Scholarly article on topic 'Long-term usage of narcotic analgesics by chronic intractable noncancer pain patients in Taiwan from 2003 to 2012'

Long-term usage of narcotic analgesics by chronic intractable noncancer pain patients in Taiwan from 2003 to 2012 Academic research paper on "Clinical medicine"

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{"chronic intractable noncancer pain (CINCP)" / "long-term use" / opioids}

Abstract of research paper on Clinical medicine, author of scientific article — I-Chen Cheng, Chih-Shiuh Chang, Wen-Ing Tsay

Background/Purpose Chronic pain is a common and important medical problem worldwide. Patients with chronic intractable noncancer pain (CINCP) are treated primarily with narcotics. We analyzed the characteristics of patients with CINCP and the pain prescriptions of Taiwan's physicians. Methods We enrolled 644 patients from 66 hospitals approved by the Taiwan Food and Drug Administration to use long-term narcotics for CINCP between 2003 and 2012. Results The majority (61.8%) of patients were 40–49-year-old men who had been treated with pethidine more often than with fentanyl in the 20–49 years age group. More than 50% of CINCP patients live in northern Taiwan, and most were treated in the department of pain; the major diagnosis (men 28.9%; women 27.7%) was neuropathy. The most frequently prescribed single analgesic was morphine (52.2%); the most frequently prescribed two-drug combination was morphine plus fentanyl (50.8%). Pethidine, however, was the most frequently prescribed analgesic in the neurology (78.0%) and plastic surgery (50.0%) departments. Conclusion To decrease malaise and addiction in patients with CINCP, Taiwan's physicians need more education on narcotic analgesics, and greater professional cooperation to develop therapeutic guidelines that will improve pain care for patients with CINCP.

Academic research paper on topic "Long-term usage of narcotic analgesics by chronic intractable noncancer pain patients in Taiwan from 2003 to 2012"

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Journal of the Formosan Medical Association (2015) xx, 1-6

ORIGINAL ARTICLE

Long-term usage of narcotic analgesics by chronic intractable noncancer pain patients in Taiwan from 2003 to 2012

I-Chen Cheng, Chih-Shiuh Chang, Wen-Ing Tsay*

Division of Controlled Drugs, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan, ROC

Received 2 February 2015; received in revised form 31 July 2015; accepted 4 August 2015

Background/Purpose: Chronic pain is a common and important medical problem worldwide. Patients with chronic intractable noncancer pain (CINCP) are treated primarily with narcotics. We analyzed the characteristics of patients with CINCP and the pain prescriptions of Taiwan's physicians.

Methods: We enrolled 644 patients from 66 hospitals approved by the Taiwan Food and Drug Administration to use long-term narcotics for CINCP between 2003 and 2012. Results: The majority (61.8%) of patients were 40—49-year-old men who had been treated with pethidine more often than with fentanyl in the 20—49 years age group. More than 50% of CINCP patients live in northern Taiwan, and most were treated in the department of pain; the major diagnosis (men 28.9%; women 27.7%) was neuropathy. The most frequently prescribed single analgesic was morphine (52.2%); the most frequently prescribed two-drug combination was morphine plus fentanyl (50.8%). Pethidine, however, was the most frequently prescribed analgesic in the neurology (78.0%) and plastic surgery (50.0%) departments. Conclusion: To decrease malaise and addiction in patients with CINCP, Taiwan's physicians need more education on narcotic analgesics, and greater professional cooperation to develop therapeutic guidelines that will improve pain care for patients with CINCP. Copyright © 2015, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.

KEYWORDS

chronic intractable noncancer pain (CINCP); long-term use; opioids

Conflicts of interest: The authors have no conflicts of interest relevant to this article.

* Corresponding author. Division of Controlled Drugs, Food and Drug Administration, Ministry of Health and Welfare, 161-2, Kunyang Street, Nangang, Taipei 11561, Taiwan, ROC.

E-mail address: wening@fda.gov.tw (W.-I. Tsay).

http://dx.doi.org/10.10167j.jfma.2015.08.001

0929-6646/Copyright © 2015, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.

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Introduction

Chronic pain is a common and important medical problem worldwide. The American Pain Society Clinical Guidelines1 define chronic noncancer pain as "back pain, osteoarthritis, fibromyalgia, and headache." The United States National Institutes of Health categorize pain as "acute pain, chronic cancer pain, and chronic intractable noncancer

pain (CINCP)," all of which can affect physiological function and produce adverse psychological effects such as depression and other negative emotions.

Patients with CINCP are treated primarily with narcotic analgesics. To prevent iatrogenic addiction caused by inappropriate long-term narcotic prescriptions for CINCP, the Taiwan Food and Drug Administration (TFDA) has stipulated clinical standards and guidelines for prescribing

Table 1 Demographic characteristics and diagnoses of patients with CINCP (chronic intractable noncancer pain) in Taiwan between 2003 and 2012.

Variables3 Male (n = 398) Female n = 246) Tota (N = 644) P

n (%) n (%) N ( %

Age (y)b <0.001*

<19 4 (1.0) 3 1.2) 7 1.1)

20-29 28 (7.0) 13 5.3) 41 6.4)

30-39 117 (29.4) 46 18.7) 163 25.3)

40-49 126 (31.7) 60 24.4) 186 28.9)

50-59 47 (11.8) 34 13.8) 81 12.6)

60-69 33 8.3) 25 10.2) 58 9.0)

70-79 30 (7.5) 36 14.6) 66 10.2)

>80 13 3.3) 29 11.8) 42 6.5)

Geographical areab <0.001*

North 197 (50.1) 129 51.4) 326 50.6)

South 112 28.5) 94 37.5) 206 32.0)

Central 64 (16.3) 23 9.2) 87 13.5)

East 20 5.1) 5 2.0) 25 3.9)

Medical department13 0.253

Pain 214 (54.2) 151 60.6) 365 56.7)

Internal medicine 54 (13.7) 30 12.0) 84 13.0)

Other departmentsc 29 (7.4) 17 6.8) 46 7.2)

General surgery 30 7.6) 10 4.0) 40 6.2)

Anesthesiology 24 6.1) 16 6.4) 40 6.2)

Neurosurgery 17 4.3) 13 5.2) 30 4.7)

Orthopedics 11 2.8) 4 1.6) 15 2.3)

Plastic surgery 8 (2.0) 4 1.6) 12 1.9)

Neurology 8 (2.0) 4 1.6) 12 1.9)

Narcoticsb 0.134

Morphine 249 55.0) 140 47.9) 389 52.2)

Fentanyl 70 (15.5) 62 21.2) 132 17.7)

Pethidine 63 (13.9) 35 12.0) 98 13.2)

Buprenorphine 39 8.6) 26 8.9) 65 8.7)

Codeine 32 7.1) 28 9.6) 60 8.1)

Opium 0 (0.0) 1 0.3) 1 0.1)

Type of pain diagnosed3 <0.001*

Neuropathy 136 (28.9) 75 27.7) 211 30.7)

Chronic pancreatitis 95 20.2) 12 4.4) 107 15.6)

Other pain 29 6.2) 48 17.7) 77 11.2)

FBSS 42 8.9) 33 12.2) 75 10.9)

Fracture, osteoarthritis 38 8.1) 36 13.3) 74 10.8)

Spinal cord injury 43 9.1) 24 8.9) 67 9.7)

Low back pain 15 3.2) 13 4.8) 28 4.1)

Autoimmune diseases 8(1.7) 18 6.6) 26 3.8)

Hematological diseases 11 2.3) 12 4.4) 23 3.3)

*p < 0.05.

FBSS = failed back surgery syndrome. a Each noncancer pain patient may be prescribed two or more opioids and might have two or more comorbid diseases. b x2 test.

c Other departments included urology, occupational and environmental medicine, and obstetrics and gynecology.

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Long-term use of narcotic analgesics

these drugs. We analyzed the characteristics of patients with CINCP and the CINCP prescriptions of physicians in Taiwan. This information will be used to formulate national policy for the long-term use of narcotic analgesics by patients with CINCP.

Methods Patients

Sixty-six hospitals that were approved for long-term use of narcotics to treat CINCP reported 644 new patients to the TFDA's Review and Approval Committee on Controlled Drugs for Medical Use (RACCDMU) between 2003 and 2012. That information was used for this study. Between 2003 and 2009, there were <100 new cases per year, but since 2010, there have been >100 new cases per year. The patients with CINCP were those not relieved from pain after they had been given other medications or treatments; thus, long-term narcotic analgesic formulations containing morphine, codeine, pethidine, fentanyl, and buprenor-phine were used. These patients had been diagnosed and treated in regional or higher-level hospitals and reported to the controlled drug review committee of that hospital for approval, and then narcotic analgesics could be continued. All hospitals in Taiwan are required to report to the TFDA each case for which any narcotic analgesic is prescribed.

Statistical analysis

Demographic characterizations and narcotic analgesics prescribed by physicians were analyzed using the SPSS version 18.0 software (SPSS Inc., Chicago, IL, USA). c2 tests were used to compare sex and other categorical variables. Significance was set at p < 0.05.

Results

Most (61.8%) patients with CINCP were male; the mean age for men was 45.9 years and that for women was 53.8 years (Table 1). The highest percentage of narcotic analgesics was used by men (31.7%) and women (24.4%) in the 40—49 years age group; however, a higher percentage of women aged > 50 years used them. A c2 test showed a significant difference (p < 0.001) in age distribution between men and women. Most of the patients with CINCP were from northern Taiwan (male, 50.1%; female, 51.4%). The c2 test also showed a significant (p < 0.001) difference between men and women in geographical area. Most patients (male, 54.2%; female, 60.6%) were treated in the pain department, but the sex distribution was not significantly different. The prescribed narcotic analgesics were mainly morphine (male, 55.0%; female, 47.9%), fentanyl (male, 15.5%; female, 21.2%), and pethidine (male, 13.9%; female, 12.0%), but the prescription percentages were not significantly different by gender. The types of pain diagnosed were primarily neuropathy (male, 28.9%; female, 27.7%), chronic pancreatitis for men (20.2%), and fracture for women (13.3%). A c2 test showed a significant (p < 0.001)

Figure 1 Narcotic analgesics used in different age groups of noncancer pain patients in Taiwan between 2003 and 2012.

difference between men and women in this category (Table 1).

Morphine was the most prescribed narcotic analgesic in all age groups except for the 70—79 years age group, for which fentanyl was most often prescribed. Fentanyl was the second most prescribed. Pethidine was prescribed more than fentanyl in the age groups 20—29 years, 30—39 years, and 40—49 years, but for those who were aged <19 years and >50 years fentanyl was prescribed more often than pethidine (Figure 1). Buprenorphine was prescribed more for those aged >50 years than for those aged <49 years, and codeine was prescribed more for those who were aged <19 years and >50 years.

For 81.0% of the cases, only one narcotic analgesic was prescribed, and for 15.0% of the cases, two were prescribed (Figure 2). The most prescribed one-drug regimens were morphine (52.2%) and fentanyl (18.9%), and the most prescribed two-drug regimens were morphine plus fentanyl (50.8%), and then morphine plus pethidine (18.6%) or buprenorphine (15.3%; Table 2).

Figure 2 Number of narcotic analgesics prescribed for patients with chronic intractable noncancer pain (CINCP) in Taiwan between 2003 and 2012.

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Table 2 Narcotic analgesics prescribed for patients with chronic intractable noncancer pain (CINCP) in Taiwan between 2003 and 2012.a

One (n = 581) Two (n = 59) Three (n = 4)

Narcotic % Narcotic Narcotic % Narcotic Narcotic Narcotic %

analgesic analgesic analgesic analgesic analgesic analgesic

Morphine 52.2 Morphine Fentanyl 50.8 Morphine Fentanyl Buprenorphine 25.0

Fentanyl 18.9 Morphine Pethidine 18.6 Morphine Codeine Pethidine 50.0

Pethidine 10.5 Morphine Buprenorphine 15.3 Morphine Fentanyl Pethidine 25.0

Buprenorphine 10.3 Fentanyl Buprenorphine 1.7

Codeine 8.1 Fentanyl Pethidine 6.8

Morphine Codeine 3.4

Codeine Pethidine 3.4

a Every patient with CINCP may be prescribed more than one opioid.

The narcotic analgesics prescribed for patients with CINCP varies by medical department, by physician, and by patient. Morphine was most often prescribed in all departments but neurology and plastic surgery, which most often prescribed pethidine ( 78.0% and 50.0%, respectively; Figure 3).

Discussion

We found that the majority of our patients with CINCP were male. According to TFDA statistics, from 1999 to 2007, almost twice as many men (63.7%) as women ( 36.3%) with CINCP were long-term narcotic analgesic users, indicating that fewer women than men were treated for pain.2 According to Ho et al3 and Chang,4 more male than female patients sought treatment. In addition, compared with patients in general, patients with CINCP required more

treatment and spent more on medication. Moreover, they also reported that the differences between men and women were significant (p < 0.001). Our findings support their results. However, there is one study5 that reports a higher prevalence of chronic pain in women than in men in Taiwan. This inconsistency might be attributable to the lower levels of physical strength and bone—muscle loading in women than in men, hence the greater effect of chronic pain.2 It is also possible that social, cultural, economic, and political factors might have contributed to the lower percentage of women who asked for treatment.6

Chang4 showed that 15—44-year-old patients with CINCP used more medical treatments than did older patients, and Ho et al3 reported that 58% of 40—65-year-old patients with CINCP were hospitalized; again, our findings support theirs. The middle-aged population (somewhere between 40 years old and 65 years old, depending on the source) is an important workforce segment in society; thus, should

Figure 3 Distribution of prescribed narcotic analgesics to the patients with chronic intractable noncancer pain (CINCP) in different medical departments. Every patient with CINCP may be prescribed more than one opioid.

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Long-term use of narcotic analgesics 5

CINCP affect the quality of life of this group of people, it would cause a great loss in the workforce. Ho et al3 also stated that the interference index of pain decreased from 8/10 to 4/10, which shows that narcotic analgesics significantly reduced pain.

We found that most patients with CINCP had been diagnosed with neuropathy—e.g., postherpetic neuralgia and diabetic neuropathy—chronic pancreatitis, and failed back surgery syndrome (FBSS), in that order. Postherpetic neuralgia usually persists for >3 months and is extremely difficult to treat. Because the mechanisms are complex and involve the peripheral and central nervous systems, the pain might manifest as burning, itching, and stabbing sen-sations.7 Treatments include medication, laser therapy, and nerve blocks.8 Regular treatment can control and attenuate the symptoms of CINCP.

Chronic pancreatitis is characterized by the destruction of pancreatic tissue structure and damage to the endocrine and exocrine function, which is caused by intermittent inflammation, and then develops into sustained chronic pain. A previous study reported that the prevalence of pancreatitis is ~3.5—4/100,000 people per year, is most frequent in 35—55-year-olds, and commonly causes severe pain.9 Although patients with pancreatitis can be treated with endoscopy or surgery, not all surgical procedures yield significant improvement. If the pain seriously affects work or social function, then long-term narcotic analgesics to control the pain become necessary.

One study10 found that the failure rate for back surgery has not declined in the past several decades. With increasing rates of spine surgery, the number of patients with FBSS has increased. In our study, FBSS accounted for 10% of patients with CINCP, which indicated that FBSS is one of the major problems for which long-term narcotic analgesics are used. Because only a few fully recover after back surgery, narcotic analgesics were needed to relieve pain. Another study11 reported that in 2249 (1.41%) of the 159,494 controlled inspections of cases involving narcotic analgesics and psychotropic drugs that the TFDA made from 2002 to 2011, the percentage of inappropriate prescriptions was even lower at 0.1%, which shows that the government believes that the reasonable prescription of controlled drugs is important. Regular inspections of inappropriate prescriptions are made each year to reduce patient addiction based on the long-term use of narcotic analgesics.

One study12 on the narcotic analgesics used in the United States between 1997 and 2007 reported that morphine was the most popular, that the popularity of morphine and fentanyl combined was increasing, and that the popularity of pethidine was decreasing. A similar study in Taiwan13 also reported that between 2002 and 2011, the popularity of morphine and fentanyl combined was increasing, whereas the popularity of pethidine was decreasing.

In Taiwan, the third most widely used narcotic analgesic for pain relief in patients with CINCP was pethidine, which is addictive. Its pain-relieving effect was not better than other narcotic analgesics according to pharmacological studies. Moreover, because its active metabolite, norpe-thidine (normeperidine), is a neurotoxin, using pethidine long term can cause adverse side effects such as seizures. Advanced countries in Europe and America have excluded pethidine as a first-line drug. In 2011, the TFDA published

pethidine clinical guidelines for Taiwan.14 These guidelines mention pethidine abuse and addiction caused by inappropriate use in Taiwan and other countries. Cross analysis of the departments and drug prescriptions in our study showed that pethidine was most often used in the departments of internal medicine, general surgery, neurology, and plastic surgery. According to the clinical guidelines, pethidine is indicated in only a few contexts.14 Pethidine is easily abused and should never be taken with alcohol or other opioids.15

The American Society of Interventional Pain Physicians developed a guide for using opioids for CINCP drugs.16 It established a policy for physicians and the legal sector in the United States. The United States Drug Enforcement Agency pointed out that physicians should fully understand narcotic analgesics. In clinical situations, if narcotic analgesics are indicated as the best treatment for pain, then the drug should be provided to relieve the pain of the patient.17 The American Chronic Pain Association (ACPA) published the ACPA Resource Guide to Chronic Pain Medication & Treatment18 in 2014 to offer patients drug-related information to "relieve the fears that can interfere with receiving maximum benefits from such treatment and medications. Information can also prevent unrealistic expectations that can lead to disappointment or even worse, a bad outcome."18 The American Pain Society and the American Academy of Pain Medicine systematically reviewed evidence and convened multidisciplinary expert meetings on pain management.1 The recommendations presented in these clinical guidelines for using long-term opioid therapy to attenuate CINCP provide (1) patient selection and risk stratification, (2) informed consent and opioid management plans; explain how to (3) initiate and titrate long-term opioid therapy, (4) use methadone, (5) monitor patients on long-term opioid therapy, (6) prevent and manage opioid-related adverse effects, (7) use chronic opioid therapy in pregnancy; and discuss (8) dose escalations, (9) driving and work safety, (10) identifying a medical home and when to obtain consultation, and (11) managing breakthrough pain.1

Unlike most other countries, the TFDA has published a user guide for using narcotic analgesics in medical practice and issues reference announcements on opioid prescriptions for physicians. A study19 on narcotic analgesic use in two medical centers in Taiwan reports that most physicians not specialized in anesthesiology, including those in surgery, internal medicine, oncology, and other specialties, are not sufficiently knowledgeable about narcotic analgesics and have negative attitudes about using them. Thus, they concluded that it is necessary to strengthen Taiwan physician education about pain medicine so that patients with CINCP can be properly cared for. In Taiwan, Schedule 1 and Schedule 2 narcotics can be manufactured or imported only by the TFDA. In the future, new ingredients and new formulations of narcotic analgesics from abroad can be introduced in Taiwan at the proper time, to offer physicians a better choice of prescriptions for patients with CINCP, to improve treatment quality, to reach effective pain control, and to protect patient health.

The TFDA user guide is a reference for legal institutions such as the courts and for physicians. In most other countries, standards are set by professional societies,

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associations, or councils. In the future, Taiwan can also follow the latter model and, in cooperation with these groups of medical professionals, develop a more comprehensive guide and reeducate physicians and the general public.

The data in this study were collected from medical institution reports to the TFDA. The cases were limited to patients with a first-reported new diagnosis of CINCP. These patients were also Review and Approval Committee on Controlled Drugs for Medical Use-approved long-term users of narcotic analgesics, which might not be representative of the general situation throughout Taiwan nor account for patients weaned off opioids or lost to follow-up. In addition, the data entered by medical staff might be incomplete owing to missing values.

This study is one of a few conducted on the national CINCP data analysis in recent years. Although the variables were limited, the findings offer a full picture of current patients with CINCP in Taiwan. The major patient group is male, middle-aged, living in northern Taiwan, treated primarily in a department of pain, has a major diagnosis of underlying neuropathy, and has most likely been prescribed morphine. It is necessary to strengthen cautionary statements and health education to patients, to offer necessary drug-use counseling, and to reduce the negative side effects of depression and opioid addiction in patients. Physicians need more education about prescribing narcotic analgesics, and need to cooperate more with groups of medical professionals to develop guidelines and manuals that will strengthen their ability to provide adequate care to patients with CINCP. Because only limited narcotic analgesics are available in Taiwan, new gradients and new drug formulations should be introduced when necessary, to offer more choices to physicians who treat patients with CINCP. To improve pain management and the quality of patient care, the public, too, needs to be educated about narcotic analgesics. In addition, our opioid management regulations should be updated to the new standards developed in other countries so that we can teach both our physicians and patients about the positive and negative impact of narcotic analgesics for treating CINCP. More thorough epidemiological studies are needed to understand more about patients with CINCP.

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