DOCTORS' BLOG

Archive for July, 2009

Few physicians are enthusiastic at the prospect of prescribing opioids for the treatment of acute or chronic pain, and for a variety of reasons, there has existed a particular bias against the use of these medications amongst clinicians who subspecialize in headache medicine.  Whatever inherent bias an individual physician harbors against the prescription of opioids may be reinforced by the very real potential for addiction associated with thisclass of drugs, “drug seeking behavior” exhibited by patients in one’s own practice and the concern that opioid therapy both may obstruct the efficacy of more conventional headache treatments and produe an unfavorable long-term outcome.

As many as 8 million Americans suffer from chronic migraine, and not surprisingly it is this segment of the migraine population that suffers the greatest migraine-related disability and accounts for a disproportionate share of the direct costs attributable to migraine diagnosis and treatment.  Clinicians who seek to treat chronic migraine must do so with an arsenal virtually bare of evidence-based therapies.  Preliminary data suggest that patients with chronic migraine may become significantly less likely to respond to therapeutic intervention if they have been experiencing daily headache for 6 months or more.

The argument in favor of considering methadone for patients with chronic migraine who have failed to respond to more conventional treatment interventions includes: 1) treatment-refractory chronic migraine is common, and any clinician whose practice is focused on headache regularly will be confronted with patients so afflicted; and 2) if these patients have failed the more commonly used prophylactic therapies, the options for management would appear to be between a) prescribing a nonopioid prophylactic therapy that is unlikely to prove efficacious b) prescribing symptomatic medication only c) referring the patient to an inpatient headache treatment center or d) prescribing a long-acting opioid (preferably methadone) for chronic headache suppression.

Intractable pain, headache or otherwise, is a devastating and life-controlling experience.  The need to effectively and aggressively control pain is a fundamental tenet of clinical care.  In the past several years, increasing adovacacy for continuous opioid therapy has become an important, if not controversial, theme in the development of treatment guidelines and teaching programs. 

Ironically, the increasing willingness of physicians to prescribe scheduled opioids for their headache and pain patients has occurred in the absence of compelling data demonstrating efficacy or long-term safety.  To the contrary, two meta-analyses on chronic noncancer pain (CNCP) and one long-term uncontrolled study on headache patients demonstrate a relatively small number of patients benefiting from the treatment. 

Recent neuroscience data on the effects of opioids on the brain raise serious concern for long-term safety and also provide the basis for the mechanism by which chronic opioid use might induce progression of headache frequency and severity.  Significant adverse effects, including influence on sexual hormonal balances, physical and psychological dependence, the development of opioid-induced hyperalgeisa, and cardiac arrhythmia and sudden death that can be seen with standard dosages of methadone, make a strong argument against widespread use of continuous opioid therapy (COT) in otherwise healthy young and middle-aged headache patients.

COT should be used in rare circumstances for chronic headache patients, and propose initial guidelines for selecting patients and monitoring treatment.  The physician should be well versed in the details of opioid prescribing, administration, and monitoring, and should be prepared to discontinue opioids when clinical justification, patient behavior, or failure to achieve therapeutic goals make discontinuance necessary.

Certain migraines are labeled as refractory, but the entity lacks a well-accepted operational definition.  A recent survey was sent to American Headache Society members to evaluate interest in a definition for refractory migraine and what were considered necessary criteria.  Review of the literature, collaborative discussions and results of the survey contributed to the proposed definition for refractory migraine.  The study also comments on considerations in formulating the criteria and any issues in making the criteria operational. 

For the proposed definition for refractory migraine and refractory chronic migraine, patients must meet the International Classification of Headache Disorders, Second Edition criteria for migraine, respectively.  Headaches need to cause significant interference with function or quality of life despite modification of triggers, lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy.  The definition requires that patients fail adequate trials of preventive medicines, alone or in combination, from at least 2 of 4 drug classes including: beta-blockers, anticonvulsants, tricyclics, and calcium channel blockers.  Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE) intranasal or injectable formulation and either nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesic, unless contraindicated.  An adequate trial is defined as a period of time during which an appropriate dose of medication is administered, typically at least two months at optimal or maximum-tolerated dose, unless terminated early due to adverse effects.

The definition also employs modifiers for the presence or absence of medication overuse, and with or without significant disability.

A recent study was conducted to identify factors that predict adherence to triptans by migraine patients.  Triptans have demonstrated efficacy for acute migraine, yet many migraine sufferers discontinue their use.  The study group used consisted of sustained users (patients who had had at least one refill of triptans within the past year), and lapsed users (patients who had zero refills in the past year).

Results of the study showed that sustained users of triptans were significantly more satisfied with their medication, had more confidence in the medication’s ability to control headaches, and reported control of migraine with fewer doses of medication.  Sustained users also switched triptans products significantly less often than lapsed users, and reported greater benefit from triptan intervention in restoring normal daily functions, including improved cognitive ability, compared with lapsed users’ ratings of their nontriptan medication.  More lapsed users than sustained users reported adverse events associated with past triptan use. 

This study shows that the patient’s satisfication and confidence in the efficacy of triptans are the strongest predictors of steady adherence to triptan use.  The study suggests that lapsed users may not be receiving optimal treatment, and that they may benefit from additional education on proper use of triptans.

A recent study was conducted to characterize menstrually associated headaches and migraine in adolescent girls and to identify any developmental or pubertal changes.  Headache and migraine are a common problem in adolescents that often transition into a more structured pattern in adulthood.  One pattern of the adult migraine is the  menstrual association in a significant number of women.

The study was conducted by a retrospective analysis of the characterisitcs of adolescent’s headaches, including association with menstrual pattern.  A detailed analysis of patient and parent reported headache characterisitics and patterns of longitudinal change with development and puberty was reviewed, including timing of headache with age and menstrual period and progression of these events over adolescence.

Results of the study demonstrated that menstrual association with migraine begins in adolescence.  Once the  menstrual pattern has developed, this association is stable.  Early identification of this pattern has potential long-term benefit for improved lifelong outcome with migraine treatment.

A recent study was conducted to assess whether family history for chronic headache and drug overuse could be a possible risk factor for headache chronification.  The study group consisted of patients with daily or near daily headaches that underwent a structured interview about family history for chronic headaches, medication overuse, substance abuse or dependence, and psychiatric disorders.

The study results indicated that family history for chronic headaches and drug overuse due in fact represent a risk factor for headache chronification.  However, a large genetic epidemiological survery would be necessary for total confirmation of this association.

We conducted a study that assessed 115 patients with refractory chronic migraine over a six year period who were treated with long-acting opiods.  This was a select group of patients who had all done well previously with short-acting opiods.  65% of the patients did well for at least nine months (average on the opioid was 4.5 years) and 44% of the patients reported adverse events.  Patients with an increased chance of success included young patients, high copers, and those without previous opioid abuse.  Predictors of failure were those with personality disorders, older patients, and particularly those with previous abuse of the short-acting opioids.  In this study, anxiety, depression, bipolar depression or ADD did not significantly increase the risk of abuse.

 Short-acting  generally refers not only to how long a drug carries the desired effect, but the speed of the onset of the drug, and how fast it drops off toward the end of the dose.  Quick onset and fast dropoff are major determinants for abuse.  Short-acting opiods (SAO’s) are not necessarily quick-onset medications.  Most oral SAO tablets are slow to take effect.  A short duration of action then leads to frequent administration and overuse may occur.  However, it has not been proven conclusively that SAO’s lead to less or more abuse, or are “more dangerous” than long-acting opioids (LAO’s).  Although certain drugs are more “abusable” it is the person rather than the drug who governs abuse.

Several previous studies have evaluated daily opiods for severe chronic daily headache.  While success rates have been relatively low, these are patients who have failed the usual ministrations, with few options available.  The advantages of long-acting opioids include:

1. Avoidance of the “end of the dose” phenomenon, with mini-withdrawls throughout the day.

2. Consistent dosing one or two times daily, decreasing the obsession with the next dose.

3. Maintenance of stable blood levels.

4. Avoidance of acetaminophen, aspirin, or NSAIDS that are included in many short-acting preparations.

5. A diminished risk of significant abuse.

6. Better compliance, with less psychological dependency on the drug.

Disadvantages of the long-acting opiods include:

1.stigma

2. fatigue and constipation

3.difficulty in obtaining scripts, with no refills available

4. need for frequent office visits and monitoring

5. risk of abuse

6. interactions with other sedating drugs or alcohol

7. risk of overdose

Most of the opioid abuse is secondary to immediate-acting opioids, or the longer ones that are easily convertible to short-acting ones (ex: Oxycodone CR).  Younger people, particularly adolescents, are the most frequent abusers.

Since their introduction in 1982, the LAO’s have not been shown to be widely abused.  A balanced approach to prescribing opioids is the best method in order to prevent over or underprescribing opioids.  In various studies, the effects of opioids on quality of life are inconsistent.  Generally, at least half of the patients prescribed opioids abandon them due to side effects or lack of efficacy.

Resources: An excellent newsletter, Nutrition Action Health Letter is $24 a year.  Visit www.cspinet.org to subscribe.  A good website for healthy living is www.sparkpeople.com, with over a million members.  It has sections for both adults and teens.  Sparkpeople has daily updates and all kinds of worthwhile information, and it is free!

Most herbal and vitamin supplements have not held up to scrutiny in controlled trials; some have turned out to be harmful.  Even multivitamins are questionable; a large study released in 2009 showed no improvement in cancer or heart disease rates among women who took multivitamins.  Another study linked multivitamins to an increase in cancer.  Don’t believe the advertising claims-multivitamins and many other supplements are not necessary for good health.

It can be confusing to know which supplements are helpful, but the following have held up to scrutiny and are recommended: Vitamin D: 2,000 I.U. daily (avoid generics) and Omega-3’s (see below).

Vitamin D is known to be important for our skin and bones, and it may help fight hypertension and autoimmune diseases.  Recently, adequate levels of Vitamin D have been linked to lowered rates of cancer, especially colorectal cancer.  People who live in cold climates are often low in Vitamin D, as they are not in the sun enough.  Most need to take a Vitamin D supplement.  The latest studies suggest that adults need at least 2,000 International Units a day.  Avoid the generic Vitamin D; use a name brand.  The Nature’s Finest brand at Walgreen’s is 2,000 I.U. in a small gelcap, easy to take.  If you take calcium with added D, you probably still need to take an extra D supplement.  Do not take more than 4,000 units of vitamin D without consulting your physician.

Omega-3’s (Fatty Acids).  Many studies have shown the benefits of Omega-3’s for the heart, for moods, and possibly for headaches.  Eating fish twice a week is a good goal, particularly fatty fish such as tuna, salmon, trout and mackerel.  Fish oil capsules are also beneficial.  Read the ingredients on the bottle and choose the brand with the most EPA and DHA.  One or two capsules a day is recommended.  Flaxseed capsules are also helpful.  Other sources of Omega-3’s in the diet are tofu, soybeans, walnuts, and canola oil.

Calcium is necessary for the heart, muscles, and nerves to function and for blood to clot.  Low intake of calcium leads to the development of osteoporosis and is associated with high rates of bone fractures.  Absorption of calcium decreases as we age.  After 45, most people, particularly post-menopausal women, should take calcium supplements.  Eating too much salt and protein, especially animal protein, increases calcium loss.

Calcium is found in milk, yogurt, cheese, broccoli, tofu, beans, sardines, calcium-enriched fruit juices, fortified cereals, and other foods.  Our systems cannot absorb more than 500mg of calcium at a time.  Calcium in the form of calcium citrate, such as in citrocal, is more easily absorbed than calcium carbonate.  Citrocal Caplets plus D are a good form of calcium (315 mg) and vitamin D (200 IU).  The usual dose is one or two tablets, twice a day; consult your physician.  To learn more about calcium, visit www.health.nih.gov . 

Aspirin.  If you are at risk for heart disease, your doctor may recommend a daily dose of aspirin.  Its properties may help prevent heart attacks and strokes, and even headaches and certain cancers.  The usual dose is one aspirin (325mg)a day.  Generic aspirin are fine.  Taking a baby aspirin (81mg) or 1/2 tablet of regular aspirin (162mg) may be sufficient; the dose varies by person.  Aspirin can cause stomach ulcers; if it hurts your stomach or causes heartburn, stop taking it and consult your doctor.

Coenzyme Q10 (CoQ10) is a crucial compound, important for your heart, muscles and nerves.  It is naturally produced by your body.  However, the statins (cholesterol-lowering drugs like Simvastatin, Lipitor, Pravochol, Vytorin and crestor) deplete the body’s CoQ10.  Sutdies have indicated a possible benefit from CoQ10 for migraine and the heart.  I suggest taking 200 mg per day of CoQ10 if you take one of the statin drugs.  It has not yet been proven that this helps the muscles, but CoQ10 is generally safe and may prevent headaches.