by admin | Jul 11, 2021 | Medication
CGRP (Calcitonin Gene-Related Peptide) and Migraine
CGRP (calcitonin gene-related peptide) has been found to play a role in causing migraine. CGRP is released from cells in the trigeminal ganglia, and migraineurs have an increased level of CGRP in blood serum. In the brain, CGRP levels are increased in inflammatory conditions. There is some evidence that at least some migraine sufferers may have inflammatory markers (such as TNF-α) present in their nervous systems during migraine attacks. CGRP is thought to increase the sensitivity of migraine pain receptors (trigeminal nociceptors). There is also some evidence that CGRP is implicated in paroxysmal hemicranias. CGRP may even play a role in hypertension.
Drug development for CGRP blockers has been a long road. Telcagepant was found to be effective in Phase III trials, but was abandoned after the discovery of concerns about liver toxicity. Olcegepant, which had undergone Phase II trials, is intravenous, and was not developed further due to adverse effects as well as an intravenous therapy for an acute medication not being the most practical option for many. Other CGRP antagonist drugs in the gepant class have emerged and more are in development (rimegepant, ubrogepant, atogepant, and vazegepant). Some gepants are used as acute medications, while others have utility for prevention of migraine.
Another form of CGRP blockade is in the form of monoclonal antibody drugs that either block the CGRP receptor or the CGRP ligand. There are currently four injectable monoclonal antibody CGRP blockers for migraine prevention: erenumab, galcanezumab, fremenezumab, and eptinezumab.
References:
1. Durham PL. Calcitonin Gene-Related Peptide (CGRP) and Migraine. Headache. 2006;46(Suppl 1):S3–S8.
2. Hoffmann J, Goadsby PJ. New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors. Curr Treat Options Neurol. 2012;14(1):50–59. doi:10.1007/s11940-011-0155-4.
3. Durham PL, Vause CV. CGRP Receptor Antagonists in the Treatment of Migraine. CNS Drugs. 2010;24(7):539–548. doi:10.2165/11534920-000000000-00000.
4. Goadsby PJ, Edvinsson L. Neuropeptide changes in a case of chronic paroxysmal hemicrania-evidence for trigemino-parasympathetic activation. Cephalalgia. 1996;16:448-450.
5. Tepper, S. J. and Stillman, M. J. (2008), Clinical and Preclinical Rationale for CGRP-Receptor Antagonists in the Treatment of Migraine. Headache: The Journal of Head and Face Pain, 48: 1259–1268. doi: 10.1111/j.1526-4610.2008.01214.
6. Rafaelli, B. Neeb, L. Reuter, U. Monoclonal Antibodies for the Prevention of Migraine. Expert Opin. Biol. Ther. 2019 Dec; 19(12):1307-1317.
by admin | Jul 11, 2021 | Complementary & Alternative Medicine, Medication
Supplement Safety
How much do you know about supplement safety? If you don’t know a lot, you are not alone. A 2002 study of primary care physicians found that 42% were not aware of any drug-herb interactions that had appeared in the medical literature, nor had they treated a patient that had one. A more recent study (2007) of internal medicine residents revealed that one-third did not know that supplements do not need to be approved by the FDA, or that safety and efficacy data are not required before supplements are put on the market.
This ignorance is not limited to physicians in training. A survey of consumers has shown that 68% of consumers believed that supplements were regulated by the government, 59% believed dietary supplements were FDA-approved like medications, and 55% believed that manufacturers could not make claims of product efficacy without scientific evidence.
Regulation of Supplements
Here are the facts: dietary supplements are currently regulated according to the Dietary Supplement Health and Education Act of 1994. This permits the initial marketing of an herbal or other dietary supplement product without proof of safety, efficacy, bioavailability, or standardization. The manufacturer is held responsible for ensuring a product’s safety. The FDA is responsible for taking action against any product that is found to be unsafe after it is on the market, and for monitoring information on labeling and package inserts. The Federal Trade Commission is responsible for any false advertising claims. You can find more detailed information about supplements and how they are regulated from the government.
Use of Herbal Supplements is Common
Studies of surgical patients have shown that nearly one third take at least one herbal product on a regular basis. The problem is that many patients don’t discuss this to the surgeon or to the anesthesiologist prior to surgery. Without the bottle in hand, one in five patients were unable to identify what they were taking when asked. A study of pregnant women in Australia revealed that 36% took an herbal product while pregnant. A 2007 survey showed that 38% of American adults and 12% of children used dietary supplements.
What is the Best Way to Be Safe with Dietary Supplements?
You can be a responsible consumer of dietary and herbal supplements by reading labels carefully.
Look for certifications such as “USP Dietary Supplement Verified”, or certification by ConsumerLab, NSF International, or Good Housekeeping. The certifications vary, but it’s a start, and they at least indicate evidence of laboratory testing. USP stands for U.S. Pharmacopeia, and the standard include testing for uniformity, cleanliness, and freedom from environmental contaminants such as lead, mercury, or drugs. It is safer to buy single-herb products that clearly show how much of the herb each dose contains than to buy a mixture of several herbals with unknown amounts of each herb. And be very wary of buying any herbs that have not been manufactured in the U.S., EU, or Canada, as supplements from other countries have been found to contain contaminants.
Resource for learning more:
http://www.nlm.nih.gov/medlineplus/druginformation.html
http://www.naturalstandard.com/
References:
1. Ashar BH, Rice TN, Sisson SD. Physicians’ understanding of the regulation of dietary supplements. Arch. Intern. Med. 2007;167(9):966-969.
2. Ashar BH, Rice TN, Sisson SD. Medical residents’ knowledge of dietary supplements. South. Med. J. 2008;101(10):996-1000.
3. Kennedy J. Herb and supplement use in the US adult population. Clin Ther. 2005;27(11):1847-1858.
4. Timbo B, Ross M, Mccarthy P, Lin C. Dietary Supplements in a National Survey: Prevalence of Use and Reports of Adverse Events. Journal of the American Dietetic Association. 2006;106(12):1966-1974.
5. Barnes PM, Bloom B, Nahin R. CDC National Health Statistics Report #12. Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. December 10, 2008.
by Christina Peterson, M.D.
updated July 10 , 2021
by admin | Jul 11, 2021 | Medication
Preventive Medications for Headache
Not everyone with migraine headaches will require a preventive medication. If you experience only a few headache days a month, and you are not disabled by your headaches, you may be able to treat your migraine headaches successfully with a migraine-specific medication alone.
Research has shown, however, that although about 40% of migraine sufferers are candidates for preventive medication, only one-fifth of those who would benefit from migraine prevention are receiving such medication therapy.
There are many, many medications used for the prevention of migraine, but only a few have been approved by regulatory agencies like the U.S. Food and Drug Administration, Health Canada, or the European Agency for the Evaluation of Medicines (EMEA) Some of the newer medications approved for migraine prevention are expensive, and may not be approved by health insurance plans or national formularies until you have tried some of the older medications.
Medications that have not yet been approved for a specific condition by a regulatory agency, but are prescribed for you by your doctor anyway are used in what is called “off-label” use. It does not mean that it is unsafe to do so; it just means that the drug has not been tested for that condition. This is why you might go to pick up your prescription, and be told by the pharmacist that you have been given a blood pressure medication, or an antidepressant, or a seizure medication. Your doctor knows you don’t have these conditions, but we have found that some of these medications are useful for the prevention of migraine. Many of them have been tested in a formal fashion for migraine, but simply have not been subjected to the very expensive and rigorous testing necessary to obtain approval of the appropriate regulatory agency for a secondary condition (migraine), since it is already known that they are safe and effective for their primary use.
Should you be taking preventive medications? This depends on how many disabling migraine days a month you experience, and can also depend on how well acute medications work to abort your attacks. This is a decision to make with your physician.
by admin | Mar 6, 2019 | Medication
Causes of Serotonin Syndrome
Serotonin syndrome is something that becomes newsworthy amongst headache patients from time to time, and has been raised to as recent level of concern because of an FDA alert issued in 2007 regarding the possibility of this problem occurring from mixing antidepressant medications and triptan migraine medications. Should you worry? This has actually become somewhat controversial.
So, What is Serotonin Syndrome?
Serotonin syndrome is a very serious drug reaction that can occur from medications that stimulate the neurotransmitter serotonin. This usually occurs when you take more than one medication that stimulates the serotonin system, but it has also been reported from high doses of anti-depressants in the category called SSRO antidepressants. Serotonin syndrome has been most commonly reported in overdose situations, and is rare in headache sufferers—unless, of course, you are also being treated for depression.
Serotonin syndrome symptoms are:
- altered mental status
- fever, rapid heart rate
- tremor
- shivering
- insomnia
- sweating
- agitation
- low or high blood pressure
- diarrhea
- nausea
- neuromuscular problems.
These serotonin syndrome symptoms come on within 24 hours of taking the offending medication, or a change in dosage. The symptoms that define a serious serotonin syndrome are altered mental status, fever, and involuntary neuromuscular movements called clonus.
Are You in Danger of Serotonin Syndrome?
Most likely not. The doses of tricyclic antidepressants used for the prevention of migraine are usually low doses. Oral triptan medications, taken alone, have not been found to be associated with serotonin syndrome. A recent study evaluated over 1700 patients who received sumatriptan injection in addition to an SSRI antidepressant, and there were no cases of serotonin syndrome.
The reason the entire matter has become controversial is this: there are many types of serotonin (or 5HT) receptors, and not all medications plug into the same kinds of receptors. The triptan medications bind to the 5HT1B and 5HT1D receptors, and serotonin syndrome is believed to be caused by the 5HT1A and 5HT2A receptors.
The rate of serotonin syndrome occurring in those treated with the SSRI antidepressants has been calculated at 0.5 to 0.9 cases per 1000 patient-months of treatment. However, there have been no cases of serotonin syndrome reported from triptans alone. The FDA issued the alert so that physicians would be extra aware of the possibility that these combinations could cause a problem, and to be on the watch for the symptoms.
If you are taking an antidepressant and a triptan, it is unlikely that you are at significant risk unless your dose is high or has been changed. Remember that it is when you have had a dosage increase that you are at the most risk, and it is usually the addition of a third medication that is the problem, such as an anti-nausea medication. an antibiotic, a second anti-depressant, or an opioid analgesic like fentanyl or Demerol (pethidine).
If you are concerned that you have symptoms that might represent serotonin syndrome, call your doctor or go directly to the emergency room. Be sure to drink lots of water, as this can help. If nothing has changed in your medication regimen, and your symptoms are mild or vague, it is probably not serotonin syndrome.
Here is the American Headache Society’s statement on serotonin syndrome.
But What If I Am Being Treated for Depression?
Mood disorders are common in migraine sufferers, and many people do take an SSRI or SNRI antidepressant, either for depression or for pain management. It is important to stay on your prescribed medication—especially for antidepressants. Stopping them abruptly can cause a withdrawal syndrome. if you have concerns, contact the prescribing physician. Keep a list of all your medications so that all your doctors and other providers know everything you are taking. When you are at the most risk for a problem with serotonin syndrome is when you have had a dosage increase, or when another medication that affects the serotonin system has been added.
Serotonin Syndrome Symptoms
To review, early symptoms of serotonin syndrome (and “minor diagnostic criteria”) are agitation, nervousness, insomnia, rapid heart rate, rapid breathing, difficulty breathing, nausea, diarrhea, impaired coordination, dilated pupils, and high or low blood pressure. Remember—some of these are also going to occur during a headache: for example, pain can increase blood pressure a little. Some of these are also symptoms of anxiety, which occurs more commonly in headache sufferers than in the general population.
Later and more serious symptoms of serotonin syndrome are fever, sweating, confusion, a change in mood (like elation, semi-coma, or even deterioration to coma), tremors, chills, muscular rigidity, seriously difficulty breathing, brisk reflexes, and myoclonus (a form of muscle hyper-reactivity.)
You should not panic if you just have some nausea or diarrhea. Although these can be some of the earlier symptoms of a serotonin syndrome, these are also migraine symptoms for a lot of people. The things that make a serotonin syndrome dangerous are high fever, high blood pressure, coma (obviously), and muscle rigidity that can lead to respiratory difficulty or collapse. The thing that a neurologist will look for in the diagnosis of a serotonin syndrome in addition to these is a muscular abnormality called clonus If you feel that you are developing warning signs, take action and call your doctor.
Are There Other Things That Can Mimic Serotonin Syndrome?
Yes, there are. Anxiety disorders can cause some of the symptoms, as mentioned, as can migraine itself. But worthy of discussion in this day and age of energy drinks is caffeine toxicity.
Caffeine-Induced Mental Disorder
The following are the criteria used by mental health professionals to diagnose a caffeine-induced mental disorder from the DSM-IV Diagnostic Manual:
Caffeine-Induced Organic Mental Disorder 305.90; Caffeine Intoxication
Diagnostic Criteria:
1. Recent consumption of caffeine, usually in excess of 250 mg.
2. At least five of the following signs:
- restlessness
- nervousness
- excitement
- insomnia
- flushed face
- diuresis
- gastrointestinal disturbance
- muscle twitching
- rambling flow of thought and speech
- tachycardia or cardiac arrhythmia
- periods of inexhaustibility
- psychomotor agitation
3. Not due to any physical or other mental disorder, such as an Anxiety Disorder. One No-Doz® tablet contains 200 mg of caffeine. Each Excedrin® tablet you take contains 65 mg of caffeine.
If you drink any coffee at all, and take two Excedrin® a day, you have gotten more than 250 mg of caffeine a day. Oh—and a Starbuck’s Vente™ contains about 500 mg of caffeine. So while, of course it’s important to avoid serotonin syndrome, it’s also important to figure out what’s going on.
Most important: stay safe, and don’t panic.
References:
1. Putnam GP, O’Quinn S, Bolden-Watson CP, Davis RL, Gutterman DL, Fox AW. Migraine polypharmacy and the tolerability of sumatriptan: a large-scale, prospective study. Cephalalgia. 1999;19:668- 675.
2. Stewart Tepper, Christopher Allen, David Sanders, Alison Greene, Stephen Boccuzzi. Coprescription of Triptans With Potentially Interacting Medications: A Cohort Study Involving 240 268 Patients, Headache 2003 43(1):44-48
3. Birmes, P, Coppin, D, Schmitt, L, Lauque, D, Serotonin syndrome: a brief review, Canadian Medical Association Journal 2003; 168 (11): 1439-1442
4. Dunkley, EJ, Isbister, GK, Sibbritt, D, Dawson, AH, Whyte, IM, The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity, QJM 2003; 96:635-642
By Christina Peterson, MD
by admin | Sep 6, 2017 | Complementary & Alternative Medicine, Medication
The Risk for Drug-Herb Interactions is Not Trivial
Herbal supplements, vitamins, and dietary supplements are widely used. Depending on the study you look at, 25-85% of people who see doctors at a given time are using herbal supplements. About 15 million adult Americans are at risk for possible adverse interactions between prescription drugs and herbs or high dose vitamins, according to the Journal of the American Medical Association. A British study (2003) found that of the 62% who took herbal preparations. 1 in 20 were taking a potentially dangerous combination. How can you make sure you’re not at risk?
The 20,000 or so herbal supplements that are on the market in the US alone only come under the direct scrutiny of the FDA if there is a problem, or when a product is selected for spot-checking. While information about interactions is increasing rapidly, it is still quite limited. The best sources of information are your pharmacist or your physician, although be aware that for many of these products, the information is simply not yet known.
Twenty Herbs and Five Classes of Medications that can Interact
This is not an exhaustive analysis of herbal supplements, but an overview of some of the more common herb and drug combinations that can affect the headache sufferer.
Barbiturates
“Well, I don’t take barbiturates!” you might to yourself indignantly. Except that you do if you take Fioricet* or anything else with butalbital in it. Combining this with kava kava can cause undue sedation. It should also be noted that there have been reports of liver failure from kava kava alone, and taking it in conjunction with acetaminophen (or paracetamol) is not wise, as this enhances risk to the liver.
Calcium channel blockers
Calcium channel blockers taken in combination with dong quai can drop blood pressure significantly. So can taking hawthorn leaf. The combination of verpamail and guarana can cause hyperstimulation of the nervous system. Gingko can inhibit the metabolism of diltiazem.
SSRI anti-depressants
SSRI antidepressants such as Prozac, Paxil, and Lexapro should not be taken in conjunction with St. John’s wort as this can result in serious side effects. St. John’s wort acts on the same brain receptors as these medications.
Tricyclic antidepressants
St, John’s wort should also not be taken with tricyclic antidepressants (amitriptyline, doxepin, imipramine, desipramine, protriptyline) as it can reduce the effective level of drug in your system. With high enough doses, serious side effects can occur.
ACE-Inhibitors
Lisinopril, enalapril, ramipril, and other ACE-inhibitors are sometimes used off-label as migraine preventive medications. Combining them with cayenne, used internally, can increase the risk of cough sometimes seen as an adverse effect of the ACE-inhibitors.
Aspirin and anti-inflammatories
There is a wide range of herbs that interact with the coagulation process. Most of these cause bleeding by interfering with the platelets (clotting cells). In small doses, this effect can be desirable. It’s why a baby aspirin is recommended in older individuals for cardiovascular protection. However, if you use these herbals in combination with one another or with pharmaceuticals that have a similar effect, you may discover—the hard way—that you have gone far beyond any desirable goal.
The four most commonly used herbs that interact with blood clotting are known as the four G’s: Ginger (also called sheng jiang, shen jing, shokyo, or shoga), Garlic, Gingko biloba (also called maidenhair or kew tree), and Ginseng (sometimes called Panax; Siberian ginseng is also known as Eleutherococcus). Many headache sufferers take aspirin-containing analgesics or other nonsteroidal anti-inflammatory medications (especially indomethacin) and should know of the potential for interactions that can result in bleeding. In the case of migraine, it should be the Four G’s and an F, because feverfew falls into this category as well.
Other herbs with anti-coagulant properties are chamomile, dong quai (or tang kuei), and horse chestnut. Other anti-platelet herbs are: bilberry, bromelain, cayenne, flaxseed oil, green tea, meadowsweet, motherwort, turmeric, and willow.
Make Sure You are not at Risk for Interactions
Be safe, not sorry. If you are taking more than one medication, the possibility for interactions increases greatly. Drug-drug interactions are already an issue for many people, especially for those who have more than one prescribing provider. If you are also taking herbal supplements, it increases the potential for further drug-herb interactions. Talk to your pharmacist if you have any concerns about this; they are far more qualified to answer your questions than the clerk at the health food store.
What Should I Do If I’m Worried About Drug-Herb Interactions?
If you are concerned that you might be experiencing an adverse reaction to a vitamin, mineral, or herbal supplement, talk to your health care provider. Some of these reactions are predictable symptoms related to taking too much. Others may be due to contaminants in a product, or due to a drug-herb interaction. If your doctor or health care provider is not certain, a call to your pharmacist may be helpful. Databases listing this information are being updated frequently. It’s important to let someone know if you think your are having a reaction. Adverse reactions to supplements are supposed to be reported to MedWatch which is a reporting program of the FDA. That way, accurate information can be collected. This can be helpful to someone else in the future.
by Christina Peterson, M.D.
by admin | May 17, 2013 | Medication
Safety of Over-the-counter Medications
We all tend to think of over-the-counter medications as being safe. After all, regulatory agencies have allowed them to be over the counter. So, they couldn’t really be all that bad, could they?
Well, it turns out that they can—if you don’t take them properly. Some people have a tendency to think that they are safe, and that therefore, it is ok to take a few more painkillers than are recommended on the label. Some people have never actually read the label. (Have you?) And some people don’t realize that they are, in effect, getting a double dose of some medications, because one of the over-the- counter analgesics they are taking may also be a component of one of the prescription medications they are taking.
It’s important to read all labels and to avoid taking excessive amounts of over-the-counter medications. Follow the recommended amounts on the label unless your physician has specifically recommended something different. Too much anti-inflammatory medication, such as aspirin, naproxen sodium, or ibuprofen, can result in stomach irritation like gastritis, cause an ulcer, or promote gastrointestinal bleeding.
Be especially careful not to take too much acetaminophen (paracetamol). Doing so can be damaging to the liver. This damage can be magnified if you drink alcohol, even moderately. Liver damage can occur even in only 24 hours if 8 extra-strength acetaminophen caplets are combined with alcohol. At this time, more than half of all liver transplants are necessary because of the medical use of acetaminophen. Alcohol also increases the risk of gastrointestinal bleeding if combined with anti-inflammatory medications. Long-term overuse of some of these medications can also contribute to kidney damage.
Be safe—read the label, and don’t take medication in excess of the recommended amounts. Don’t combine acetaminophen, paracetamol, naproxen sodium, ibuprofen, ketoprofen or other anti- inflammatory medications with alcohol. Do remember that using over-the-counter medications more than three days a week can lead to medication overuse headache. And be aware that many prescription medications contain acetaminophen (paracetamol).
If your headaches are not responding to over-the- counter pain medication, see a doctor—more specific headache management will not only help your head, it may protect your liver, stomach and kidneys as well.
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