Abstract
PREVALENCE OF MEDICATION OVERUSE
Migraine and other primary headaches cause significant disability in Canada. For some individuals medication overuse can exacerbate this disability, particularly in those with migraine. There is little information on the prevalence of medication overuse in the general population in Canada. Clinical experience would indicate that it is common and a major cause of headache-related disability. More information is available on medication overuse in patients with headache who are referred to neurologists. The Canadian Headache Outpatient Registry and Database (CHORD) study investigated the clinical characteristics of patients referred to six neurologists with a special interest in headache in Canada. These neurologists were located in five different Canadian metropolitan areas: Calgary, Alberta (W. J. Becker, A. G. Eloff), Richmond, British Columbia (Greater Vancouver area, G. F. Mackie), Ottawa, Ontario (S. N. Christie), Hamilton, Ontario (R. Giammarco) and Toronto, Ontario (M. J. Gawel). The discussion which follows will focus primarily on patients referred to neurologists/headache specialists in Canada.
In patients with migraine referred to headache specialists, 20.6% had medication overuse (1) as defined by Silberstein et al. (2). Based on this definition, patients were considered to be over-users if they took opiates, ergotamines or triptans on > 2 days/week, non-opiate combination analgesics on > 3 days/ week, or paracetamol/non-steroidal anti-inflammatory drugs (NSAIDs) on > 5 days/week. Medication overuse was not confined to the migraine population and occurred, for example, in 14.7% of patients referred with tension-type headache, 32% of patients with chronic headache attributed to head trauma and in 25% of patients diagnosed with new daily persistent headache (3). Of interest, of 216 patients with migraine who had headache on ≥ 15 days/month, only 48% were considered to have medication overuse.
It is important to note that according to current International Headache Society diagnostic criteria (4), medication overuse headache (MOH) cannot be diagnosed until a patient demonstrates resolution of headache or return to the previous pattern within 2 months after discontinuation of medication overuse. Although the data shown above tabulated the prevalence of medication overuse in patients referred to headache specialists in Canada, they did not indicate how many of these patients actually had MOH, because follow-up data were not available.
MEDICATIONS OVERUSED BY MIGRAINE PATIENTS
The symptomatic medications overused in the migraine referral population included virtually all medications used in the symptomatic treatment of migraine. Most patients overused more than one medication due to the frequent overuse of combination analgesics. The most commonly overused medications by far were medications in the paracetamol and NSAID category, but these medications were not commonly overused alone. Sixty-seven per cent of over-users overused medications in this class, but only 5% overused paracetamol alone, and 11% overused NSAIDs alone. The second most commonly overused drug category was the opiate category, with 42% of medication over-users overusing opiates. These were also usually overused in combination with other medications. Only 6% of over-users were overusing opiates alone (1).
The triptans were overused by 22% of over-users. Interestingly, they were often overused alone, and at 13% of over-users constituted the largest ‘single drug’ overuse group. Data collection for the CHORD study ended in January 2004, and one might speculate that the amount of triptan overuse may have increased since that time as the use of triptans has become more widespread.
Barbiturate-containing combination analgesics are still available in Canada, but are not in widespread use in many parts of the country. Only 8% of the over-users overused barbiturate-containing analgesics. Even by 2004, ergotamines were no longer widely used in Canada, and only 2.4% of over-users were overusing ergotamine.
ATTITUDES TOWARDS MEDICATION OVERUSE
In Canada, medication overuse is considered a major clinical problem and a significant source of headache-related disability. The problems posed by medication overuse have long been recognized. The Guidelines for the Diagnosis and Management of Migraine in Clinical Practice (5), published in 1997, highlighted the problem of medication overuse. Most neurologists would agree that patients should stop their medication overuse for several months to determine how large a role the medication overuse is playing in their chronic daily headache syndrome. Many family physicians also strongly discourage medication overuse, yet medication overuse remains common in the Canadian headache population. This may occur because family physicians become trapped into prescribing frequent analgesia in patients with difficult headache problems. Canadian headache specialists have published articles focusing on medication overuse in family physician journals for over a decade (6), but some family physicians still do not seem sufficiently aware of the problems that medication overuse can cause, particularly in migraine sufferers. The situation is also made more difficult in that not all chronic daily headache in migraine sufferers is driven by medication overuse. As noted above, only half of the patients with migraine and chronic daily headache in the CHORD study appeared to have medication overuse.
MEDICATION OVERUSE AND DEPRESSION
Many patients referred to headache specialists in Canada have psychiatric comorbidity. It is important that all physicians recognize this and understand that successful treatment may involve much more than simply focusing on the patient's headache. As measured by the Beck Depression Inventory-II, 17% of patients with episodic migraine in this referral population and 34% of patients with migraine and chronic daily headache had moderate or severe depression (7). Although depression was initially associated with medication overuse in our analysis (unadjusted odds ratio 1.90, 95% confidence interval 1.30, 2.76), after adjusting for other variables in the multivariable logistic regression model, this relationship was no longer significant. Patients with migraine and chronic daily headache (‘transformed migraine’) without medication overuse showed a prevalence of moderate or severe depression of 33%, compared with those with medication overuse who had a depression prevalence of 39%.
TREATMENT OF MEDICATION OVERUSE
A Canadian review of the management of MOH has been published (8). The treatment of migraine with medication overuse is difficult, and Canadian physicians struggle to treat these patients adequately. These issues were discussed at the Canadian Migraine forum, held in May 2006 (9). This forum brought together 24 health professionals and six patients with migraine from across Canada to discuss issues related to migraine management. The presentation on MOH at the forum pointed out that the cornerstone of MOH treatment is patient education regarding the disorder, and cessation of medication overuse. The overused medication can be stopped abruptly or in a tapering fashion, depending on the drug overused (10) and the amount of medication that is being taken. Because patients often worsen for a time before they begin to improve, especially with overuse of codeine-containing combination analgesics, various bridging medications including steroids, NSAIDS and dihydroergotamine are used by some neurologists, depending upon patient circumstances. Most patients are also given a migraine prophylactic medication, and careful attention is paid to providing appropriate symptomatic medications for severe headache attacks. Strict limitations on the frequency of use of these symptomatic medications are important, and diary documentation is very helpful to ensure that these are being met. For patients who are overusing analgesics, triptans can be very useful as symptomatic medications during the time of withdrawal, whereas dihydroergotamine can be useful if the patient is being detoxified from triptans.
The discussion at the forum (9) concluded that stopping medication overuse can be a very difficult experience for the migraine patient. If treatment is initially successful, relapse back into medication overuse can occur related to the severity of the underlying migraine disorder, various psychological stressors, and psychiatric comorbidity. Some patients develop overuse in the first place, or relapse again after successful treatment, because of fear that a migraine attack will disrupt their busy lives. They will medicate almost automatically at the first sign of anything wrong in order to treat pre-emptively a possible migraine attack. This habit can be hard to break and can easily lead to medication overuse in the patient with difficult migraine.
It was also felt important that most patients be clearly told that they are not drug addicts. This certainly is true for the great majority. In a recent population-based Canadian study it was found that, despite recurrent pain and the use of symptomatic medications by migraine sufferers, there was no difference in the 12-month adjusted prevalence of drug, alcohol or substance dependence in migraine subjects compared with non-migraine subjects (11). At the forum it was also felt that patients should be given realistic goals and be informed that they have about a 50% chance of major improvement with stopping medication overuse. Treatment is more difficult because there is no guarantee that cessation of medication overuse will result in significant improvement in the patient's headache, although it often does. There was concern, although direct evidence is lacking, that longstanding medication overuse might be more difficult to treat because of increasing degrees of central sensitization.
It is appropriate to advise patients with migraine to use their symptomatic medications early in their attack, but in patients with frequent migraine this can easily lead to medication overuse. Patient education, medical follow-up and the use of headache diaries that document medication use are essential to prevent these migraine patients from falling into medication overuse.
There are two shortcomings in the Canadian public healthcare system that can make treatment of the headache patient with medication overuse more difficult. The first is a relative shortage of in-patient beds, which makes it difficult to hospitalize for a sufficiently long period of time the minority of patients with MOH for whom out-patient detoxification is very difficult or impossible. The second is a relative lack of out-patient multidisciplinary headache programmes that might benefit patients with medication overuse and chronic daily headache, particularly those with psychiatric comorbidity, by teaching them the necessary skills to manage their headache syndrome successfully and by providing some of the support needed by these patients. However, further research is needed to demonstrate conclusively the efficacy of such programmes in this patient population, and to determine the type of programme that might be most effective. In the mean time, family physicians, assisted by neurologists and other consultants as necessary, will need to provide most of the care required by these patients.
At the forum, it was emphasized that patients with migraine need to develop good self-monitoring skills, including monitoring of their medication use. To this end, a website has been developed (headachenetwork.ca), which provides patients with general headache treatment information and also allows them to download a headache diary suitable for monitoring their symptomatic medication use.
Treatment of medication overuse headache in the patient with migraine is complex. There are times in a patient's life when it is very difficult to stop medication overuse. Patience on the part of the physician and the development of a strong physician–patient relationship can be helpful in this circumstance, and eventually the patient may be able to make the necessary lifestyle changes or put the necessary supports in place for detoxification to occur. Some patients may not be convinced initially that they must stop their medication overuse, but will gain more insight over time. Non-judgmental flexibility on the part of the physician is important so that a good outcome can eventually be achieved. At the same time, there appears to be a small minority of patients who may achieve their best function with daily opiate use. This is clearly a last resort, and, when necessary, this option is best pursued with long-acting opiates. It would seem advisable, however, that every patient with migraine and medication overuse be strongly encouraged to stop all medication overuse at least once for several months. This time period should be carefully documented with headache and medication diaries as the results of this test may well influence further treatment for many years to come. Finally, it needs to be recognized by both patient and physician that medication overuse has its own complications and medical hazards, e.g. gastrointestinal bleeding from NSAIDs, and this should factor into the decision making by the patient.
PREVENTION OF MEDICATION OVERUSE
Prevention of medication overuse is by far the best approach. Most patients with medication overuse who are referred to a specialist in Canada are taking prescription medications. However, in Canada, several combination analgesics containing up to 8 mg of codeine per tablet are available from pharmacists ‘over the counter’ without a physician prescription, and a significant number of patients develop overuse of opiate-containing combination analgesics with these medications. Better education of both pharmacists and physicians with regard to the levels of analgesic consumption that place migraine patients at risk for MOH is needed. More effective family physician education regarding headache management is needed, and some research has been done with various educational formats (12). The public at large also needs to be educated regarding this problem. In Canada today, some patients with migraine and medication overuse still tell the specialist upon referral that they were never made aware that frequent use of symptomatic medications could make their headaches worse.
In summary, MOH remains a very significant problem in Canada, and it will take a concerted effort by the public, health professionals and those who fund healthcare to provide better prevention and treatment for this problem. It can at times be difficult for patients to find a physician who will expend the time, energy and skill to help them escape from the prison of medication overuse. The patient with migraine and medication overuse often brings to the physician many difficult elements, including chronic pain, questions of addiction, and psychiatric comorbidities of anxiety and depression. In addition, in some patients migraine may be a progressive disorder (13), and cessation of medication overuse may not resolve their chronic daily headache. These difficult challenges, however, should not be met with either indifference or hostility to the patient's plight. As health professionals we must rise to meet the challenges that these patients present to us. At the same time, the patient's active participation in the treatment plan is essential to success. Health professionals must ensure that the patient is adequately informed and educated, but the efforts of the health professional alone are not sufficient for successful treatment.