OK, enough of gods, goddesses, cardiologists and the beings that they impregnate. Those cardiologists will never listen to me any way. Soon everyone over 50 will be on a statin! Anyway, back to the humble world of emotion, psychiatry, and the question of…

…will you be my friend?

That’s right, folks, facebook time. And blogging. Front and center.

I had a story about the ‘will you be my friend’ quote but it isn’t appropriate for public consumption.

Anyhoo, you know what I am talking about. Using your mouse to point your cursor at someone’s name on Facebook and then waiting for their response, and then…

…voila! You have a new friend!

[heart goes pitter patter, etc]

I have become ‘friends’ with people I have never met, who ‘friended’ me because they read my book, and then ‘introduced’ me to others who had written books on similar topics, or had similar views, or were liberals like me, and I became ‘friends’ to them site unseen. I found the exchange all quite exhilarating, liking being at a fancy ball. It didn’t matter much to me that I had never met them. I just liked reading their posts, causes, status updates. And for old college friends and the like the where are you now stuff is kind of interesting.

My fellow shrinks blogging on ShrinkRap have written about the psychological meaning of facebook.

I agree with them that you should not “friend” your patient, your doctor, your children or your parents. You can, however, friend nieces and nephews, siblings, spouses, old schoolmates, and (disagreeing with them, I feel that if you want you can friend) people you have never met but who share similar interests.

As I wrote on their site, facebook is a way for vapid narcissists (such as myself) to form weak relationships with others through the internet. In my “book” it is fine to friend people you don’t know who share a similar interest, in my case health and drug news.

However, I have attempted to ‘friend’ others who had similar interests, who responded:

Hi Doug, Have we actually ever met?

To which I had to reply in the negative, although I said I had read his writing, and sent him a link to my blog, which he never responded to, which left me with a feeling of…

sadness… [head down, sniff]… emptiness (especially since Mrs. Bremner is away at the AHA this week)

Which leads me to the next topic, being ‘out there’ on the internet.

A friend of mine was sending some of my post to a yahoo group and so I joined, not knowing anything about these groups. And then when I quoted some of the things they were saying someone said they felt ‘violated’ because these comments were not for public discussion. She informed me that the ‘rules’ were that comments in the ‘group’ were private.

I realized I really knew nothing of these ‘groups’ or whether the comments were public or private. I needed Emily Post for the internet.

Here is another example. In my initial enthusiam for my blog when I got copied on emails for health related things I would put people on my email list. I posted that they should say ‘unsubscribe’ if they wanted off. But I have since learned that some people think that is a violation to have to say ‘unsubscribe’. So I no longer put people on my list unless they ask. Now I have figured out RSS feed (say Dinosaur, Duh!) people can choose for themselves.

And if you want to get off of this list say *unsubscribe* or f**k off!

Or, if you don’t take me off of this list I will blog about you! (real comment)

Ciao.

[Originally posted November 11, 2008]

COMMENTS

Great blog as always Doug!

Check out the Wikipedia link for facebook.

With the advent of social networking, an irony is occuring. On some such site, one may share intimate details about themselves and their lives, yet have not spoken with their neighbor across the street since last year. Is is because we are bombarded with [information from the internet]

Greetings from the Shrink Rappers!

Dinah on the web site Shrink Rap pointed out her post on psychiatrists as bloggers here.

And I got the quote of the day therebased on my comment that psychiatrists are not magicians or mind readers and cannot be blamed for all the adverse reactions our patients have to psychiatric drugs which led to a lively ongoing discussion on that site.

btw the person I blogged about agreed to be my friend! [not sure if he read my post first though]

Mrs. Bremner [DOCTOR BREMNER to YOU guys!] is attending the Annual Meeting of the American Heart Association this week in New Orleans and texted me some news about the release today of results from the JUPITeR study (”Justification for the Use of statins in Prevention: an Intervention Trial evaluating Rosuvastatin (JUPITeR)”) published in the New England Journal of Medicine

.

(gasp), Oh really. I think this one would definitely not have been a turn on for Aphrodite.

Ha, ha.

Based on the results of this study, that a biomarker of heart disease, C-reactive Protein (CRP), predicts response to the drug Crestor (rosuvastatin) (and not just total cholesterol or LDL cholesterol), the authors of this study would apparently like us to come to the conclusion that, basically, all of us should be on a statin medication for the prevention of heart disease. In fact, I can already hear the shills and the media saying “revolutionary” and “likely to change practice”! In fact there is even a cheesy site on the New England’s website asking us how it will change our practices (gasp, shame).

We’ve been through this drill before, when our country’s “leading” cardiologists informed us that statins were so great that they should be put in the drinking water.

But now, let us turn our attention to the results of the JUPITeR trial.

17,802 healthy men and women with LDL cholesterol of less than 130 mg per deciliter and CRPs of greater than 2.0 mg per liter were given either rosuvastatin 20 mg per day or placebo. They were then followed for the occurrence of the “combined primary endpoint” of heart attack, stroked, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.

First of all, whenever doctors start combining real disease outcomes (like dying of a heart attack) with what are primarily… er… inconveniences, like going to the hospital, you have to start wondering about the study.

OK. So what about the results, you say. For their primary outcome out of 100 people treated each year there were 0.77 versus 1.36 who had an event like heart attack, hospitalization, etc. That is a difference of 0.59%. But I am going to ignore their cheesy primary endpoint and look at what to me matters, which is heart attacks. For each year of treatment out of 100 people 0.17 in the Crestor group versus 0.37 in the placebo group had a heart attack, or a difference of 0.2%, which would have amounted to a 1% difference over five years if the study had continued for that long, but the study committee cheerfully “stopped” the study after 1.9 years since they thought things were going so well that it would be “unethical” to continue the study (Hooray!).

I guess that 1% of responders outweighs the 3% or so that will develop liver toxicity or muscle damage.

Study results that will change clinical practice, indeed.

BTW, look at the end of the article for the long list of consulting agreements to the pharmaceutical industry engaged in by the authors of the study. And funding by AstraZeneca.

[originally posted November 10, 2008]

COMMENTS

The study excluded subjects with diabetes or hypertension and there was a four week “placebo” run in phase and subjects who were not compliant during that phase were dropped. 80% of the patients were excluded and many more were excluded during the placebo run in phase. What this means for the regular patient is unknown.

Marilyn Mann wrote on November 10, 2008

Just read this. Wondering why you did not mention 20% reduction in total mortality. Also interesting that women benefited to the same extent as men.

See studies published ahead-of-print yesterday in Circulation and Circulation Cardiovascular Quality and Outcomes for more info on CRP.

C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction. The Reynolds Risk Score for Men Paul M Ridker, Nina P. Paynter, Nader Rifai, J. Michael Gaziano, and Nancy R. Cook Circulation published 9 November 2008, 10.1161/CIRCULATIONAHA.108.814251

C-Reactive Protein and Reclassification of Cardiovascular Risk in the Framingham Heart Study Peter W.F. Wilson, Michael Pencina, Paul Jacques, Jacob Selhub, Ralph D’Agostino, and Christopher J. O’Donnell Circ Cardiovasc Qual Outcomes published 9 November 2008, 10.1161/CIRCOUTCOMES.108.831198

Doug Bremner wrote on November 10, 2008

The reduction in total mortality was 1.0 per 100 patient years versus 1.25 in the placebo group, a difference of 25% in relative risk, but of 0.25% in absolute risk (i.e. not that great). I think one thing this study highlights is that maybe LDL reduction is not the “cause” of risk reduction, or at least exclusively.

The other issue is what the clinical implications of this study are. Are doctors going to check CRP and LDL in everyone and treat whoever fits either profile? That means everyone will be on this stuff. Crazy.

David Diamond wrote on November 10, 2008

Doug – great commentary on the Jupiter trial and kudos to you for your muckraking blog

the whole statin revolution seems driven by big pharma greed with little real benefit to the population, followed by sheep-like docs who can’t see the flaws in the research

can you imagine turning the CHD word upside down by showing better CHD outcomes with a diet low in sugar and high in chocolate vs a statin?

Odysseas wrote on November 10, 2008

Again, I think people get so enamored by the relative risk that they dont even consider the difference in absolute risk or the NNT… (The calculation may be useful for some readers) As the fanfare dies down, perhaps a thoughtful discussion will ensue..

Doug Bremner wrote on November 10, 2008

Yes, the relative risk v absolute risk distinction is critical. The story I use is for primary prevention in men with risk factors. Out of 100 men, 4 men on placebo will have a heart attack in five years v 3 on a statin. If you told someone that a drug would reduce his risk of having a heart attack by 25% (and told him none of the risks, he would take it! If you went into a room of 100 men and said I want you all to take a drug and it will prevent only one of you from having a heart attack, but three of you will have some liver damage or muscle pain, and maybe it causes cancer but we are not sure, they wouldn’t take it. Both describe the same situation (going from 3 to 4 is a 25% change (relative risk) but 4%-3%=1%). Crucial distinction. Most doctors don’t understand, but the pharma detail people do. And they always use the one that suits them best. Also, NNT is the number needed to treat. Means that (in this case) 31 patients need to be treated for four years to save one from a cardiovascular event or procedure (their primary outcome). Which isn’t all that great. The authors pointed out that this is similar to prior studies of those with high LDL, but all that says is that LDL is not the be all and end all (the cardiology research community has been moving toward the inflammatory pathways area for several years now; elevated CRP is probably associated with the metabolic syndrome, etc).

Thanks for making these important points. They deserve a press story.

Mathew? Caleb? Anyone?

David dcsciencewrote on November 11, 2008 on his blog

Here is a link to a discussion of should we all take statins and relative versus absolute risk

[David is currently discussing creationism; recommended blog for fans of science and skepticism]

Therapy Patient wrote on November 12

I groaned when I heard that report on NPR today and was disappointed none of the interviewed doctors mentioned muscle and liver problems. My Dad was one with muscle pain and weakness and a deteriorating liver but his cardiologist insisted he stay on the drug. Dad stayed on the drug and Dad died. Well he was 90 and had a host of problems, so who is to say what killed him? The autopsy listed a long list of problems. I take a statin, that’s for sure!

With statins as a class of medications: A.E.s are often under-reported with high doses of potent statins in particular. Additionally, there is no reduction in mortality or increase in the lifespan with those on statin therapy.

Dan Abshear wrote on November 12

Several risk factors should determine if one is placed on statin therapy, and not just one. Statins do decrease CV events and risks significantly.

The meds. increase endothelial function, stabilize coronary plaque build up, and decrease thrombus formation. Maximum reduction in LDL is evaluated after about a month of therapy from any particular statin. There is evidence to suggest that statins have other benefits besides lowering LDL, such as reducing inflammation (CRP), those with dementia or Parkinson’s disease, and some forms of Cancer and cataracts. It appears those statins produced by fermentation, such as Zocor and Pravachol, have less myopathy than the other synthetic statins, possibly due to being more hydrophyllic. Yet overall, the existing cholesterol lowering recommendations should be re-evaluated, as they may be over-exaggerated. With children, diet needs to be controlled with them so they do not develop arteries of one who is middle age and a possible candidate for statin therapy,

Dan Abshear

That’s a translation into person speak from a letter I got today from Bayer Healthcare Pharmaceuticals that started out with “Dear Healthcare Professional” and went on to their new “black box warning” for their antibiotic drugs Avelox (moxifloxacin hydrochloride) and Cipro (ciprofloxacin). Here is their warning:

Fluoroquinolones, including Avelox/Cipro, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.

Well it’s about time. I wrote about this nasty habit of cipro to snap tendons and mess up joints over a year ago in my book because at the time Cipro was the most poorly rated drug on askthepatient.com. I hate to say I told you so, but, I did tell you so. It’s just too bad that it took the manufacturers a couple of years to get the word out. I wish people in the healthcare industry would read these websites, which patients go to only out of desperation.

Unfortunately, 81% of the time this toxic drug, Cipro is prescribed inappropriately, and 32% of women get this drug inappropriately for new onset urinary tract infections, when the preferred first drug is Septra.

Another drup in the same class as Cipro is Levaquin, which is the third most discussed drug on medications.com, just behind my other two faves, Yasmin (the birth control pill that might make you nuts) and Singulair (asthma drug with similar problems). Levaquin and like drugs also seems to drive people nuts, which reinforces my conclusion that when it comes to drug companies, if they don’t kill you they might drive you crazy.

So let’s all sing “I need a drug that won’t drive me crazy” to the tune of I need a lover that won’t drive me crazy,” by John Cougar Mellencamp.

[originally posted November 8, 2008]

[updated Feb 15, 2009]

See site of a patient suffering from long term effects of Levaquin “Death by Levaquin.”

I don’t care if it may give me breast cancer or heart disease. Thanks, APHRODITE Study Team!!

APHRODITE Study Team? ROTFL!!

I SWEAR TO GOD I am not making up this goofy study name.

I wonder if the study investigators ever got horny at one of their research meetings? Or by looking at their data?

Anyway, seriously folks. The results of the “A Phase III Research Study of Female Sexual Dysfunction in Women on Testosterone Patch without Estrogen (APHRODITE)” study published in the NEJM today showed that if post-menopausal women who have a loss of libido put a testosterone patch on their arms that they will have satisfying sex once a month more than they are currently having, although there may be a risk of breast cancer or cardiovascular disease [read on]

I’ve got a tip for the marketers of this testosterone patch. If the women are having satisfying sex only once a month, and now they have it twice, why don’t you say that the drug results in a 100% increase in satisfying sex!!!

Ha ha ha ha ha!

OK folks all fun aside lets look at the data. In this study Davis et al (Davis SR et al NEJM 2008; 359(19): 2005-2017. November 6 2008) studied 814 women treated for 52 weeks with 300 or 150 microgram testosterone patches or placebo patches. There was an increase in “satisfying sexual episodes” of 2.1 in treated versus 0.7 for placebo, an increase that was statistically significant. There was about a 10% difference in scores on a sexual pleasure scale. 30% grew unwanted hair v 23% for placebo. Breast cancer was diagnosed in 4 out of 527 treated women and in none of the women on placebo.

That’s right folks, sex once a month. And possible risk of getting breast cancer.

And a beard.

Nonconclusive results about cancer you say. And Mrs Robinson asks if she has anything to worry about.

Well a recent study by Tamimi et al (J Natl Cancer Inst 2007; 99(15): 1178-1187) found that women who naturally had the highest testosterone levels (top 25%) had a two fold increase in breast cancer compared to women in the lowest 25%.

And another study by Maturana et al (Metabolism, 2008; 567 (7):961-965) found that postmenopausal women with elevated testosterone had increases in markers of inflammation and endothelial dysfunction, C-reactive protein (CRP) and endothelin, that have been associated with increased risk of atherosclerosis.

And let’s not forget the increased risk of heart disease and cancer associated with hormone replacement therapy (HRT) which I have written about before, and testosterone has to have a suspicion of similar risk.

The authors of the current study point to the fact that about a third of post-menopausal women have sexual dysfunction, and imply that even the meager gain they eak out with their patch is worth it in terms of keeping their mans happy. However they need to provide evidence for their implied claim that libido is killed by menopause and that women need to use a hormonal patch for that. They seem to hark back to the physician author of Feminine Forever, who implied that menopause was a disease to be treated with HRT, and that women became old crones, wrinkled and ugly, nasty, and incapable of sex, and that they needed HRT to treat this malady. Well I won’t belabor that now, and you can follow the links on this web site if you want to learn more about HRT, but I can tell you that controlled studies show it has no effect on libido, and only increases risk of cancer and heart disease. So there.

The authors imply that menopause is associated with an inevitable decline in libido for women, and that they need to take a drug to correct that. But I am not aware of any literature to support this conclusion, and if anyone has something, let me know. I mean, Mrs. Bremner seems to be doing OK so far.

As far as I know these testosterone patches are approved for hypogonadism in men with low testosterone, but are widely used off label for loss of libido in men and women. The APHRODITE study results may be used to promote off label use of the patches. Stay tuned.

The FDA posted some slides on this topic here.

Thanks to Marilyn Mann for sending me articles and comments on this topic.

[originally posted on November 6, 2008]

Therapy Patient wrote on November 12, 2008

What always bothers me about many studies (such as this one) is that they don’t seem test moderate treatments. Why would women be treated with JUST testosterone? That is not a treatment designed to bring a woman back to her former natural state. My female gynecologist, a UC San Francisco Medical Center clinical faculty member, Dr. Rikki Pollycove, recommends very low dosage hormone replacement. I am on Divigel (estradiol gel) 0.5mg which keeps me just barely out of the range of having hot flashes plus 25 mg. per day of DHEA (dehydroepiandrosterine) which I understand is a testosterone replacement. The DHEA DID increase my libido, but it wasn’t absent before I took it. However, the DHEA makes me think about sex in a way I had not done in a number of years (age 57 female). I’d be ready once or twice a day for sex if I had a ready partner. I found HRT difficult to adjust to due to side effects which for me are swollen, painful breasts, plus occasional hot flashes (which I do NOT have off HRT). On the positive side I think I have younger looking skin than my peers, and my vaginal tissue is moist and pliant rather than dried, and I have more sexual interest and ability. I am hoping it helps put off cognitive decline of aging, also.

Bristol Myers Squibb (BMS) recently started a TV ad for their drug Abilify (aripiprazole) which has gotten a lot of people in a tizzy prompting me to look closer at this new claim for a psychiatric drug. First of all, I previously gave honorable mention to Abilify as one of the medications with the goofiest names “Where Do They Come Up with those Goofy Names for Prescription Medications Anyway?”)

Back then I mused that perhaps the manufacturers thought that their anti-psychotic pill would make non-functional mental patients jump out of their chairs and start climbing the corporate ladder. Well I don’t know if it will make you climb the corporate ladder, but the akathisia you could get might make you feel like you wanted to jump out of a chair. Not to mention wanting to jump up and go pee if you develop second generation antipsychotic induced diabetes. This medication is an antipsychotic (apparently not mentioned in the TV ads) and these drugs can can have some nasty side effects.

So is this drug really useful for depression? The ads hype the fact that over half of people may not respond to antidepressant medications, but that seems like a self serving turnaround on the part of the drug companies (including BMS maker of Serzone (nefazodone)) who have been telling us for years that their antidepressant drugs are magic bullets for depression.

So what do the studies actually show?

In the first study of Abilify, 362 patients were randomly assigned to Abilify or placebo for six weeks after a failed trial of antidepressants. There was a -8.8 v -5.8 change on the Montgomery Asberg Depression Rating Scale (MADRS), a difference of 11.5%. 23% of patients on Abilify versus 5% on placebo had akathisia, a potentially very disturbing side effect where you feel like you are jumping out of your skin or cannot sit still. Restlessness was seen in 14% v 3%. Fatigue was also more common. Berman RM et al J Clin Psychiatry 2007; 68: 843-53.

In the second study of Abilify, 381 patients who had failed at least one antidepressant medication trial were treated for eight weeks with an antidepressant followed by the addition of Abilify or a placebo for six weeks. Abilify showed an -8.5 change on the 26 item Montgomery Asberg Depression Rating Scale (MADRS) versus -5.7 for placebo, a difference of 2.8 points, a difference of 11%. 26% of patients on Abilify versus 4% on placebo had akathisia, and 10% versus 1% had restlessness. Marcus RN et al, J Clin Psychopharm 2008; 28(2):156-165

.

Conclusions? Abilify is more likely to make you want to jump out of your skin than it is to cure your depression. An 11% improvement over placebo is not that great and is set off by the fact that Abilify has a lot of nasty side effects and doesn’t work better than other treatments of refractory depression like lithium (which also can have nasty side effects). I don’t watch TV ads because I have TiVo but I can only imagine how it was presented by BMS

That settled, now we can move on to my favorite study that I found in the literature: Egashira N et al, Aripiprazole inhibits marble-burying behavior via 5-hydroxytryptamine (5-HT)1A receptor-independent mechanisms. European Journal of Pharmacology. 592(1-3):103-8, 2008 Sep 11.

I wonder if the September 11 publication date is a coincidence? OK, conspiracy theory time now. Maybe BMS is trying to tell us that if our government officials had been on Abilify they wouldn’t have lost their marbles and allowed 9/11 to become a reality?

Any other theories?

[originally posted on November 6, 2008]

Anonymous Reader wrote on November 7 2008

Doug

I think you’ve gone too far this time. For years, I’ve been trying to find a way to stop my mice from burying their marbles without affecting their locomotor activity, and now we finally have an effective agent, thanks to the creative genuises at Kyushu University and Otsuka Pharmceuticals. At least our taxpower money didn’t go into this one!

Doug Bremner wrote on November 7 2008

Anonymous, just writing in jest. I have nothing against research on marbles, just thought the study title sounded funny. Cheers.

This post was discussed by Philip Dawdy at Furious Seasons with an active discussion there.

Therapy Patient wrote on November 12 2008

I couldn’t link to the marble-burying article because it required a password, but if marble-burying represents anxiety (in a lab animal?) then I’d agree (though I enjoyed your humorous interpretation more). My interpretation of what I feel when I take Abilify (1 pill of 5mg dose after not having been on the medication for many months) is a dramatic reduction in anxiety in 20-30 minutes, so I imagine if I buried marbles when anxious that I’d stop.

Not counting the many things I experienced which were possible side-effects, the effect I disliked the most about Abilify was the way it took away my feelings. Gone. I did not feel happy or sad. I lost my sense of humor and effectively became a robot. I typically am not depressed though, so am not in the same situation as the study subjects. A positive effect was that oddly, I lost all tendencies to procrastinate, focused on the most important thing first and got large quantities of work done. It’s not a fair trade off for me, though.

Doug Bremner wrote on November 12 2008

Welcome, therapy patient. I have no idea what marble burying is supposed to represent. I just thought it sounded funny. Personally I lost my marbles years ago and haven’t been able to find them since.