PA Victory?

I know everyone has problems with prior authorizations. The Byzantine bureaucracy and obscure explanations for denials are maddening.

I'm suddenly reminded of the DMV scene in Zootopia, except I think insurance companies do it on purpose.

Today I had a minor and unexpected victory, and I think I might know why it worked, so I thought I'd share it.

Unfortunately, I have to mask any clinical information, so you'll have to take my word on a number of points. Some things may sound peculiar or not-thought-out, but like most cross-sectional views of a patient's medication regimen, if you knew the full history, it would make sense.

Here's what happened. I needed to get a PA for a new medication, M. The patient had had trials of multiple cheaper covered medications, and had either failed them, or had been unable to tolerate them. The insurance company's criteria seemed to be having failed a 4 week trial of, or been unable to tolerate, two medications.

A number of months ago, I had tried to get a PA for a new med for this patient, and the application was rejected, despite the fact that the criteria were obviously met. I didn't have the energy to pursue it then, and there were one or two more covered meds left to try.

The difference now seems to be that I've since had a Genesight test done on this patient. As I've described in the past, I have my doubts about the whole genetic testing business, but I used the test results as documentation to support my rationale. M was in the "Green Column", and the other meds in that column had already been tried.

It worked! Who knew? I'm only guessing that that's the reason, but I can't think of any other difference. Same patient, same insurance company.

It wasn't a pure victory, though. This medication has a starter pack that's used to titrate gently. THAT wasn't approved. And using a single dose form, starting lower, and then increasing the number of pills per day, well, that wasn't covered, either, because it involved too many pills. What I needed to do was skip the recommended titration, and go straight to the next dose up. Not dangerous, but possibly hard to tolerate.

To me, it feels like a punishment for asking the insurance company to cover the medication.

I guess with insurance companies, you take what you can get.

In the genes?

I'm starting to look into genetic testing to help my work with patients who have not responded well to multiple psychotropic medications. It feels like a desperate bid, but I'm not sure what other help I can offer.

There are three main testing products, that I could find:

Genesight

Genecept Assay

and

Genelex


I have three main questions about these products:

1. What do they tell me?

2. How accurate/helpful are they?

3. How easy are they to use?


Genesight

Genesight seems to be the one mentioned most by people I asked. Practically speaking, it involves a buccal swab sent to Genesight via prepaid FedEx, with access to results online 36 hours after the sample is received. They are covered by some insurance plans, and have a financial assistance program. And it looks like, in order to try out the test, you need to speak with one of their representatives-there's no way to order online.

In terms of how well it works, their claim is, "Patients with uncontrolled symptoms who switch off of genetically discordant medications show the greatest reduction in depressive symptoms."

They also claim that, "70% of patients who have failed at least one medication are currently taking a genetically sub-optimal medication," and that, "GeneSight testing may help avoid drug-drug interactions and compounding side effects."

Finally, for patients younger than 18, Genesight can help in decisions about efficacy, tolerability, and dosing.

They site a paper, A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder, the results of which were:

Between-group trends were observed with greater than double the likelihood of response and remission in the GeneSight group measured by HAMD-17 at week 10. Mean percent improvement in depressive symptoms on HAMD-17 was higher for the GeneSight group over TAU (30.8% vs 20.7%; p=0.28). TAU subjects who had been prescribed medications at baseline that were contraindicated based on the individual subject's genotype (i.e., red bin) had almost no improvement (0.8%) in depressive symptoms measured by HAMD-17 at week 10, which was far less than the 33.1% improvement (p=0.06) in the pharmacogenomic guided subjects who started on a red bin medication and the 26.4% improvement in GeneSight subjects overall (p=0.08).

You'll notice that they talk about "trends" without any statistics, and mean percent improvement showed no significant difference (p=0.28), even though they point out that improvement in the Genesight group was higher. Recall that p=0.28 means there is a 28% chance that the differences they found were due to chance alone.

The "red bin" is a reference to the way Genesight presents its results, which I find easy to understand, if not entirely illuminating. This is an example:

I don't get the impression that the results give me information about which drugs will be helpful, as much as which drugs won't be harmful.

How does the test work? Genesight measures polymorphisms among 5 genes, CYP2D6; CYP2C19; CYP1A2; the serotonin transporter gene, SLC6A4; and the serotonin 2A receptor gene, HTR2A.

The CYP genes are clearly measures of rates of metabolism. A repeat length polymorphism in the promoter of SLC6A4 has been shown to affect the rate of serotonin uptake. The implications of this fact are not clear to me, but according to Wikipedia, genetic variations in the SLC6A4 gene have resulted in phenotypic changes in mice, including increased anxiety. HTR2A influences serotonin transporter binding potential, and variations in the gene have been associated with variations in outcome in treatment with citalopram.

So the answers to my three questions, for Genesight, are:

1. It tells me which drugs are more and less safe and tolerable to use. And if I accept their conclusion that patients switched off red bin drugs improved significantly, then perhaps it tells me which drugs will be effective, but I'm skeptical about this part.

2. The results are less impressive than they'd like me to think.

3. Results are clear and easy to read.  Turnover time is good. Getting hold of a test is not that easy.



Genecept Assay

The genecept FAQ page is much more informative than the Genesight pages. The test can be ordered online or by phone. It's covered by most insurance and they have a patient assistance program. Turnaround time is 3-5 business days from receipt of the sample, also a buccal swab, and they provide expert staff to help interpret results.

The online order form also gives you the option of becoming a "Preferred Provider", which means they'll send patients who are looking for genetic testing to you.

As for function:

The Genecept Assay® report is intended to aid clinicians in making personalized treatment decisions tailored to a patient’s genetic background and helps to inform psychiatric treatments that:

Are more likely to be effective
Have lower risk for side effects and adverse events
Are dosed appropriately

The report consists of two pages, and looks like this:

So they look at more genes than Genesight, and they provide one report about what's safe to use, and another about what's potentially helpful.  And in all honesty, I don't have the energy right now to look up how believable their first page markers are in terms of efficacy, and I think I would need their help to interpret these results, but they do provide more information than Genesight.

Answers:

1. Safety, tolerability, and efficacy

2. I'm too tired to check

3. Easy to get the test, harder to interpret results


Genelex

Genelex allows you to order tests online, too. They claim there is some insurance coverage (See *, below), they have some fancy software that's supposed to be helpful, in addition to their report, and they have a 3-5 day turnaround time.

Genelex restricts itself to CYP450 genes, but it includes three that Genesight doesn't, 3A4, 3A5, and 2C9, but doesn't include 1A2. This is a link to a sample result, which is too long to include as an image. And like Genesight, it's mainly about what is and isn't safe or tolerable to take.*

*Actually, I just learned on the FAQ page that Genelex also includes CYP1A2; NAT2;DPD Enzyme; UGT1A1; 5HTT; and HLA-B*5701, but that these are generally not covered by insurance. I also couldn't figure out what data these additional tests provide.

Answers:

1. Safety, tolerability, maybe efficacy?

2. For the CYP tests, same as above, for others, I don't know

3. The software seems like overkill. The report is clear and moderately informative. You can order the test online.


That's it for this topic, for now, for me. I have yet to decide whether I'm going to use any testing.

Shrinks: The Untold Story of Jeffrey Lieberman's Oedipal Victory Over Papa Freud

I finally finished reading Shrinks, and I submitted a 1 star review to Amazon, with the heading, "Painful to read, misleading, and with no insight into its own deficits. Don't buy it! Don't borrow it! Don't read it!" The following is not what I wrote on Amazon, but it's related.

I've given a lot of thought to how I want to write this full review (see my partial review here). Shrinks is an excruciating rant-sneering, caustic, and just so wrong in so many ways. It was tempting to just shred it point by invalid point. But the truth is, there's something pathetic about the lengths to which Lieberman goes to "prove" that his version is the only true psychiatry.

So I decided to focus on my real concern-the impact this book may have on a lay audience. This is where I think it's downright dangerous. Lieberman writes about present day psychiatry as though it's already achieved all the goals it aspires to. He speaks as though current brain imaging has already explained the etiology of all mental illness, and as though DSM has classified every possible psychiatric disorder: 

...the book precisely defines every known mental illness. It is these detailed definitions that empower the DSM's unparalleled medical influence over society.


He writes about the wonderful breakthroughs that Thorazine, lithium, and imipramine represented-and I agree that these drugs were godsends to many people, but he includes virtually no information about the problems that these and other meds can cause, or about the fact that they don't always work. To hear him tell it, biomarkers are already in widespread use and predictive of treatment response in many psychiatric illnesses. And most of all, his version of psychiatry is, wait for it, SCIENTIFIC.

As I read Shrinks, I tried very hard to imagine what it would be like if I were a reasonably intelligent adult with no particular knowledge of psychiatry, but who was interested in learning about the field. (Okay, cue the jokes about my being reasonably unintelligent and questionably adult)

It's an unrealistic thought exercise, but I imagine I might think I'm reading a book by someone who is an expert in his field, chair of psychiatry at a prestigious hospital, former president of the APA, so he must know what he's talking about. I'm pretty sure I wouldn't be familiar with the immensely varied modes of thinking that exist in psychiatry. I suspect I'd assume psychopharmacology and psychoanalysis are areas that all psychiatrists are trained in. And since Dr. Lieberman is a psychiatrist, psychoanalysis must be part of his field, so if he's claiming there's no validity to it, he must be telling the embarrassing but necessary truth. And if he claims drugs and CBT are effective and "scientific", he must be right about that, too. 

I hope I would pick up on the painfully disparaging tone, and the fact that sneering does not constitute evidence, but I'm not sure I would. 

At some point, I realized I didn't need to speculate about what a layperson would think of the book, I could, instead, read reviews on Amazon. And it turns out that, for the most part, it got good reviews from people outside the field, and bad reviews from people who know something about psychiatry, or its history. Here are some examples, both good and bad:

April 12, 2015
Shrinks by Dr. Jeffrey Lieberman is a fantastic read and a real eye opener for those of us who know next to nothing about psychiatry...The bottom line is that Shrinks brings to light many myths about psychiatry, but it also points out its historic shortcomings. More importantly it presents mental illness not as something to be ashamed of or for which there is no cure, but rather as a medical condition just like any other which can and should be addressed with proper treatment. Thankfully the advances in neuroscience and psychiatry, reviewed by Dr. Liberman in his book, have enhanced the understanding of the causes of mental illness and vastly improved the methods of its treatment.

April 1, 2015

...In his book, Dr. Lieberman clearly offered his experience as a scientist and physician and the history of psychiatry...The best parts of the book describe the rise and fall of theories championed by Freud and how they stymied real science and the description of the motivation behind some of organized psychiatry's most barbaric practices...

Dr. Lieberman explains so well the past failures, the research being presently done and the future of psychiatry. What an honest book...

Lieberman tells this story with remarkable clarity, complete honesty about his own viewpoint, and unusual humility for someone in the field. The human mind, whether it functions well or ill, is poorly understood, but recent progress in both understanding and treatment is significant...but most importantly, there is help.. the right help and the exciting future with DNA exploration...

This top psychiatrist says his field of medicine has recently turned a corner and he shows how it is offering real help to those with anxiety, eating disorders, phobias, obsessions, PTSD, bi-polar disorder, etc. And for people facing brain issues like Parkinsons, autism, Alzheimers, etc, scientists are getting oh so close.

March 28, 2015

I'm biased. I am a historian of psychiatry. Really. I have a PhD from the University of Michigan, served on the faculty of the University of Chicago, and wrote a book on the history of psychotherapy. ...So arrogant as this may sound, I know what I'm talking about. This book is compendium of errors -- at least from a historian's perspective. It fails to consider virtually all of the scholarship produced over the past fifty years on the subject, cites virtually no primary sources, and simply recycles common stories -- many of which have long since been discredited....this book does an extraordinary disservice to those who have been producing exceptional scholarship in the field for decades. What's more, it reveals how easy it is for a well-respected (and deservedly so) physician to publish nonsense about a subject about which he knows little and has probably read even less....You might not agree with me. But I can promise you this: I did my homework. That's not something Dr. Lieberman can say. What's more, I didn't pay someone to write my book for me.

Self-promotion at its worst...and most dangerous

March 22, 2015

To read this book, you would think that everyone who was treated with psychotropic drugs was miraculously cured and anyone who was not sunk into misery or worse. There is no mention of the millions of prescriptions written to treat questionable disorders for children as young as two, or of the terrible side effects of the some of the powerful medications that Dr. Lieberman evidently eagerly dispenses to virtually every patient who walks into his office. You would further conclude that no one was ever helped by psychoanalysis, nor for that matter any other form of therapy than his. This is a book filled with half truths, omissions, distortions, and propaganda. The "untold story of psychiatry" indeed.

In my earlier review, I wrote that I was willing to buy into the historical information included in the book. I stand corrected.


The basic outline of the book is this: first we had "alienists", who oversaw the care of the mentally ill in institutions, even though there was nothing much to be done for these patients. Then Freud came along and treated the "worried well" with what we now know is a bogus treatment designed by Jews and for Jews (not clear to me why Lieberman emphasizes that particular point, but he seems to feel it's important). Beginning in WWII, a taxonomy of mental illness was finally! developed, by an analyst, no less, and this ultimately led to the DSM-III, the savior of psychiatry. Then meds came along, and brain imaging, and CBT, and more recently, genetic markers. And today, psychiatry can proudly state that it understands the etiology of mental illnesses, and has the tools to successfully treat them. 

The book's argument reminds me of people who understand evolutionary process to mean that living beings have maintained a progressive course over eons just to reach the pinnacle of existence that is humanity. 

Lieberman never explains why the things he sneers at are unscientific. He just states it as fact. He has no understanding or knowledge of, nor does he make any reference to, psychoanalysis as it has been practiced and understood for the last 30 or so years. His bio on the Columbia site indicates that he is a, "Physician and scientist," so it's hard to understand why he doesn't even attempt to give a factual basis to his assertions. 

And he seems completely unaware of his own internal contradictions. He criticizes psychoanalysis for blaming family members for a patient's illness, such as the idea of the "refrigerator mother" in autism, or the "schizophrenogenic mother". 

But then he goes on to describe several of his cases, in which his recommended treatment failed because of the patients' families, who he criticized. 

I told them quite bluntly that their decision to withhold treatment was both cruel and immoral-though tragically, not illegal...

Lieberman seems to think that only his recommendations matter, and once he's made them, there's no need to establish a rapport with a patient's family, in order to help the patient. They should just do what he says because he's right. 

He has no clue about the limitations of the DSM, which he refers to repeatedly as "The Bible of Psychiatry". He's convinced that everything in the DSM is "scientific", despite his own descriptions of how many of the decisions about its content were made-often as compromises and to reassure the public and get proper insurance reimbursement.

He thinks that knowing there's an amygdala-hippocampus-prefrontal cortex loop in PTSD explains why people get PTSD. He claims that some people have genetic differences that predispose them to PTSD, and that's why some get it and some don't.
He proudly describes two traumatic experiences of his own-his apartment was invaded and he was robbed at gunpoint when he was in medical school, and 12 years later, he accidentally dropped an air conditioner out of his 15th floor apartment window. No one was hurt in either incident, but he was not traumatized by the former (the robbery), and had some PTSD symptoms following the latter (the air conditioner). Obviously, he can't claim his genetic predisposition changed in the intervening 12 years. Instead, he comes up with a long-winded story about how he had the illusion of control when being robbed, but not when dropping the air conditioner and that created a different amygdala loop. It never occurs to him to ask WHY he had the illusion of control in one situation but not the other. He has no sense that the two events had different meanings for him. And it certainly doesn't occur to him that HE was the aggressor in the incident that gave him PTSD symptoms.

Meaning, for Lieberman, is meaningless. All that matters are symptoms and getting the diagnosis right.

I'm trying not to harp on this part, but another truly dangerous aspect to the book is the way Lieberman disses any type of talk therapy that isn't CBT. Especially psychoanalysis. Here's some of the language he uses:

Gradually, physicians came to recognize that focusing on unobservable processes shrouded within a nebulous "Mind" did not produce lasting change...

...Sigmund Schlomo Freud stands in a class of his own, simultaneously psychiatry's greatest hero and its most calamitous rogue. (Incidentally, Freud's accurate birth name was, "Sigismund", not "Sigmund")

Freud ended up leading psychiatry into an intellectual desert for more than half a century...

As a psychiatrist who lived through many of the worst excesses of the psychoanalytic theocracy, I regard Freud's fateful decision (to discourage scientific questioning) with sadness and regret.

(On the move of many early analysts to American due to WWII): These psychiatric refugees would soon change the fundamental nature of mental health care in the United States, but not necessarily for the better. They brought with them the dogmatic and faith-based approach to psychiatry that Freud had espoused, discouraging inquiry and experimentation. Eventually,...psychoanalysis would become a plague upon American medicine, infecting every institution of psychiatry with its dogmatic and antiscientific mind-set...
...By 1940, American psychoanalysis had become a unique phenomenon in the annals of medicine: a scientifically ungrounded theory, adapted for the specific needs of a minority ethnic group (Jews).

Knowing that the path to influence ran through medical schools and teaching hospitals, psychoanalysts began targeting universities.

Had it been able to lie upon its own therapeutic couch, the psychoanalytic movement would have been diagnosed with all the classic symptoms of mania: extravagant behaviors, grandiose beliefs, and irrational faith in its world-changing powers.



Talk about projection!


Psychoanalysts  and psychoanalysis are compared to or described as:

omen-divining wizards

the primeval sorcery of the jungle witch doctor

the circus Big Top

a mangled map of mental illness

the psychoanalytic hegemony

The Oracle of Delphi

I get a definite sense of a man with no tolerance for ambiguity or ambivalence. 

He writes about his college experimentation with recreational drugs, which involved his researching which drug would be the best for him, before going on to try it. This is clearly not a guy who dropped acid because someone offered him some at a party. 

He idolizes Robert Spitzer for creating the DSM-III. He relates an anecdote in which a teenage Spitzer, at summer camp, was confused about his feelings towards girls, so he made charts of those feelings and kept them on his bunk wall. This is viewed, in the book, as a demonstration of Spitzer's great promise as a researcher, not as an indication of a highly intellectualized defense.

Lieberman also dislikes the notion that mental illness exists on a spectrum, that there is no clear defining line between sickness and health, and he feels this was one of Freud's great mistakes:

It was no longer acceptable to divide human behavior into normal and pathological, since virtually all human behavior reflected some form of neurotic conflict, and while conflict was innate to everyone, like fingerprints and belly buttons, no two conflicts looked exactly alike...the psychoanalysts set out to convince the public that we were all walking wounded, normal neurotics, functioning psychotics...

No wonder the DSM-III had such great appeal for these men. When Lieberman writes about the standing ovation Spitzer got when the DSM-III was approved, it feels like a conquest, like he has vanquished the evil empire established by Freud, the community from which he was excluded for his "scientific" beliefs, and the sun is finally beginning to shine on psychiatry. 

The title of this post was intended to be provocative, but there really is an Oedipal victory feel to the book. As you can tell from the quotes above, there's a lot of disparaging comparison of psychoanalysis to magic or religion, along with some comments that flirt with antisemitism, but then he keeps calling the DSM the "Bible of Psychiatry". Apparently, his is the better religion.

Lieberman, (or maye it's Ogas) writes with particular vehemence about the period when most psychiatrists did analytic training. It made me wonder if he was rejected from a training program at one point, or if he was in an analysis that he quit because he found it intolerable. I have absolutely no basis for these thoughts- they're just conjecture. But here's the description:

Think about that for a minute. The only way to become a psychiatrist-a bona fide medical professional-was to share your life's history, innermost feelings, fears, and aspirations, your nightly dreams and daily fantasies, with someone who would use this deeply intimate material to determine how devoted you were to Freudian principles. Imagine if the only way you could become a theoretical physicist was to confess an unwavering and unquestioning dedication to the theory of relativity or the precepts of quantum mechanics, or if the only way you could become an economist was to reveal whether Karl Marx appeared as an angel (or devil) in your dreams. If a trainee wanted to rise within the ranks of academic psychiatry or develop a successful practice, she had to demonstrate fealty to psychoanalytic theory. If not, she risked being banished to working in the public-hospital sector, which usually meant a state mental institution. If you were looking for an indoctrination method to foster a particular ideology within a profession, you probably couldn't do much better than forcing all job applicants to undergo confessional psychotherapy with a therapist-inquisitor already committed to the ideology.

Nowhere does he indicate that he has even considered the possibility that understanding ones own limitations can make one a better clinician. He doesn't even seem to get that if one is caring for patients, it might be helpful to know what it's like to be a patient. And forget the idea that an analysis is intended to be helpful. He seems to view it as nothing but a threat. The analyst as, "therapist-inquisitor".

Reading the paragraph above, it really is hard to believe Lieberman's claim that he likes psychoanalysis. 

The final concern I have has to do with Lieberman's inability to imagine that other people may not think the same way he does. Here's a quote:

...a psychoanalytic diagnosis of Abigail Abercrombie might account for her spells of anxiety by connecting them to the way she reacted to her parents' strict Lutheran upbringing, combined with her decision to leave home at an early age to work rather than marry. A Kraepelinian diagnosis would characterize Abbey as suffering from an anxiety disorder based upon her symptoms of intense fear and discomfort accompanied by heart palpitations, sweating, and dizziness, symptoms that occurred together in regular episodes.

Lieberman obviously believes that the analytic approach is wrong, and the Kraepelinian approach is right. But leaving aside the issue of which is correct (and why can't there be some of both?) I feel like he's assuming everyone prefers to have his internal

experience described by symptoms and their duration. There's no sense that some people might prefer his way, but others might prefer to have their experiences of anxiety considered in the context of a fuller narrative of who they are, with some continuity to how they got to be this way. Some might even find it offensive to be reduced to a bunch of symptoms and a diagnosis code. 

And unlike Lieberman, some people might be comfortable with a little ambiguity. 

Reference:
J Am Psychoanal Assoc. 2015 Apr 24. pii: 0003065115585169. [Epub ahead of print]
The Psychiatrist, Circa 2015: "From Shrink to Pill-Pusher".
Hoffman L. PMID: 2591090

RateRx

A little while back, I wrote a post, Virtual Care Physician, about HealthTap, the app that lets you post a medical question and get rapid answers from doctors. The way I checked out Healthtap was by signing up under a false name as a patient, and posting a question about club soda. So now I get occasional email updates from them, and they've come up with an interesting feature called, RateRx, in which, "67,000 top U.S. doctors share their experience and expertise to guide millions toward the best indications."

RateRx is a study that surveyed thousands of US doctors about the clinical utility of medications for specified conditions. Doctors are not permitted to see other doctors' ratings and comments until they've submitted their own, although I'm not sure how they could stop me from viewing ratings as a patient, and then signing on as a doctor and submitting my own ratings. Doctors can also comment on other doctors' comments. The study is ongoing, and contributing doctors can also add ratings for new medications not already on the list.

The way you look up ratings is alphabetically, by condition:

Then you click on the number of treatments or the condition, and you'll get a dropdown list of individual drugs, with ratings and a link to reviews:

The drugs are listed from highest to lowest rated. So it turns out, Prozac is the most highly rated antidepressant, with 4.0 out of 5 stars. The lowest rated is Liothyronine or T3, with 2.2 stars.

Prozac seems to be the only SSRI on the list, which also includes, in descending number of stars:

Effexor                      3.9
Wellbutrin                3.9
Remeron                   3.3
Imipramine               3.0
Desipramine             3.0
Nortriptyline             3.0
Tranylcypromine      2.9
Isocarboxazid           2.8
Phenelzine                2.8
Protriptyline             2.8
Trazadone                 2.7
Trimipramine           2.6
Amoxapine               2.5
Maprotiline              2.5
Chlordiazepoxide     2.2
   & Amitriptyline
Liothyronine            2.2


One nice feature is that when you click on the reviews, you can see each doctor who submitted a rating, and link to his or her profile. Not everyone comments. For instance, in the case of Prozac, there were three comments up at the top, and none below. These are the comments, and all three commenters are psychiatrists:

Actually, I counted, and 23 of the 47 raters of Prozac are psychiatrists. A bunch of the others are neurologists. Then there are a few family medicine docs, as well as some internists. A couple of OB/Gyns, a pediatrician, a couple nephrologists, 1 pharmacologist, 3 clinical psychologists, and 1 labeled, "American Board of Phlebology". Personally, I'm not comfortable having people who can't prescribe or don't see patients comment on how patients respond to medications.

The drug that was most frequently rated, 103 to be exact, was desipramine. The comments were mainly about side effects. One comment I thought was useful was, "If the side effects can be tolerated, it can work. Usually, the prescribed dose is too low."

Most of the comments about Phenelzine were about dietary concerns, with some good general descriptions:

Phenelzine or Nardil is an antidepressant in the group called MAO Inhibitors. These older medications have the highest response rate, which is about 80%. They also require dietary restrictions to prevent a high blood pressire reaction to foods containing tyramine (cheese, processed meat, red wine, soy and some others). Other side effects: insomnia, dizziness.

and

Useful for atypical depression. People with atypical depression tend to feel better during enjoyable activities, have increased appetite and sleep a couple hours more each day than when not depressed, have a feeling that their arms & legs are heavy, & have an ongoing fear of rejection. Problem with this med: dangerous interactions with MULTIPLE other meds and SEVERAL foods.

So here's my assessment:

It's not a bad idea to have a large survey of doctor ratings and comments. The comments are probably more useful than the ratings, and can be very informative for patients.

It would be helpful to have more statistics listed, like how many of the raters of cardiac medications are cardiologists. I mean, it's not like I know nothing about cardiology, but I wouldn't presume to comment on how well those meds work in the clinical setting, because that's not what I do. By the way, the American Board of Phlebologist also put in his two cents about Amlodipine/HCTZ/Valsartan. I suspect he pops up in most ratings, and gets his name out there that way.

The main drawback is that the setup can be misleading. It seems like a gross oversight to have ratings for lots of MAOI's and Tricyclics, but only one SSRI. I think that would confuse a patient who is looking for advice about commonly prescribed antidepressants. I don't know if RateRx just expects doctors to add the most commonly prescribed meds, but it seems to me the people running the survey should encourage ratings of those drugs. It's not like it's hard to get prescribing information. Drug companies certainly know which meds are most popular.

So check out RateRx, and let me know what you think.

Analytic Evidence

One of my goals, or maybe wishes, in writing this blog, is to educate a wider audience about psychoanalysis. Let's face it, analysis is, at best, passe. Mostly it's dissed. After all, everyone "knows" there's no evidence that analysis works, but there's lots of evidence that CBT works, so why spend all that time and money in analysis when you could be in and out in 30 sessions?

Just see this article in the NY Times:

As Jeffrey A. Lieberman, chairman of psychiatry at the Columbia University College of Physicians and Surgeons, makes clear in his chatty, expert, sometimes scathing but ultimately upbeat account of the history of psychiatry, the evidence, quite simply, doesn’t exist.

Maybe analysis was cool back in the 50's and 60's, when everyone smoked during sessions, and the analyst had a beard and a deep-voiced German accent and was a blank screen who only made comments about oedipal conflict. It's fun to watch in Woody Allen movies, but really, it's just a silly, archaic modality that thinks penis envy is the cause of everyone's problems, and now functions only as a narcissistic indulgence for the wealthy.

I once mentioned to a colleague I had just met that at certain hospitals, psychiatrists are not permitted to wear white coats because it makes the patients anxious. His response was, "That's just analytic bullshit!" I guess to most people, analysis qualifies as its own special category of bullshit.

Well, there is evidence that analysis works. Not only that it works, but that it works better than meds or CBT. I highly encourage readers to watch a 35 minute video on YouTube entitled, The Case for Psychoanalysis, Version 4, by John Thor Cornelius, a psychiatrist and psychoanalyst from California, who took on the challenge of convincing residents at UC Davis, who had been taught otherwise, that there is evidence for the usefulness of psychoanalysis. Obviously, he's made 3 earlier versions of the video, and he updates as new evidence becomes available. But I'm going to use highlights of the video (with his permission), and include other evidence, in this post.

Cornelius looked at effect size in meta-analyses of meds, CBT, and psychoanalytic psychotherapy, which he uses as a stand-in for analysis. The difference between analysis and analytic psychotherapy is something I'll get to in another post. Maybe. There's a lot of literature on it. For now, it'll have to be an adequate place-holder, and obviously, for my purposes, this is one of the limitations of his presentation.

Just quickly, effect size is the difference between treatment groups, expressed in standard deviations. Roughly speaking, a large effect size is 0.8, medium is 0.5, and small is 0.2. So, for example, if the effect size of A v. B is 0.8, then A did 0.8 of a standard deviation better than B, and this is considered a large effect.

 First, Cornelius looked at effect sizes at the ends of studies:

Erick H Turner, MD, Annette M Matthews, MD, Eftihia Linardatos, BS, Robert A Tell, LCSW, and Robert Rosenthal, PhD. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. NEJM 2008; 358:252-260 January 17, 2008.
Butler, AC, Chapman, JE, Forman EM, & Beck, AT. (2006). The empirical status of cognitive-behavioral therapy: A review of meta-analyses. Clinical Psychology Review, 26 (1), 17-31.
Abbass AA, Hancock JT, Henderson J, Kisely S, Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst Rev. 2006;4:CD004687.
Maat S, De Jonghe F, Schoevers R, Dekker J. The effectiveness of long-term psychoanalytic therapy: a systematic review of empirical studies. Harv Rev Psychiatry. 2009;17(1):1-23.

You'll notice antidepressants aren't great, and CBT for chronic pain isn't either, but everything else does okay.

Then he looked at long-term follow-up, and this is what he found.

For antidepressants:

For Psychotherapy, there is evidence that its benefits endure and increase over time (Psychodynamic Psychotherapy Research: Evidence-Based Practice and Practice-Based Evidence (Current Clinical Psychiatry) [Kindle Edition]Raymond A. Levy (Editor), J. Stuart Ablon (Editor), Horst Kächele (Editor)):

Leichsenring F, Rabung S. Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis. J Am Med Assoc. 2008;300:1551-65.

MBT is Mentalization Based Treatment, an 18 month psychoanalytic partial hospitalization protocol for borderline personality disorder. 

Bateman A, Fonagy P. Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder. Am J Psychiatry. 2009;165:556-9.

As for CBT, some of the results fall under Steps 2, 3, and 4 of the STAR-D trial, which had CBT arms. But here are some more results to consider:

40-50,000 patients per year for 5 years, $500 million dollars, and no effect of CBT. Those numbers big enough for you?


Next up, head to head comparison of psychoanalysis (PA), psychodynamic psychotherapy (PD), and CBT.

Comparison of cognitive-behaviour therapy with psychoanalytic and psychodynamic therapy for depressed patients – A three-year follow-up study (Z Psychosom Med Psychother 58/2012, 299–316), by Huber et al, is a prospective study of 100 patients diagnosed with unipolar depression and randomized into the three groups. I'm not including the studies this one follows-up on because this post is already too long.

"...mean duration of PA was 39 months (range 3–91) or 234 sessions (range 17–370), of PD was 34 months (range 3–108) or 88 sessions (range 12–313), and of CBT was 26 months (range 2–78) or 45 sessions (range 7–100); minimal values are due to the intent-to-treat approach."

PA was practiced at a frequency of 2-3 sessions per week, on the couch. PD was once a week, sitting up. And CBT was once a week.

There were 21 therapists, all past training, with mean duration of practice 15 years. 7 did CBT, and 14 did PA or PD, and there was no significant difference in respective training, expertise, and experience.

Raters were blind to treatment modality. They used a 3 year follow-up period to account for the naturally fluctuating course of depression. Treatment fidelity was also assessed.

"Outcome measures were the Beck Depression Inventory and Global Severity Index for measuring symptoms, the Inventory of Interpersonal Problems and the Social Support Questionnaire for measurement of social-interpersonal functioning, and the INTREX Introject Questionnaire for measuring personality structure."

I'm leaving out a lot of the methodological details, but I did want to give you the general sense that the study was conducted in a rigorous way. And these were the results:

"...at three-year follow-up, rate of remission from depressive symptoms was 83% in the PA group, 68% in the PD group, and 52% in the CBT group. When controlling age and gender, the odds of remission were significantly greater in the PA group as compared to the CBT group, with odds ratio (OR) = 4.79, 95% CI [1.29 to 17.74], and did not differ between the PD and CBT groups, with OR = 2.06, 95% CI [0.60 to 7.10]."

More generally, they found, "significant outcome differences between psychoanalytic therapy and cognitive-behaviour therapy in depressive and global psychiatric symptoms, partly social-inter- personal and personality structure at three-year follow-up. Psychodynamic therapy was superior to cognitive-behaviour therapy in the reduction of interpersonal problems."

In the discussion section, the authors were pretty good at describing the limitations of the study. They also addressed the question of a dose effect. We're talking 45 sessions of CBT vs. 88 sessions of PD vs. 234 sessions of PA. This is a fair question to ask, i.e., would 234 sessions of CBT have been as effective as the same 234 sessions of PA? However, the CBT lasted, on average, 26 months, while the PA lasted 39 months, only about a year longer than the CBT. At the rate of 1 session a week, or roughly 4 sessions a month, a CBT of 234 sessions would last for 58.5 months, or about 5 years, 2 years longer than the average psychoanalysis in the study lasted.

This was pretty farschlepped, but I hope you can see that there is some evidence that psychoanalysis is effective. Jeez, Dr. Lieberman, do your homework!

What's In A Name?

Interesting article in Clinical Psychiatry News, Psychoactive Drug Nomenclature System Devised, by Mitchel Zoler.

Joseph Zohar, David J. Nutt, David J. Kupfer, Hans-Jurgen Moller, Shigeto Yamawakie, Michael Spedding, and Stephen M. Stahl have all been busy coming up with a new way to describe psychoactive medications. It's a 5 Axis system (I guess they were homesick for DSM-IV), and the plan is for it to be web-based, so it can be in a constant state of revision.

The idea behind it is that, according to the example in the article, you have a patient with an anxiety disorder, for whom you prescribe, say, celexa, which is an antidepressant. So the patient wonders why you're telling him he has one condition, and giving him a drug for another.

Here's my list of the axes-but you can view them in the article, in a nice table, complete with two examples:

Axis 1- Class and Relevant Mechanism
What neurotransmitters it affects, and what it does at the molecular level.

Axis 2- Family
This seems to overlap with Axis 1.

Axis 3- Neurobiologic Activity
Includes neurotransmitter effects, and broader physiologic effects.

Axis 4- Efficacy and Major Side Effects
What conditions it's good for, and what else it does on the experiential level.

Axis 5- Indications
Formal FDA approvals, I think.


The Pros:

The physicist, Richard Feynman, had an interesting father. He would say to young Feynman, "You see that bird over there? I can tell you its name, but first, I'll tell you what it does."

Names, categories, titles, they're all important, but they often don't give you that much information about whatever they're naming. "Sparrow" doesn't tell you anything. You need to connect that word with a certain type of bird.

So it's a good idea to describe drugs by what they are and what they purportedly do. You end up with a lot more information than you get from "SSRI" or "Prozac".

And on the flip side, "antidepressant" only tells you one thing that a particular drug does. If it does other things, you won't know it from that one word.

I quite like the idea of putting all the relevant information out there right from the start.

The Cons:

Who is this for? I can see where it would be useful for medical students studying for pharmacology exams. Or for psychiatrists, to tweak our memories, or help us clarify things to our patients, although personally I'd like an Axis 6 with Cyp450 enzyme data.

But what about non-psychiatrist prescribers. Could this be a sneaky way to promote off-label prescribing? If you look at the chart in the article, Axis 4 for amytriptyline is "anxiety;chronic pain", not "depression", which is listed in Axis 5 as "Major Depressive Disorder".

And does listing the known molecular mechanism of action, e.g "Increases synaptic 5-HT and norepinephrine" right next to the conditions the drug is used to treat, e.g. "Depression", sneakily imply that too little synaptic 5-HT causes depression, and more synaptic 5-HT is what "cures" depression? Because we just don't know if that's true.

Is this system for patients? Will it really be helpful, or more helpful than just telling these details to patients as part of discussions surrounding medication?

The question of who this system is for, as well as the plan to make the classification system web-based are particularly relevant, in light of the fact that I couldn't access the original article. Well, I could, for $35.95.

My feeling is that this idea is being presented as an ongoing collaborative model, but really, it's proprietary. And forgive me if I have concerns about where they're heading with it. This quote is from the Zoler article:

"This is the first step in a long process. We’re trying to wake up a 50-year-old nomenclature into a living document that will be used over the next decades and may someday merge with DSM [Diagnostic and Statistical Manual of Mental Disorders]," said Dr. Stephen M. Stahl, a panel member and psychiatrist affiliated with the University of California, San Diego.


What will it mean to "merge with DSM"? Will new diagnoses be created based on how medications are being prescribed? Or with what frequency they're being prescribed? After all, David Kupfer, one of the authors, was the chair of the DSM-5 task force.

And how will this affect getting FDA approval for medications? If a drug is being used off label at a high frequency, will this be a way to extend a patent? In other words, is noting the usage of a drug a way of establishing that said drug is effective for a different indication than the one it was originally approved for. 

My main concern stems from the memory of those little books I got from drug reps when I was a resident. Nice little pictures with colorful neurotransmitters happily making their way around a bunch of big receptors. All written by Stephen M. Stahl.

The final paragraph of the Zoler article:

Dr. Zohar said he has been an adviser or consultant to or received research support from eight drug companies. Dr. Nutt said he has been an adviser or consultant to eight drug companies. Dr. Stahl said he has been an adviser or consultant to more than 30 drug companies. Dr. Goodwin said he had been an adviser or consultant to 12 drug companies.


Bottom line: I think more information about medications is a good thing. But not if it's misleading. And not if there's an ulterior motive to presenting the information. Hopefully, this type of system can be used for the good of patients.

Generics

A recent letter in the NY Times got me thinking about generics. Specifically, how good are generics, compared to their brand name counterparts. (For the purposes of this post, I'm going to ignore the question of how good the brand names are, and how we know that, etc.) The letter, by Jack Drescher, states that, "the current accepted standard for bioavailability can range from 80 to 125 percent of the brand-name drug’s delivery system." But what does that mean?

About a year ago, people taking a certain generic form of Wellbutrin XL 300mg, called budeprion, started reporting what sounded like symptoms of depression. The FDA went on to announce the in-equivalence of this generic, which was taken off the market. This past Thursday, the FDA released an update:

Based on data submitted by Watson, FDA has determined that that company’s generic bupropion HCl ER 300 mg tablet product is not therapeutically equivalent to Wellbutrin XL 300 mg. Watson has agreed to voluntarily withdraw this product from the distribution chain. Also, FDA has changed the Therapeutic Equivalence Code for the Watson product from AB (therapeutically equivalent) to BX (data are insufficient to determine therapeutic equivalence) in the Orange Book. FDA does not anticipate a drug shortage.
We recommend that patients taking the Watson product continue taking their medication and contact their health care professional or pharmacist to address any concerns.


 So how does a generic drug come to be?
First, let's have some definitions and review.

According to the World Health Organization, "A generic drug is a pharmaceutical product, usually intended to be interchangeable with an innovator product, that is manufactured without a license from the innovator company and marketed after the expiry date of the patent or other exclusive rights."

What makes a generic drug "interchangeable with an innovator product" is the fact that it contains the same Active Pharmaceutical Ingredient (API), and demonstrates Bioequivalence:


Generics are not required to replicate the extensive clinical trials that have already been used in the development of the original, brand-name drug. These tests usually involve a few hundred to a few thousand patients. Since the safety and efficacy of the brand-name product has already been well established in clinical testing and frequently many years of patient use, it is scientifically unnecessary, and would be unethical, to require that such extensive testing be repeated in human subjects for each generic drug that a firm wishes to market. Instead, generic applicants must scientifically demonstrate that their product is bioequivalent (i.e., performs in the same manner) to the pioneer drug.
One way scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream and its concentration in the bloodstream in 24 to 36 healthy, normal volunteers. This gives them the rate and extent of absorption-or bioavailability-of the generic drug, which they then compare to that of the pioneer drug. The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the pioneer drug.
Using bioequivalence as the basis for approving generic copies of drug products was established by the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act. Brand-name drugs are subject to the same bioequivalency tests as generics when their manufacturers reformulate them.




You may recall this graph:

It's blood concentration vs. time for an oral drug. Sequential blood samples are taken after ingestion of the drug, to generate the curve. Peak concentration, Cmax occurs at time, Tmax.

Rate of Absorption = Cmax/Tmax.

and Total Extent of Absorption = Area Under the Curve (AUC)

(which is simply the integral of the function that describes the curve).

A generic drug is considered equivalent to the brand drug if its Rate of Absorption and Extent of Absorption do not significantly differ from those of the brand drug. In other words, the curves look the same, or almost the same.

How much is almost?

"Most regulators worldwide have decided that a 20% variation is generally not clinically significant.

Two versions of a drug are generally said to be bioequivalent if the 90% confidence intervals for the ratios of the geometric means (brand vs. generic) of the AUC and Cmax fall within 80% and 125%. The tmax (brand vs. generic) must also be comparable — and there should not be any significant differences between different patients." (same source as graph).

Once they've established bioequivalence, generic drugs are given Therapeutic Equivalence Codes. There are different codes for different types of meds, e.g. tablets vs. injectables. The highest rating seems to be AA-drugs that "contain active ingredients and dosage forms that are not regarded as presenting either actual or potential bioequivalence problems or drug quality or standards issues. However, all oral dosage forms must, nonetheless, meet an appropriate in vitro test(s) for approval." I'm not clear on what would constitute a "bioequivalence problem". An example of an AA drug is Acetaminophen/codeine, and this is what the heading looks like in the Orange Book (see below):

AB seems to be a more typical rating for generics. There are some subcategories in which a drug is rated compared to a specific version of the drug, for example, levothyroxine:

For those who are interested in the whole shpiel, this is a link to Approved Drug Products with Therapeutic Equivalence Evaluations , aka The Orange Book. It's called The Orange Book because the original edition was published in October, and with Halloween coming up, they decided on an orange cover.

And here's another link to FDA slides on bioequivalence:

FDA pdf

DSM-5 in Action

Last week, I saw a new patient who was referred to me by her therapist for evaluation for med management, specifically, for depression.

The therapist wasn't certain the patient needed meds. And the patient wasn't sure she needed, or wanted meds.

She was suffering-that was the only certain thing.

I'm a decent psychopharmacologist, despite the fact that I mostly do therapy and analysis. The reason I'm good with meds is not because I'm an expert on the Cytochrome p450 system, or I'm the first shrink on the block to prescribe a brand new med. I believe it's because I listen to my patients, so important feelings/experiences/symptoms don't get overlooked, or boxed into neat little 15-minute med check categories that don't really fit.

So I listened to this patient, and while I was listening, I started thinking about everything I've learned regarding DSM-5. Like, maybe Major Depression, as defined by the DSM, doesn't really exist. (Note: I am NOT saying I don't believe depression exists. I'm just referring to the DSM definition of depression). And even if it does exist in DSM form, if I run through the checklist, and the patient meets five of the nine criteria, does that imply that she'll benefit from medication? And if she doesn't meet 5/9, does that mean she won't?

And what about the meds? What exactly am I treating? And how? A world-outlook? A traumatic childhood loss? If I can't be sure there's a disease process going on, and I can't be sure which aspect of the disease, if such it is, I'm treating, and no one even knows how the meds work, then why would I medicate?

I thought about how easy it would be to say to her, "You meet criteria for MDD, here's a pill, take it and you'll feel better." But I just couldn't bring myself to do that. I didn't believe it would help.

This is not the first patient I've sent home prescription-less. But it's the first time I've thought about it this way. In the past, I might've said to myself, the patient doesn't meet criteria, and therefore doesn't have the disorder in question, and consequently won't benefit from medication for this condition.

But now I'm reminded of the joke about the philosophy exam question, asking students to describe the physical characteristics of the chair at the front of the room. One student's response: What chair?

What disorder?

I came up with the following analogy: Suppose I decide that people who have more than 5 bad hair days per month carry a diagnosis of BHDD (Bad Hair Day Disorder). Am I describing an entity? Yes, people who have too many bad hair days. Does that make it a disorder, or disease?

I'm not sure the analogy is valid. At least some of the DSM diagnoses have a basis in clinical experience.

The truth is, and I realized this while I was writing, that I do find the DSM criteria for MDD useful, as a line of questioning.
This patient did not fit into any nice little DSM category. And I didn't try to make her fit. My thinking was, let's explore what she's been experiencing, using DSM criteria as a starting point. And that was useful.

I haven't purchased a copy of DSM-5. I don't want to. And I resent that, despite all the protests to the contrary, it remains the "bible" of psychiatry, and decisions are made based on its contents-reimbursement decisions, legal decisions.

But I do wish it could be what it professes to be: a guideline. Then it could sit on my book shelf with all the other books I use as references and guidelines, not with pride of place, and not with shame, either.

Quick CPT Link

I just want to refer anyone who is interested to the blog, Shrink Rap, for 4 quick video tutorials on CPT and E&M coding.
And a shout out to Dinah for mentioning Psych Practice at the end of the last video.
The videos are clear, and Dinah claims they're boring, but they're not because of her fun style.

Abilif-Eyeballs

What's up with the eyeballs in Abilify ads?  Like this one:

Are they supposed to be cute?

A pair of eyeballs following around someone taking an antipsychotic. Seriously?

Oh yeah! This isn't an ad for Abilify the antipsychotic. It's an ad for Abilify the antidepressant augmentation med.

And if you watched through the ad, did you notice that 40 of the 90 seconds are spent describing side effects? Okay, you probably didn't bother to count like I did, but you get the idea.

I do not like drug ads on TV. But why?

Is it because they're a blatant manipulation of lay people by Big Pharma? Well, there is that.

Dammit, if pharmaceutical companies are going to manipulate people, then by golly let those people be doctors so we can get free pens and clipboards out of it.

Did you know that the amount of money pharmaceutical companies spend on advertising is 19 times what they spend on research? Huffington Post Link

One figure I found (click here) is 4.8 Billion dollars spent annually on direct to consumer marketing. That doesn't even include pens.

Now, don't get me wrong. I don't hate pharmaceutical companies the way I hate insurance companies. After all, the meds we prescribe have to come from somewhere. And some of them actually work. You can't blame a trillion-dollar conglomerate for tryin' to make a buck. They have  products to offer that actually do some people some good. Unlike insurance companies, which offer a product designed to do as little as possible of the job it was purchased to do (i.e. reimburse).

Plus, drug companies will take you out to dinner every now and then. When was the last time United Healthcare bought you so much as a cookie?

I think it bothers me that the ads are misleading. Depression not improving? Here, this'll fix it.

In a recent study (2012), Fava, et al assessed the efficacy of low-dose aripiprazole added to antidepressant therapy (ADT) in 225 major depressive disorder (MDD) patients with inadequate response to prior ADT.They concluded that low-dose (2-5mg) aripiprazole was well-tolerated, but had only marginal efficacy in augmenting ADT.

The commercial never mentioned that. Nor did it state, or even imply, that abilify's original indication was for psychosis. It's as though, just when you thought antidepressants were inadequate to the task of treating depression, a magical pill appeared and saved everyone.

So they're lying. Or exaggerating. But is this really any worse than advertising candy bars, or laundry detergent, or tires?

I think there's a fine line between empowering people to be active participants in their health care, and convincing them they have greater expertise than they do, which is the real way drug ads mislead. You don't need to know much about candy bars to chose one. And maybe you should do a little research when you're purchasing new tires. But you don't need years of education and hands-on experience to make those decisions.

If I needed my car fixed, I wouldn't go to a mechanic and say, "I know what's wrong with my car and which components you need to fix it." And Google is not the great equalizer people would like it to be.

So watch out for those eyeballs.