Lost Creek Wilderness
I have been writing about the newly released draft of the Diagnostic and Statistical Manual -- DSM V for the last few weeks. Let's recap:
The DSM V -- What's at Stake: The pharmaceutical and health insurance industries have a huge financial stake in who gets diagnosed with what in the mood disorder section of the Diagnostic and Statistical Manual. This stake has skewed the new draft version of the DSM to support the status quo/current market conditions.
The DSM V made almost no changes in the
Mood Disorders section. (Well, a few, not so minor for children and the bereaved.) This despite the evidence that the current criteria for bipolar II exclude people who are instead diagnosed with recurrent unipolar depression, but who get much worse when treated as though they had recurrent unipolar depression, and who eventually are diagnosed with bipolar II anyway, if they are still alive. Women spend eleven years on average before being diagnosed correctly. That's eleven years of a lot of suffering on a lot of antidepressants. One helpful modification in the bipolar II area will become important below.
The Draft DSM V -- How Did We Get Here?: Advances in the treatment of depression have come about by serendipitous discoveries, followed by pharaceutical companies' desires to improve their own market share. These have been genuine advances. However, their manipulation of research to support their products is a national disgrace.
The AMA is finally embarrassed by it.
That is where last week's post left us, at
Mile Marker #3 in "Up a Creek Wilderness" -- the sorry state of research on this map that is owned by the pharmaceutical companies.
So now we have arrived at:
Goose Creek Trailhead
Mile Marker #4 -- Their goose is cooked. They have run out of product. There are lots of ideas out there besides the tired old "chemical imbalance/neurotransmitter" fixation on one aspect of depression. And research
is being done on other neurological mechanisms of depression. But Big Pharma got lazy and has been
slow to develop these ideas into useful medications.
Patents have expired on almost all the antidepressants on the market today. The sleight of hand trick is to repackage the same medication by altering its formulation a little bit (Celexa/Lexapro, Effexor/Pristiq) or by doing a time-release version to add a few years to the patent (Paxil CR, Wellbutrin XL). But that strategy has a time limit, and lack of development has caught up with these companies.
I think Eli Lilly's new product Symbyax is the ultimate in failed strategies, combining the patent-expired Prozac/fluoxetine (originally used for major depression) with the newer and controversial Zyprexa (originally used for psychosis and lately the subject of successful lawsuits). If it really were a good idea, you could get the same results with two prescriptions, the antidepressant that worked best and an antipsychotic less dangerous than Zyprexa, instead of the two products owned by Eli Lilly. With the combination package, you get the
side effects of both: sexual dysfunction, agitation, akathisia, insomnia, etc. for Prozac and ballooning weight gain, high blood sugar, risk of diabetes, high cholesterol, tardive dyskinesia, etc. for Zyprexa.
Nevertheless Symbyox will make Eli Lilly a bit of money for a while, because it has widened the market for Zyprexa. They need another market since
that successful lawsuit reduced its use among older people with psychosis (who experience a rather nasty side effect of
death from Zyprexa's off-label use for dementia.) Symbyax now is also indicated for people with treatment-resistant depression, whose doctors need to keep coming up with something new to give them. God forbid they should reexamine the diagnosis, or that the DSM V should encourage them to do so. People with treatment-resistant depression account for half of the depression market, the half that
stays on the market, because they "keep trying," like everybody tells them they should. So good luck, Lilly. I hope you are in court again soon.
That's Mile Marker #4. And it makes me as depressed as Mile Marker #3 makes me mad.
Mile Marker #5 -- It turns out that we have been traveling in a circle, and now looped back to the beginning. This is where I find the
good news.
We have another serendipitous discovery! Lamictal was first used as an anti-convulsant. Following the pattern of other advances in the treatment of depression, Lamictal's mood-related effects first became apparent in people with epilepsy. Happy seizures. -- Though unlike previous medications, Lamictal works just fine for its original purpose, as well.
Lamictal (generic name lamotrigine) is now approved for use in managing seizures and bipolar I. Its off-label uses include bipolar II and treatment-resistant unipolar depression. (When a doctor prescribes a medication for something that it hasn't been approved for, that's called "off-label" use.)
This "off-label" use issue is critical here to advance the treatment of depression, especially for those who are misdiagnosed (using DSM V guidelines) with unipolar depression.
The
rules regarding marketing of off-label use are in flux. Currently, sales representatives may not recommend their products for off-label use, but they may direct doctors to
research about such use. They may not, however, pay doctors to tell other doctors about their experiences with off-label use, at continuing education conferences and the like.
That's what got Pfizer busted, for their marketing of Geodon, another anti-psychotic like Zyprexa, while searching for
their market share of dementia and depression. The money in these cases generally goes to Medicaid and Medicare, who paid for the prescriptions.
See, there's a swamp out there between Mile Marker #5, the next serendipitous discovery and:
Mile Marker #6: Ca-ching! Ca-ching! -- that huge new money-making machine.
Doctors prescribe medications for off-label use all the time. Drugs that have been tested and approved only for adults are tried on children. Otherwise, there wouldn't be anything they could give to kids, because who wants to risk clinical trials on kids? Drugs approved for one type of cancer are tried for another, because who wants to say "no" to somebody whose cancer has metastasized?
Off-label use gets turned into approved use if it works out in new clinical trials. If it doesn't work out, it goes away. That's the way it's supposed to work. But if the trials don't work out, and the drug companies fudge the data and market the medication anyway, then they get sued.
My doctor told me that Lamictal is the "go-to drug" for bipolar II, evidently very common off-label use. I don't know how she knows, whether she read the research, whether the medical journals have been flooded with articles commissioned (or maybe not) by GlaxoSmithKline, whether she heard about it from other doctors who are on (or maybe not on) GlaxcoSmithKline's payroll, or whatever. It is also on the top of her list for treatment-resistant unipolar depression. I am not expressing doubt about Lamictal's effectiveness. I am simply explaining how off-label use works in clinical practice.
So we are currently at Mile Marker #5. Now we start climbing that hill to #6. Just like they did with tricyclics and SSRIs, everybody is asking, "How does Lamictal work?" They think it has something to do with calcium, but I won't go into that here.
The answer to the "how" question is particularly important to the other pharmaceutical companies, because they will use the answer for a grab at
their market share, by trying to improve on the side effect profile.
Lamictal's side effect profile isn't so bad, as far as mood stabilizers go. It is light years better than Lithium, which is beyond nasty, but desperate people take it, because it has been their only relief. Lamictal also is not so bad compared to antidepressants. It causes fatigue, headaches, muscle pain, but not in as many people. Its big drawback is this pesky rare (but potentially fatal) skin rash.
Potentially fatal. Wow. Now, one in 500 people get this rash, and all you have to do to get rid of it is stop taking the drug. I am not sure why this rash is the major concern about the medication. Except there is no denying the cause. Antidepressants cause suicidal ideation and behavior at a much higher rate than Lamictal causes rash. But try to prove it in your case. You already have a disease that carries a risk of suicide. And even on the antidepressant in question, it might be that your disease is simply progressing. You are as likely to get your dose
increased as discontinued. And you will
not get your day in court. Lamictal causes
some kind of rash in 1 of 10. But even if your rash is caused by the new soap you are using, looks nothing like the bad rash, and even if you are free from suicidal thoughts for the first time in a decade, you get yanked off Lamictal.
So here is an excellent opening for other companies, to come up with something with no rash, or even a rash that only one in 1000 get. We can expect other mood-stabilizers to reach clinical trial stage in the near future. Ca-ching! Ca-ching!
Mile Marker #7: At that point, interests will align, of the pharmaceutical companies and those who have been misdiagnosed because of the not-yet-published but already dated DSM V. The pharmaceutical companies are looking for Ca-Ching! Ca-Ching. And depressed people are looking for better medications. We finally reach the operation of the free market system. This is the United States of America. Fortunately for depressed people, there are enough of us to make it profitable to treat us.
The fly in the ointment is the DSM V. It does loosen restrictions on the diagnosis of bipolar II a bit. The DSM IV said that a hypomanic episode brought on by antidepressant use does not count as a real hypomanic episode, and the person has unipolar depression -- suggesting to more conservative doctors that they keep looking for a better
antidepressant. The DSM V says that an
episode brought on by antidepressant use is a real hypomanic episode, with a diagnosis of bipolar II -- pointing doctors toward
mood-stabilizers.
So the task of the drug reps will be to direct doctors to the research demonstrating:
- more than half of those with severe depression eventually are diagnosed on the bipolar spectrum;
- incredible harm is done to these patients when given antidepressants;
- therefore these depressed patients might benefit from receiving a mood-stabilizer from the very beginning of treatment, particularly the mood-stabilizer of which the drug rep happens to have samples.
The true conservative treatment course might be to treat
all depressive people with mood stabilizers, unless the doctor has time to sort between those with genuine unipolar depression (presenting their first episode and no history of anything that looks even slightly like hypomania) and those who have recurrent depression (or "cycling" depression), especially when Lamictal and future mood-stabilizers have better side effect profiles. First do no harm.
Never mind what the DSM V says.
If the meds work, if they increase their makers' market share, then the pharmaceutical companies will continue to find ways to do their own education of doctors, including education in how out of touch the DSM V is with clinical practice. These same market forces will make irrelevant the DSM's refusal to define a diagnosis for pediatric bipolar. If the meds work,
children may receive a nonsensical diagnosis, but they will also receive the appropriate medication.
Mile Marker #8: Now all hell breaks loose with health insurance and HMOs. They depend on the DSM for billing. But the gap between the DSM and clinical practice in mood disorders will be so wide that case reviews and billing procedures will fall apart. Doctors will either code according to the DSM and treat according to reality, or code according to reality and ignore DSM criteria.
But our health care delivery system is already broken, and will collapse anyway, long before we reach Mile Marker #8.
sign at Goose Creek Trailhead photographed by Steven Bernard
in public domain
photo of Lamictal by Parhamr and in the public domain
money bag from Microsoft clipart
I haven't read The Eyre Affair by Jasper Fforde. Yes, I spelled his name correctly. Another friend, a bookophile who knows loony recommends it. It is the first of Fforde's loony alternate reality series, starring Special Operative Thursday Next, a literary detective who is chasing down the evil Acheron Hades who has stolen... It's a Lost in Austen/Inkheart kind of alternate reality, blurring the boundaries between the world of normals and the many worlds of books.
Hitchhiker's Guide and The Eyre Affair are my segue into alternate worlds. I was heartbroken when we got to the end of the Harry Potter series by J.K. Rowling and lost that annual Hogwarts fix with its witches and wizards, port keys, Marauder's Map and all the rest. According to a Face Book quiz, if I were a Hogwarts teacher, I would be Remus Lupin. I may reread all seven books in preparation for the last two movies. And I am delighted that seven books became eight movies.
Another friend fave and mine, too, is The Wrinkle in Time series by Madeline L'Engle. These are cross-over youth/adult sci-fi, but you don't have to be a sci-fi fan to appreciate them. One summer vacation/road trip, my six-year-old listened to Wrinkle on tape. Every time we stopped for lunch, he wanted to discuss it. Every time he got to the end, he started again at the beginning, and I was happy to listen with him. I wonder if this was the root of his vocation as a philosopher. The misfits are the heroes who save the planet from IT, the force that wants to eliminate unhappiness by eliminating deviance in the universe. (I suspect that IT really just wants to get rid of deviance. The unhappiness thing is just part of the sales pitch.) In the first volume Meg figures out, same and equal are NOT the same thing. Bonus: it turns out that It was a dark and stormy night is a great way to start a book, after all.
Michael Chabon rewrites history in The Yiddish Policemen's Union. Imagine that at the end of World War II, Jewish people went to Alaska instead of Israel. Fifty years later, Alaska is about to revert to the United States. Enter your basic hapless detective. Combine a murder mystery, political intrigue, orthodox Jewish mobsters, chess and a red calf. Shake vigorously. Serve on the rocks.
Chabon provides another alternate world in a tale of two Jewish adventurerers, Gentlemen of the Road. Set in 10th century Khazaria, two con men/bodyguards/swashbucklers star in a dime store novel with elegant prose, inadvertently fighting for justice and the rightful heir to the Khazarian throne.
Not all alternate worlds are fantastical. Like Gentlemen of the Road, books set in real times and places can sweep you up so that you leave your own world and enter the author's. The day my mother left her third husband, the good stepfather, separating hers and theirs from his, I postponed going crazy by moving to China via Pearl Buck's The Good Earth. Never mind the 1931 copyright. It won a Pulitzer Prize, and seventy years later, Oprah made it a Book Club pick.
Lately I have been living in nineteenth century England. Jane Austen's biggest hit is Pride and Prejudice. I haven't tried the graphic novel nor the sequels it inspired, including one with zombies. You're on your own there. Currently I am doing the Bronte sisters. Emily Bronte wrote Wuthering Heights. That link takes to you the edition that is easy to read in bed -- whatever that means. Jane Eyre by Charlotte Bronte has inspired the same kind of take-offs as Pride and Prejudice. All of them have been made into multiple movies and mini-series, if you want to extend your reading experience into other media.
Rounding out our alternate world category, Ellis Peters takes us to a Benedictine monastery in twelfth century England, in the midst of a civil war. Cadfael is a second career monk, a crusader turned herbalist and forensic scientist detective. The series starts with A Morbid Taste for Bones and goes on for nineteen more volumes -- God bless Ellis Peters. This series has also been filmed, with Derek Jacobi as Cadfael.
Douglas Adams and Hebrew poetry have both inspired me through the years. I told you I had two categories. So here is a third -- compelling nonfiction. These two are on my own to read list:
The first is friend-recommended The Spirit Catches You and You Fall Down by Anne Fadiman. It is a tragic story of the clash between two cultures, that of the Hmong and that of Western medicine. The parents say Baby Lia Lee's soul is outside her body, captured by an evil spirit. She needs a shaman. The doctors say she has epilepsy. She needs medication. The doctors win. The results are not good. I haven't been reading biographies of people who live with mental illness lately. But I might make an exception for this one.
The second and last is Invictus: Nelson Mandela and The Game That Made a Nation by John Carlin. This edition has pictures from the movie. The original edition is titled Playing the Enemy: Nelson Mandela and the Game That Made a Nation. Combine the typical sports narrative structure: loser team triumphs, with that incredible, grace-filled moment in human history: oppressed people triumph and don't wreck vengeance on the oppressors.
So there are more than enough books to fill out my local library's summer reading club requirements.
What are you reading this summer? Enjoy.