Benefits and Risks of Opioids in Arthritis Management

by Michael Clark, M.D., M.P.H.

Introduction

Chronic pain is a significant public health problem and frustrating to everyone affected by it, especially the elderly who feel that healthcare has failed them but wish to remain in their own homes, live independently, and avoid becoming a burden to others. Psychiatrists offer skills with pharmacological and psychological treatments now recognized as effective in the management of chronic pain. Recent advances in the treatment of chronic pain include the diagnosis and treatment of psychiatric co-morbidity, the application of psychiatric treatments to chronic pain, and the development of interdisciplinary efforts to provide comprehensive health care to the patient suffering with chronic pain. The psychiatrist can provide expertise in the examination of mental life and behavior, an understanding of the individual person and the systems in which they interact, and facilitate the integration of the delivery of medical care with other health care professionals and medical specialists. However, not all patients with pain require psychiatric evaluation, which should be reserved for patients who have severe symptoms, multiple treatment failures, or problematic behaviors such as substance abuse or noncompliance. The majority of patients can be treated exclusively and successfully by their primary physician.

The use of opioids as a treatment for non-malignant chronic pain remains a subject of considerable debate. Until recently, opioids were reserved for use only in the treatment of acute pain and cancer pain syndromes. Non-malignant chronic pain was considered to be unresponsive to opioids, or the use of opioids was associated with too many risks. Fears of regulatory pressure, medication abuse and the development of tolerance create a reluctance to prescribe opioids and many studies have documented this “underutilization”. Fortunately, recent studies of physicians specializing in pain, as well as those who do not, have shown that prescription of long-term opioids is increasingly common. Surveys and open label clinical trials support the safety and effectiveness of opioids in patients with chronic non-malignant pain.(refs 1-6)

Efficacy

Recently, several controlled trials have documented the effectiveness of opioids in the treatment of chronic non-malignant pain such as low back pain, post-herpetic neuralgia, and painful peripheral neuropathy. These studies support the use of opioids to provide direct analgesic actions and not just to counteract the unpleasantness of pain. In the treatment of chronic low back pain, transdermal fentanyl significantly decreased pain and improved functional disability.(ref 7)

In a randomized, double-blind, placebo controlled trial, controlled-release oral opioids were more effective than tricyclic antidepressants in decreasing the pain of post-herpetic neuralgia.(ref 8) Other studies have documented the presence of opioid receptors in the peripheral tissues activated by inflammation. These findings suggest a role for opioids in the treatment of chronic inflammatory diseases such as rheumatoid arthritis and connective tissue disorders.

The use of opioids for the treatment of non-inflammatory musculoskeletal conditions is more confusing. A randomized double-blind, placebo-controlled crossover study of oral controlled release morphine was performed in patients with chronic regional, soft tissue musculosketal pain conditions that were resistant to codeine, anti-inflammatory agents and anti-depressants. Although patients experienced a decrease in pain, they did not experience significant psychological or functional improvement.(ref 3) In contrast, another randomized, placebo-controlled clinical trial in patients with chronic non-malignant pain found that treatment with controlled-release codeine reduced pain as well as pain-related disability.(ref 1)

Risks of Abuse and Dependency

  • studies found that all patients who developed problems with opioid use had a prior history of substance abuse
  • maladaptive behaviors such as stealing or forging prescriptions rarely occur in patients suspected of dependence

Terms such as addiction, misuse, overuse, abuse, and dependence have been used inconsistently to describe various behaviors, making interpretation of many research studies difficult. Nonetheless, studies investigating the risk of opioid abuse have been reassuring. In one study of 12,000 medical patients treated with opioids,(ref 9) only 4 patients without a history of substance abuse developed dependence on the medication. Dependence, in this article, was defined as a psychological rather than physical dependence involving a subjective sense of need for a specific psychoactive substance, either for its positive effects or to avoid negative effects associated with its abstinence. This now is the approved definition of the American Society of Addiction Medicine for psychological dependence.

Dependence used alone SHOULD be reserved for physiological dependence that leads to a stereotyped withdrawal syndrome upon discontinuation of the medication, particularly in the field of pain medicine. Unfortunately, psychological dependence is generally confused with many terms and therefore best avoided in my opinion. The psychiatric literature is somewhat inconsistent with the substance abuse literature, e.g., the Diagnostic and Statistical Manual, edition IV, (DSM-IV) defines substance dependence as a more serious form of substance abuse. This maladaptive pattern of substance use is characterized by tolerance, withdrawal, overuse, craving, inability to cut down, and excessive preoccupation with respect to obtaining the substance. Substance abuse is characterized in the DSM-IV by use leading to failure to fulfill roles/responsibilities, use in hazardous situations, legal problems resulting from use, and use despite negative consequences.

Other studies of chronic opioid therapy found that all patients who developed problems with opioid use had a prior history of substance abuse. Even when the diagnosis of dependence is suspected in patients taking opioids for chronic pain, maladaptive behaviors such as stealing or forging prescriptions rarely occur.

In a study of patients attending a clinic specializing in pain management, almost 90% of patients were taking medications.(ref 10) Opioid analgesics were prescribed to 70% while antidepressants and benzodiazepines were being taken by only 25% and 18%, respectively. In this population, 12% met DSM-III-R criteria for substance abuse or dependence, however, the misuse and abuse of medications was not limited to just psychoactive substances. In a review of 24 studies of drug and alcohol dependence in patients with chronic pain, only 7 studies used standard accepted criteria for dependence and addiction. The prevalence of dependence/addiction in these studies ranged from 3.2-18.9%.(ref 11) In a study of chronic low back pain patients, 34% developed a substance use disorder, and in all cases, a history of substance abuse was present before the onset of their chronic pain.(ref 12) In addition, individuals with a previous history of substance abuse prior to study entry were found to be at increased risk for recurrence during treatment for chronic pain. The mechanism of relapse back to substance abuse in these patients is not well understood and probably involves multiple factors; however, a cycle of pain followed by relief after taking medications is an example of operant reinforcement of their future use. Therefore, if the patient has unresolved pain and perceives a lack of commitment to treatment by the physician, they are at high risk for relapse into substance abuse. The best prevention of relapse comes from aggressive treatment of pain and close follow-up to monitor the patient for signs of relapse into dependence/addiction.

Abuse harmful use of a specific psychoactive substance

Addiction continued use of a specific psychoactive substance despite physical, psychological, or social harm

Misuse any use of a prescription drug that varies from accepted medical practice

Physical dependence physiological state of adaptation to a specific psychoactive substance characterized by the emergence of a withdrawal syndrome during abstinence, which may be relieved in total or in part by readministration of the substance

Psychological dependence subjective sense of need for a specific psychoactive substance, either for its positive effects or to avoid negative effects associated with its abstinence

Guidelines to Minimize Risks and Optimize Benefits

Source Type of Information
Agency for Health Care Policy and Research (1992); (ref 13)
Cancer Pain Management Guideline Panel 1994
guidelines for the treatment of acute pain and cancer pain
The Federation of State Medical Boards (1999)(ref 14) guidelines for the treatment of chronic pain
The American Academy of Pain Medicine and the American Pain Society a consensus statement: “The Use of Opioids for the Treatment of Chronic Pain”
American Geriatric Society (1998) clinical practice guidelines for the management of chronic pain in older persons

Short Versus Long-Acting Opioids

Opioids with a short duration of analgesic activity generally create more problems than they solve. These medications must be taken multiple times a day often interfering with the patient’s daily activities including sleep. But more importantly, opioids with short duration result in serum levels of considerable variability. Analgesia is difficult to achieve and side effects are more likely to occur. Controlled release (CR) formulations of morphine, oxycodone, and fentanyl are now available with a hydromorphone preparation soon to be released. Multiple studies describe the more favorable pharmacokinetic and pharmacodynamic profiles of these medications. However, a recent study comparing CR oxycodone and CR morphine found comparable analgesia but more vomiting occurring with CR morphine and more constipation with CR oxycodone.(ref 15) Transdermal fentanyl is an effective analgesic with generally fewer side effects than oral medications and over 90% of patients choosing to continue the medication after completion of a study trial. Tolerance leading to dosage escalation is generally not a problem in the management of patients taking long-term opioids. Standard tables comparing the drugs are not very helpful in dose conversion, which really varies particularly because of variability with chronic administration versus use acute/post-operative settings. Street value of the various opioid drugs varies by region of the country and there is no consistent data. In general, most addicts like to use drugs that have high potency or fast onset of action. Therefore, the controlled release drugs like Transdermal fentanyl have the lowest abuse potential. Oral controlled release opioids like Oxycontin can be crushed to destroy the matrix and they become the equivalent to immediate release forms.

Side Effects

The most common side effect of chronic opioid therapy is constipation secondary to decreased gastrointestinal motility.

However, concerns about potential cognitive impairment are more often the reason opioids are not prescribed, particularly in the elderly. However, the available research has not demonstrated deleterious effects on cognition by neuropsychological testing or electroencephalography (EEG) except in patients prescribed multiple types of medications, especially sedatives and hypnotics. Elderly patients are more susceptible to delirium than younger patients. Although no studies have examined this risk of delirium in chronic pain syndromes treated with opioids, post-operative patients are less likely to develop cognitive impairment with fentanyl than morphine. A similar study found that cognitive performance was poorer in patients receiving hydromorphone compared to those receiving morphine.(ref 16) Many metabolites of opioids are excreted by the kidney increasing toxicity in the elderly. Creatinine clearance should be monitored to minimize potential toxicity.

Discontinuation of Opioid Treatment

No treatment should be continued without benefit. If treatment is unsuccessful, it should be discontinued and patients carefully monitored to minimize physiological withdrawal symptoms such as yawning, rhinorrhea, piloerection, perspiration, lacrimation, mydriasis, tremors, restlessness, vomiting, muscle twitches, abdominal cramps, and anxiety. The essential element for successful opioid detoxification is the gradual tapering of the dose. Opioid withdrawal is generally not dangerous except in patients at risk from increased sympathetic tone, such as those with increased intracranial pressure or unstable angina. However, opioid withdrawal is very uncomfortable and distressing to patients. Tapering opioids often results in exacerbation of the patient’s primary pain symptom (rebound pain). Increases in pain can occur even if the analgesic effects of opioid therapy had not been appreciable. Although it is generally not possible to avoid discomfort completely, the goal of detoxification is to ameliorate withdrawal.

Several non-opioid pharmacological agents are commonly used as adjunctive agents to provide patients additional relief from withdrawal symptoms. Clonidine, an alpha-2-adrenergic agonist that decreases adrenergic activity, is commonly prescribed. Clonidine can help relieve many of the autonomic symptoms of opioid withdrawal such as nausea, cramps, sweating, tachycardia, and hypertension, which result from the loss of opioid suppression of the locus ceruleus during the withdrawal syndrome. Other adjunctive agents include nonsteroidal anti-inflammatory drugs for muscle aches, Pepto-Bismol for diarrhea, anticholinergics for abdominal cramps, and antihistamines for insomnia and restlessness.

Summary

Opioids offer an appropriate and safe treatment for some but not all patients with non-malignant chronic pain. Experimental research and clinical experience are needed to define those patients most likely to receive specific benefits from treatment with opioids. The benefits of treatment are now being documented in controlled trials. Potential risks, including drug abuse and intolerable side effects mentioned above, appear to be manageable in most cases. Anyone with chronic pain who has failed traditional treatments should be considered for a trial of chronic long acting opioids. If they have neuropathic pain, then opioids are now worth considering as a first line choice, especially if the patient cannot tolerate antidepressants or anticonvulsants. A recommended approach is to start low and go slow with a willingness to increase the dose until the person becomes toxic or delirious, complains of intolerable side effects, or gets complete relief of pain. Because patients with chronic pain suffer many consequences of their illness, any treatment with the potential to improve their symptoms should be prescribed and the results carefully studied.

References

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Updated: July 31, 2012

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