Journal of Pain & Palliative Care Pharmacotherapy. 2014;28:308–310. ISSN: 1536-0288 print / 1536-0539 online DOI: 10.3109/15360288.2014.943383
EUROPEAN PERSPECTIVES ON PAIN AND PALLIATIVE CARE
The Pros and Cons of Long-Term Opioid Therapy Rui Duarte and Jon Raphael AB STRACT Evidence supporting the efficacy of long-term opioid therapy for chronic noncancer pain is scarce. However, weak evidence suggests that those who are able to continue opioids long-term experience clinically significant pain relief. Fear of opioid abuse or addiction should not impede the prescribing of opioids if the patients are carefully selected and monitored. In patients taking opioids who experience intolerable side effects or unsatisfactory pain relief, alternatives should be sought as soon as possible. This report is adapted from paineurope 2014; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. KEYWORDS abuse, benefits, long-term, monitoring, opioid, risks
the pain persists or is severe, strong opioids should be provided and the dose adjusted until pain relief is achieved (step 3).1 Although the use of opioids is widely accepted for the treatment of severe acute pain, cancer pain, or end-of-life pain, the management of chronic noncancer pain with long-term opioid therapy remains controversial. Long-term opioid therapy in chronic noncancer pain is only justified if other drugs and methods with less risk of side effects have been tried and failed, the pain relief obtained with the opioid is significant and sustained, and if the improvement in quality of life is sufficient to tolerate side effects and the risks of long-term adverse events.2
INTRODUCTION Treatment strategies for the management of chronic pain start with those that are least invasive and have the lowest risk and cost associated with them. Conservative treatment options include exercise programs, relaxation, off-the-counter (OTC) medications (such as ibuprofen), adjunctive medications (e.g., antidepressants), physical rehabilitation, and cognitive-behavioral therapy (CBT). If these treatments do not provide sufficient pain relief, oral opioids may be attempted. The World Health Organization (WHO) recommends a three-step approach for the use of analgesics for cancer pain relief in adults, starting with nonopioids for minor pain (step 1), followed by mild opioids if the pain continues or is moderate (step 2), and if
COMMON CONDITIONS REQUIRING LONG-TERM OPIOID THERAPY Following positive treatment results observed in cancer patients, oral opioids started to be prescribed to patients with chronic noncancer pain if the cause of the pain could not be treated and/or when other treatment methods did not provide pain relief.3 Chronic pain is a highly prevalent condition. The Health Survey for England 2011 showed that 31% of men and 37% of women reported chronic pain.4 In Europe, a large-scale survey showed that one in five adults
Rui Duarte, PhD, is a postdoctoral research fellow and Jon Raphael, MD, is Professor of Pain Science, Birmingham City University, Birmingham, UK. This report is adapted from paineurope 2014; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. Address correspondence to: Dr. Rui Duarte (E-mail: [email protected]).
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European Perspectives on Pain and Palliative Care
(19%) suffer from chronic noncancer pain, with approximately a third of these people suffering severe pain and half experiencing pain constantly.5 In-depth interviews with 4839 respondents with chronic pain showed that 34% had severe pain (8–10 on the Numeric Rating Scale).5 Common causes of chronic pain include arthritis/osteoarthritis or rheumatoid arthritis (42%), herniated discs, degeneration or fractures of the spine (21%), trauma or surgery (15%), nerve damage (4%), or whiplash (4%).5 Chronic noncancer pain can include nociceptive and neuropathic pain, and both conditions may be responsive to opioid therapy.6,7 A narrative review observed that in Europe, opioids were the most frequently prescribed WHO class for patients with chronic pain (22.4–23%), second only to nonsteroidal anti-inflammatory drugs (NSAIDs) (43–44%).7 However, those with any general chronic neuropathic pain also were frequently prescribed antiepileptic agents (50.7%) and antidepressants (28.7%) among other nonstandard pain medications. From this review, it is not possible to confirm an association between the duration, severity, or type of pain with the analgesic provided. It could be hypothesized that the frequency of opioid prescription was not higher because the pain was not severe enough to warrant opioids, or because of the prescribing doctor’s concerns regarding long-term opioid therapy.
PROS AND CONS OF LONG-TERM THERAPY A retrospective evaluation of 38 patients on long-term oral opioids, of whom 19 patients were treated for 4 or more years and 6 patients for more than 7 years, showed only occasional escalation of the dose. Two thirds of patients required less than 20 mg morphine equivalent per day and only four patients took more than 40 mg per day.3 In a separate study, an openlabel extension of a 14-day double-blind trial enrolled 106 patients with persistent moderate to severe osteoarthritis pain to assess the analgesic efficacy, need for dose adjustments, effect on function, and safety during long-term treatment with controlled-release oxycodone. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. The pain was controlled, the mean dose remained stable at approximately 40 mg per day after titration, and it was also observed that several of the opioid side effects decreased in duration as therapy continued.8 Nevertheless, evidence supporting the efficacy of long-term opioid therapy in chronic noncancer pain
309
is scarce. A Cochrane systematic review concluded that many patients discontinue long-term oral opioids due to adverse events or insufficient pain relief.9 However, weak evidence suggests that those who are able to continue opioids long-term experience clinically significant pain relief.9 Similarly, an expert panel suggested that although the evidence is limited, chronic opioid therapy can be an effective therapy for carefully selected and monitored chronic noncancer pain patients.10 Common side effects include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression.11 Associations with endocrine effects and low bone mineral density have also been reported.12,13 In the context of patients with pain, the risk of psychological dependence occurring appears to be low, but clinicians should be regularly checking for its development. Paradoxically, this can act as a potential barrier to administration, perhaps because opioid addiction, which is more common outside the clinical pain setting, is not considered separately.9 A systematic review observed that signs of opioid addiction in pain management patients corresponded to seven cases in 4884 participants, indicating a low rate of opioid addiction development (0.14%).9 Careful patient selection and monitoring is essential not only in order to maximize pain relief, but also to identify potential misuse. Strong predictors of opioid misuse or abuse in chronic pain patients include a personal history of illicit drug and alcohol abuse, although no set of predictor variables is currently sufficient to identify those at risk.14
MONITORING REQUIREMENTS Patients on long-term opioid therapy should be routinely monitored. It has been suggested that reviews should take place monthly for the first 6 months of therapy after stable pain relief has been achieved.6 Frequency of ensuing reviews can vary depending on the complexity of the case. Regular monitoring is essential to reassess changes in the risks and benefits of therapy, the underlying pain condition, presence of comorbidities, and changes in psychological or social circumstances.10 Monitoring should also be used to evaluate substance misuse or abuse. Some of the commonly observed features of noncompliance with opioid therapy include unexpected results on toxicology screening, frequent requests for dose increases, concurrent use of nonprescribed psychoactive substances, failure to follow the dosage schedule, frequent loss of prescriptions or medications, frequent extra appointments at the clinic, and tampering with prescriptions.6,15 The fear of opioid abuse
310
Journal of Pain & Palliative Care Pharmacotherapy
or addiction should not impede the prescribing of opioids if the patients are carefully selected, however.
ALTERNATIVE TREATMENT OPTIONS Some patients may experience intolerable side effects or may not obtain satisfactory pain relief with opioids. For such patients, alternatives should be sought as soon as possible, because a state of pain may cause changes in the brain structure, potentially leading to a decrease in efficacy of subsequent treatments.16,17 Initial strategies consist of titration to achieve adequate pain relief, a change of opioid starting at a lower dose or weaning followed by discontinuation of therapy, or restarting the opioid after a period of abstinence if required.15 Patients with pain refractory to opioids should be considered for alternatives in the pain treatment algorithm, including neuromodulation techniques such as spinal cord stimulation and intrathecal drug delivery, which have demonstrated efficacy for the management of certain intractable noncancer pain conditions.18,19
CONCLUSION The long-term use of opioids remains controversial, although there is some evidence suggesting that patients who can continue long-term opioid management may experience clinically significant pain relief. Chronic pain is highly prevalent in Europe, and fear of opioid abuse or development of addiction should not prevent administration, provided that patients are appropriately selected and monitored regularly. Alternatives are available for those patients experienc-
ing unbearable side effects or unsatisfactory pain relief and should not be perpetually postponed due to clinical inertia. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES [1] World Health Organization. WHO’s cancer pain ladder for adults, 2014. Available at: www.who.int/cancer/palliative/ painladder/en/. Accessed 25 February 2014. [2] Breivik H. Eur J Pain. 2005;9:127–130. [3] Portenoy RK, Foley KM. Pain 1986;25:171–186. [4] Health and Social Care Information Centre. Health Survey for England—2011: Chapter 9: Chronic pain. Available at: www.hscic.gov.uk/catalogue/PUB09300. Accessed 18 March 2014. [5] Breivik H, Collett B, et al. Eur J Pain. 2006;10:287–333. [6] The British Pain Society. Opioids for Persistent Pain: Good Practice. London, The British Pain Society; 2010. [7] Reid KJ, Harker J, et al. Curr Med Res Opin. 2011;27:449–462. [8] Roth SH, Fleischmann RM, et al. Arch Intern Med. 2000;160:853–860. [9] Noble M, Treadwell JR, et al. Cochrane Database Syst Rev. 2010;(1)CD006605. doi: 10.1002/14651858.CD006605. pub2. [10] Chou R, Fanciullo GJ, et al. J Pain. 2009;10:113–130. [11] Benyamin R, Trescot AM, et al. Pain Physician. 2008;11(2 Suppl):S105–S120. [12] Duarte RV, Raphael JH, et al. Pain Physician. 2013;16:9–14. [13] Duarte RV, Raphael JH, et al. BMJ Open. 2013;3:pii:e002856. [14] Turk DC, Swanson KS, et al. Clin J Pain. 2008;24:497–508. [15] Ballantyne JC, Mao J. N Engl J Med. 2003;349:1943–1953. [16] Borsook D. Brain. 2012;135(Pt 2):320–344. [17] Kumar K, Rizvi S, et al. Pain Pract. 2013. Epub ahead of print. doi: 10.1111/papr.12126. [18] Kumar K, Taylor RS, et al. Pain. 2007;132:179–188. [19] Raphael JH, Duarte RV, et al. BMJ Open. 2013;3:pii:e003061.
Journal of Pain & Palliative Care Pharmacotherapy
Copyright of Journal of Pain & Palliative Care Pharmacotherapy is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
EUROPEAN PERSPECTIVES ON PAIN AND PALLIATIVE CARE
The Pros and Cons of Long-Term Opioid Therapy Rui Duarte and Jon Raphael AB STRACT Evidence supporting the efficacy of long-term opioid therapy for chronic noncancer pain is scarce. However, weak evidence suggests that those who are able to continue opioids long-term experience clinically significant pain relief. Fear of opioid abuse or addiction should not impede the prescribing of opioids if the patients are carefully selected and monitored. In patients taking opioids who experience intolerable side effects or unsatisfactory pain relief, alternatives should be sought as soon as possible. This report is adapted from paineurope 2014; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. KEYWORDS abuse, benefits, long-term, monitoring, opioid, risks
the pain persists or is severe, strong opioids should be provided and the dose adjusted until pain relief is achieved (step 3).1 Although the use of opioids is widely accepted for the treatment of severe acute pain, cancer pain, or end-of-life pain, the management of chronic noncancer pain with long-term opioid therapy remains controversial. Long-term opioid therapy in chronic noncancer pain is only justified if other drugs and methods with less risk of side effects have been tried and failed, the pain relief obtained with the opioid is significant and sustained, and if the improvement in quality of life is sufficient to tolerate side effects and the risks of long-term adverse events.2
INTRODUCTION Treatment strategies for the management of chronic pain start with those that are least invasive and have the lowest risk and cost associated with them. Conservative treatment options include exercise programs, relaxation, off-the-counter (OTC) medications (such as ibuprofen), adjunctive medications (e.g., antidepressants), physical rehabilitation, and cognitive-behavioral therapy (CBT). If these treatments do not provide sufficient pain relief, oral opioids may be attempted. The World Health Organization (WHO) recommends a three-step approach for the use of analgesics for cancer pain relief in adults, starting with nonopioids for minor pain (step 1), followed by mild opioids if the pain continues or is moderate (step 2), and if
COMMON CONDITIONS REQUIRING LONG-TERM OPIOID THERAPY Following positive treatment results observed in cancer patients, oral opioids started to be prescribed to patients with chronic noncancer pain if the cause of the pain could not be treated and/or when other treatment methods did not provide pain relief.3 Chronic pain is a highly prevalent condition. The Health Survey for England 2011 showed that 31% of men and 37% of women reported chronic pain.4 In Europe, a large-scale survey showed that one in five adults
Rui Duarte, PhD, is a postdoctoral research fellow and Jon Raphael, MD, is Professor of Pain Science, Birmingham City University, Birmingham, UK. This report is adapted from paineurope 2014; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication. Address correspondence to: Dr. Rui Duarte (E-mail: [email protected]).
308
European Perspectives on Pain and Palliative Care
(19%) suffer from chronic noncancer pain, with approximately a third of these people suffering severe pain and half experiencing pain constantly.5 In-depth interviews with 4839 respondents with chronic pain showed that 34% had severe pain (8–10 on the Numeric Rating Scale).5 Common causes of chronic pain include arthritis/osteoarthritis or rheumatoid arthritis (42%), herniated discs, degeneration or fractures of the spine (21%), trauma or surgery (15%), nerve damage (4%), or whiplash (4%).5 Chronic noncancer pain can include nociceptive and neuropathic pain, and both conditions may be responsive to opioid therapy.6,7 A narrative review observed that in Europe, opioids were the most frequently prescribed WHO class for patients with chronic pain (22.4–23%), second only to nonsteroidal anti-inflammatory drugs (NSAIDs) (43–44%).7 However, those with any general chronic neuropathic pain also were frequently prescribed antiepileptic agents (50.7%) and antidepressants (28.7%) among other nonstandard pain medications. From this review, it is not possible to confirm an association between the duration, severity, or type of pain with the analgesic provided. It could be hypothesized that the frequency of opioid prescription was not higher because the pain was not severe enough to warrant opioids, or because of the prescribing doctor’s concerns regarding long-term opioid therapy.
PROS AND CONS OF LONG-TERM THERAPY A retrospective evaluation of 38 patients on long-term oral opioids, of whom 19 patients were treated for 4 or more years and 6 patients for more than 7 years, showed only occasional escalation of the dose. Two thirds of patients required less than 20 mg morphine equivalent per day and only four patients took more than 40 mg per day.3 In a separate study, an openlabel extension of a 14-day double-blind trial enrolled 106 patients with persistent moderate to severe osteoarthritis pain to assess the analgesic efficacy, need for dose adjustments, effect on function, and safety during long-term treatment with controlled-release oxycodone. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. The pain was controlled, the mean dose remained stable at approximately 40 mg per day after titration, and it was also observed that several of the opioid side effects decreased in duration as therapy continued.8 Nevertheless, evidence supporting the efficacy of long-term opioid therapy in chronic noncancer pain
309
is scarce. A Cochrane systematic review concluded that many patients discontinue long-term oral opioids due to adverse events or insufficient pain relief.9 However, weak evidence suggests that those who are able to continue opioids long-term experience clinically significant pain relief.9 Similarly, an expert panel suggested that although the evidence is limited, chronic opioid therapy can be an effective therapy for carefully selected and monitored chronic noncancer pain patients.10 Common side effects include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression.11 Associations with endocrine effects and low bone mineral density have also been reported.12,13 In the context of patients with pain, the risk of psychological dependence occurring appears to be low, but clinicians should be regularly checking for its development. Paradoxically, this can act as a potential barrier to administration, perhaps because opioid addiction, which is more common outside the clinical pain setting, is not considered separately.9 A systematic review observed that signs of opioid addiction in pain management patients corresponded to seven cases in 4884 participants, indicating a low rate of opioid addiction development (0.14%).9 Careful patient selection and monitoring is essential not only in order to maximize pain relief, but also to identify potential misuse. Strong predictors of opioid misuse or abuse in chronic pain patients include a personal history of illicit drug and alcohol abuse, although no set of predictor variables is currently sufficient to identify those at risk.14
MONITORING REQUIREMENTS Patients on long-term opioid therapy should be routinely monitored. It has been suggested that reviews should take place monthly for the first 6 months of therapy after stable pain relief has been achieved.6 Frequency of ensuing reviews can vary depending on the complexity of the case. Regular monitoring is essential to reassess changes in the risks and benefits of therapy, the underlying pain condition, presence of comorbidities, and changes in psychological or social circumstances.10 Monitoring should also be used to evaluate substance misuse or abuse. Some of the commonly observed features of noncompliance with opioid therapy include unexpected results on toxicology screening, frequent requests for dose increases, concurrent use of nonprescribed psychoactive substances, failure to follow the dosage schedule, frequent loss of prescriptions or medications, frequent extra appointments at the clinic, and tampering with prescriptions.6,15 The fear of opioid abuse
310
Journal of Pain & Palliative Care Pharmacotherapy
or addiction should not impede the prescribing of opioids if the patients are carefully selected, however.
ALTERNATIVE TREATMENT OPTIONS Some patients may experience intolerable side effects or may not obtain satisfactory pain relief with opioids. For such patients, alternatives should be sought as soon as possible, because a state of pain may cause changes in the brain structure, potentially leading to a decrease in efficacy of subsequent treatments.16,17 Initial strategies consist of titration to achieve adequate pain relief, a change of opioid starting at a lower dose or weaning followed by discontinuation of therapy, or restarting the opioid after a period of abstinence if required.15 Patients with pain refractory to opioids should be considered for alternatives in the pain treatment algorithm, including neuromodulation techniques such as spinal cord stimulation and intrathecal drug delivery, which have demonstrated efficacy for the management of certain intractable noncancer pain conditions.18,19
CONCLUSION The long-term use of opioids remains controversial, although there is some evidence suggesting that patients who can continue long-term opioid management may experience clinically significant pain relief. Chronic pain is highly prevalent in Europe, and fear of opioid abuse or development of addiction should not prevent administration, provided that patients are appropriately selected and monitored regularly. Alternatives are available for those patients experienc-
ing unbearable side effects or unsatisfactory pain relief and should not be perpetually postponed due to clinical inertia. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES [1] World Health Organization. WHO’s cancer pain ladder for adults, 2014. Available at: www.who.int/cancer/palliative/ painladder/en/. Accessed 25 February 2014. [2] Breivik H. Eur J Pain. 2005;9:127–130. [3] Portenoy RK, Foley KM. Pain 1986;25:171–186. [4] Health and Social Care Information Centre. Health Survey for England—2011: Chapter 9: Chronic pain. Available at: www.hscic.gov.uk/catalogue/PUB09300. Accessed 18 March 2014. [5] Breivik H, Collett B, et al. Eur J Pain. 2006;10:287–333. [6] The British Pain Society. Opioids for Persistent Pain: Good Practice. London, The British Pain Society; 2010. [7] Reid KJ, Harker J, et al. Curr Med Res Opin. 2011;27:449–462. [8] Roth SH, Fleischmann RM, et al. Arch Intern Med. 2000;160:853–860. [9] Noble M, Treadwell JR, et al. Cochrane Database Syst Rev. 2010;(1)CD006605. doi: 10.1002/14651858.CD006605. pub2. [10] Chou R, Fanciullo GJ, et al. J Pain. 2009;10:113–130. [11] Benyamin R, Trescot AM, et al. Pain Physician. 2008;11(2 Suppl):S105–S120. [12] Duarte RV, Raphael JH, et al. Pain Physician. 2013;16:9–14. [13] Duarte RV, Raphael JH, et al. BMJ Open. 2013;3:pii:e002856. [14] Turk DC, Swanson KS, et al. Clin J Pain. 2008;24:497–508. [15] Ballantyne JC, Mao J. N Engl J Med. 2003;349:1943–1953. [16] Borsook D. Brain. 2012;135(Pt 2):320–344. [17] Kumar K, Rizvi S, et al. Pain Pract. 2013. Epub ahead of print. doi: 10.1111/papr.12126. [18] Kumar K, Taylor RS, et al. Pain. 2007;132:179–188. [19] Raphael JH, Duarte RV, et al. BMJ Open. 2013;3:pii:e003061.
Journal of Pain & Palliative Care Pharmacotherapy
Copyright of Journal of Pain & Palliative Care Pharmacotherapy is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
