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10 Articles in Volume 14, Issue #3
Practical Guide To Safe Use of Nonprescription Pain Medications
Common Causes of Acute Abdominal Pain
Early Treatment of TMD May Prevent Chronic Pain and Disability
Insomnia: Focus on New Dosing Concerns In Women
Is Marijuana Use Associated With Non-adherence To Opioid Therapy—Insights Gained From Urine Drug Monitoring
New Evidence-Based Diagnosis Criteria for TMD
New Rating Scale Helps Evaluate Refractory Chronic Migraine Patients
The Effect of Prolonged Knee Extension Immobilization on Knee Active Range of Motion: A Case Study on Arthrofibrosis
Opioid Bias Hurts Pain Patients
Can misoprostol be used for refractory chronic constipation?

New Rating Scale Helps Evaluate Refractory Chronic Migraine Patients

There is a subset of chronic migraine patients who go on to develop refractory chronic migraines (RCM) and are perhaps the most difficult migraine patients to treat.

Headaches are the most common neurological disorder seen by primary care physicians.1 Migraines, characterized as unilateral, pulsating, severe headaches with or without aura, occur in up to 18% of adult women and 10% of men.2 Up to 4% of adults will develop chronic migraines, defined by the International Classification of Headache Disorders as chronic daily headaches for at least 3 months, occurring greater than 15 days per month, where at least 8 of the days are migrainous.2 However, there is a subset of chronic migraine patients who go on to develop refractory chronic migraines (RCM) and are perhaps the most difficult migraine patients to treat.3

In an effort to better understand and study this disorder, the American Headache Society has proposed a set of 5 diagnostic criteria for RCM, which are outlined in Table 1.4,5 Patients filling these criteria satisfy the diagnosis of chronic migraine but have failed adequate trials of both abortive and preventive migraine treatments. In addition, patients with RCM are more likely to have suffered from migraines over many years, have migraines more days per month, and have medication overuse headaches (MOH). RCM patients frequently suffer from a comorbid medication condition, such as irritable bowel syndrome (IBS), fibromyalgia, temporomandibular disorders (TMD), chronic pelvic pain, painful bladder syndrome, and chronic fatigue, as well as psychiatric comorbidities, such as anxiety, depression, bipolar spectrum, personality disorders, somatization, and post-traumatic stress disorders.3

To better measure the severity of the disorder, we developed a novel rating scale for RCM severity. In this article, we present the results of our 10-year study, as well as the use of the rating scale to evaluate patients with RCM.

Why Categorize Patients

RCM often is a debilitating illness, with an enormous impact on quality of life (QOL). Long-term outcomes for patients with RCM have not been thoroughly studied. In addition, RCM ranges in severity from mild to severe. For clinical and research purposes, it is important to categorize RCM patients according to severity. Knowing the severity of the disease helps clinicians better plan treatments. There are a number of major challenges clinicians face when dealing with RCM, with each diagnostic category requiring a different approach.3 These challenges include:

  • Determining the role of disability, and whether disability should help to define RCM
  • Determining how resistant to the myriad of treatments a patient has to be to be considered to have RCM
  • There is no accepted, identifiable biological marker for RCM
  • The degree of refractoriness can change over time, improving or worsening. What role does this varying severity play?
  • There are various subsets of RCM—post-traumatic headache, RCM with or without MOH, RCM with or without major psychiatric comorbidities, etc.

Study Design

From 2000 to 2010 at our headache center, we followed 129 patients (109 women) who were 18 years or older at start of study and who met criteria for RCM. The study design and the results of the study were recently published in the Journal of Headache Pain.6 A refractory scale of this author’s design was used for assessment. The scale ranges from 2 (least severe) to 10 (most severe) (Table 2).5,7-10 The patients were assigned a number between 2 and 10 at the start of the study and then were reassessed in 2010. The severity groupings were as follows: a score of 2, 3, or 4 was defined as mild RCM; a score of 5, 6, 7 was defined as moderate RCM; and a score of 8, 9, 10 was defined as severe RCM.

QOL was measured by adding pain, functioning, and mood scores (each on a 1-10 scale, with 1=best, 10=worst). The QOL rating scale ranged from 3 (best) to 30 (worst). Pain was assessed via a visual analog scale of 1 to 10 (10=worst). The patient’s ability to function was determined by the level of the work and/or home activities. Mood assessment included symptoms of depression, anxiety, and insomnia using the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria.

Because this was a retrospective study, treating physicians collected the data, which we then ‘‘de-identified’’ and collected as anonymous ‘‘batch’’ data. We obtained informed consent and consulted our local Institutional Review Board. To analyze if these pre–post scores differed across the 3 pain severity groups (mild, moderate, severe), we conducted a one-way analysis of variance (ANOVA). To determine if treatment was significantly effective at decreasing the level of pain and improving QOL, we calculated pre–post paired sample t tests for each severity group and then used Cohen’s effect size formula for paired sample t tests.

Study Results

Of the 129 patients included in the study, 24 (18.5%) were categorized as mild (average score, 3.79), 67 (52%) as moderate (average score 6.04), and 38 (29.5%) as severe (average score, 9.02). Table 3 summarizes the changes in QOL over the 10-year period. Overall QOL improvement was 33%. Broken down in more detail, of the mild RCM patients, 66% improved by 30% or more in QOL during the 10 years. In the moderate severity group, 57% improved by 30% or more, and in the severe group, 61% improved by 30% or more. QOL over 10 years was the same, or worse, in 4% of those in the mild group, 16% of those in the moderate group, and 18% of those in the severe group.6

Improvements in pain scores were even more dramatic (Table 4). Over the 10-year study period, pain levels declined by ≥30% in 80% of the mild RCM group, 72% of the moderate group, and 71% of the severe group. Pain levels were the same, or worse, over the 10 years in 4% of the mild group, 15% of the moderate group, and in 18% of the severe group.6

Overall, the results suggest that the treatment was effective in improving QOL and reducing level of pain for all severity groups. Most of the RCM patients (60%) had at least a 30% improvement in QOL, whereas 73% experienced a ≥30% improvement in pain levels. While the patients categorized as severe also improved over 10 years, they had significantly lower QOL and higher pain scores than patients categorized as mild or moderate.6

Effective Therapy

Overall, the medications that were the most effective over the 10-year period included: opioids (63%), triptans
(4/wk) (31%), butalbital compounds (17%), and onabotulinumtoxin A (Botox, 16%) (Table 5). The majority of opioid patients were taking long-acting opioids. Only 9 patients had worsening headaches due to opioid therapy. Patients who took triptans frequently were carefully screened and assessed for triptan-induced headache; patients who had increasing headaches due to triptans were taken off those drugs.6

Discussion

The refractory rating scale presented here is an initial attempt to classify RCM patients according to severity. A refractory scale may be beneficial for both clinical and study purposes. Patients with mild RCM generally will be easier to treat than those with severe RCM. Therapeutic studies on patients with RCM may be less likely to succeed if the patients have severe RCM versus milder RCM. The individual components of the scale reflect various elements of refractoriness, including comorbidities.

This author awarded more weight to ‘‘refractory to preventives’’ (2 points) or ‘‘refractory to abortives’’ (2 points) than to the other components (1 point each), primarily because refractoriness to preventive or abortive agents is a central hallmark of RCM. In virtually all of the published RCM classification papers, refractoriness to preventive agents and refractoriness to abortive agents are the main criteria for labeling a patient as having refractory headache.4,5 Therefore, each of those is more heavily weighted than the other components. One could easily argue that certain components of our proposed scale warrant 2 points instead of 1. Heavier weighting could be given to the number of years of chronic migraine, the number of days per month, and MOH. Future studies may address this.

Because the plasticity of the brain may be an important factor in refractoriness, it is important to include the length of time of headache (>10 y selected for this study). The average number of headache days per month is important, with ≥25 days probably being associated with a more refractory condition than 15 to 24 days per month. Those with headaches every day (defined as 30 d/mo) may deserve 2 points (as opposed to the current 1 point) in our scale. This is particularly true for those with constant (24/7, 365 d/yr) RCM, and this should be considered in future papers.

Comorbidities Play Major Role

Associated medical comorbidities, which often occur in those with chronic migraine, were included. These conditions may complicate treatment and add to the refractory nature of the disease. For this study, we included the following comorbidies: IBS, fibromyalgia, TMD, chronic pelvic pain, painful bladder syndrome, and chronic fatigue.

Psychiatric comorbidities, also commonly seen in RCM patients, certainly complicate treatment. Significant abuse in childhood may predispose one to RCM. Important comorbidities include anxiety, depression, the bipolar spectrum, personality disorders, somatization, and post-traumatic stress disorder.11,12 For this study, severe DSM-IV Axis I (affective disorders) or any Axis II (personality disorders) were considered important in contributing to the refractory nature of the disease.10

Disability also should be a part of a RCM scale. Those who function at a low level, at work or at home, often are more resistant to treatment. Patients exhibit a wide range of coping abilities and resilience. Resilience is a combination of nature and nurture; one can almost predict resilience based upon the shape of the serotonin transporter gene. This author believes that disability, or a chronically low level of functioning, renders it less likely that the patient’s RCM will improve. The level of functioning should factor into a RCM rating scale.

Medication Overuse

MOH is a remarkably complicated concept and a common cause of chronic daily headaches. MOH must be distinguished from medication overuse without resulting headache. It can be exceedingly difficult to determine who has MOH.8 For this study, we used IHS guidelines regarding MOH. Patients should be asked about all symptomatic treatments used, including over-the-counter analgesics. The prevalence of MOH in the general population is 1.4%; and two-thirds of all MOH patients are chronic migrainuers (prevelance, 0.9%).13

“Regular overuse” is defined as taking ergot, triptan, opioid, or butalbital analgesics on a regular basis >10 days per month, other non-opioid analgesics ≥15 days per month, or a total exposure of all acute (ie, abortive) drugs ≥15 days per month. The odds ratio of developing chronic migraine is approximately 2 in patients who use barbiturates >5 days per month and those who use opioids >8 days per month. Triptans and short-acting nonsteroidal anti-
inflammatory agents (NSAIDS) may be associated with MOH; dihydroergotamine (DHE) agents and long-acting NSAIDS (such as naproxen, diclofenac, ketoprofen and tramadol) rarely cause MOH. Treatment requires the withdrawal of offending agent(s); the strategy of withdrawal (ie, gradual, sudden, incorporating other agents such as long-acting NSAIDS, long-acting triptans, steroids, or methadone) depends on the medication(s) being overused. Bridge therapy often is employed because the headache initially worsens after discontinuation of an analgesic. If the patient is not already taking a preventive medication, it is helpful to initiate a preventive agent while the analgesic is being withdrawn.13

MOH contributes to resistance to treatment and, therefore, was included in a refractory scale.8 MOH can almost be considered to be part of the syndrome of RCM. Only 1 point was given to MOH for the following reasons: MOH is not a ‘‘hallmark’’ of RCM and MOH may be difficult to distinguish from simple medication overuse (without resultant headache). However, in future studies, it may be justified to assign MOH to 2 points in the refractory scale.

Medical Treatment

The medications used by patients in this study included: opioids, (usually long-acting opioids), triptans, butalbital, onabotulinumtoxin A, and stimulants. Virtually all of the patients in this study consumed at least one daily medication for the entire 10 years.

We have previously published information on most of these patients.14,15 For RCM patients, it often takes a combination of medications to achieve even minimal benefits. Many of the patients in the study took 2 or more of the listed medications. For the opioid patients, the vast majority were taking long-acting opioids, with which rebound headache was less of a concern. These patients were carefully screened for ‘‘opioid-induced rebound headache.’’ The opioid patients had been on these medications prior to the year 2000; I almost never begin opioid treatment in an opioid-naıve patient. Nine patients in this study did appear to worsen over time due to chronic opioid use. The frequent triptan users were screened and assessed for ‘‘triptan-rebound headache.’’ These patients were given triptan-free ‘‘drug holidays’’ to ascertain if they were in the rebound state. If they worsened due to triptans, or improved off of the triptans, the triptan medications were withdrawn.

Non-pharmaceutical Treatment

As for all headache patients, recommended lifestyle modifications include sleep regulation, diet, exercise, weight loss, and reduction of caffeine intake. Physical therapy, acupuncture, biofeedback or self-hypnosis, relaxation therapy, and cognitive behavioral therapy may be effective non-pharmacologic adjunctive measures.

Neuromodulation therapy has become a viable alternative for a small minority of RCM patients. In addition, various nerve blocks may be of benefit. These therapies are beyond the scope of this article.

Limitations of Study

There are some deficiencies of this article. For example, the small number of patients in the mild group may limit conclusions. The refractory scale has not yet been validated. This is an initial attempt to use such a scale, and additional work needs to be done. In the refractory scale (Table 2), the associated medical conditions (item 5) were chosen because they frequently complicate headache treatment, add to dysfunction, and are, to some degree, related pathophysiologically to chronic migraine. Other conditions (diabetes, lupus, etc.) could reasonably be included as well. The QOL tool included pain, functioning, and moods. This specific tool for measuring QOL has been previously used but is not yet well-validated. Patients who stopped treatment at the clinic over the 10 years of the study were not included. Follow-up of these dropouts could strengthen (or possibly challenge) our conclusions.

Summary

RCM constitutes a small but important subset of migraine patients. For clinical and study purposes, it is helpful to categorize RCM patients as to the degree of refractoriness. After 10 years, the severe patients remained behind the other groups regarding QOL and level of pain. However, over the 10 years, all of the groups (mild, moderate, severe) improved in their QOL and level of pain. This initial attempt to create a refractory rating scale should be refined and improved with further study and research.

Other major areas of study within RCM include pathophysiologic mechanisms, the role of medication overuse, biomarkers, psychological comorbidities, non-medication approaches, and pharmacotherapy. Patients with RCM who have MOH or psychological comorbidities require a combination of approaches. It “takes a village” to help those with severe, refractory headaches, and we need to guide the patient into comprehensive treatments. There are a number of viable therapeutic approaches, 5 of which are presented in this article—opioids, triptans, butalbital, onabotulinumtoxin A, and stimulants. However, we desperately need breakthrough medications and technologies that can prevent headache pain.

 

Last updated on: December 12, 2016
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Refractory Chronic Migraine

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