Neurontin 0, Placebo 1. Pfizer loses, Placebo wins.

Stephany at soulful sepulcher has a post up on how Neurontin has not shown itself to be more effective for bipolar disorder than placebo in clinical trials.

It's actually kind of funny that this discovery has been made in April 2008 because I'd reported on this back in January of 2007:

So let's recap: gabapentin is FDA-approved for epilepsy ONLY. But gabapentin has a slew of off-label uses.

Don't know what off-label means? It means "not FDA-approved to be prescribed for this use."

Now that we've got that out of the way, gabapentin is prescribed off-label for migraines, bipolar disorder, social anxiety disorder, OCD, treatment-resistant depression, insomnia, multiple sclerosis, neuropathic pain, and in some instances, post-operative chronic pain.

Where did this off-label usage come from? Basically, one journal article published data on beneficial effects for patients on Neurontin for bipolar disorder and then other articles would cite that article as supporting evidence then more articles cited all the other articles that published the positive efficacy data on the drug, creating what UNC researcher Tim Carey calls the "echo chamber effect."  From Fierce Pharma:

Hearing it over and over, doctors were led to believe that Neurontin worked for bipolar patients, and prescribed it to lots and lots of them.

These articles that touted the benefits of Neurontin were cited 400 times. Carey:

It “becomes a rumor mill in which physicians may be exposed to these types of articles, and citations of articles, which then gives credibility to off-label use.”

The conclusion?

“No scientifically acceptable clinical trial evidence supports use” of the drug in bipolar disorder.

Ouch. Hitting Pfizer where it hurts.

Hirschfeld developed MDQ for GSK

“GlaxoSmithKline, one of the world’s leading research-based pharmaceutical healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better, and live longer.”

OK, I’ll be honest. I can’t keep up with my own posts and have no idea whether or not I’ve posted on this yet. Judging from the fact that I still have this bp booklet, I’m going to guess not. If I have, then there’s more.

When my psychiatrist diagnosed me with bipolar disorder in November, he handed me a bunch of material: a mood tracker (PDF), an article touting the benefits of Seroquel, and a booklet titled, “Bipolar Disorder,” which refers the reader to www.1on1.health.com.

The booklet seems pretty harmless to a patient newly diagnosed with bipolar disorder:

“Highs and lows can be part of life. But, with bipolar disorder, they can be severe. You may feel too depressed to get out of bed one day. Soon after, you may feel full of energy. You may have normal times between the highs and lows. When people have mood symptoms, it’s more likely to be depression.

Mood swings can be hard to predict. But you may have warning signs. You may even learn what can trigger your symptoms. You’ll read about this and more in this booklet.

Bipolar disorder is complex. Doctors docn’t know what causes it. They know that genes play a role. The illness may be linked to brain chemicals. These chemicals can get out of balance.

There are treatments to help control the symptoms. Learn about your condition. Get help for it. This booklet is a good first step.”

Thank you, GlaxoSmithKline.

GSK, the provider of such psych drugs as Lamictal, Paxil, and Wellbutrin, issues a series of booklets for patients referring them to 1on1health.com. The topics include depression, anxiety disorders, epilepsy, type 2 diabetes mellitus, high cholesterol, among others. The tips seems pretty simple and straightforward:

“Health and lifestyle chances may trigger your symptoms. Some common changes are:

Not having a sleep schedule
Misusing alcohol or drugs
Stopping your medicine, or starting medicine for depression or another illness
Having thyroid or other health problems”

Then it gets into the general stuff about the difference between mania, depression and further clarifies what hypomania and mixed moods are. Then, the kicker follows:

“If you think you may have bipolar disorder, fill out the checklist on the next two pages. Share it with your doctor. He or she can use it to help diagnose you.”

Furious Seasons posted a link about a fake drug named Havidol (which I totally got suckered into because I skimmed the post and missed the “OK, it’s a gag” part), but the hilarity stems from similarly stupid (and vague) questions. I’ve put a screenshot of the PDF GSK provides on their Web site to the right. My issue is not so much with the questions necessarily, but with the lead-in to them:

“Has there been a time when...” [emphasis mine]

It doesn’t matter whether you were 3 years old or 46 years old, if you answered “yes” to more than one “there’s ever been a time when” question, guess what? You MAY qualify for bipolar disorder! A sampling:

Has there ever been a time when…

• You were easily angered that you shouted at people or started fights?
• You felt much more sure of yourself than usual?
• You talked or spoke much faster than usual?
• You were so easily distracted that you couldn’t focus?
• You had much more energy than usual?
• You were much more active or did many more things than usual?
• You were much more social than usual?
• You were much more interested in sex than usual?

Guaranteed everyone reading this said “yes” to at least TWO questions. If not, I question whether you’re breathing. (Sadly enough, this makes me realize how easy it was for me to get fooled by the phony Havidol quiz.)

The follow-up to the questions above asks, “If you checked YES to more than one of the questions above, have several of these things happened during the same period of time?” Then, “How much of a problem did any of these things cause you (like not being able to work, or having money or legal troubles)? Choose one[:]

1. No problem
2. Minor problem
3. Moderate problem
4. Serious problem”

The multiple choice question above may not matter. Answering some of the lead-in questions in the affirmative may qualify you for the disorder.

Here’s a nice little tidbit. The questionnaire was “adapted with permission from Robert M.A. Hirschfeld, M.D.” So as an uninformed patient reading this (which I was at the time), I’m thinking, “Oh, this must be legit since they got permission from a doctor to use this checklist.” There’s more than meets the eye here.

On the surface, Dr. Hirschfeld seems like an awesome doctor – and he very well may be. Dr Hirschfeld’s bio from the University of Texas Medical Branch at Galveston (UTMB) extols the “Professor and Chair” of its psychiatry deparment. He has history of working with various national organizations such as the National Depressive and Manic-Depressive Association,  National Institute of Mental Health (NIMH), and National Alliance for Research on Schizophrenia and Depression (NARSAD). He’s written all kinds of articles and blah blah blah. He’s considered a leader in his research of bipolar disorder.

In fact, because Dr. Hirschfeld is so great, he’s a member of pharmaceutical boards and has acted as a consultant for pharmaceutical companies, according to ISI Highly Cited.com. Some of our favorite guys appear here: Pfizer, Wyeth, Abbott Labs., Bristol-Myers Squibb, Eli Lilly, Forest Labs, Janssen, and – lookee here! – GSK.

The duration of Dr. Hirschfeld’s affiliations with these pharmaceutical companies are unspecified. All other “appointments/affiliations” have assigned years, i.e. 1972-1977, 2001-Present. His consulting affiliations follow his internship in 1968-1969. It looks a bit misleading to follow the consulting jobs after, oh say, 1969, and not provide dates of when he became a consultant for all of these pharma companies. Toward the end of the document that I found, his affiliations from 1986-Present are listed with various boards, associations, journals, and a slew of pharmaceutical companies.

Hello, hello, hello. He is a MEMBER of the Zyprexa U.S. Bipolar Academic Advisory Board, the Celexa/Excitalopram [sic] Executive Advisory Board, the Lamictal National Advisory Board, and the Zoloft Advisory Board.

Humor me here. His clinical trials include:

• 1994 Paroxetine for Dysthymia (SmithKline Beecham)
• 1995-97 Several (I found five) double-blind studies on sertraline and imipramine in patients qualifying for the DSM-III definition of major depressive disorder
• 1996-98 Gabapentin therapy for bipolar patients

And the list, including mirtazapine, fluoxetine, venlafaxine, lamotrigine, goes on. You can also find the “grants” pharma companies gave to fund these clinical trials.

From 1997-2000, Hirschfeld received a $100K grant from Abbott Labs to develop “a new checklist for bipolar symptoms.” (I’m not sure what the old one was.) In 2001, he received a $142K grant for the “Bipolar Prevalence and Impact MDQ Project.”

I don’t even need to look MDQ up. It’s Mood Disorder Questionnaire. The grant came from GSK, who “adapted” the questionnaire with Hirschfeld’s “permission.” That sounds simply gravy.

To understand more about bipolar disorder, you can listen to the stories of Greg, Stuart and Leslie – all your classic bipolar cases and how medication and/or therapy has helped them so much. You can also watch the bipolar
disorder animation that regurgitates all the things that we’ve become skeptical about.

In the meantime, remember the instructions included in Seroquel’s safety information that no one reads (excuse the crappy “Paint” job):

Neurontin: Pfizer and Eli Lilly share a common history

My mother-in-law was telling me yesterday about how her hairdresser’s daughter has been diagnosed bipolar with OCD characteristics. She says her daughter’s on “Neo-something” – she couldn’t quite remember the name.

I racked my brain for a bipolar med name that began with “n.” Nothing really came to mind except for neurontin. I told myself, “No, that can’t be right. Isn’t that associated with VNS?”

Nope; Neurontin really is a medication associated with bipolar disorder. Neurontin’s generic name is gabapentin.

Pharmaceutical roundup

Nearly every mental health blog I know is talking about this post from intueri.org. It’s definitely worth the read. I don’t know much about Abilify, but I don’t think most uneducated bipolars know that it is prescribed specifically for those with psychosis. On the flip side, I don’t think uneducated PCPs know that tidbit either. A person with bipolar without symptoms of psychosis who asks for Abilify may be in for a rude awakening. [UPDATE: Who paid this chick? I only skimmed the post but I don’t see any negative side effects listed.]

I’m not deep into the pharmaceutical industry like all of these heavyweights: CL Psych, PharmaGossip, and Furious Seasons, among many others whom I may have failed to mention. However, there’s a wealth of information to be found. My newest discovery:

“The approach is called ‘ethical pharmaceuticals,’ and it was unveiled on January 2 by Sunil Shaunak, professor of infectious diseases at Imperial College, and Steve Brocchini of the London School of Pharmacy, the Guardian reports. Their team of scientists in India and the UK, financed by the prestigious Wellcome with technical assistance from the UK government, have developed a method of making small but significant changes to the molecular structure of existing drugs, thereby transforming them into new products, circumventing the long-term patents used by the corporate giants of Big Pharma to keep prices – and profits – high. [emphasis mine] This will give the world’s poorest and most vulnerable people access to life-saving medicines – now priced out of reach – for mere pennies.”

I read the above on CLPsych’s blog (originally from Chris Floyd at truthout) and couldn’t believe what I was reading. It somewhat ties into what I’ve been researching about Neurontin (which will probably be posted later in the day):

“Pfizer has developed a successor to gabapentin [Neurontin’s generic name], called pregabalin (being marketed as Lyrica®). Structurally related to gabapentin [emphasis mine], pregabalin is effective for neuropathic pain associated with diabetes and shingles, and for the treatment of epilepsy and seizures.”

Pfizer, in an attempt to distance itself from the trouble surrounding Neurontin, developed another medicine – pregabalin, which is similarly structured to gabapentin. Pfizer can now claim, “Don’t like Neurontin? You can have Lyrica instead!” Pfizer also tried to pass off the (illegal) off-label marketing practices with Neurontin off to their acquired division Parke-Davis. So now we’ve got two options: Pfizer either has learned from Parke-Davis’ issues with Neurontin or is pretty stupid and pushing Lyrica for off-label usage similar to that of Neurontin’s. No evidence to support either option… yet. But CLPsych delves into an interesting practice that Pharma companies use to circumvent a drug patent running out:

“News Flash — PhRMA does NOT believe in the free market: While PhRMA likes when the market works in their favor, they also believe in circumventing that same market when it comes to competition. When drugs are slated to come off-patent, which would allow generic version of the drug to be made, PhRMA members have increasingly turned to buying off the competition. That’s right; they simply pay the generic manufacturer to not make a generic version of the patented drug, so that the consumer can continue to pay a hefty price for the drug which is still under patent. [emphasis sorta mine]“

Wow. That bit of information has left me speechless. Screw the consumer that can’t afford psych meds without health insurance; we as Big Pharma need our DAMN money!!! [end rant]

This practice, called “reverse payments,” is not something new and, at the current moment, is relatively legal. Supposedly, the FTC and the Department of Justice are keeping their eyes on reverse payments and patients can only imagine what might occur in the future. PharmaGossip has more, but slips this bit of info before linking to the Star-Ledger:

“And with the patents on 70 blockbuster drugs — with a total of $48 billion in annual sales — set to expire by 2011, the industry expects reverse-payment deals to proliferate further.”

The FTC and Justice Department better hurry up and step in so we can finally have a generic version of Lipitor!

In all honesty, my mind can’t simply fathom the depths to which Pharma will stoop to make money. (Perhaps because I don’t work directly within the medical industry.) It has me wondering if Pharma is worse than gas companies. Is OPEC more trustworthy than Eli Lilly? I’ll leave it up to you to decide.

Loose Screws Mental Health News

Yay for the New York Times! Alex Berenson, doggedly keeping up on the Zyprexa story, has written an article about how state prosecutors in Vermont and Illinois are now demanding that Eli Lilly submits documents to them about their marketing practices of Zyprexa. Something I didn’t know:

“Federal prosecutors in Philadelphia have also recently accelerated their own investigation into Lilly’s marketing of Zyprexa.”

My residence in the Philly area has prompted me to follow this closely now. More juicy information:

“In a statement yesterday, Lilly said it would cooperate with the investigations and had done nothing wrong. ‘We intend to cooperate with the Illinois attorney general’s civil investigative demand relating to Zyprexa,’ the company said.

While the investigation being led by Illinois is civil, other investigations into Lilly’s conduct are both civil and criminal. [emphasis mine] Attorneys general in California and Florida may seek to recover Medicaid payments that the states made for Zyprexa. Any fine or cost recovery could be sizable, because Zyprexa has been a commercial success.”

Because investigators need to search through more than 10,000 documents relating to Zyprexa and its marketing and talk to former and current employees about the matter, it could take years for anything to happen. Berenson’s last paragraph at the end brought my excitement to a quick halt:

“As long as drug makers comply with federal requirements to provide data about their products to the Food and Drug Administration, companies have a relatively strong defense against criminal prosecution, according to lawyers who are experts in drug marketing.”

Great. So as long as Lilly complies with the FDA and state and federal prosecutors, they can escape criminal prosecution. Please don’t tell families who have loved ones who died over this medication. Lilly’s settlements are nice and all, but money is never restitution for someone’s death. I’ll soon have a post up about how Pfizer had this issue with Neurontin from 2002-2004. They, too, had to pay more than $430 million to settle lawsuits on civil and criminal charges. Pfizer plead guilty; let’s see if Eli Lilly follow suit (no pun intended).

I’ve been a little late on the bus with this, but I’ve previously written about Andre Waters who killed himself in November. Despite theories of depression surrounding his suicide, a neurologist has claimed that Waters sustained brain damage from playing football which triggered his depression and led to his death. Dr. Bennet Omalu, an expert in forensic pathology, says that Water’s brain tissue “had degenerated into that of an 85-year-old man with similar characteristics as those of early-stage Alzheimer’s victims.” Omalu gets pretty grim though:

“If [Waters] had lived, within 10 or 15 years ‘Andre Waters would have been fully incapacitated.'”

The NFL has no comment.

As I’ve been trying to tell my husband recently, pets can relieve symptoms of depression. Come on, who can be sad when you’ve got an happy little dog wagging its tail at you with bundles of love? (I’m thinking cute little Yorkies or friendly Golden Retrievers.) Owning a pet can have great mental health benefits:

• Can reduce anxiety
• Induce social contact
• Promote a better quality of life
• Help kids develop higher self-esteem and lower levels of fear

The only downside: animals can cause stress. But it seems like the stressors can be addressed, i.e. animal training, neutering. (source: The Trouble With Spikol)

Also linked to by Liz Spikol, another interesting mental illness combatant: sports therapy. It seems that it can help those suffering from PTSD, abuse, amnesia, and shyness. Italian doctors, however, a testing to see if soccer can treat illnesses like depression and schizophrenia. This should be interesting.

Oh, and NOTHING to do with mental illness, but I found this NYT article on weight loss and maintaining it quite interesting.