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Long-Acting Opioids as Preventive Medicine
for Severe Headaches
Lawrence Robbins, M.D.
Posted May 2000

Preventive medications only help no more than half of those patients with chronic daily headache (CDH). The medication options for those, whose headaches have not responded to the usual preventives, remain limited. Long-acting opioids, taken as preventives several times per day, are one of the "end-of-the-line" options. In my experience, treating 450 severe CDH patients with these opioids, a small number of people (15 to 20%) achieve long-lasting relief, reporting a greatly enhanced quality of life. While the short-acting opioids, like hydrocodone, codeine, meperidine and propoxyphene, often lead to rebound headaches and overuse, this is rarely observed with the longer-acting opioids. Of course, prior to utilizing any stronger therapy, we must be sure that the patient is not experiencing rebound headaches from analgesics.

One drawback to short-acting opioids, lasting only several hours in the body, is that patients have a good effect, then rapidly come down, and have "mini-withdrawals" throughout the day, which can lead to overuse. Rebound headaches also can occur with these short-acting opioids. The smoother, longer-acting opioids give a much steadier level in the bloodstream, protecting against the ups and downs and rebound. A number of patients who experienced rebound headaches due to short-acting opioids have done well with the longer-acting formulations. Another disadvantage of the short-acting narcotics is that they contain acetaminophen or aspirin. The long-acting forms are pure narcotics, without these extra ingredients. The longer-acting opioids I have given to patients include MS Contin, Oramorph SR and Kadian (all forms of morphine), Oxycontin (oxycodone), and Dolophine (methadone). I have not had success with Duragesic (fentanyl).

When they are not overused, the opioids are safe medications. The major side effects that lead to discontinuation include constipation, nausea and fatigue. They have not been associated with weight gain, often seen with antidepressants, such as MAO inhibitors. When the usual daily preventives do not work, alternatives for patients with severe headaches include the MAO inhibitors, stimulants, daily DHE, or even daily triptans. The side effects of even several opioid tablets per day are generally less than those from most other headache preventives.

The doses must be kept low with the daily opioids. My patients have averaged daily doses of 40 mg. of morphine, 30 mg. of oxycodone, and 10 to 15 mg. of methadone. These are relatively low doses. It is necessary to achieve a balance between medication and headaches, and to strive not to over-medicate. If a low to medium dose decreases the pain by 40 to 80%, we may need to accept this level, keeping in mind that these patients had no relief from other daily headache preventives. Relief of pain by 40 to 80% is enough to greatly improve functioning and quality of life.

Each of the opioids has its pluses and minuses. The longest-lasting form of morphine is Kadian, which lasts 12 to 24 hours in the body. I dose this at 20 mg. (a low dose) twice per day. Patients often state they do not feel as if they are "on" a medication; they experience no "ups or downs," only pain relief. However, some people do better with MS Contin or Oramorph SR, 15 to 30 mg. three times per day. Oxycontin (oxycodone) is generally well tolerated, with pain relief lasting from six to twelve hours. Methadone causes more fatigue, and typically more severe withdrawal. However, methadone is the most effective medication for some patients. Despite its original development as a narcotic painkiller, methadone has been widely used to control heroin addiction. Thus, there is more social stigma associated with being prescribed methadone. On the other hand, methadone is much less expensive than the other long-acting opioids.

In some patients, the body develops tolerance to the narcotic and the patient needs increasing doses to achieve the same effect. Rather than increase doses, at times, we will discontinue the opioid for one to two months to restore efficacy. Another strategy is to switch to a different opioid. A small number of patients have remained on the same low-dose opioid for many years.

While dependency is to be expected after continuous use of an opioid, addiction to the long-acting opioids is relatively uncommon. Only 3 to 5% of people will show addictive behaviors. In treating chronic severe pain, dependence has to be accepted, but not addiction. Addictive behaviors include: accelerating the dose without discussion with the doctor; seeing multiple physicians for the same medication; obsessing about the supply; calling the physician with phony stories to obtain additional refills; selling or hoarding the drug; or concurrent use of other addictive or illicit drugs. It is the pervasiveness of these behaviors that labels the person "addicted" to the opioid. Previous addiction to short-acting opioids has proven to be only a mild risk factor for addictive behavior with the longer-acting ones. A number of patients, who previously had overused short-acting opioids, have done very well on the longer-acting ones, without addiction. Patients on daily opioids require close monitoring by the physician, with office visits every one to two months.

The opioids may ease depression in certain patients either by a direct effect, or by decreasing the headache pain. A few patients have become depressed as an adverse effect of the medication itself. It has been controversial and is generally not a good practice to treat depression or anxiety with opioids, because of the risk of addiction. However, among my patients who have continued on the long-acting opioids for a number of years, they report less depression and anxiety, along with enhanced quality of life. Most importantly, pain is decreased in these headache sufferers, and they function daily at a much higher level.

For those suffering with severe CDH, the usual treatments often are ineffective. It is not realistic to expect these people to accept no relief. For a small number of patients, the long-acting opioids offer a chance at a greatly enhanced quality of life.