On the one hand, there are many strong proponents of their use.^{1, 2} They tend to argue that opioids are an effective treatment for chronic pain and that fore-going their use is inhumane. Patients too are often strong advocates for their use.

On the other hand, there are valid concerns that make their use controversial. They are the following:

• Their questionable effectiveness for long-term use
• Tolerance
• Opioid-induced hyperalgesia
• Hormonal changes
• Mental cloudiness
• Physiological dependence
• Psychological dependence
• Addiction

The following briefly reviews these concerns about the long-term use of opioids for chronic pain.

Questionable effectiveness for long-term use

In their review of this research, Kroenke, Krebs, and Bair³ found that the use of opioid medications on a short-term basis are modestly better at reducing pain than placebo. However, they found that opioid medications were slightly less effective than non-narcotic pain medications on functional outcomes (i.e., helping patients to do more things).

There is little research on the long-term effectiveness of opioids for chronic pain.⁴ Ballantyne and Shin⁵ reviewed the literature on the effectiveness of opioid medications and found that opioids are likely ineffective when used on a long-term basis.

In their meta-analysis of the research, Martell, et al.,⁶ found that opioid medications are in fact no better than placebo when it comes to reducing pain.

Tolerance

Tolerance is when the body becomes adjusted to the use of opioid medications and as a result the medications lose their effectiveness over time. In short, the longer a patient takes opioid medications for pain the less effective the medications become. In actual practice, what this means is that, over time, patients commonly need periodic increases in their dose of opioids in order to get the same level of pain relief.

Tolerance is a significant problem. For most patients, it is not feasible to use opioid medications for pain on an indefinite basis. Assuming a normal lifespan, most patients eventually get so tolerant to opioids that the medications become ineffective. After five, ten, or fifteen years of use, the highest doses of opioids are no longer helpful. As such, when taking opioid medications on a long-term basis, patients buy pain relief today at the cost of their future well-being. Once having become tolerant to the highest doses of opioids, the medications will be ineffective down the road should there be a need for their use, like an altogether different injury or recovering from a surgery.

Opioid-induced hyperalgesia

Another significant problem associated with the long-term use of opioid medications is that opioid medications, when used over time, can actually come to increase pain rather than decrease pain. Patients often find it hard to believe. But, it is true. It’s called opioid-induced hyperalgesia.^{7, 8, 9, 10 "}Algesia" means sensitivity to pain and "hyper" is a prefix meaning above, beyond or excessive. What happens is that, when taking opioids over a long period of time, the nervous systems become more and more sensitive to pain and so patients subsequently experience more pain. Over time, patients complain that their pain is worsening even though tests or other evaluations show no overall change in the underlying medical problem that causes the pain.

The physical basis of opioid-induced hyperalgesia is not well understood. It is thought that changes occur in the brain or the dorsal horn of the spinal cord or both. In actual practice, it is often difficult to differentiate opioid-induced hyperalgesia from increasing levels of tolerance to medications. In most situations, patients and their providers will simply think that they are becoming increasingly tolerant to opioid medications and will increase their dose. It is hard to know whether the pain is worsening because of opioid-induced hyperalgesia or whether the medications are losing their effectiveness because of tolerance. Now, it may in fact be true that both are occurring. But opioid-induced hyperalgesia becomes evident when patients begin to taper off of their opioid medications. Their pain lessens!

Hormonal changes

Another issue is that chronic use of opioids can lead to changes in the levels of important hormones in the body. In both men and women, long-term use of opioids leads to low levels of testosterone¹¹ as well as other hormones.¹² These side-effects can then cause a number of other problems such as loss of sexual desire, reduced fertility, fatigue, depression, and osteoporosis.

Mental cloudiness

A common complaint of patients on long-term opioid management is that mentally they are not as sharp as they used to be. Cognitively, they are dulled. They say that their focus and concentration is limited. Healthcare providers use the term ‘mental cloudiness’ to refer to this sense of mental dulling.

Research shows that when using opioids on a long-term basis patients tend to have significantly lower scores on measures of concentration, short-term memory, timed performance and multi-tasking.^{13, 14, 15} 

Physiological dependence

When taking opioid medications over a long period of time, patients become physiologically dependent. The body becomes adjusted to having the medication in its system. As a result, patients become tolerant to the medication and will experience withdrawal symptoms if the medication is abruptly stopped. All patients develop physiological dependence when taking opioid medications over time.

Physiological dependence is different than addiction.addiction. The American Academy of Pain Medicine and the American Pain Society define addiction to opioid medications as a loss of control over the use of the medication or continued use of the medication despite real or potential harm to oneself.¹⁶ Even if patients never engage in any behaviors that are indicative of addiction, and take their medications only as prescribed, their bodies will develop physiological dependence.

Physiological dependence is also a concern. Many patients simply don’t like their dependency on the medication. There might be many situations in which patients inadvertently do not have access to their medication or to their provider. As a consequence, they go into withdrawal. This dependency produces a sense of vulnerability and fear. One might argue that the minimal effectiveness of opioid medications is not worth the dependent state of vulnerability and fear with which patients must live when taking such medications.

Psychological dependence

When patients use opioid pain medications on a long-term basis, they tend to develop subtle yet strongly held beliefs that lead to a loss of confidence in their own abilities to cope with pain. As such, they come to believe that it is impossible to successfully manage pain without the use of opioid medications. Moreover, they become unwilling to entertain alternatives to their use. As a consequence, patients come to overly rely on the medications long after they are no longer helpful. In other words, opioid medications foster psychological dependence.

This issue is difficult to talk about. It’s difficult because these beliefs are subtle and don’t really come to the foreground unless actually named. It’s also difficult to talk about because it’s a sensitive issue. It can evoke strong emotional reactions. Patients who are psychologically dependent on opioids view the notion that it is possible to manage pain well without opioids as ridiculous. When a healthcare provider raises the notion, they take it that the healthcare provider is incompetent. At other times, patients see it as evidence that the healthcare provider doesn’t understand what it’s like to have chronic pain. They can also see the notion that it is possible to manage pain well without opioids as invalidating the legitimacy of their pain. In any of these ways, patients can get angry. As described, it is a sensitive issue. However, the sensitivity is also indicative of psychological dependence.

Patients who are psychologically dependent on opioids rely on the medications long after they cease to be helpful. They tend to demonstrate tolerance to the medication, describing their pain as severe despite taking high doses of opioids. They may also remain disabled by pain, despite the use of opioid medications. Nonetheless, they swear that the medications are helpful. This disconnect between their subjective belief that the medications are helpful and the objective evidence of their reports of continued high levels of pain and disability is an indication of psychological dependence.

It bears remembering that most people with chronic pain do not manage their pain with opioid medications. In an epidemiological study, Toblin, et al., found that a quarter of the population has chronic pain; but among people with chronic pain, they found only 15% using prescription opioids to manage their pain.¹⁷ Now, it might be argued that the majority of people with chronic pain should be on opioids and that in fact it’s inhumane that in this day and age the majority of people with chronic pain are still being denied the use of such medications. But, that’s not what these researchers found when they asked people with chronic pain in the study. They found that the vast majority – 80% of them – were satisfied with their pain management. So, it’s true that the majority of patients with chronic pain manage their pain without opioid medications.

Patients who are psychologically dependent on opioid medications tend to believe that it is impossible. They are sensitive to the notion that it is possible and can get emotional when it is brought up. They lack an openness to any alternative to opioid medications. Lastly, they maintain the belief that the medications are helpful and necessary despite their continued reports of high levels of pain and despite the fact that they remain disabled.

Addiction

Addiction, of course, is also a significant problem. As earlier described, the pain management field defines addiction as a loss of control over the use of opioid medications or continued use of the medications despite harm. In the meta-analysis cited above, Martell, et al.,⁶ found that upwards of 20% of patients on opioid pain medications demonstrate problematic behaviors that are suggestive of addiction.

Conclusion

Opioid medications are helpful pain relievers for many purposes. Patients with terminal cancer pain use them with great benefit. Patients benefit from their short-term use when recovering from an acute injury or following a painful surgical procedure. However, the long-term use of opioid medications for chronic, noncancer pain remains controversial. While many advocate for their use as beneficial and humane, there are valid concerns about their long-term use. These are their questionable effectiveness when used on a long-term basis, tolerance, opioid-induced hyperalgesia, hormonal changes, mental cloudiness, physiological dependence, psychological dependence, and addiction.

References

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2. Passik, S. D., Heit, H., & Kirsch, K. L. (2006). Reality and responsibility: A commentary on the treatment of pain and suffering in a drug-using society. Journal of Opioid Management, 2, 123-127.

3. Kroenke, K., Krebs, E. E., & Bair, M. J. (2009). Pharmacotherapy of chronic pain: A synthesis of recommendations from systematic reviews. General Hospital Psychiatry, 31, 206-219.

4. Chou, R., Ballantyne, J. C., Fanciullo, G. J., Fine, P. G., & Miaskowski, C. (2009). Research gaps on use of opioids for chronic noncancer pain: Findings from a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. Journal of Pain, 10, 147-159.

5. Ballantyne, J. C. & Shin, N. S. (2008). Efficacy of opioids for chronic pain: A review of the evidence. Clinical Journal of Pain, 24, 469-478.

6. Martell, B. A., O’Connor, P. G., Kerns, R. D., Becker, W. C., Morales, K. H., Kosten, T. R., Fiellin. D. A. (2007). Systematic review: Opioid treatment for chronic back pain: Prevalence, efficacy, and association with addiction. Annals of Internal Medicine, 146, 116-127.

7. Angst, M. & Clark, J. (2006). Opioid-induced hyperalgesia: A quantitative systematic review. Anesthesiology, 104, 570-587.

8. Chen, L., Malarick, C., Seefeld, L., Wang, S., Houghton, & Mao, J. (2009). Altered quantitative sensory testing outcome in subjects with opioid therapy. Pain, 143, 65-70.

9. Hay, J., White, J., Booner, F., Somogyi, A., Semple, T., & Rounsefell, B. (2009). Hyperalgesia in opioid-managed chronic pain and opioid-dependent patients. Journal of Pain, 10, 316-322.

10. Mitra, S. (2008). Opioid-induced hyperalgesia: Pathophysiology and clinical implications. Journal of Opioid Management, 4, 123-130.

11. Vuong. C., Van Uum, S. H., O’Dell, L. E., Lutfy, K., Friedman, T. C. (2010). The effects of opioids and opioid analogs on animal and human endocrine systems. Endocrine Review, 31, 98-132.

12. Katz, N. & Mazer, N. A. (2009). The impact of opioids on the endocrine system. Clinical Journal of Pain, 25, 170-175.

13. Kamboj, Tookman, A., Jones, L. & Curran, H. V. (2005). The effect of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care. Pain, 117, 388-395.

14. Mintzer, M. Z., & Stitzer, M. L. (2002). Cognitive impairment in methadone maintenance patients. Drug and Alcohol Dependence, 67, 41-51.

15. Prosser, J., Cohen, L. J., Steinfeld, M., Eisenberg, D., London, E. D., & Galynker, I. I. (2006). Neuropsychological functioning in opiate-dependent subjects receiving and following methadone maintenance treatment. Drug and Alcohol Dependence, 84, 240-247.

16. American Academy of Pain Medicine and the American Pain Society. (1997). The use of opioids for the treatment of chronic pain: A consensus statement. Clinical Journal of Pain, 13, 6-8.

17. Toblin, R. L., Mack, K. A., Perveen, G., & Paulozzi, L. J. (2011). A population-based survey of chronic pain and its treatment with prescription drugs. Pain, 152, 1249-1255.

Date of publication: April 27, 2012

Date of last modification: October 5, 2019