Kevin L. Zacharoff, M.D.
Globally, it was estimated that a total of 365 million prescriptions were written for opioids in 2005, with 235 million of those written in the United States. A significant proportion of them were for the treatment of chronic pain. In the USA, 20% of prescriptions for opioid therapy were for over 30 days’ duration1. Today, the number of prescriptions for opioids is an even higher number.
Opioids are often considered as the gold standard for treating chronic pain when other analgesics do not achieve adequate pain control, but adverse effects can sometimes compromise their therapeutic potential. The gastrointestinal tract is a significant site of opioid-related adverse effects due to various factors. These include, but are not limited to, the presence of opioid receptors, whose activation can disrupt motility and secretion, thereby inhibiting normal bowel function. This unintended action commonly causes bothersome gastrointestinal side effects, the most common being constipation. A meta-analysis2 in 2004 found that in randomized-controlled trials of non-cancer patients receiving opioids for moderate-to-severe pain, 41% experienced constipation, with individual studies estimating from as low as 14%, to as high as 90%. Some reasons for this discrepancy might be differing definitions of constipation, e.g., the number of bowel movements per week, or including discomfort associated with constipation. Additionally, it can be difficult to estimate the prevalence of constipation caused by opioid therapy in cancer patients because there are many other factors that may also induce constipation.
Accompanying signs and symptoms of constipation can include:
- Formation of hard dry stools
- Painful defecation
- Incomplete evacuation
- A sensation of ano-rectal bowel obstruction
In addition to a high occurrence rate, opioid-induced constipation (OIC) can be one of the most debilitating adverse effects associated with the use of opioid therapy for the management of chronic pain.3,4 Patients with OIC do not only suffer from a broad range of symptoms. They often complain of a seriously negative impact on the quality of their life (QOL) and the daily activities they can perform. Ironically, the burden of OIC can sometimes even lead patients to alter or abandon their opioid medications, potentially sacrificing its analgesic efficacy. Patient dissatisfaction stems not only from the direct impact of the opioids, but also in many cases from the side effects of treatments taken to relieve the constipation.
In view of the rate of occurrence and potential impact on patient QOL, it seems prudent that constipation prophylaxis should be considered whenever initiating opioid therapy. It is also important to consider that several other confounding factors may aggravate OIC during the initial phase of treatment for moderate to severe pain: dehydration, confusion, other concomitantly prescribed medications, and immobility.
There are a number of ways that OIC can be prevented by various forms of prophylaxis, and treatment.
- Clinicians should review patients’ pain medication requirements regularly, inquire about experience with adverse effects, and encourage frank and open dialog about any side effects.
- Non-pharmacologic strategies:
- Increased dietary fiber and fluid intake
- Encouraging activity
- Encouraging attempts at a daily bowel movement at the same time every day
- Stool softening agents
- These may have limited efficacy due to decreased motility, and they should be administered with appropriate amounts of fluid
- Osmotic laxatives, such as mannitol or sorbitol, can be effective in palliation of opioid-induced constipation, as they produce an osmotic-directed influx of fluid into the small intestine, thus increasing peristalsis as well as softening stool.
- Peristalsis-inducing agents
- Agents such as senna and bisacodyl often work well with softening agents. They rely predominantly on their ability to stimulate the myenteric plexus directly. Increase the dosage as the dosage of opioid increases; these agents should not be given on an as-needed basis, but should be continued unless diarrhea occurs. If diarrhea does become a problem, decrease the dosage of laxative or softener until the patient is comfortable.
- Bulk-forming laxatives may have a lesser role for non-ambulatory patients, since a bulk mass may predispose these patients to obstruction or potential impaction.
- Opioid antagonists
- These are thought to produce laxation in patients on chronic opioid therapy due to a mechanism of action theorized to reside within the myenteric plexus. These agents should be used with caution, as they may promote systemic opioid reversal, and pain crisis and opioid withdrawal may occur.
- Opioid rotation
- Patients who experience OIC while taking a particular opioid may benefit from opioid rotation using one of two distinct methods of rotation:
- Use of an alternative opioid
- Opioid cross-tolerance is incomplete, and switching to an equianalgesic dosage of a different opioid may allow for continued analgesia with the potential for a lower likelihood of adverse effects, such as OIC
- Different route of administration
- The same opioid, may have a direct local effect, and changing to parenteral or transdermal administration, instead of oral administration, may partially alleviate the symptoms
Although symptomatic management can provide relief for some patients, there is clearly a need for new therapies that act upon the underlying mechanisms of OIC without deactivating the intended analgesic effects. Agents that specifically target the underlying cause of OIC are currently under investigation for routine ambulatory use. The availability of these investigational agents may provide additional treatment options for patients on chronic opioid therapy.
Opioid-induced constipation can, at a minimum be a bothersome adverse effect for patients who receive chronic opioid therapy. Although it is sometimes considered counter-productive to treat the side effects of a medication with additional medications, in this situation it is considered to be an appropriate practice in order to maintain a balance of adequate pain and symptom management.
Once there is a decision to include an opioid as part of the treatment plan, it is important to obtain a thorough history of the patient’s exposure to the agent or class of agent, the side effects they have experienced, as well as their baseline bowel habits. By anticipating OIC the clinician may confidently select the most appropriate agents to alleviate these symptoms.
A corresponding version of this article that is appropriate for your patients, titled "Constipation: A common side effect of opioid use" is now available at www.painaction.com.
- IMS Health National Prescription Audit.
- Kalso E. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112:372–80.
- Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am Journal of Surgery. 2001;182:11S–8S.
- Walsh TD. Prevention of opioid side effects. Journal of Pain and Symptom Management. 1990;5:362–7.