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Some Migraine Drugs Linked to Cognitive Impairment, Dementia in Older Adults

migraine drugs linked to dementia, cognitive impairment in older adultsThis post was updated at 12:40 p.m. PDT on April 19, 2016.

What kind of long-term impact will taking migraine drugs have on my body? Am I trading a better present for more problems in the future?

These and similar questions have flitted through my mind for years. I usually push them aside—I need these drugs to function, so I don’t feel like I have much choice. Besides, an abstract future worry is so vague that it doesn’t seem to require much attention. Thanks to new research, that worry no longer seems abstract or vague.

Cognitive impairment and dementia in older adults have been linked to anticholinergic drugs, which block the neurotransmitter acetylcholine, in an increasing number of studies over the last decade. Some popular antihistamines, antidepressants, and anti-nausea meds used as migraine drugs have anticholinergic effects.

The research may not be cause for alarm, which I’ll explain in a moment. The first question you want answered is likely: Which drugs put me at risk?

Migraine Drugs With Anticholinergic Effects

This list contains drugs I’m aware of people using for migraine, but it is not an exhaustive list of anticholinergics. Indiana University has a more complete list of anticholinergic drugs (PDF). A JAMA article on the topic also includes Vivactil (protriptyline) and Compazine (prochlorperazine). ACB score refers to “anticholinergic cognitive burden,” which determines if a drug has mild or moderate anticholinergic effects.

Mild Anticholinergic Effect (ACB Score 1)

  • Actiq (fentanyl)
  • Duragesic (fentanyl)
  • Effexor (venlafaxine)
  • Flexeril (vyclobenzaprine)
  • Immodium (loperamide)
  • Valium (diazepam)
  • Wellbutrin (bupropion)
  • Xanax (alprazolam)

Moderate Anticholinergic Effect (ACB Scores 2 & 3)

  • Advil PM (diphenhydramine)
  • Atarax (hydroxyzine)
  • Benadryl (diphenhydramine)
  • Dramamine (dimenhydrinate)
  • Elavil (amitriptyline)
  • Flexeril (cyclobenzaprine)
  • Gravol (dimenhydrinate)
  • Norflex (orphenadrine)
  • Norpramin (desipramine)
  • Pamelor (nortriptyline)
  • Periactin (cyproheptadine)
  • Phenergan (promethazine)
  • Sinequan (doxepin)
  • Tegretol (carbamazepine)
  • Tylenol PM (diphenhydramine)
  • Vistaril (hydroxyzine)

Anticholinergic Burden Unknown

(have an anticholinergic effect, but do not have an ACB score)

  • Compazine (prochlorperazine)
  • Vivactil (protriptyline)

Anticholinergic Drugs, Cognitive Impairment, and Dementia: The Research

Keep in mind that:

  1. These studies do not provethat anticholinergic drugs cause cognitive impairment or dementia. They have found that a link exists between taking the drugs and cognitive impairment or dementia.
  2. All published studies have focused on older adults, most with an average participant age in the early 70s. It is speculated that increased age makes the body more susceptible to these effects, possibly because these drugs permeate the blood-brain barrier more readily in older people.

Risk depends on strength of cholinergic effect

Drugs with a mild cholinergic effect (an ACB of 1) can cause cognitive impairment in older adults within 90 days of continuous use. Those with a strong cholinergic effect (ACB of 2 or 3) can cause cognitive impairment in 60 days of continuous use. Non-continuous use can also have an impact, though the exact length of time varies. Cognitive effects were increased with the number of anticholinergic drugs a patient took. (See Just 2 Months’ Exposure to Anticholinergics Affects Cognition)

Dose matters (somewhat)

The higher the drug’s dose, the greater the risk, according to a study published in 2015. However, even at the minimum effective dose, taking the drugs for prolonged periods were linked to a greater likelihood of cognitive impairment or dementia than for those not taking anticholinergic drugs. “This is not excessive use,” said the lead author Shelly Gray, PharmD, from the University of Washington. “Many of these agents are used chronically, and chronic use—even at low doses—would put you in the highest risk category.” (See ‘Strongest Evidence Yet’ Links Anticholinergic Drugs, Dementia)

Changes in the brain

Brain imaging found lower brain metabolism and reduced brain sizes among participants taking anticholinergics, as reported in a study published this week. Participants taking the drugs also scored lower on cognitive tests than those not taking the drugs. This is the first study looking at the underlying biology of the link identified by earlier research. (See IU Scientists: Brain Scans Link Physical Changes to Cognitive Risks of Widely Used Class of Drugs)

Age of participants

The published studies I found are focused on older adults. Researchers believe that a person’s central nervous system becomes more sensitive to anticholinergic medications with age. It could be that younger patients don’t have the same risks, but that’s uncertain. This warning from Dr. Gray haunts me: ‘There is no data on how these drugs may affect younger people, but I personally will avoid taking anticholinergic agents.”

I found one study presented at a conference that looked at the ACB of younger patients with chronic pain. Participants with chronic pain had significantly higher ACB scores than healthy participants and their cognitive function appeared to be affected. The burden was greatest in patients aged 30 to 39. (See Pain Patients at Cognitive Risk From Anticholinergic Burden?)

Cognitive Impairment vs. Dementia

Cognitive impairment and dementia are very different things. Several studies show that cognitive impairment due to the drugs could be reversible. The drugs could magnify symptoms of an already present mild dementia or bring symptoms on earlier than would have happened otherwise. However, brain atrophy, as found in the study published this week, doesn’t sound reversible.

What’s the Actual Risk?

No one knows for sure. The research is concerning, but is far from conclusive. Many questions still remain. Talk to your doctors and pharmacists for advice that’s best suited to you—it will depend on your age, the medications you take and why you take them, how effective the medications are for you, what alternative medications might help you, and other health problems you may have. Please don’t stop taking your medications without first talking to your health care providers—doing so could put you at risk of other problems.

I plan to ask all my doctors and pharmacists for input. My gynecologist and endocrinologist haven’t prescribed anticholinergics, but I trust them both and want them to weigh in on this, too.

Why I’m Sharing This Research

I freaked out when I first learned about this research last year. I started to write about it, then set it aside. I decided the research was too inconclusive to scare people by reporting it. When I saw the study published this week, I changed my mind. The research is still very preliminary and I don’t want people to panic. Nonetheless, patients should be aware that this research exists so they can make an informed decision about which medications are best for them. Your doctor will probably tell you that it’s not cause for concern, but it’s better to be able to ask them about it than remain completely in the dark.

Kerrie’s Uneasy Truce

The two medications I take daily, cyproheptadine and Wellbutrin, are on the list. My paternal grandmother had Alzheimer’s and I have been afraid of the disease for as long as I can remember. I doubt I would have started the drugs if I’d known about this research. I’m not sure that’s a good thing. These medications allow me to get out of bed. The past four years have been relatively manageable thanks to them. They have improved my quality of life enough that I’ve been able to aggressively pursue other treatments.

I was terrified when I started writing this post, but I have calmed down considerably the more I have learned. This is preliminary research. Cause and effect hasn’t been established. I’m 28 years younger than the average patient in the studies. I’m actively trying to find alternative treatments to these medications. Migraine research is making tremendous strides in preventive treatment. Of course I’m still a little worried that I’m trading the present for the future. I’d be worried about that even without these drugs.

REFERENCES

American Academy of Pain Medicine (AAPM) 29th Annual Meeting. Poster 221. Presented April 12, 2013.

Anderson, P. (2013, May 22). Just 2 Months’ Exposure to Anticholinergics Affects Cognition. Medscape. Retrieved 4/18/16 from http://www.medscape.com/viewarticle/804558.

Anderson, P. (2013, Apr 15). Pain Patients at Cognitive Risk From Anticholinergic Burden? Medscape. Retrieved 4/18/16 from http://www.medscape.com/viewarticle/782520.

Cai, X., Campbell, N., Khan, B., Callahan, C., & Boustani, M. (2013). Long-term anticholinergic use and the aging brain. Alzheimer’s & Dementia9(4), 377-385.

Hughes, S. (2015, Jan 27). ‘Strongest Evidence Yet’ Links Anticholinergic Drugs, Dementia. Medscape. Retrieved 4/18/16 from http://www.medscape.com/viewarticle/838788.

Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., … & Larson, E. B. (2015). Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA internal medicine,175(3), 401-407.

Indiana University (2016, Apr 18). IU scientists: Brain scans link physical changes to cognitive risks of widely used class of drugs [Press release]. Retrieved 4/18/16 from http://news.medicine.iu.edu/releases/2016/04/anticholinergics-brain-effects.shtml.

Risacher, S. L., McDonald, B. C., Tallman, E. F., West, J. D., Farlow, M. R., Unverzagt, F. W., … & Saykin, A. J. (2016). Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. JAMA Neurology, April 2016 DOI:10.1001/jamaneurol.2016.0580

Salahudeen, M. S. and Nishtala, P. S. (2016) Examination and Estimation of Anticholinergic Burden: Current Trends and Implications for Future Research. Drugs & Aging, April 2016 DOI: 10.1007/s40266-016-0362-5

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Ketogenic Diet for Migraine: A Comprehensive Introduction

I’ve told you about my difficulties starting a ketogenic diet for migraine and have tried to assess whether it is working for me, but haven’t told you how the diet works or why I decided to try it. Here’s a comprehensive introduction to using a ketogenic diet for migraine. It’s based on five months of research and more than three months of living with the diet.

Why a ketogenic diet?

Diet and headache was one of the presentations at the American Headache Society conference last November. Topics included biogenic amines (including tyramine and histamine), MSG, food allergies (actual immune responses rather than food sensitivities), gluten, low fat diets, a ketogenic diet, a high omega-3/low omega-6 diet, and a low-sodium diet. The research on a ketogenic diet for migraine was small and the results weren’t overwhelming. But I’d tried almost everything else the presenter mentioned and was feeling desperate. In the last couple years, I’ve heard more anecdotal evidence of it being effective for migraine and my naturopath recommended I look into it.

This was not my first flirtation with a ketogenic diet for migraine. I’ve looked into it multiple times over the last decade, but couldn’t find enough information to do one on my own. Until recently, the information was tightly controlled by doctors and dietitians who work with epilepsy patients. That’s because ketogenic diets are not nutritionally complete and can have serious side effects. As ketogenic diets have become really popular for weight loss, more information has become available. Simultaneously, some of the gatekeepers of the diet for epilepsy began to share details. Here’s what I’ve learned.

What’s a ketogenic diet?

Ketogenic diets shift the body’s fuel source from carbohydrates to fat. Burning fat for fuel causes the body to produce a substance called ketones, which is why the diets are called ketogenic (keto = ketones, genic = producing). When you produce ketones, you are in a state called ketosis and your metabolism mimics fasting or starvation. While that doesn’t seem like it would be a good thing, it works pretty well for treating epilepsy. Medically, ketogenic diets have been in use for epilepsy for nearly 100 years. They are increasingly being used for other conditions, like brain tumors, traumatic brain injuries, and autism, and have recently become popular for weight loss.

What are the different types of ketogenic diets?

ketogenic diet percentagesThe classic medical ketogenic diet is 90% fat. It’s referred to as a 4:1 ketogenic diet—which means that for every four grams of fat, you eat one gram of protein+carbohydrate. This is not a high-protein diet; the goal is to just meet your recommended daily allowance of protein. Your carb count is whatever is leftover in the protein+carbohydrate equation.

That’s the classic ketogenic diet, but there are many variations. For epilepsy, a 3:1 ratio tends to be the starting point for infants and teenagers. The Modified Atkins Diet is becoming increasingly popular for epilepsy, particularly for adults; it contains about 63% of calories from fat. Ketogenic diets for weight loss aren’t as strict in their breakdown. They range from about 60% to 75% calories from fat, 15% to 30% calories from protein, and 5% to 10% calories from carbohydrates. A quick internet survey found that the typical weight loss formula is 75% fat, 20% protein, and 5% carbohydrates.

[click on chart to enlarge]

What’s the best ketogenic diet for migraine?

It depends on the person. Some people see results at lower levels of fat, while others need higher amounts. Start with the lowest ratio you can and work your way up. Readers have reported success on the Modified Atkins Diet. I didn’t get noticeable relief until I worked up to a 3.5:1 ratio; my migraine attacks were worse when I increased to a 3.75:1 ratio (possibly because my blood sugar got too low).

How long does it take to see migraine improvement on a ketogenic diet?

Some people see improvement within a week of starting the diet or increasing their ratio. Almost everyone who sees improvement sees it in the first month. However, it takes about three months for the metabolism to fully shift, so some people don’t see results until a few months in.

It’s also important to manage adverse effects, which could worsen migraine attacks. I became hypoglycemic on the diet and hypoglycemia is a migraine trigger. Since I got the hypoglycemia (mostly) under control, my migraine attacks have been less severe. I can even eat small amounts without triggering an attack.

How long do you have to say on a ketogenic diet for migraine?

Kids with epilepsy can often be on the diet for a year or two, then return to a fairly normal (though generally lower carbohydrate) diet. My dietitian said it often functions as a sort of reset, but does not require a permanent change. Less is known about how adults respond to the diet. In one book I read, a woman in her early 20s with epilepsy had been on the diet nine years with no plan to stop. In naturopathic circles, it is often talked about as a lifelong change. For now, I think it’s an individual thing depending on the severity of your symptoms, your triggers, and how long your migraine attacks have been at their current level.

Why are medical ketogenic diets successful?

Almost all the research is on epilepsy. No matter the illness, the answer is that no one actually knows. Researchers have tested many hypotheses in the last century, but have not come to any conclusions. Ketosis is the probable cause, but that hasn’t been proven. Some researchers speculate that ketosis isn’t actually what’s responsible for improvements, it’s just the visible marker of some other physiological change. In the study on a ketogenic diet for migraine presented at AHS, the benefit could have come from weight loss rather than ketosis.

Why are the risks of ketogenic diets?

Ketogenic diets are not nutritionally complete. Carbohydrates are so restricted that you can’t eat enough vegetables and fruit to get adequate nutrition, so supplementation is imperative. Side effects can range from mild annoyance to death. Although highly unlikely, patients have died in multiple studies of ketogenic diets for epilepsy. Those deaths are typically attributed to hidden metabolic disorders, but it’s still important to be aware of the potential risk.

Please, please do a lot of research before jumping into a ketogenic diet and consider working with a dietitian. I’ve had a DIY approach to my diet for years and would have done this one on my own had I thought I could safely manage the 4:1 ratio without a dietitian. I’m so glad I didn’t. Even working with two dietitians and a naturopath, having blood work every month, and being hypervigilant, I’ve had issues with my blood becoming too acidic, hypoglycemia (that went undiagnosed for five weeks despite the best efforts of my health care team), and wildly fluctuating liver enzymes and inflammation markers. While my migraine attacks have been better on the diet, I overall feel less healthy than before I started it.

The popular version of the diet is less potentially damaging to health than the classic medical version, but I’ve heard enough scary stories from smart people who have educated themselves on the diet to urge anyone considering it to work with a dietitian, at least to start.

What about weight loss?

This diet is popular for weight loss for a good reason—it works. Because the diet mimics starvation, it suppresses hunger. And if you’re doing a 4:1 or 3:1 ratio, you have to weigh everything you eat, so you know exactly how many calories you’re getting. Even though my dietitian kept increasing my calorie intake, I lost 20 pounds unintentionally. My weight finally stabilized when I got to 2,300 calories a day—600 calories more than my dietitian thought I should need and more than I’ve eaten in years. I have yet to gain any of the weight back.

Learn More About Ketogenic Diets

Google “ketogenic diet” or search for it on Amazon and you’ll find information for bodybuilders and people who want to lose weight. That might be the best approach for you, but I recommend starting with the epilepsy-related information. It provides a foundation that explains the medical uses for the diet, is based in solid science (whereas much of the popular information is from not-quite-accurate interpretations of research), includes rational assessments of risks, and explains how to follow the diet in a way that doesn’t otherwise compromise your health. The following resources contain excellent information and were my sources for this post.

Even if you read nothing else, start with these:

More good resources include:

  • The Charlie Foundation and Matthew’s Friends (Nonprofits started by parents of children with epilepsy who have benefited from ketogenic diets. Both sites have good introductions to the diets and helpful guidance. The Charlie Foundation’s information is written or reviewed by a leading dietitian in the field.)
  • Fighting Back With Fat (A book by two moms who have implemented ketogenic diets to treat their children’s epilepsy. *Amazon affiliate link)

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What kind of help during a migraine attack do you want?

help-during-a-migraine“I’m really worried about her and wonder what I can do to better support her before, (especially) during, and after an attack.” The boyfriend of a woman with migraine sent me this. Since different people want different kinds of help during a migraine attack, I recommended asking her directly. But it prompted me to create a list of the kinds of help that people with migraine actually want during an attack.

I need your help. Here are the questions I’d like to address. Please leave your responses in the comments (or respond to this message if you receive posts by email). Answer as many or as few as you’d like.

  • What can someone do to help you in the early stages of a migraine attack?
  • During a migraine attack, do you want someone with you or to be left alone? If someone’s with you, what do you want them to do? If you’re alone, do you want someone to check on you?
  • What would help you when you’re recovering from a migraine attack (postdrome)? Do you need to take it easy for a while or do you resume life as if the attack never happened?
  • Between migraine attacks, is there any way someone could help you make your next attack easier?

In my dual migraine household, we have a different routine depending on who is having the attack. When Hart has one, I put water, ear plugs, an eye pillow, and the remote control for the light/fan beside the bed while he takes his meds. I smooth the bedding, arrange his pillows, and turn on the air filter for white noise. I make sure he has his phone and that my ringer is on so he can reach me if I’m out of earshot. Then I leave him alone. After the worst of the attack, I make sure he’s fed and we usually do something low-key, like watch TV or a baseball game.

My migraine attacks are so varied that we take a case-by-case approach. Sometimes I only need help getting my meds. Sometimes I need help to bed, with gathering my migraine supplies, or finishing up something I was in the middle of doing (which usually means having Hart put food away). Depending on how severe the attack is and if I can sit up, I either spend it alone or watching TV. If I can think clearly (which is rare), we play a game. Same goes for postdrome.

I’m looking forward to hearing your thoughts!

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Talking About Migraine at Work: Your Thoughts?

migraine-at-workWhat’s your take on this statement?: “The key to managing migraines and work is communication. It’s important to let coworkers and managers know about your condition and educate them about it.”

That comes from Migraine at Work on UCLA Health’s migraine information page. The article’s recommendations for “initiating effective communication” include (paraphrased):

  • Educate your coworkers—because they don’t know what migraine is, they don’t know how disabling an attack can be. The article recommends getting pamphlets from your doctor to share with coworkers.
  • Talk to your manager—to reduce triggers by modifying your work environment and gain access to a dark, quiet room during an attack.
  • Be honest—say that migraine attacks can be disabling and you hate to miss work. Tell coworkers that you miss out on fun activities, too, not just work.

I haven’t worked in an office in 13 years, but these recommendations strike me as idealistic and tone-deaf. Other than the suggestion to be honest that you don’t like to miss work because of a migraine attack, this advice raised more questions for me that it resolved: Is it really a good idea to tell your coworkers and manager that migraine attacks can be massively debilitating? Is a person with migraine responsible for educating coworkers? Will pamphlets be fodder for gossip? Do coworkers even listen to attempts at awareness-raising? Are managers receptive to requests for accommodations? Do coworkers care if your migraine attacks prevent you from enjoying leisure activities?

I’d love to know what you think. Please leave a comment below (or if you get posts by email, reply to the email with your response).

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Migraine Stories: Chronic Migraine, Pain Without Suffering

In this beautiful essay, John Ptacek describes how he’s learned to live with the pain of chronic migraine without suffering. Want to share YOUR story? Submit it here.

Walking the Line Between Pain and Suffering

We We learn to avoid pain, but who teaches us to deal with it?learn to avoid pain at an early age. We are taught that hot irons, sharp objects and electrical outlets portend danger. Parents counsel children about such dangers, but sometimes the most effective teacher is pain itself. Pointed lectures are no match for a bright purple bruise. Incident by painful incident, we learn to sidestep misfortune through increasingly observant behavior.

We learn to avoid pain, but who teaches us to live with it? I, along with a billion and a half other people in the world dealing with chronic pain, could have benefited from a lesson or two on this subject.

We can all avoid trips to the emergency room by treading carefully on icy sidewalks and tucking in our fingertips when speed chopping carrots, but preventive strategies are of little use to people experiencing ongoing physical pain. People dealing with fibromyalgiaLyme diseasemigraine and a long list of other chronic conditions understand that their pain cannot be outwitted. They are chained to it, and probably forever.

The urge to resist pain is instinctive. What could be more natural than to hate hurt? One of my earliest memories of pain was the electric jolt of a bumblebee sting. I wailed hysterically as my mother patted a wet baking soda mixture around my throbbing thumb. I wondered how something so horrible could happen to me. All I did was touch a flower! This isn’t fair, I decided, unknowingly adding a layer of emotional distress to the mix. Soon, the pain went away, and along with it my existential uncertainty.

This rapid recovery cycle would repeat itself in coming years as I endured broken bones, concussions, pinched nerves, kidney stones, shingles and other assorted agonies. A “why me?” inner narrative often accompanied these events, but the pain passed too quickly for me to perceive that such mental resistance came with a price. That is, until the headaches showed up at my door.

Sometime in my fourth decade I started getting frequent headaches. At first I shrugged them off to my highly stressful job. Rather than seek medical attention, I started meditating, exercising and eating healthier. None of this put the slightest dent in my pain. In subsequent years, I sought the help of every traditional and alternative health care provider who might have even a remote chance of helping me. They gave it their best shot, but nothing helped. My headaches continued unabated. The lack of progress shuttled me off to a cold dark place familiar to chronic pain sufferers, a solitary space that is all but impossible to describe to outsiders for whom pain is a just passing affair.

Frustration at having to drag my evil friend around with me nearly every day compounded my painful existence. My mind had gotten in on the act, and now I had two fires to put out. Here’s the kind of nonstop chatter I had to endure: How much more of this can I take? If it gets any worse, how will I be able to work? Am I always going to be in pain? What’s the point in living? Why can’t these damn doctors do their jobs?

Anyone experiencing chronic pain knows what it’s like to be tuned in to this unnerving frequency. My unanswerable questions pitched me further and further into an unknowable future.

Even if someone would have counseled me early in life that embracing pain, rather than resisting it, was a winning strategy, I probably wouldn’t have known what to do with it. Wisdom can be baffling at first, and brilliant only later. And anyway wisdom can’t be taught. Moments of great anguish served as my bright purple bruises, and one day, I can’t say exactly when, I got wise to the voices in my head that were the cause my suffering. I achieved a degree of separation from them. I could still hear them, but it sounded like they were coming from the next room. Without really looking for it, I discovered that there was a dividing line between pain and suffering, and depending on how I walked that line, my situation could be either bad or much worse. Who knew bad could sound so good?

This dividing line can look awfully blurry when pain pins me to the mat. Because I am not at my rational best during such moments, I keep a note in my sock drawer reminding me not to push myself and to refrain from making important decisions. I also have a secret password to pull me up when I feel myself slipping into the pit of suffering: Allow. I allow the pain, and immediately suffering leaves the room. Without resistance, suffering cannot exist. That leaves just two of us in the room, me and my constant companion, locked in an uncomfortable but tolerable embrace.

Let me be clear. Pain is a rude and abusive house guest. No secret password will put it out on the street. I will be forever forced to cover its rent. But knowing this relieves me of my duty to resist it, and in that simple act of surrender, I know that I am opening myself up to all the goodness that life will allow.

chronic-migraine-john_ptacekRead more of John’s writing on his blog, On Second Thought, where he explores “the unquestioned assumptions that limit our capacity for happiness.” His writing is thoughtful and insightful.

Reader-submitted stories solely represent the personal point of view, experience, and opinion of the author, not of The Daily Headache or Kerrie Smyres.