Benefits and Risks of Opioids for Chronic Pain

Managing Your Arthritis / Benefits and Risks of Opioids for Chronic Pain Management – Johns Hopkins Arthritis Center – July 31, 2012 – by Michael Clark, M.D., M.P.H.

This article from a respected medical institution comes to completely different conclusions than the CDC guidelines.

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 healthcare to the patient suffering with chronic pain.

Fears of regulatory pressure, medication abuse and the development of tolerance create a reluctance to prescribe opioids and many studies have documented this “underutilization”.

Surveys and open label clinical trials support the safety and effectiveness of opioids in patients with chronic non-malignant pain.  

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.


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.

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

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 musculoskeletal pain conditions that were resistant to codeine, anti-inflammatory agents and antidepressants.

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.

Risk 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.

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 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%.

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

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.

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/postoperative settings.

Side Effects

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

Discontinuation of Opioid Treatment

If treatment is unsuccessful, it should be discontinued and patients carefully monitored to minimize physiological withdrawal symptoms such as










muscle twitches

abdominal cramps

and anxiety.

Although it is generally not possible to avoid discomfort completely, the goal of detoxification is to ameliorate withdrawal.

Clonidine, an alpha-2-adrenergic agonist that decreases adrenergic activity, is commonly prescribed.

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.


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 [opioid] 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.

#I’ve listed the references for this reasonable article that suggests opioids as a good medication for pain of many kinds.


Arkinstall W, Sandler A, Goughnour B, et al: Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial. Pain62:169-178, 1995.

Dellemijn PL, Vanneste JA: Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain. Lancet349:753-758, 1997.

Moulin DE, Iezzi A, Amireh R, et al: Randomised trial of oral morphine for chronic non-cancer pain. Lancet347:143-147, 1996.

Schug SA, Merry AF, Acland RH: Treatment principles for the use of opioids in pain of nonmalignant origin. Drugs42:228-239, 1991.

Turk DC, Brody MC, Okifuji EA: Physicians’ attitudes and practices regarding the long-term prescribing of opioids for non-cancer pain. Pain59:201-208, 1994.

Watt JW, Wiles JR, Bowsher DR: Epidural morphine for postherpetic neuralgia. Anaesthesia 51:647-651, 1996.

Simpson RK Jr, Edmondson EA, Constant CF, et al: Transdermal fentanyl as treatment for chronic low back pain. J Pain Symptom Manage14:218-224, 1997.

Raja SN, Haythornthwaite JA, Pappagallo M, Clark MR, Travison TG, Sabeen S, Royall RM, Max MB. A Controlled Trial on the Analgesic and Cognitive Effects of Opioids and Tricyclic Antidepressants in the Management of Postherpetic Neuralgia. Pain (In review).

Porter J, Jick H: Addiction rate in patients treated with narcotics. N Eng J Med302:123, 1980.

Kouyanou K, Pither CE, Wessely S: Medication misuse, abuse and dependence in chronic pain patients. J Psychosom Res43:497-504, 1997.

Fishbain DA, Rosomoff HL, Rosomoff RS: Detoxification of nonopiate drugs in the chronic pain setting and clonidine opiate detoxification. Clin J Pain8:191-203, 1992.

Polatin PB, Kinney RK, Gatchel RJ, et al: Psychiatric illness and chronic low back pain. Spine18:66-71, 1993.

U.S. Department of Health and Human Services, Agency for Health Care Policy and Research, Clinical Practice Guidelines for Acute Pain Management: Operative or Medical Procedures and Trauma, AHCPR Publication Number 92-0032. Rockville, MD. February 1992.

The Federation of State Medical Boards of The United States, Inc. Model Guidelines for the use of controlled substances for the treatment of pain. S D J Med52:25-7, 1999.

Heiskamen T & Kalso E.: Controlled-release oxycodone and morphine in cancer related pain. Pain73:37-45, 1997.

Rapp SE, Egan KJ, Ross BK, et al: A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia. Anesth Analg82:1043-1048, 1996.


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