Thursday, August 20, 2015

Flibanserin: 5 Things to Consider Before Passing Judgment on the “Female Viagra”


Flibanserin (brand name Addyi) has just received a controversial and complicated FDA approval for the treatment of low sex drive in women. There’s a lot of outrage in the blogosphere, much of it centered on the lobbying of the FDA by disease advocacy groups.  I agree that this politicization of what should be a scientific process is embarrassing to both Sprout and its supporters. Nonetheless, I'm not nearly as hard on flibanserin as some of my colleagues.

Here’s why.

1. Hypoactive Sexual Desire Disorder is as real as any other source of distress, and deserves treatment.
 
Sure, I get that when it comes to subjective problems, it’s easy to stretch the definition of what constitutes a disease. But who are we to judge whether an affliction is severe enough to merit treatment? An example is social anxiety disorder. Some call it the medicalization of shyness. But if you’ve ever treated someone with this problem, you know that extreme shyness can limit your potential for a normal, happy life.

Low sexual desire may not be a public health emergency, but it’s a real problem for about 10% of women.  If they want to take a pill to make their lives a little better, why not? We allow Botox for wrinkled eyebrows, Rogaine for hair loss, Provigil for jet lag. Why not a drug for low sexual desire?

2. Flibanserin is a female Viagra—just a much less effective version. 

Lots of bloggers are saying that Flibanserin is no female Viagra. I don’t buy it. Trivially, yes, they are different drugs because they have different mechanisms of action. Viagra and the rest of the PDE-5 inhibitors enhance erection by shunting more blood to the vessels of the penis. Addyi’s specific mechanism isn’t known, but the drug is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist and enhances sex via greater desire. But the purpose of both drugs is the same—they are supposed to improve peoples' sex lives. Whether they do it via blood flow or serotonin doesn’t really matter.

However, there is one huge difference between Viagra and Addyi—namely, Viagra is extraordinarily more effective than flibanserin. Studies of Viagra and other PDE-5 inhibitors have found that around 80% of men on the active drug report erectile improvements vs. 20-30% of men taking placebo. That means that 50-60% of men gain benefit over and above placebo. Flibanserin? The FDA’s analysis of the data concluded that 8-13% of women had some desire benefit beyond the effects of placebo. If Viagra is a Starbuck’s triple espresso, flibanserin is a Dixie cup of cafeteria coffee.

3. Flibanserin causes side effects. In addition, water is wet. 

Come on, the nature of all medical treatment is a balance between benefits and side effects. Antipsychotics cause weight gain, antidepressants cause impotence, Viagra causes lightheadedness and low blood pressure especially if combined with nitrates. Flibanserin causes side effects too, such as sedation, dizziness, and low blood pressure.

There’s also an interaction with alcohol but we don’t know how dangerous it is. The company did a study of 25 people (most of whom, oddly enough, were men), and found that one person fainted when combining flibanserin with a moderate amount of alcohol. Five people got dizzy on the combination, but three people also got dizzy in the alcohol plus placebo group, and 4 got dizzy with flibanserin alone. (For the results of the Alcohol Study, see page 77 of this PDF report.)

So it’s not clear from these data how concerned we should be. Certainly, Sprout needs to do more studies. An alcohol contraindication is reasonable. Do we really need to limit flibanserin scripts to certified prescribers? Do we really need a REMS, and the requirements for CME that will inevitably be funded by the manufacturer? It sounds like a case of FDA over-reaction to me. I’ve been prescribing MAOI antidepressants (another "dangerous" drug) to patients for years. There’s a long list of foods they can’t eat and meds they can’t use. Our discussion of side effects is part of a standard medical visit. I don’t need a special certification to talk to my patients about these things.


4. Flibanserin will, indeed, be prescribed off-label, just like virtually every other FDA-approved medication. 

The FDA indication for flibanserin is highly restricted. It’s indicated only if there is low sexual desire without any clear cause. Thus, if the patient is depressed or anxious, and you think that may be contributing toward the low desire, it’s off-label. If there’s a medical condition, like cancer, causing the problem, it’s off-label. It's undoubtedly true that in the real world, doctors are going to be prescribing the drug for these off-label populations and many more. That’s no different from most other meds we prescribe. In psychiatry, for example, almost all the medications we prescribe for children are off-label, because there are so few meds with FDA approval.

5. Adriane Fugh Berman said it best as quoted by the New York Times: Flibanserin is a “mediocre aphrodisiac with scary side effects.”
 
But often in medicine, that’s exactly what we have to work with: mildly effective medications with side effects. Flibanserin may be mediocre, but it’s not ineffective. I look forward to cautiously prescribing it to those women in my practice who might benefit from it. Time will tell whether it becomes popular. If it’s as mediocre as the data suggests, patients won’t refill their prescriptions—in which case the market will quietly close the door on the little pink pill.


Wednesday, August 5, 2015

Vyvanse: Is History Repeating Itself?

One of the benefits of having the Carlat World Headquarters here in beautiful Newburyport, Massachusetts is that we get to work next door to an iconic antiques barn called Oldies. It's a wonderful stockpile of odds and ends that range from decommissioned lobster traps to faded movie posters.


The other day I came across an old issue of LIFE Magazine with a cover story on “The Dangerous Diet Pills: How Millions of Women are Risking their Health with Fat Doctors.” The date? January 26, 1968, which was smack dab in the middle of the amphetamine epidemic that prompted Congress to pass the bill creating our current system of scheduled, and controlled medications.


What, if anything, does this issue of LIFE teach us about the potential dangers of Vyvanse’s recent approval for binged eating disorder? This “exclusive report” was based on investigative journalist Susan McBee’s undercover visits to 10 “fat doctors.” She was given cursory exams and, although she was not overweight (5’5”, 125 pounds), virtually every physician prescribed her various pills, including amphetamines, barbituates, sex hormones, and diuretics. One office insisted she pay cash--no personal checks--in order to receive the pills.

How is this nearly 50-year-old article relevant to the age of Vyvanse? This was a story of unscrupulous doctors running pill mills for women who wanted to lose weight. The diagnostic process--if there was one--was sloppy and all-inclusive. If you came to one of these doctors requesting amphetamine, you were assured of getting a script, regardless of your diagnosis.

As a recent New York Times article shows, history is repeating itself. The Affordable Care Act has a provision requiring coverage of obesity treatment, and doctors are taking advantage of this by opening chains of lucrative weight loss clinics. Some are selling medications directly to patients, such as phentermine, which, like Vyvanse, is an stimulant.

It seems only a matter a time before Vyvanse pops up in the menu of options for patients being seen by the new breed of diet doctors.

Don't get me wrong--Vyvanse is effective for binge eating disorder, as we discussed in our recent CME article (subscribers to The Carlat Psychiatry Report can read it here).

If a patient came to me and said, “Doctor, I’ve heard about Vyvanse for binge eating, and I’d like to try it,” I would carefully ask about their eating habits in order to establish an actual pattern of binge eating. But what if the patient was more of a grazer than a binger? What if I sensed that the patient was simply looking for a weight loss drug and had no binge eating problem at all? I wouldn't prescribe a drug that has a high risk of abuse and diversion.

As was true in 1968, doctors are free to prescribe meds for indications not approved by the FDA. I predict that many women (and men) will be asking for Vyvanse to lose weight, and will walk away with the prescription, whether or not they have BED.

It's been nearly a half century since the LIFE article, and we're still prescribing speed for weight loss Let’s not let it get out of hand.

Wednesday, July 1, 2015

Hospitality and Pharma: Relationship on the Rocks?

Decades of mutually beneficial economic ties have bound the fortunes of hotels, restaurants, and drug companies. But in an era of Sunshine Act disclosure, renewed calls for professional ethics, and ballooning healthcare costs, that relationship may be souring.

It used to be a veritable love-fest. As recently as 2011, I was writing about a restaurant's attempt to rebrand itself as a "pharmaceutical dinner facility."  In 2010, I debated a restaurant chain owner who was calling for the Massachusetts legislature to repeal the state's 2009 gift ban so drug companies could once again wine and dine doctors at his restaurants. His lobbying turned out to be successful. The state's previously strict law was revised in 2012. Now it allows industry representatives to purchase meals of a "modest value" outside the office or hospital as long as they provide educational information about their products between courses.

However, it turns out that while hospitality industry owners are working double time to book reservations for doctors and pharmaceutical reps, their employees have an entirely different idea. They--correctly--see drug company relationships with doctors as a driving force in their rising health care costs, and they want pharmaceutical companies to stop funding educational CME programs at their hotels.

Last week I wrote about this brave stance from the hospitality worker's union Unite Here ("Hotel Workers Against Industry-Funded CME?"). The Wall Street Journal​'s Pharmalot blog got in touch with me to discuss the matter further and yesterday they posted a follow up that includes more of my thoughts on the matter and more of ACCME's self-serving response.

Looking back over the recent history of these industry dynamics, it's easy to see more workers taking this stand against business as usual. After all, they go to work every day in the middle of a money storm while simultaneously seeing their health costs rise year after year. That's a pretty good reason for them to want to stand up.

You can help them out by signing the No More Drug Money petition they are promoting and by sharing it around.

Friday, June 26, 2015

Hotel Workers Against Industry-Funded CME?

In a fascinating new chapter in the battle over industry funding of CME, a huge hotel workers' union has started a campaign to end the practice. Unite Here represents 270,000 workers, and the organization claims that industry funding of CME drives up their health care costs, which is undoubtedly true. So they have created a website, No More Drug Money, to advocate their cause, and they are inviting us all to sign the Pledge: "Add your name here to encourage the ACCME to kick drug money out of CME for good."

You have to respect an organization willing to bite the hand that feeds them. Hotel workers are, after all, an integral part of the grand machinery transporting industry marketing messages into the hearts and minds of doctors. They're quite aware of this:

"We work in hotels, airports, and convention centers, and we do the hard work that make many CME meetings run. We cook the food, we change the sheets, we do the laundry, and we pass out the agendas. We see first-hand what kind of presence pharmaceutical companies have during these meetings. And we are ready for a better system."

For ACCME's formulaic response, click here.

Industry funding of medical education, whether accredited CME or promotional talks, has always created strange bedfellows, but now it has created particularly strange antagonists.

Sunday, May 17, 2015

The GeneSight Test: A Wing, a Prayer and 13 Patients

We just published the May issue of The Carlat Psychiatry Report, and the topic is "Biomarkers in Psychiatry."

I contributed an article reviewing the evidence for the GeneSight genetic test, which is being quite heavily marketed as a way to choose the right medications for patients. According to company's website:

"Multiple clinical studies have shown that when clinicians used GeneSight to help guide treatment decisions, patients were twice as likely to respond to the selected medication."



That's misleading, I found. The vast majority of the GeneSight data are based on studies with an unreliable methodology. These were so-called "open label" studies in which patients were non-randomly assigned to two groups: guided treatment vs. unguided treatment. All patients and clinicians knew which patients were assigned to which group, leading to the very real possibility of various biases--along with a heavy helping of the placebo effect.

One single randomized, blinded study has been published (not even properly blinded, since the clinicians knew which patients were in which group). It enrolled 49 patients (25 in the guided group, 24 in the unguided group). There was no significant difference in the depression improvement scores between the groups. There was a secondary analysis of 13 patients showing a potential benefit for those whose meds were categorized by the test as being particularly problematic.

13 patients? I don't think I would use a genetic test based on good results from an N of 13--and I would suggest that you think twice before you do so!

By the way, I'm at the APA meeting in Toronto and will be going to a lecture today sponsored by Assurex, the maker of GeneSight--if I learn anything new I'll let you know.


Thursday, April 30, 2015

How Drugs Collide: What Every Psychiatric Prescriber Should Know

Please file this blog post under "Shameless Self-Promotion."

I just published a new edition of my book, Drug Metabolism in Psychiatry: A Clinical Guide. You can buy it here, and you can read a free preview of the first two chapters here.

It's mostly a book for psychiatrists and psychiatric nurse practitioners. It's pretty short at 145 pages, but it's very concise and in my opinion fun to read.

If you are not a prescriber you might also find it useful because it explains in clear language how we make decisions about which drugs to prescribe based on how they are metabolized. Therapists, patients, and those simply interested in psychiatry might find it educational, and strangely entertaining.

Anyway, that's it. Sorry if you were looking for a piece of muckraking investigative journalism. Maybe next time!

Thursday, April 16, 2015

How a New Blood Test for Depression is like Apple Recognition

Four years ago I wrote a blog post about the MDDScore blood test for depression. That was before there were any peer-reviewed publications describing it. Now there are at least two. The latest came out a couple of months ago in the Journal of Clinical Psychiatry, and you can access the article, along with two interesting commentaries, for free.

While I won't go into the article in any detail, suffice it to say that the overall accuracy of the test for diagnosing depression was between 91% to 94%, depending on the group studied. Based on this, the authors report that the test "has excellent performance in confirming a diagnosis of MDD (major depressive disorder)."

The article is a classic example of the pitfalls of focusing on glitzy-sounding statistics while downplaying the actual clinical usefulness, which in this case is close to nil, as both of the Journal's commentators agreed.

I recently discussed the same problem in an article I wrote for CCPR about the NEBA EEG test for ADHD. Like the MDDScore, the NEBA test promises to aid in the diagnosis of a psychiatric illness. The NEBA's accuracy is high, with a positive predictive value for ADHD of 96% for kids, and 81% for adolescents. But no matter how accurate it is, the crucial question is whether it adds value above and beyond the standard psychiatric interview. Neither the MDDScore nor the NEBA do.

In my article, I used a hypothetical analogy of a new test to diagnose apples:

"Let’s imagine that there’s a new apple-recognizing device on the market called the “Apple Rec,” which uses various technologies to measure the wavelength of light reflected by an object, its mathematical curvature, etc. The manufacturer provides impressive data showing that the Apple Rec has 100% sensitivity and 100% specificity for diagnosing (recognizing) an object as being an apple. Given these dazzling statistics, would you buy the Apple Rec? No, because even though it’s exquisitely accurate, it provides you with no useful diagnostic information beyond what you can obtain by looking at the apple yourself. However, if the Apple Rec provided you with added value, you might consider it a good investment. For example, if, in addition to correctly recognizing it as an apple, it also calculated its sweetness and crispness, the Apple Rec suddenly becomes a useful tool, because these are qualities that you would otherwise struggle to ascertain."

The apple principal applies to diagnostic tests in psychiatry. Before you refer your patients to an expensive test that diagnoses ADHD, depression, or anything else, you need to make sure that it does something that you can’t easily do yourself.