To determine which severe, refractive chronic daily headache patients are appropriate for long-acting daily opioids.
This was a retrospective study accomplished by chart review and patient interviews with the neurologist.
This study was done at the Robbins Headache Clinic and all patients were long-term patients at the Clinic.
Three hundred and two patients (302), ages 23 to 59, were all long-term patients at the Robbins Headache Clinic. Refractive chronic daily headache was the primary diagnosis for each of the patients. Each patient had been placed on methadone or Oxycontin. The patients had been refractive to the standard therapies.
Main Outcome Measures
The patients were interviewed as to side effects, efficacy, and quality of life.
Thirty-nine of 302 (13%) patients continued on the opioids long-term (for at least nine months). The 263 patients who discontinued the opioids did so primarily due to lack of efficacy and/or side effects. Patients with no identifiable psychiatric illness were more likely to do well. Forty-four percent (44%) of the 39 patients who continued long-term on the opioids did not have psychiatric illness. Patients with anxiety occasionally overused
the opioids due to their anxiety. Methadone was more likely to decrease anxiety than was Oxycontin. The opioids eased depression in certain patients. In others, depression was increased; this was particularly observed during withdrawal. Borderline and narcissistic personality disorder patients did not do well on the opioids; several patients with histrionic personality disorder did well long-term. While only 39 patients did well long-term, quality
of life was considerably enhanced in these people. Work, home and social life were significantly improved in the patients who were able to continue on the opioids.
The medication options for patients with severe, refractive chronic daily headache (CDH) remain limited. The choices include: opioids, amphetamines, monoamine oxidase inhibitors (with or without tricyclics, beta blockers, or calcium blockers), daily triptans or DHE, etc. The use of daily opioids for nonmalignant pain, such as CDH, remains somewhat controversial. Previous studies have demonstrated that, in a small number of refractive headache patients, opioids can result in a greatly enhanced quality of life. Most of the patients on opioids do not do well for the long term. The patients in the current study were either methadone, averaging 10 mg. per day, or Oxycontin, averaging 32 milligrams per day. This study was done in order to determine which patients may be suitable candidates for long-term opioid therapy.
Subjects and Methods
The 302 patients, ages 23 to 59, were all long-term patients at the Robbins Headache Clinic. Refractive chronic daily headache was the primary diagnosis for each of the patients. Most patients also had concurrent migraine. The standard medication therapies had all failed with these patients and included: NSAIDs/calcium channel blockers/beta blockers/Depakote/antidepressants (including MAOIs)/Sansert/stimulants/triptans, etc. These patients had also been refractive to nonmedication strategies such as acupuncture, psychotherapy, physical therapy, massage, pain management strategies, exercise, etc.
The patients and charts were reviewed retrospectively after at least nine months of therapy by the treating neurologist. The patients were either on methadone, averaging 10 mg. per day, or Oxycontin, averaging 32 mg. per day.
39 out of 302 patients (13%) continued on the opioids long term (for at least nine months). The 263 patients (85=7%) who discontinued the opioids did so primarily due to lack of efficacy and/or side effects. Twenty-four patients (8%) displayed enough addictive behavior to qualify for "prescription opiate abuse" and the medication was discontinued.
Patients with no identifiable psychiatric illness were more likely to do well. Seventeen of 39 (44%) did not have psychiatric illness.
Many of the patients stated that opioids did decrease their anxiety; however, this did not necessarily translate into fewer headaches. Patients with anxiety occasionally tended to overuse the opioids due to the anxiety. The methadone was more likely to decrease anxiety than the Oxycontin. The Oxycontin, while helping anxiety in some, was stimulating and increased anxiety in others. Many of the patients did describe the "rush/tranquil/tired" triad characteristic of narcotics; methadone was less likely to produce initial euphoria than was Oxycontin. Several patients did note that with the narcotics their panic disorder was improved, but it is not justifiable to utilize the medication for this purpose. Thus, anxious patients may benefit secondary to decreased anxiety, but this can lead to overuse. If the headaches did not also decrease significantly, the opioid was discontinued.
The opioids eased depression in some patients via either a direct effect or by decreasing the headache pain. The patients generally stated that it was because the headaches were better that depression was eased. In a few patients, the opioid caused or increased depression; this was also apparent in a number of patients during withdrawal of the medication. Methadone was more likely to increase depression that Oxycontin, particularly during withdrawal. Several bipolar patients did well long-term; increased mania was not observed. As a group, patients with a diagnosis of bipolar were more likely to overuse the opioids.
Four (4) patients with borderline personality disorder were placed on the opioids; all were taken off due to misuse of the mediation. Patients with narcissistic personality disorder did not do well, primarily due to misuse of the medication. The patients with narcissistic personality disorder generally did not feel that they had to abide by restrictions on the medications, even after signing an "Opioids Contract." Two patients with histrionic personality disorder, and one with avoidant personality disorder did well long-term on the opioids.
Quality of Life
While only 39 patients (13%) overall did well long-term, quality of life was considerably enhanced in these people. After years of incapacitating headaches, frustrated by lack of efficacy of the usual medication regimens, they felt that work, home, and social life were significantly improved.
Previous Opioid Use and Abuse
Virtually all of the 302 patients had previously been exposed to opioids; a positive response to short-acting opioids (codeine, hydrocodone, etc.) was a good indication that they would do well with the longer-acting opioids. Previous opioid overuse did not always accurately predict who would overuse the methadone or Oxycontin; four patients who did well long-term had previously been treated for addiction to short-acting opiates. However, in general, the patients who previously had overused short-acting opiates were more likely to overuse the long-acting ones as well.
Twenty-four patients (8%) qualified for "prescription opiate abuse,"
necessitating discontinuation of the methadone or Oxycontin. The patients more likely to overuse the mediations were those with: borderline or narcissistic personality disorder (and, to a lesser degree, other personality disorders as well), severe anxiety, previous opiate abuse, previous drug or alcohol abuse (particularly recent), and unstable or abusive family situations. However, a number of patients who abused the opioids did have supportive spouses and
stable family situations. The age of the patient was not a factor in prescription opiate abuse.
Out of the 302 patients in this study, 30 (13%) remained on the opioids long term. Most of the 263 patients who discontinued the medication did so either due to lack of efficacy and/or side effects. No psychiatric illness was identified in 17 out of 39 (44%) of the patients who did well long-term.
Anxious patients occasionally overused the opioids due to their anxiety; methadone was more likely to decrease anxiety than was Oxycontin. In some patients, the opioids decreased depression, either through direct mechanisms or via alleviating the pain. In a few patients depression was increased, particularly during withdrawal. While several bipolar patients did well long-term, as a group they were more likely to overuse the opioids.
All four patients with borderline personality disorder were taken off of the opioids due to addictive behaviors. Patients with narcissistic personality disorder did not do well. The signing of an "Opioids Contract" did not seem to deter opiate abuse. Several patients with histrionic personality disorder did well.
A previous beneficial effect from short-acting opioids was indicative of benefit from longer-acting opioids as well. Patients who had overused short-acting opioids were more likely to abuse methadone or Oxycontin. However, a few patients previously treated for addiction to short-acting opiates did well long-term on methadone or Oxycontin. The opioids were discontinued in 8% of the patients due to prrescription opiate abuse." Overuse of the opioids was seen more often in patients with: borderline or narcissistic personality disorder, severe anxiety, previous opiate abuse, and previous drug or alcohol abuse. In addition, poor support systems or unstable family situations rendered it more likely to overuse the opiates. However, a number of patients who did abuse the opioids had stable family situations with supportive spouses.
Many severe, refractive chronic daily headache (CDH) patients do not adequately respond to our "usual" ministrations. Where do we go with these patients? All of the current "end-of-the-line" medication choices are hazardous. In a small number of these people opioids are the only choice that they have in order to live with any reasonable quality of life. The economic impact alone of untreated chronic nonmalignant pain is enormous. Pain is at the root of one quarter of sick days lost in the workplace. Despite this, chronic nonmalignant pain and, in particular CDH, remains undertreated. Reasons for this include: (1) the health care system places pain relatively low in its scale of priorities; (2) patients and physicians have fears about side effects and addiction that are not always justified; (3) physicians fear of the wrath of medical boards, DEA, and the courts; and (4) insufficient knowledge about the treatment of long-term nonmalignant pain.
The health and psychological consequences of untreated chronic pain are staggering; quality of life suffers greatly when the pain is not under control. Suicide is always a risk in this population. Pain is one major reason for requests from patients for physician-assisted suicide.
Several previous studies have evaluated daily long-acting opioids for severe CDH. While success rates are relatively low, the patients have few options and have failed all of the previous treatment modalities. The advantages of long-acting opioids in treating chronic pain are several: (1) avoidance of the "end-of-the-dose" phenomenon, with "mini-withdrawals" throughout the day; (2) maintenance of stable blood levels; (3) consistent dosing two or, at most, three times per day, decreasing the obsessiveness with medication that engulfs patients on PRN dosing; (4) methadone, Oxycontin, MS Contin, Duragesic patches, etc. avoid the acetaminophen and aspirin that is included in many of the short-acting preparations; and (5) decreased risk of addiction. These medications do have several disadvantages, particularly with the stigma attached to certain medication, such as methadone. In the states where triplicate prescriptions are utilized, most physicians do not order these forms and cannot prescribe the long-acting opioids. The longer half-life is usually an advantage. However, with methadone the unpredictability of blood levels and build-up of medication in the tissues can lead to overdoes and death. The opioids should not be used as the sole modality; they should be part of a "biopsychosocial" approach. Biofeedback, psychotherapy, exercise, physical therapy, relaxation or yoga, etc., also need to be utilized. However, many of the patients have failed when these non-medication options are used by themselves.
It is difficult to predict who will do well with the long-acting opioids. The ideal candidate for this regimen would be a patient with severe, refractive CDH who: (1) has no significant psychiatric illness, particularly severe anxiety or a personality disorder; (2) previously had a positive response (without overuse) to short-acting opioids; and (3) has a stable family and support situation. Unfortunately, many patients with severe, refractive CDH do not satisfy all of these criteria, and some of these patients will do well on long-acting opiods, even with pre-existing psychiatric illness or abuse of previous medications.
In assessing addiction, DSM IV and WHO criteria are better suited to psychiatric patients. We need improved guidelines for "prescription opiate abuse" in the headache population. The following are some of the criteria that may be useful in assessing opiate abuse: (1) the patient and physician spend almost all of the office time discussing the opiate 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 opiate medication; (4) the patient is calling 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) concurrent use of street drugs, such as cocaine and marijuana, or use of alcohol; (7) hoarding or selling the drug; (8) obtaining medications that are similar (such as opiates or sedatives) from other physicians; and (9) increasing the dose without discussing this with the treating physician. To qualify as a prescription opiate abuser, it is the degree and frequency with which patients display any of the above criteria. The above abuses, even once, should serve as a warning to the physician.
Physical dependence and tolerance will develop in long-term opioid patients. It is vital to not accelerate doses in these patients. The patients need to accept a certain amount of pain, and, at times, we need to add adjunctive medications, such as low doses of hydroxyzine or tricyclics in lieu of accelerating the opioid dose. Occasionally, it is helpful to switch opioids periodically in order to limit the daily dose. However, the withdrawal period and changeover period often is very difficult. Occasionally, it may be useful to use the Catapres-TTS patch (clonodine), 0.1 mg. per 24 hours, in opioid patients in order to limit the dose or to ease withdrawal. However, this does add side effects, particularly sedation and hypotension. In a small number of opioid patients, dextromethorphan, an OTC antitussive agent, may have some role in limiting the opioid use. Some patients need to withdraw off of the opioid for periods of time and have a "drug holiday" for one to two months.
The fear of disciplinary action remains a problem for physicians in prescribing these opioids. Medical malpractice concerns are, of course, always present. In prescribing daily opioids, the following should be present: meticulous monitoring of medication, good record-keeping, informed consent, careful initial evaluations and continuing re-evaluations, and demonstration of adequate efficacy. However, the signing of opioids contracts does not seem to deter abuse.
For a small number of severe, refractive chronic daily headache patients, long-acting opioids greatly increase quality of life. With proper patient selection, close monitoring, and limiting of doses, long-acting opioids do deserve a role in the treatment of severe chronic daily headache.