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Long-Acting Opioids for Severe Chronic Daily Headache
Posted April 2001

The daily use of opioids for chronic daily headache is controversial. Studies have shown that some patients obtain relief and improved quality of life with long-acting opioids.

Medication options for patients with severe, refractory chronic daily headache (CDH) are limited and include opioids; amphetamines; monoamine oxidase inhibitors with or without tricyclics; beta blockers, or calcium blockers; triptans; and dihydroergotamine.  The daily use of opioids for nonmalignant pain such as CDH remains controversial.

Clinical Evaluations: A number of studies have evaluated long-acting opioids in patients with severe, refractory CDH.  In one study, 24% of patients reported moderate relief and 27% reported excellent relief after 6 months of treatment with low doses of methadone.  Patients who continued to take methadone had significantly improved work performance, spousal relationships, and relationships with children or friends.

According to another study, 36% of patients receiving controlled-release oxycodone hydrochloride (Oxycontin) obtained moderate or excellent relief after 6 months. The other 64% had discontinued this treatment because of lack of efficacy or intolerable side effects.  As in the methadone study, the patients who continued treatment had greatly enhanced quality of life. The daily dose of oxycodone averaged 32 mg. in divided doses. In a study using sustained-release morphine (Kadian), 51% of patients reported moderate or excellent relief after 6 months. This particular form of morphine is extremely long lasting and provides smooth, even blood levels. The usual dosage was low, average 40 mg/d. A retrospective study of 302 patients who had been prescribed long-acting opioids for CDH found that after at least 9 months of therapy, only 13% of patients had chosen to continue use of the opioids. The 87% of patients who discontinued the opioids did so primarily because of lack of efficacy or side effects. Although the long-term success rate in this study was low, quality of life was greatly enhanced for those patients who were able to continue treatment.  In this study, 8% of the patients met the criteria for prescription opiate abuse, necessitating discontinuation of the medication.

Results after 3 years have been reported from a prospective long-term schedule opioid study. Of the original 83 patients, 41% remained in the program for the 3 years. Eight percent of the patients who remained on scheduled opioids for the 3 years improved by more than 50%. Interestingly, the investigators claimed that after 1 month of therapy, they could predict which patients would do well and which would do poorly with the long-acting opioids.

Advantages and Disadvantages of Long-Acting Opioids:
Although success rates with long-acting opioids are low, all previous treatment modalities had failed, and the patients have few remaining options.  Long-acting opioids offer a number of advantages for treating chronic pain: avoidance of the “end-of-the-dose” phenomenon, with “mini-withdrawals” throughout the day; maintenance of stable blood levels; consistent dosing no more than 2 or 3 times a day; reduction of the obsession with medication that engulfs patients on as-needed dosing; avoidance of the acetaminophen or aspirin that is included in many of the short-acting preparations; and reduction of the risk of addiction.

A disadvantage of these medications is the stigma attached to certain medications such as methadone. Furthermore, in states where triplicate prescriptions are utilized, most physicians do not order these forms and cannot prescribe the long-acting opioids.  The prolonged half-life is usually an advantage. However, with methadone, the unpredictability of blood levels can lead to overdose and death, particularly if patients overuse methadone at the onset of therapy. The opioids should not be used as the sole modality but should be part of a biopsychosocial approach. Such techniques as biofeedback, psychotherapy, exercise, physical therapy, relaxation, or yoga also need to be utilized.  However, many of the patients do not obtain relief when nonpharmacologic options are used alone.

Predicting Success
It is difficult to predict which patients will respond to long-acting opioids. The ideal candidate for this regimen would be a patient with severe, refractory CDH who has no significant psychiatric illness, particularly severe anxiety or a personality disorder; previously had a positive response (without overuse) to short-acting opioids; and has a stable family and support situation.  Unfortunately, many patients with severe, refractory CDH do not satisfy all of these criteria, yet some will do well on long-acting opioids, even with preexisting psychiatric illness or abuse of previous medications. Patients with moderate or severe personality disorders, bipolar illness, or severe anxiety rarely succeed with long-term opioid therapy.

Opioid Abuse
The addiction rates in our studies have varied between 3% and 13%. In assessing addiction, Diagnostic and Statistical Manual, 4th edition, and World Health Organization criteria are better suited to psychiatric patients than to headache patients. We need better guidelines for detecting prescription opioid abuse in the headache population.

Following are some criteria that may be useful:

  1. The patient and the physician spend almost all of the office time discussing the opioid medication.
  2. There is an overwhelming concern and obsession for the drug.
  3. The patient calls the office frequently and creates disturbances revolving around the opioid medication.
  4. The patient calls early for refills.
  5. There are calls with questionable stories about what happened to the medication and why the patient needs an early refill.
  6. There is concurrent use of street drugs, such as cocaine and marijuana, or use of alcohol.
  7. The patient hoards or sells the drug.
  8. The patient obtains similar medications (such as opiates or sedatives) from other physicians.
  9. The patient increases the dose without discussing the increase with the treating physician.

Qualification as a prescription opioid abuser depends on the extent and frequency with which a patient displays any of the listed criteria. However, even a single instance of abuse should signal a warning to the physician.

Physical dependence and tolerance often develop in long-term opioid users. In my experience, it is important to make every attempt not to accelerate doses.

It may be helpful to add adjunctive nonopioid medications, switch to a different opioid, or temporarily discontnue opioid use. The fear of disciplinary action remains a problem for physicians prescribing opioids. Medical malpractice concerns are, of course, always present. In prescribing daily opioids, the physician should maintain meticulous monitoring of medication; good record keeping; informed consent; careful initial evaluations and continuing reevaluations; and, demonstration of adequate efficacy.

For a small number of patients with severe, refractory CDH, long-acting opioids greatly improve quality of life. However, even a single instance of abuse should signal a warning to the physician. With proper patient selection, close monitoring, and limiting of doses, long-acting opioids deserve a role in the treatment of severe CDH.