Mirena Price Increase

You may be wondering how, in the wake of healthcare reform, Bayer has seen fit to raise the price of a Mirena IUD to over $700.

Some providers are outraged, and concerned that they will no longer be able to afford to provide this contraceptive method for their patients.

But check out this thread on the Café Pharma boards, where drug reps in the know think the price increase came because Bayer got an indication for use of Mirena to treat heavy menstrual bleeding  –

Mirena prices are already high. I assume the increase is do to the MBL indication. I have never seen a forcast but guessing it could add 100 million to the US market.

That seems about right to me. Mirena has moved from a contraceptive market, where it must enter the field in the same price range as its competitors, to the abnormal bleeding market, where its new price compares quite favorably to interventions such as surgery and endometrial ablation.

And sure enough, it looks as if the plans are already buying into the new price –

Due to a recent price increase by the manufacturer, UMP has increased the allowed amount for the Mirena IUD from $515.85 to $742.42, effective March 15, 2010. Claims for dates of service from March 15, 2010 and later will be paid based on the higher allowed amount depending on the network status of the provider (network 85%; non-network 60%).

Wonder when the birth control pill manufacturers will get wise and try the same thing? After all, we’ve been prescibing oral contraceptives to treat heavy periods for years.

And the game goes on. The losers, in the end, will be the uninsured. Oh wait – there will be no more uninsured now that healtcare reform has passed. I think I finally get it…
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Updates

  • It appears Medicaid has also adjusted its reimbursement to match the new price. So relax, everyone.
  • Docs who don’t want the upfront expense of stocking Mirena can have patients obtain it directly from Caremark through their insurers (though I’d always keep a backup or two around the office in case the one the patient brings drops or is defective…)
  • Bayer has a program to assist uninsured women with the cost of Mirena




Cherry Blossom Time in Washington DC

This year, Spring Break coincided with peak Cherry Blossom Season, so off we went to Washington, DC. A rather last minute home exchange landed us in a beautiful townhouse in Adams Morgan, a perfect home base for our 4 day stay. Here are some highlights of the trip this year –

1. The Smithsonian National Museum of American History – It’s open late during spring break, which meant we could arrive at 4:30 pm and see everything we wanted before closing time at 7:30 pm with no lines. We hung out at Julia Child’s Kitchen for over an hour, watching old videos of Julia’s TV shows and listening to her interviews. It really is such a special exhibit.

2. The National Gallery of Art – Truly a national treasure. The kids loved it!

3. Hillwood Estate and Gardens – in Cleveland Park. If you like Russian Art, French pottery and beautiful gardens, it’s worth a visit. The Japanese Garden, though small, is really quite special.

and the orchid greenhouse is magical.

Probably a better time to visit is in May or June when more is blooming that a few Cherry Blossom trees. If gardens aren’t your thing, then head instead to the nearby Zoo. Combine it with an al fresco lunch at Yanni’s Greek Taverna (best gyro meat I’ve ever had).

4. Potomac Monument and Cherry Blossom Bike Tour – We rented bikes for the kids at the Washington Marina (warning – bring your own helmet or be forced to buy one for $20 and get a trail map ahead of time) and rode along the Washington Memorial Highway portion of the Mt Vernon Trail into the city.

The well-paved and mostly flat trail took us past the small and attractive Reagan Airport, where planes were landing practically over our heads as we rode. We left the trail to cross the Arlington Bridge to visit the Lincoln, Roosevelt and Jefferson Monuments, then rode back across the Mason memorial Bridge to return to the Marina. Total distance  – about 12.5 miles. If you do this ride, do pack a picnic lunch, as food is scarce among the monuments – just some tourist food kiosks with long lines at the Lincoln and Jefferson Monuments. (We ended up parking the bikes and sneaking into the Holocaust Museum Cafe for lunch.)

5. The newly gentrified area around 14th and P. We did our food shopping at Whole Foods and ate at ThaiTanic with the chic young working crowd who are living and flocking to this area in droves. If I were of that age, this might be where I’d live.

6. Shopping in Adams Morgan – We loved Idle Times Books, the Tibet Shop (Tibetan Imports) and Bazaar Atlas (Moroccan and Senegales imports). Having kids along, we did not hit the bars, but would have loved to have had a beer and listened to some West African music.

7. Visiting friend and blogger Linda and her family in nearby Frederick, Maryland. Wish we had more time to visit this lovely little town. Hope to return one day for a meal at Volt.

This was our second spring break in a row in DC, and I want to do it again next year. I loved having a house to stay in, food shopping with the locals, cooking dinner and hanging in the kitchen over coffee in the morning overlooking the garden.  Not to mention having bikes to ride! Thanks to our hosts for opening up their warm and lovely home to us – we’re so glad you had a good time at our place. Let’s do it again next spring!
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Thanks to Nats for lending me her photos from the Gallery visit.

Rustic Shrimp Bisque – A Soup Worth Waiting For

I’ve been waiting for this soup for weeks. Eleven weeks, to be exact. That’s how long I was enrolled in a research diet study, and unable to eat anything other than the food they provided me, which was nowhere near as delicious as this soup.

The study is designed to compare the effects of three different diets – the American Diet, the AHA low fat diet and a maintenance Atkins-type Diet – on weight loss and cardiovascular disease risk. I randomized to the American Diet, meaning that Thursday’s lunch was a slice of pizza with potato chips and an afternoon snack of oreos and chocolate pudding, Saturday’s lunch was hamburger and fries, and the most veggies I ever saw at one sitting was a measly stalk of broccoli. Despite this, I lost 30 lbs over the 11 weeks of the study, primarily because my caloric intake was only 1200 cals per day, carefully calculated based on my basal metabolic rate.

The best part about my diet was that they supplied me all the food, free of charge. Since the research kitchen is located on the floor above my office, that meant stopping in on the way to work for my breakfast, then having lunch delivered to my desk at 1 pm, and dinner dropped off late afternoon for me to take home. Easiest diet I’ve ever undertaken. Not to mention knowing they’d kick me out if I was caught cheating….

I don’t know yet how my cholesterol fared during the diet, but if the pilot data are right, it will be lower simply because I lost so much weight. The big question, of course, is how well I fared compared to my cohorts on the other diets. That, my dears, will have to await publication of the final results.

Before you go congratulating me on my weight loss, let me tell you that much of the weight I lost was poundage I had already shed last year on a Zone Delivery Diet and subsequently regained. This makes me quite typical, a fact that I now understand and have stopped feeling guilty about since reading David Kessler’s book “The End of Overeating“, which I highly recommend for anyone struggling, as I have, to lose or maintain their weight.   Now that I am finished the research diet, however, I intend to be anything but typical. I plan not only to maintain my weight loss, but to keep it going until I reach my wedding weight. What’s different this time?

I’ll be sharing this over the weeks as I continue this new phase of my life, but will give you one major difference. I no longer think of foods as “good’ or “bad” when it comes to losing weight. After all, I lost a lot of weight eating potato chips, pizza, bacon, pancakes, sausage, cookies and french fries.  While I am not advocating a diet composed primarily of these kinds of food, I now inherently understand that I can enjoy previously “forbidden” foods and still lose weight, provided I am conscious of portion control and calories.

I have lost 3 more pounds in the week on my own since finishing the research diet, and have no sense at all that I am dieting. I am just eating the way I ate for the past 11 weeks, which is consciously, slowly and at around 1200 calories per day. Breakfast most days is steel cut oats with chopped dates and a side of turkey bacon or sausage. Lunch today was one of my all time fave sandwiches – part skim mozarella on a sourdough baguette with pesto and tomatoes – and an apple. And dinner? Well, that brings me to this marvelous Rustic Shrimp Bisque.

Mr TBTAM had the nerve to make this soup my first week on the research diet, and all I ever got was the tiniest taste. Talk about torture! Naturally, the minute I was let loose again in the kitchen, the first thing I decided to make was this soup. I calculated it to have about 270 calories a cup – an amount which is plenty filling, especially when the soup is served with a side salad and a small piece of bread. Total cost for the meal – around 540 calories.

It’s still only my first week on my own, and as the growing season arrives, I expect that I will be increasing the fruit and veggie components of my diet. But for now, I am very happy with what I am accomplishing. And loving this soup…

RUSTIC SHRIMP BISQUE

You can go to the NY Times website for the recipe, but let me tell you a few things first –

1. The recipe calls for one fennel bulb, and does not specify a size. I used one half of a large bulb with three stems, and ended up with 6 cups of soup total.  I think if you want to use a whole large bulb, the fennel flavor would not overpower.
2. I pureed my soup much more finely than the original recipe. I found the shrimp, if cooked properly and not too long, get a funny shred if you go for a coarser puree.
3. I would love to try this soup using olive oil instead of butter – if anyone tries it before me, do post a comment and let us know how it tastes.
4. The shrimp stock alone is to die for.
5. This is not a quick soup, but don’t try to shortcut it. In every step, you’ll see marvelous flavors building – just thinking about those shrimp shells browning in the butter, or the tomato paste carmelizing in the bottom of the pot gives me goose bumps.  Take your time, have a glass of wine while you cook if you need it to slow yourself down, and enjoy the experience.
6. The lemon juice and cayenne at the end are critical. You could also pass a little hot sauce at the table if you’ve kept the cayenne to just a pinch.

Enjoy!

More Questions About Questions About Mammography

A well-done analysis in the BMJ this week calls into question previous research that has been used to tout mammography as an effective tool for lowering breast cancer mortality in Denmark.  That previous study compared breast cancer death rates in Copenhagen, where women were offered screening mammography in 1991, to areas in Denmark where mammograms were not offered until 17 years later, and concluded that the introduction of mammogram screening resulted in a 25 % reduction in breast cancer mortality in screened areas.

The new study adds an additional county where screening was offered (with a little implication that perhaps the previous researchers should have included this other area, but I’ll stay out of the academic finger pointing) and then reanalyzes the data.

The researchers found that breast cancer deaths declined nationwide during the time period studied, in all areas, regardless if that area was one offering the screening program. Much of this decline occurred in women ages 40-49, who were too young to have been offered screening. This suggests that it is breast cancer treatment rather than screening that should take the credit for most of the mortality declines in Denmark over the time period studied.

The researchers then go on to make this statement-

We believe it is time to question whether screening has delivered the promised effect on breast cancer mortality.

-practically guaranteeing that I’d have to read their paper and comment on it. So I am.

My take

I’m not convinced that this paper makes the point that mammograms are ineffective. The authors themselves argue that the effect size of mammography, estimated at about 15-16% in randomized trials, is too small to be measured in epidimiologic studies. I  agree. It is just impossible to control all the confounding factors inherent in an entire population of individuals to tease out the effect of a single intervention over time, particularly when breast cancer treatment was evolving so rapidly over the time period being studied.

I have to admit that I have a hard time believing that, for 17 years, women living outside of Copenhagen never entered that fair city to have a mammogram on their own dollar once they found out that their city-dwelling friends were being offered the test and they weren’t. (The paper used to support the claim doesn’t make the case in my opinion.) I know that Europeans have not bought the whole mammogram thing hook, line and sinker the way we here in the States have, but I don’t think it is as black and white as the Danes would like us to believe. (If you are a Danish woman reading this, feel free to enlighten us…) But that’s just an aside.

Bottom Line

This is an important paper in that it effectively refutes previous conclusions about the Danish mammogram screening program. Unfortunately, I don’t think this study stands on any stronger ground in arguing that mammograms are ineffective. Nothing in this paper rescinds the results of the randomized trials, which the authors themselves state find a mortality reduction of about 15-16% for mammography. In my opinion, their results primarily show us that population based data is nearly impossible to use to make any valid conclusions about mammogram screening – either for or against it.
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Hat tip to Gary Schwitzer for pointing me to this study

Already missing him

NHS Blogdoctor has retired from active practice in the NHS and closed his blog.

Healthcare and the NHS is a big topic but I have said what I have to say and increasingly I am just going round and round the houses. I remain committed to the ideal of a decent standard of healthcare being available to all, independent of means and status. Sadly, we are further away from that ideal than we were five years ago when I started NHS BLOG DOCTOR. I am not optimistic about the future.

He will be missed.

What I find interesting is that Dr Crippin not only stopped blogging, he took  his blog down. Completely. Just try googling him – Nothing there.

I wonder what led him to pull the whole thing off the servers.   I guess he just didn’t want to be bothered with dealing with any repercussions of previous writings.  Close the books. Turn the page. Move on.  I get it.

Still, it would have been nice if he had left it up there for posterity.

Enjoy whatever comes next, Dr Crippin.

There’s No Place Like Home

It’s funny, but I barely remember the first time I visited New York. I was nine years old, and went with my Dad and brother to see the World’s Fair in Queens. I remember the It’s a Small World Exhibit, but mostly I remember the car ride home on the Jersey Turnpike, gazing out at the brightly lit New York skyline and realizing for the first time that if it’s dark outside, you can actually look sideways out the window and not get car sick.

The next time I visited New York, I was on an eight grade class trip. I think we went to the United Nations, but I don’t recall that. Here are the two things I do remember – (1) singing “99 Bottles of Beer on the Wall”while stuck in traffic coming out of the Lincoln Tunnel onto 42nd Street, which in those days was lined with Peep Shows and Porn Shops and (2) being a smart-ass with my friends and leaving a one-cent tip at the restaurant in Tudor City where we were packed in and served overcooked Salisbury Steak, which was basically inedible. (Even then, I was a food critic..)

The third time I visited New York, I fell in love.

It was a day trip I took during college with my best friends. I think we must have seen a play, but for the life of me, I don’t remember what it was. This time it was lunch at Mama Leone’s, which even I, the rube from Philly, recognized as cattle call for tourists – the place was loud and packed and I felt like a number.  And the portions?  HUGE. Like “I think I’m gonna’ be sick”, huge.  So we decided to walk it off with a stroll in Central Park. And it was there, sitting under the Wisteria Arbor on the West Drive, that I fell. Hard.

Maybe it was  the intoxicating floral perfume. Combined with post-prandial carbohydrate overload and a bit of a buzz from the wine we had with lunch. And a warm spring day and best friends. And that skyline. (Clearly, it was not the food…) All I knew was – I was in love. With a city. And I knew – I had to move here.

So after college, I did. I spent two years living in the Village and going to grad school at NYU, a time during which I moved four times with a succession of three different room mates, ran out of money after 6 months and started working full time and going to school at night, lost my innocence and my baby fat, suffered a few bouts of great loneliness, fell in love,  had my heart broken and broke one myself, and tried and failed to get into medical school, until I tried again and was accepted to a school back in Philly. I was so happy to just get in that I didn’t think twice about leaving New York. I had more important things to do than be in love with a city.

So, I moved back home. Where I got my MD, did a residency, joined a med school faculty, moved a few more times. Alone the way, I met Mr TBTAM and the rest is history on that front. We had a kid, bought a house – you know the deal. I think I came back up to New York to visit once or twice, but my heart was in Philly. Or so I thought. Until one day, during a time when I was feeling a bit frustrated in my job, someone offered me another one here. It took me about a minute to consider it before I knew the answer had to be yes. It took Mr TBAM a little longer than that to warm to the idea, but he pretty quickly did (not that I gave him much choice). So we sold the house and the car, took the kid and moved to the Big Apple.

That was almost 16 years ago. Since then, we’ve only moved once, within the same building, to a bigger apartment. We lucked into the world’s best nanny, had another kid and sent both our girls to NYC public schools, which have their problems but have overall served us well. And I learned that while New York City can sometimes be a lonely place for a single person, it’s heaven for a family.

Needless to say, New York City and I are still going strong. Which is not to say that I am happy 24-7, or that life has been perfect. Because it is not. For a time there around 9-11, New York and I were in a rough patch. Not that I ever thought of leaving, because I didn’t.  But it wasn’t fun in those days – how could it be?  And yet, we came through it, New York and I, stronger than ever. We made it through the worst and are still together.

Now, I don’t think a day goes by that I don’t get that little jump of joy to realize that I call this place home. Like when I walk home from a play on Broadway. Or head to the bus after a parent teacher conference and find myself on the steps of Lincoln Center. Or stop in at St Patrick’s to light a candle for my Mom. Or strike up a conversation at the hair dressers with another client and find out she’s getting ready to sing in the Opera that night at the Met. Or ride my bike in Central Park, shop for dinner at the Union Square Market, go to a Friday night movie at the Film Forum, get off the subway at Bryant Park to meet a friend for lunch, stop in at the Metropolitan Museum after a doctor’s appointment or gaze out the window of the bus home from Laguardia Airport and realize I’ve just passed 5 Equadorian restaurants in two blocks and wonder how soon I can come back to try one of them.

You know that feeling you get when you walk in the door of your house after a crazy day, or a long trip away? You drop your bags and your heart rate slows down, your spine softens, your feet sink into the entryway carpet and you feel every muscle in your body relax. Everything’s right again. You’re home.

Well, that’s exactly how I feel now when I come out of the Lincoln Tunnel onto 42nd street. It’s absolutely  true. I just sink down in my seat, look out the window, take a long, deep, contented breath, and smile as I head into that bright as day all night long, neon-plastered, subway faster, tourist gawking, vendor hawking, corporate whoring, pigeon soaring, traffic stalling, theater crawling, Big Ball falling, pedestrian malling, tour bus loading, restaurant rowing, taxi honking, honkey-tonking place called Times Square.

I’m home.

Moving Pains and More MedBlog Finds

Sorry if things have been a bit quiet around here lately. I’m in the midst of a blog makeover as I migrate from Blogger to WordPress.  Being both an idiot and a cheapskate, I’m trying to do all the work myself, which is beginning to suck away both my time and my energy. But I love how the new site is looking, and hopefully so will you. You can expect to find all the recipes compiled and categorized, travelogue links and lots of medical info that will hopefully be more accessible than it is now via the blog archives.

At the moment, however, I’m crashed over at WordPress. This nice Headway theme I found that seemed so easy to use isn’t as easy as it looks. Waiting on customer support to help me fix what seems to be a really big bug before I can do anything further.  Not to mention all the tweaking I need to do to the old post images to get them transferred over. I’ll let you know when it’s all done…

In the meantime, new Medical blogs are cropping up all over. It’s fun finding them. Here are a few more recent finds –

Gyno Gab – Billed as “All things gynecology, STDs, obstetrics, women’s health. Your questions, my thoughts, the buzz on what’s new and in the news by a Board Certified Obstetrician and Gynecologist.”

OB Cookie – All Hail the gyno-food blog!

Dr Griever’s EMR – A Canadian physician documents her experience with EMR implementation and usage in a family practice. Most interesting is reading how she begins to tap the EMR to track and improve the quality of care in her practice.
Mommy Doctor – Self described anesthesiologist by day, suburban Ninja mom by night, scientist, iPhone addict, internet geek, occasional blogger, grateful Christian, cookbook reader but not user, tiny Asian bombshell happily married to big white guy. Hmm….I’d add excellent blogger to that list. Just read this post and you’ll know what I mean.
Forbes Science Business Blog – Another excellent mainstream blog, joining the ranks of the WSJ healthblog and Tara Parker Pope’s blog in the NY Times.

See you all soon, hopefully at my new place!

Research Results Reporting by Press Release

Roche has decided they can’t wait for either a scientific meeting or a journal publication – they’re releasing their clinical trial results now by press release.

Here’s their latest press release on the ‘results’ of their clinical trial of Avastin in ovarian cancer –

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that a phase III study showed the combination of Avastin (bevacizumab) and chemotherapy followed by maintenance use of Avastin increased the time women with advanced ovarian cancer lived without their disease worsening (progression-free survival or PFS) compared to chemotherapy alone. A preliminary assessment of safety noted adverse events previously observed in pivotal trials with Avastin. Data from the study will be submitted for presentation at the 2010 American Society of Clinical Oncology (ASCO) annual meeting, June 4 to 8, 2010.

Note, if you will, the complete absence of any data.

Which means one of two things – either  (1) “lived longer” means something like a few weeks, and Roche figures they’d better hurry up and get their little stock bump now before the real results come out in June; or (2) the results are so fantastic that they just couldn’t wait to tell us all. Anyone wanna’ venture a guess as to which it is?

Doesn’t the FDA regulate this sort of stuff?

Vaginal Estrogen – Less May Be More

If there’s one thing I’ve learned over the years when it comes to medications, it’s this – more is not necessarily better. You can have too much of a good thing, and less can sometimes be more.

Certainly that’s been the mantra when it comes to hormone replacement in menopause. Since the WHI findings were released in 2002, we’ve all been going lower and lower with estrogen dosing, and finding that, for many women, it’s more than enough to treat the symptoms.

Now, a new low dose formulation of vaginal estrogen, Vagifem 10 ug, approved in Dec 2009, has hit the market. I have to say that I am thrilled to have this option for my patients.(I know, some of you are in shock that I would actually be talking favorably about a new drug, but hey, when they get it right, they get it right.)

Research has shown that vaginal 10 ug estradiol tablets are effective in treating symptoms of postmenopausal vaginal atrophy and dryness. While the previously marketed 25 ug vaginal estradiol preparation was superior in some measures when the two were compared, the lower dose may be all that some women need.

Why go lower dose? After all, the 25 ug vaginal estradiol dose is pretty darned low, and does not typically lead to elevation of estrogen levels above the normal postmenopausal background after the first two weeks of use. But I have had occasional patients complain of breast tenderness in those first two weeks of more intense Vagifem use (you use it once a night in the beginning, then twice a week after that) and even one or two for whom the use of vaginal estrogen triggered a headache. I’ve been anxiously waiting for the lower vaginal dosing ever since the research was published on its relative efficacy. Glad to see it’s finally here.

Medicare recently moved this Vagifem off its preferred formulary, which has been a real problem for a lot of my older patients who no longer can afford it, even though they prefer it over the vaginal creams. As do I, since absorption is probably lower with the vaginal tablets than the creams. (The vaginal ring had the lowest systemic absorption until now, but unfortunately it is too large for some women to use.)  Fortunately, we can customize the cream to a lower dose by just using less of it.

Of course, some women, particularly those at increased risk for breast cancer, are uncomfortable with estrogen in any form. For these women, there are over the counter vaginal moisturizers. And a good  lubricant is helpful for sexual activity, even for some women using vaginal estrogen.

The big question is, will this new low dose vaginal estrogen be low enough for women using aromatase inhibitors? These women suffer terribly from vaginal dryness, but even vaginal estrogen may be too much for them, since we aim for serum estrogen levels of zero in this group. It’s an important question that will need to be studied before any of us are comfortable using even this lower dose preparation in this important subgroup of postmenopausal women.

Brussel Sprouts Gratin with Pine Nuts and Breadcrumb Topping

As I was preparing this dish for dinner, my sister and brother-in-law flatly informed me – “We’re not going to like it. We hate brussel sprouts.” I proceeded to lecture them that the brussel spout flavor they and so many others loved to hate is actually the result of over-cooking, and that I was sure they would love this dish. They did not believe me, and we almost got into a shouting match when I tried to push the point.

You know, of course, how this story ends. Yes! Two more converts to Brussel Sprouts!

Brussel Sprouts Gratin with Pine Nuts and Breadcrumb Topping

This recipe beats my previous fave preparation of sprouts. It’s a modification of a recipe from Bon Appetit that also includes cauliflower. I left the cauliflower out, seeing no need to have to confront the cauliflower haters as well. I use homemade bread crumbs in this recipe. If you use store bought, toast them up in a pan with some olive oil before combining with the pine nuts.

This dish can be assembled beforehand, covered with foil and refrigerated for up to 24 hours before baking. Increase bake time to 45 minutes if going straight from the fridge to the oven.

3 pounds brussels sprouts, trimmed, quartered lengthwise
2 3/4 cups heavy cream or half and half
1/2 cup chopped shallots
1 tablespoon finely chopped fresh sage
1/2 cup homemade breadcrumbs
1/2 cup pine nuts, lightly toasted
2 tablespoons chopped fresh Italian parsley
3 cups grated Parmesan cheese, divided

Cook brussels sprouts in large pot of salted boiling water for 5 minutes. Drain. Transfer sprouts to bowl of ice water to cool. Drain well.

Combine cream, shallots, and sage in large saucepan. Bring to boil. Reduce heat; simmer until mixture is reduced to 2 1/2 cups, about 10 minutes. Season with salt. Remove from heat. Cool slightly.

Combine breadcrumbs, pine nuts and parsley. Season with salt and pepper. (Seasoning not needed if you use seasoned homemade crumbs as I do.)

Butter 13x9x2-inch glass baking dish; arrange half of vegetables in dish. Sprinkle with salt and pepper, then 1 1/2 cups Parmesan. Arrange remaining vegetables evenly over, then sprinkle with remaining 1 1/2 cups Parmesan. Pour cream mixture evenly over. (Can be made ahead up to this point.)

Cover gratin with foil. Bake covered 40 minutes at 375 degrees fahrenheit. Uncover; sprinkle breadcrumb topping over and bake uncovered 15 minutes longer.

Paroxetine (Paxil) Impairs Tamoxifen Benefits in Breast Cancer

An important Canadian study has shown that the use of paroxetine (Paxil) in breast cancer patients taking tamoxifen is associated with an increased risk of death from breast cancer. These findings, which were published this week in the British Medical Journal, add to a growing body of evidence that certain (but not all) SSRI antidepressants neutralize tamoxifen’s beneficial effects in treating breast cancer by interfering with it’s metabolism.

First, a few things about the study –

  • The study was done using a combination of pharmacy records, cancer registry records, hospital databases and death certificates in seniors, the age group for whom this data were readily available.
  • The study included women taking both tamoxifen and an SSRI between 1993 and 2005.
  • The median age was 74 years old (range 70-79 years)
  • We know nothing about the stage of breast cancer in these patients
  • By the end of the 2.8 year follow up, 44% of the participants had died from any cause (not surprising given the age of the study cohort), including 15% in whom breast cancer was listed as one of the causes of death.
  • No comparisons were done among women taking tamoxifen only. The researchers compared women taking different SSRI’s to one another, and within each SSRI group, compared different duration of uses as a way to measure the effect of the potential interaction.

What the researchers found

Use of Paxil was associated with an increase in deaths from both breast cancer and other causes during the follow-up period. (See PowerPoint graph ). The increase in risk was higher with longer overlapping use of Paxil with tamoxifen, and ranged from 25% to 91% increase as time on the two drugs together increased, meaning that the risk was almost double with longest use in the study. All of these results were statistically significant. (For those who know statistics, that’s a relative risk of 1.24 to 1.91 and the 95% confidence intervals did not include 1).

In more meaningful layman’s terms, there will be 1 additional breast cancer death for every 20 women taking Paxil and Tamoxifen together 41% of the time (the average in the study). If Paxil is taken the entire time tamoxifen is used, there will be 1 additional death for every 7 women treated with both drugs.

What is additionally interesting about these numbers, according to the study’s researcher Dr. David Juurlink (who graciously agreed to speak to me today), is that 7 is the number of women need to treat with Tamoxifen to prevent one breast cancer death. So, Paxil essentially is neutralizing the tamoxifen effect.

The Results are Biologically Plausible

In order to be effective, tamoxifen must be converted in the body to its active metabolites, the most potent of which is 4-hydroxy-N-desmethyltamoxifen or endoxifen. The conversion of tamoxifen to endoxifen is catalyzed by an enzyme called CYP2D6. SSRI antidepressants interfere with CPY2D6 to varying degrees, with Paxil being the most potent of the SSRI’s in this regard . (So potent that they actually call it “suicide inhibition”.) Thus, use of Paxil makes tamoxifen less effective, attenuating the survival advantage imparted by tamoxifen use.

(Note – Not all women are inherently able to optimally metabolize tamoxifen to its active metabolites, and research suggests that so called slow metabolizers of tamoxifen may have worse breast cancer outcomes. Genotyping for CYP2D6 variation may prove to be a useful genetic marker for tailoring of cancer treatment in this group.)
Another expected finding of the study was that women taking Venlafaxine (Effexor) had a reduced risk of breast cancer deaths. Venlafaxine is used to treat the hot flashes associated with tamoxifen use, and women who have hot flashes while using tamoxifen may have better survival, probably because the hot flashes are a good sign that the Tamoxifen is being activated to Endoxifen. So this group would be selected to have better survival from the start, and the use of a weak CYP2D6 inhibitor doesn’t appear to impede this survival advantage within the study group.

What was unexpected in the study results was that fluoxetine (Prozac), another known potent inhibitor of CYP2D6, was not associated with an increase death risk compared to the other less potent CYP2D6 inhibitors. The researchers warn, however, that this may be due to the relatively small numbers of women on this drug in their population. “We want to be careful that this study is not used to bless the use of fluoxetine in tamoxifen users”, says Dr Juurlink.

A few more notes on study design

Given the robustness of the data sets they had, which appear to include both cancer registry and hospital records, it’s a shame that the researchers did not have information on breast cancer stage, an important potential confounding factor. It’s a limitation of the study that they acknowledge in the paper.

I also found it odd that the researchers chose only to compare the SSRI’s to one another, without having a control group of tamoxifen users not taking an SSRI. Juurelink explained that this was a deliberate choice, to avoid potential unknown variables that would affect mortality and be associated with the need to use antidepressants.

Importance of Drug-Drug Interactions

We were first clued in to the potential interactions between SSRI’s and tamoxifen in 2005, when a landmark paper was published in JNCI on the pharmacologic interactions of these two classes of drugs. Since them, several other pharmacologic studies have confirmed the interactions and clarified which SSRI’s are problematic and which are not, and concomitant use of the more potent PYP2D6 inhibitors has decreased. In 2009, a paper presented at the American Society of Clinical Oncology reported that women who used a potent or moderate CYP2D6- inhibiting SSRI (paroxetine, fluoxetine or serttraline) in conjunction with tamoxifen had a two-fold increase in breast cancer recurrence compared to use of weakly-inhibiting SSRI’s (citalopran, escitalopram and fluvoxamine). This BMJ study is the first to report an increase in breast cancer mortality resulting from these interactions.

Enormous credit goes to those who first suspected this interaction between SSRI’s and Tamoxifen, did the excellent research to confirm it, and then went the extra mile to help identify which SSRI’s are safe to use with tamoxifen and which are best to avoid. Treatment of depression in cancer patients can be critical to both their physical as well as emotional recovery, and it’s important that we continue to have options that are effective for depression without interfering with cancer treatment.
What should you do if you are on an SSRI and Tamoxifen?

First of all, DO NOT suddenly stop your SSRI, since severe withdrawal symptoms can occur. DO talk to your doctor about which SSRI medication you are taking. If it is paroxetine or fluoxetine, it is recommended that you try to change to an SSRI that is a less potent or non-inhibitor of tamoxifen metabolism.
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Kelly, C., Juurlink, D., Gomes, T., Duong-Hua, M., Pritchard, K., Austin, P., & Paszat, L. (2010). Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study BMJ, 340 (feb08 1) DOI: 10.1136/bmj.c693

Photo licensed from Istockphoto.com

Claims Based Quality Measurement – Wasting My Time

I got a letter from an insurer the other day, warning me that my patient, who had just refilled a prescription for a bisphosphonate I had prescribed almost a year ago for severe osteoporosis (yes, I do still prescribe dugs, despite how I feel about Big Pharma marketing), also had a claims diagnosis in their system for a bleeding peptic ulcer, and was I really sure she should be taking this medication, which could worsen her ulcer?

So do what any conscientious physician would do – I call her. (Of course, no one is ever home when I call these days, so it’s another few days of phone tag before I get her.) No, she has not been diagnosed with anything of the kind. Feels great, in fact.

I press the point – did she see her primary for an upset stomach? Have a recent endoscopy? Pain? GI Bleeding? Is she taking any new meds, maybe something for her stomach like an H2 blocker (I name them all).

Nope. Nothing’s new.

Okay, I tell her. Take you meds and I’ll see you in the spring for your check up.

Waste of my time….

Chocolate Zucchini Cake – What a Batter!

I have a confession to make – I am a batter taster.

I love those moments just after the cake pan is put into the oven, when the empty bowl beckons. The kids have absconded with the mixer paddle, which they have licked clean and left somewhere around the apartment, where I will have to fetch it in a few minutes. But for the moment, I am left standing at the counter next to the sink scavenging the Kitchen Aid stainless steel mixing bowl.

My technique is to use the thumb side of the pointer finger, trying to get as much as possible with one swipe as I run it across the bottom and around the rim of the bowl. I lick the batter from my fingers with abandon and without shame, going for every last bit of loveliness I can find. Towards the end, I often have to resort to using the red rubber spatula, but somehow this does not bring the same satisfaction as the finger swipe.

When it becomes clear that I have gotten all I can get without resorting to licking the bowl itself (that would be going too far), I reluctantly let go of the bowl, dropping it into the soapy water in the sink as I imagine that I am Rose, prying Jacks’ frozen fingers from mine and releasing him into the icy blackness alongside the sunken Titanic.

Rules for Batter Eating

As you might expect, there are certain rules for batter eating. This lends to the act a sacredness shared by other religious dietary laws. First, one must wait until the entire batter is made. Baking is chemisty, and early tasting risks upsetting the delicate balance of ingredients in the final product. Just try telling this to your daughter as she reaches into the bowl for a clump of brown sugar and butter you have just creamed while making chocolate chip cookies…

Secondly, one must limit oneself to small amounts of batter, since removing too much for tasting risks not having enough final product to fill the pan. As you might expect, this sets up great personal conflict, and I often feel the inner struggle as I use the rubber spatula to get the last bits of batter into the cake pan, knowing that in doing so, I am leaving less for myself to taste later. (Ah, sweet turmoil!)

Finally, batter is not something to be eaten in anything other than small amounts – some would say not at all – and most certainly not if you are pregnant or immuno-suppressed, since, after all, eating raw eggs risks salmonella. I must say, however, that in almost half a century of licks I have yet to become ill.

You can judge a cake by its batter

I truly believe that one can judge a cake by its batter. In fact, I can say with confidence that if I don’t love a cake uncooked, I won’t like it when it’s finished – so I might as well not waste the energy baking it up. Which reminds me of a tongue twister my mother taught me as a child –
Betty Batter bought some butter.
“But”, she said, “this butter’s bitter!”
“When I put it in my batter,
It makes all my batter bitter.”
So, she bought some better butter
and put it in the bitter batter,
to make the bitter batter better.

If you are a batter taster, you’re going to love making this Chocolate Zucchini cake, which comes from a recipe I found at Alpineberry, who got it from the King Arthur Flour Website. I don’t even care that I didn’t win her King Arthur Cookbook giveaway. This batter is prize enough.

Oh, right. The baked cake was lovely.

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Everyone loves this cake! (But did they taste the batter?)