasing number of Americans have been using prescription pain relievers for nonmedical purposes; 5.2 million people abused pain relievers in 2006, an increase from 4.7 million in 2005.93 Historically, conventional wisdom suggested that SAOs are more likely to lead to abuse and that aberrant behavior is less likely with LAOs because of their pharmacokinetic and pharmacodynamic features.94, 95 Several studies,

IMPLICATIONS FOR MANAGEMENT OF CHRONIC PAIN

Although SAOs and LAOs are efficacious in a variety of chronic pain conditions, their appropriate roles in the management of chronic pain are specific to the individual patient. Chronic noncancer pain should be managed like other chronic conditions. For example, in the treatment of hypertension, the goal is to maintain consistent control over the condition as soon as possible, using medications that provide consistent blood pressure control. In appropriately selected patients with chronic pain

CONCLUSION

Management of CNCP should be tailored to the individual patient. Because patients will have different pain profiles and therapeutic goals, optimal treatment must be individualized, accounting for not only the characteristics of the pain state but also its effects on QOL and the therapeutic goals.

REFERENCES (104)

  • ME Hale et al.

    Efficacy and safety of oxymorphone extended release in chronic low back pain: results of a randomized, double-blind, placebo- and active-controlled phase III study

    J Pain

    (2005)
  • AH Vallerand

    The use of long-acting opioids in chronic pain management

    Nurs Clin North Am

    (2003)
  • CE Argoff et al.

    Consensus guidelines: treatment planning and options: diabetic peripheral neuropathic pain [published correction appears in 2006;81(6):854]

    Mayo Clin Proc

    (2006)
  • CP Watson et al.

    Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy

    Pain

    (2003)
  • Y Harati et al.

    Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy

    J Diabetes Complications

    (2000)
  • RH Dworkin et al.

    Core outcome measures for chronic pain clinical trials: IMMPACT recommendations

    Pain

    (2005)
  • GE Ruoff et al.

    Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: a multicenter, randomized, double-blind, placebo-controlled outpatient study

    Clin Ther

    (2003)
  • BS Galer et al.

    Individual variability in the response to different opioids: report of five cases

    Pain

    (1992)
  • NA Hagen et al.

    Efficacy, safety, and steady-state pharmacokinetics of once-a-day controlled-release morphine (MS Contin XL) in cancer pain

    J Pain Symptom Manage

    (2005)
  • HW Daniell

    Hypogonadism in men consuming sustained-action oral opioids

    J Pain

    (2002)
  • G Chang et al.

    Opioid tolerance and hyperalgesia

    Med Clin North Am

    (2007)
  • C Harstall et al.

    How prevalent is chronic pain?

    Pain: Clin Updates

    (2003)
  • National Center for Health Statistics

    Health, United States, 2006 With Chartbook on Trends in the Health of Americans

    (2006)
  • NK Tang et al.

    Prevalence and correlates of clinical insomnia co-occurring with chronic back pain

    J Sleep Res

    (2007)
  • JM van der Waal et al.

    Health-related and overall quality of life of patients with chronic hip and knee complaints in general practice

    Qual Life Res

    (2005)
  • National Institutes of Health, US Deptartment of Health and Human Services
  • WF Stewart et al.

    Lost productive time and cost due to common pain conditions in the US workforce

    JAMA

    (2003)
  • Task Force on Pain Management

    Practice guidelines for chronic pain management: a report by the American Society of Anesthesiologists Task Force on Pain Management, Chronic Pain Section

    Anesthesiology

    (1997)
  • AD Furlan et al.

    Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects

    CMAJ

    (2006)
  • JC Ballantyne et al.

    Efficacy of opioids for chronic pain: a review of the evidence

    Clin J Pain

    (2008)
  • AM Trescot et al.

    Opioid guidelines in the management of chronic non-cancer pain

    Pain Physician

    (2006)
  • D Brookoff

    Chronic pain: 2, the case for opioids

    Hosp Pract (Minneap)

    (2000)
  • E Eisenberg et al.

    Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials

    JAMA

    (2005)
  • R Chou et al.

    Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society

    Ann Intern Med

    (2007)
  • American Academy of Pain Medicine et al.

    The use of opioids for the treatment of chronic pain: a consensus statement from American Academy of Pain Medicine and American Pain Society

    Clin J Pain

    (1997)
  • NB Finnerup et al.

    Chronic neuropathic pain: mechanisms, drug targets and measurement

    Fundam Clin Pharmacol

    (2007)
  • DE Moulin et al.

    Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society

    Pain Res Manag

    (2007)
  • BH McCarberg et al.

    Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia

    Am J Ther

    (2001)
  • DS Bennett et al.

    Consensus Panel recommendations for the assessment and management of breakthrough pain, part II

    P&T (Pharm Ther)

    (2005)
  • J Gimbel et al.

    The efficacy and safety of oral immediate-release oxymorphone for postsurgical pain

    Anesth Analg

    (2004)
  • Vicodin [package insert]

    (2007)
  • Percocet [package insert]

    (2006)
  • Combunox (oxycodone HCl and ibuprofen) tablets [package insert]

    (2007)
  • Vicoprofen [package insert]

    (2006)
  • OxyContin (oxycodone controlled-release) tablets [package insert]

    (2007)
  • AK Matsumoto et al.

    Oxymorphone extended-release tablets relieve moderate to severe pain and improve physical function in osteoarthritis: results of a randomized, double-blind, placebo- and active-controlled phase III trial

    Pain Med

    (2005)
  • CE Inturrisi

    Clinical pharmacology of opioids for pain

    Clin J Pain

    (2002)
  • MP Adams et al.

    Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: results of a randomized crossover study

    Pharmacotherapy

    (2004)
  • Physician's Desk Reference

    (2005)
  • Cited by (109)

    View all citing articles on Scopus

    Dr Argoff acknowledges that he has served as a consultant/speaker for Endo Pharmaceuticals, King Pharmaceuticals, Pricara, Alpharma, and Cephalon and has served as a consultant for Abbott Laboratories. Dr Silvershein has acted as a consultant to the McMahon Group relating to their work with King Pharmaceuticals.

    This article is freely available on publication.

    View full text