Role of Sustained-release Opioids in Treating Chronic Pain
In the November/December 2007 issue of Practical Pain Management, Dr. Forest Tennant presented a thoughtful and detailed assessment of the role of sustained-release (SR) opioids in a primary care practice, describing when and how he recommends that PCPs transition chronic pain patients from immediate-release drugs such as hydrocodone/APAP to SR opioids.1 Given the critical importance of sustained release opioids in ambulatory pain treatment, I present my methods and experience in this article. Physicians who prescribe sustained release opioids should study the various methods used by other physicians to develop an optimal procedure for safety and effectiveness that fits their practice.
The subjects that need to be understood regarding the transition from short- to long-acting opioids are:
- Why it is desirable to treat round-the-clock pain with SR opioids
- The pharmacologic properties of long-acting and sustained-release opioids
- How to transition from short-acting to SR opioids
Why Make the Switch?
There are both safety and efficacy reasons for preferring SR opioids for chronic pain. The most commonly used short-acting opioids are combinations of hydrocodone or oxycodone with acetaminophen (and sometimes aspirin). The most frequently prescribed opioid analgesic is a combination of hydrocodone and acetaminophen (Vicodin, Lorcet, Norco). Regular Vicodin contains 5 mg hydrocodone and 500 mg acetaminophen. Pure mu opioid agonists (such as the drugs discussed in this article) have no ceiling analgesic effect and may be titrated as needed to achieve analgesia.2 There is no absolute upper limit of how much of an opioid is safe to take (as long as it’s titrated slowly to decrease the risk of respiratory depression)—but there is definitely a maximum dose of acetaminophen, above which liver toxicity may ensue. This maximum is generally accepted as 4 grams per day (that’s eight regular Vicodin or four Extra-strength Tylenol), but for patients who already have liver damage or who drink alcohol, it is lower. Patients who take more than the maximum safe daily dose of acetaminophen risk liver damage. In contrast, SR opioids are single-entity drugs containing only the opioid element.
Short-acting opioids typically have a plasma half-life of 2-3 hours, with a duration of action of 4-6 hours. At night, this often results in nocturnal awakening due to a resurgence of pain. Taking a sustained-release opioid in the evening is more likely to provide better sleep at night, as compared with repeated dosing of a short-acting opioid.3 When multiple doses are given, plasma levels of the drug follow a sine curve, going up and down several times over the 24 hours. At the peak, patients will get good pain relief but, at the trough, the pain is likely to return. Then the patient takes the next dose and the cycle continues. Rather than preventing pain, the patient is “chasing the pain” all day. Sustained-release opioids provide a more consistent blood level and more uniform pain relief. This can result in a lower 24-hour opioid dose than when the same drug is given in a short-acting form requiring multiple dosing.3 As pain specialists Drs. Richard Payne and Russell Portenoy wrote in 2002, “Short-acting opioids are characterized by a rapid rise and rapid decline in serum levels, which may be beneficial for the treatment of acute pain and breakthrough pain, whereas long-acting drugs or sustained-release formulations provide a more effective means of controlling chronic pain. Opioids with long half-lives or extended-release formulations are preferred for the management of chronic pain. These drugs may facilitate patient adherence with treatment regimens, increase convenience for caregivers, provide consistent levels of analgesia, and allow the patient to focus less on pain and pain medications.”4
Another potential problem with short-acting opioids relates to the mechanism of CNS euphoria. What causes a person to feel a “buzz” is not the concentration of a drug in the blood stream, but rather the rate of increase of the drug’s concentration in the brain. The faster the drug level rises, the more euphoria the person may feel. This is the reason that addicts and abusers like to crush a sustained-release opioid tablet and then inject it, which will get the drug into the brain more quickly. This, of course, is also the reason that recreational cannabis users prefer to smoke a marijuana cigarette than to eat a marijuana brownie. Marijuana smoke gets into the capillaries of the lung within seconds, and goes right up to the brain; marijuana in the stomach has to proceed throughout the digestive tract and only gradually gets into the blood stream. Some chronic pain patients, who are neither drug addicts nor abusers, report that when they take a short-acting opioid, they get not only some pain relief but they also feel better. Pain and addiction specialist Dr. Seddon Savage explains, “Some addiction researchers believe that the use of short-acting, acute-onset opioids may increase the risk of addiction, possibly as a result of enhanced reward stimulation, perceived by users as a rush or high. For this reason, when pain is more constant than episodic, use of long-acting medications may be preferred.”2
Finally, the goals of treating chronic pain consist primarily of reducing pain and improving function. Part of improving function is to decrease the patient’s focus on his or her chronic pain and on the medications. The ideal is to have the patient consider their pain pill the same way they consider, for example, their blood pressure pill—a medication to take once or twice a day and then get on with one’s life. This is the opposite of the relationship patients have with the short-acting opioids that they take multiple times a day, often watching the clock while waiting for the opportunity to take the next pill. The pain pills should not be the center of the patient’s life. Long-acting opioid preparations go a long way towards aiding in this goal.
What do you need to know about sustained-release and long-acting opioids? First, it is crucial to understand that a distinction needs to be made between methadone and the other commonly used SR opioids, such as sustained-release oral morphine, oxycodone, oxymorphone, and fentanyl patches. All except meth-adone are drugs with a short half-life, but which are packaged in a delivery system that releases them over an average of 12 hours (OxyContin, MSContin, Opana ER), 24 hours (Avinza, Kadian), or 3 days (Duragesic patches). Once they are released into the body, these drugs are metabolized over a several-hour period, the same as when given in a short-acting formulation—meaning they do not accumulate in the body when dosed every 12 hours, 24 hours, or 3 days as directed. If the dose of such drugs is increased every two days (three days for the fentanyl patch), the plasma concentration of the drug will not rise. From a safety perspective, therefore, the drug can be titrated upwards fairly quickly.