Thursday, September 18, 2008

Big Drugs, Small Brains?

I've read on and off about brain shrinkage being linked to antipsychotics. I have not paid a lot of attention to research on the topic but kept it on my mental backburner. And now Furious Seasons notes that Nancy Andreasen is reporting that her research shows antipsychotics are strongly linked to brains getting smaller. The longer one takes these drugs, the smaller the brain. Does anyone want to set up a YouTube "This is your brain on drugs" video?

Interestingly, a group of researchers has claimed that olanzapine (Zyprexa) has "neuroprotective" qualities; it's good for your brain. Um, color me skeptical. Their research was based on rats, whereas Andreasen's work is on humans. Andreasen's latest work is not yet published, making it difficult to judge the quality of the findings. But research on monkeys exposed to antipsychotics found that:
In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume.
I am not a neuroscientist, but if both sets of findings were accurate, then we'd have people taking antipsychotics who have smaller but better brains. The more neuroscientifically inclined may wish to comment on this possibility, because it seems a little odd to me.

15 comments:

NeuroPsych15 said...

These people also swear up and down that lithium is also neuroprotective (based on rat evidence). However, cognitive problems are one the most frequently reported side effects. So, you're neurons are in great shape, you just can't use them. That would make a great marketing campaign.

therapyfirst said...

I'd post this comment over at Furious Seasons, where I read this issue first, but I will not engage with the "rebuke" that would follow, so I hope I can present this opinion here and this blog site would allow commentary to proceed as allowed:

One of the reasons I have seen an increase in antipsycotic use these past ten years is due to the misdiagnosis of Bipolar disorder for what is really a primary disorder know as Axis 2 disorders, known as Personality Disorders, or what I like to call characterological features/problems. I won't waste space with more details and my position, but I would like to throw this out to the readers: When you have mood lability that is so fragile and brittle, which is what is characteristic with Axis 2 disorders, why do people rush to go on drugs in general, much less more potent in nature as I view the antipsychotics, when such individuals need to work on insight and judgment as much as look for some form of chemical intervention?

Let's be honest and realistic here, folks, Lilly/AZ/Bristol Meyers/Janssen/Pfizer make good money on these drugs, and as long as they get away marketing them for any and every psychological ill outside psychosis, which is a somewhat legit indication in this case, when will all the involved parties in the utilization of said drugs wake up and say "Whoa, wait a damn minute here!!"

You wait, WHEN AZ get Seroquel an FDA indication for anxiety, duck, 'cause you know what's coming off the fan. And don't underestimate BM's agenda with Abilify. Man, Lilly has seeded one ugly turf for all their competitors to ride gleefully over.

And you folks are the turf. My opinion, and advice, you have psychological struggles, go from least to most invasive. Drugs are more invasive than therapy for a good number of people who present with problems. People may need to turn to meds fairly quickly, but don't lose track of the role of therapy, when it is offered by qualified and responsible providers.

Me personally, I don't like the look of tire marks across my face, in a figurative meaning. Don't be the turf!

Anonymous said...

As someone who took atypical antipsychotics for 6 or 7 years, I find this research frightening.

First, they (Big Pharma) failed to tell us we would gain weight (I gained 60lbs on Zyprexa), then they neglected to mention the possibility of developing diabetes and metabolic syndrome. Now, it seems likely longterm use causes brain shrinkage. I feel like we patients are participating in extended clinical trials.

I had noticed significant cognitive changes over the past few years, more than you would expect for someone in early middle-age, and sure enough, psychological testing showed an 18% reduction in IQ, as well as memory and thought processing deficits.

I quit taking atypicals (the last was Abilify) about 6 months ago, and, although the weight is coming off, alas my brain still feels stunted.

I wonder what the final result of this will be? Very disturbing information.

Anonymous said...

Therapyfirst, you made a very good point. I'd like to counter with an unfortunate reality.

My insurance pays for drugs and med checks. It reimburses very little for therapy.

I had to pay $65/week out of pocket (which isn't much to some people, but a lot for me) to see a clinical social worker. Anyway. I went for awhile, it helped, but then other members of the family needed medical care and Wham! suddenly we were about $6,000 in debt to various providers--thanks to 20% co-insurance and high deductibles. I can't put my therapy ahead of my family's health, and I can't afford to pay for both, even through the local CMHC.

What I can afford now is generic meds and a visit to my psychiatrist once a month. That's it. I'm fortunate, though, because some people only get to see their primary care MD or a doctor in a clinic.

I'm not writing this out of self-pity (although I feel some of that, especially after reading today's blog entry), but to illustrate that mine is the reality faced by many in society. If you don't have much disposable income and your insurance is restrictive, the choices are pretty limited.

At least, this is the reality in the United States. I know it differs in other countries.

Sara said...

I wonder on what basis these drugs are being called "neuroprotective." If it's because they are linked to neurogenesis, then that's weak evidence for a protective effect. Neurogenesis occurs when there's been an insult to the brain, a shock or trauma such as a stroke and it's not necessarily healthy neuron growth. There's no proof that just because there are suddenly a lot more cells that they are good cells. The day someone proves to me that a psych drug is "neuroprotective" is a day frankly when I think hell will freeze over. It's just not gonna happen anytime soon on the basis of what I already know. By the way those eggs look really good. When's breakfast served?

Anonymous said...

TF,

Aside your opening paragraph, I see no reason why your comments wouldn't be well received. Please don't lay the seeds for a flame war here as you have done at FS.

I have difficulty envisaging circumstances where neuroleptics (why not just say major tranquilizers?) serve any useful purpose other than putting a patient down, as in chemical restraint. Even in such cases, the use would be for acute episodes not for maintenance. It still baffles me how these drugs get approved for said uses.

WD said...

TherapyFirst said:

...don't lose track of the role of therapy, when it is offered by qualified and responsible providers.


I agree whole heartedly from personal experience. Unfortunately it's much easier to get a prescription of medication than a competent provider.

therapyfirst said...

To the above Anonymous who writes about the "don't lay the seeds of a flame war here", I have no argument with that point. I would hazard to guess the blog owner here will maintain accountability on all parties' part, me included. I just want fair and reasonable dialogue on issues that these sites raise. I hope my points and comments are received as intended.

As per Wd, you are right about access, and that is one of my mission statements as a commenter. The bigger, and original issue that laid the ground work for the intrusion of over simplification of a biological philosophy to mental health care was managed care setting the price for therapy, setting the limits who could provide it, and now telling the consumers who pay for the care who can get it.

Doesn't that last comment outrage others who have been impacted by such intrusion? I don't seem to read this anywhere on the internet?

Maybe because the adage, 'hear the lie enough and it becomes the truth' is what managed care has banked on. Other opinions?

If we as a collected group of providers and patients don't fight for what is right, the poisons of overmedicating will tarnish much more than what we see now. Hey, I'm on the front lines of this battle, so respect I have some experience and perspective here. I am a patient advocate. I won't mention F.S. again hereon, but I have to wonder if it only benefits the money makers to let the extremists in psychiatry and patients battle it out when the middle of the pack just gets squashed. As I say alot, just my opinion.

Stephany said...

CP-- great post as usual. I find it really intriguing that any medication is ever touted as "neuro-protective", as Li has been in the past. It's hard to imagine antipsychotics (like Zyprexa for example)as being anything but damaging to a brain, it's chemical altering.

This brain shrinkage topic is of grave concern to me, due to my 20 yr old being on Zyprexa from age 11 to age 18, and Clozaril since then. I seriously fear for her lifespan, and hope her brain is not affected adversely too.

She was placed on Zyprexa when she was misdx childhood bipolar, as you probably remember.

Thanks for your perspective.

Stephany

Anonymous said...

Eli Lilly’s Wrongdoing Illustrates The Real Dangers of Anti-Psychotics


Not long ago, I got the joy and despair of viewing many documents that were initially not to be seen, by order of the Department of Justice, yet found their way on various locations on the internet- specifically, the website: www.furiousseasons.com. The documents are, or were, in fact, evidence against Eli Lilly entirely representing their decade of deception promoting and over-medicating others with their drug called Zyprexa, which is in a class of medications called atypical anti-psychotics that, while a new molecular entity by definition, are in fact chemically similar to the older and typical anti-psychotiics, such as Haldol, which have proven to be safer than the new class that appears to be quite damaging to those who ingest these atypical antipsychotics. Of the several available atypical anti-psychotics now available, Zyprexa and Clozaril, which was the first atypical anti-psychotic, are believed to be the most adverse to the consumer of these medications compared with other medications in this class of drugs.

Launched in 1996, Eli Lilly did not appear to consider any adverse effects that may occur to those who take this drug, yet it is believed that there was reason to believe that there should be caution regarding its use. With the belief that the maker of Zyprexa is and will be exonerated from any responsibility related to Zyprexa, many surmise that Eli Lilly was pleased that others were taking Zyprexa , and was confident that they would be exonerated from any responsibility from the adverse effects of the drug.

At the time Zyprexa was granted approval for marketing, the medication was indicated only for schizophrenia and mania that exists in those with bipolar disorder. Schizophrenia has been defined as a disease that causes the sufferer to deviate from true reality, along with visual and auditory hallucinations. Bipolar disorder is another mental disorder where the victim alternates from states of heightened neurokinetics to periods of what can be brutal depression for the sufferer.

Eli Lilly, known in recent years for their focus on marketing over science or research, greatly desired and hoped that Zyprexa would be a welcome blockbuster, which is a medication that exceeds a billion dollars a year in sales as a minimum. Likely because of this state of greed of Eli Lilly, they did not consider or evaluate any possible damage this flagship drug may cause others. And Eli Lilly appeared to have the obedient and manipulated sales force presumed to be a necessity for this monetary goal to occur without interference.

Pharmaceutical representatives overall are attractive and young individuals with little if any medical knowledge or training, but are determined to have charming personalities along with a perception of obedience, and this is all Eli Lilly in particular wanted from the members of their sales force. The sales vocation is normally associated to contain members with a high affinity for money, so corruptive acts such as off label promotion or overt kickbacks is not typically a consideration of such people, overall, as history has shown.

Therefore, if Eli Lilly’s sales representatives who happen to be instructed to sell Zyprexa for dementia or depression, the orders will likely be followed. Or if this sales force is instructed to pay specifically targeted doctors large amounts of money for doing little or no work for this money given to such doctors, it still is not a problem for the sales force to maintain their obedience to their corporate God.

A few years after Eli Lilly launched Zyprexa, they appeared anxious due to their obvious disappointment regarding the initial prediction that was speculated about the growth of this drug that was not meeting their expectations, so they had meetings throughout the nation, known as ‘plan of action’ meetings, and concluded afterwards that there is great benefit from a monetary paradigm of implementing ‘seeding trials’, as they are a mechanism for generating needed, although fabricated data void of any scientific gain of knowledge. This amazingly was done and implemented afterwards rather overtly. Even more unbelievable is that around this time, the Zyprexa sales force was instructed by Eli Lilly management to seek out clinical trial sites, along with investigators for these trials. One voiced stipulation was that the investigators had to either be Eli Lilly prescribing supporters or high volume prescribers. This protocol described was written internally, along with the etiology for performing these sham clinical trials. Anything in writing can be golden, from an illegal situation such as this.

In addition to the clinical trial plan of action, Eli Lilly instructed its sales force to utilize inaccurate promotional material that Eli Lilly gave its Zyprexa reps without exception, even though this material was false and misleading, which was the intent of Eli Lilly, according to others, along with this material being greatly unbalanced and suggested uses for Zyprexa that were not indicated if not unproven, which can and has been harmful to patients because of this. To further saturate and corrupt the Zyprexa sales force, they were coerced to blunt assertively what are at this time widely recognized adverse effects of this medication, such as massive weight gain, along with glucose and lipid abnormalities- all of which are dangerous to the user of this medication.

The corrosive promotion of Zyprexa by Eli Lilly continued as the dangerous company intentionally altered certain Zyprexa articles by rewriting them, followed by being reviewed internally after this art work. The purpose was to stimulate what Eli Lilly believed was clearly absent, which was much needed commercial interest related to Zyprexa.

Then it came time to essentially buy benign support groups in hopes that this would improve the growth of Zyprexa. One example is that Eli Lilly paid the American Diabetes Association for their assistance in obtaining endocrinologist consultants, which is a medical specialty that treats, among other things, diabetes. To reduce any possibility of an unexpected contingency doing this, they went ahead and hired a good sized team of diabetes educators. In 1999, Eli Lilly altered a Zyprexa report that originally illustrated the glucose problem with the medication, and did so with deliberate intent and reckless disregard for others. Eventually, the American Diabetes Association became quite the critic of Eli Lilly because of their harmful behavior regarding Zyprexa.

Amazing alliances between Eli Lilly and the Bush administration have existed as well. George H.W. Bush became an Eli Lilly director after leaving the CIA and lobbied to infect third world countries with Lilly medications. He also did his best to maximize tax breaks further for this industry that now employs both himself and his political affiliation. In fact, many members of this administration have some connection with Eli Lilly. It seems to be a revolving door issue once again. One could speculate that the Zyprexa campaign continued for so long because of the relationships the maker of the drug had and has with other powerful people.

The next psychotic tactic Eli Lilly created was an advisory board paid well by this company to focus on the progressing concerns of Zyprexa. This tactic did work briefly, but did not change the view of the drug by the medical community in any way, or the maker of this drug.

It is at this point that the medical community began to get vexed and irritated by Eli Lilly’s deceptive and overtly destructive tactics, which included the company’s own speakers that were utilized in the past. This event of Eli Lilly being ostracized was because of their disregard for those they are obligated to serve in the medical community. Perhaps most disturbing was the company’s intentional holding of crucial safety information related to Zyprexa even before the drug was even approved. For example, Eli Lilly’s Zyprexa representatives were instructed without doubt to neutralize the legitimate concerns doctors may have about Zyprexa, if not outright fear regarding this deadly drug they now perceived as being a clear reality. The representatives were in agreement of continuing to dodge or neutralize legitimate concerns about Zyprexa, with the promise of Eli Lilly’s management team to fill their wallets more if they maintain obedience regarding this directive that caused harm in the form of such physiological disorders as metabolic syndrome associated with Zyprexa, yet the sales force still denied the association due to the insistence of their employer. Essentially, the Zyprexa representatives with Eli Lilly were trained, perhaps aggressively, to disarm negative perceptions about Zyprexa, even though these perceptions continuously proved to be valid. This deeply troubled many Zyprexa representatives, as at this point they were aware of the dangers of the drug they were promoting in order to maintain employment.

Also, and of no great surprise, off label promotion with Zyprexa was a norm within the organization and certainly encouraged by Eli Lilly management. Encouraging doctors to prescribe Zyprexa for depression is one example.

Amazingly, reflecting back on the behavioral flaws by Eli Lilly for quite some time, they did not alter their method of business even though there was a strong perception regarding this company being both aggressive and greedy, and likely criminal in the way they chose to conduct their business. And depression was not the only off label claim with Zyprexa. Eli Lilly considered such criminal acts as off label promotion as ‘redefining the market’. Another example of their absurdity:

In the year 2000, Eli Lilly greatly expanded what was called their long term care sales force to expand Zyprexa intake in the elderly. This, as a reminder, is dangerous, as Zyprexa is harmful to older citizens- specifically pneumonia and eventual premature death result from Zyprexa intake. At the same time, Eli Lilly developed a strategy to neutralize the obvious weight gain associated with Zyprexa with other patient populations. Does the whole corporation believe U.S. citizens are without thought or intelligence?

Yet in 2002, Eli Lilly was having financial disappointments, which again did not shock many. So to stay in form, they went on a mission to develop speakers to align with them and to not educate others, but to pacify other doctors in hopes that their problems with Zyprexa would disappear. After the speaker episode, Eli Lilly had the audacity to claim that Zyprexa was indeed the best in the class of atypical antipsychotics. Such a statement appears psychotic, to say the least. And now the market for atypicals is about 5 billion a year, so there seemed to be no end as to what Eli Lilly might try next. Also in this year our FDA called Eli Lilly ‘a sponsor’. I find that a bit disturbing. As disturbing as the covert meetings Eli Lilly had with the FDA as well. Well, if you are going to have a friend….. or friends, as around this time, Eli Lilly also bribed select reporters to speak or annotate favorably about Zyprexa, and they did.

As the new millennium progressed over a few years, lawsuits became a concern for Eli Lilly regarding Zyprexa. Doing what any responsible corporate entity would most certainly do, the upper management of Eli Lilly had the audacity to blame the media for the way they handled their patients. Around this time, Eli Lilly needed and did hire a public relations firm because of their image crisis. About the same time, Eli Lilly implemented a nationwide program entitled, “Operation: restore confidence”. I’m not sure how a fully rational and conscious group of Eli Lilly people could create something so ridiculous and unrealistic. Equally deviating from reality of Eli Lilly’s behavior is that they actually thought they could increase Zyprexa growth by hammering home astronomical efficacy with the drug which, of course, does not outweigh the damage of the drug to the patient who takes it.

Another failure illustrated above caused Eli Lilly to hire a group called Lifeplan Marketing, who convinced the organization to create a brand new market establishing Zyprexa as the standard of care. Another psychotic act by this Midwest group of manipulators who were at one time a well respected pharmaceutical corporation. Humans do not forget. Especially pain.

At least one human wanted to let everyone know he did not, nor will he ever forget his experience as a Zyprexa representative with Eli Lilly. His name is Shahram Ahari and he aligned with a group called Pharmedout, which was created due to a state settlement from another pharmaceutical company. He spends his days now making others aware of things such as what you have read. I’ve spoken with Shahram, and I admire his assistance with others trying to correct this medical mess.

Eli Lilly appears pathologically persistent in frightening ways. Next was a national implementation plan of action which focused on training the Zyprexa sales force to use what was called a J.C.P. study to emphasize the numerous off label benefits of Zyprexa. At the same time, Eli Lilly determined that primary care doctors should be their number one Zyprexa targets. With this new focus, the sales force for Zyprexa were somehow convinced to tell doctors that fatigue is really the only side effect that presents itself with Zyprexa use. Again, citizens are overall not catatonic about such actions.

While on this off label role with Zyprexa, they resurrected their long term care efforts by taking on Aricept, and alzheimers drug, and encouraged others to switch to Zyprexa. The reaction for this misbehavior was Zyprexa being removed from Medicaid in 2004.
Allan Reier was the Zyprexa product team leader at the time. He may have developed the unbelievable strategy of visiting psychiatrists to assure them they will not be sued if they prescribe Zyprexa for their patients.

So, now we are at a point where Eli Lilly had a flash of reality and preferred no media contact. Gosh, what a surprise.

The other tactical plan from Eli Lilly was to re-implement blunting techniques regarding Zyprexa. My guess is that they dragged this into a week long meeting. This of course included dodging concerns by doctors that they are normally encouraged to partner with, historically. Such tactical plans of action were associated with such clever names as, ‘Viva Zyprexa’, or Zyprexa Limitless”. Maybe the next one will be ‘Zyprexa Revenue Regression’.
Another tactic authorized by Eli Lilly was to use those bonafide contract research organizations (CROs) to manufacture safety, health, and outcomes database studies. A deceptive publication plan followed. CROs are commercial research organizations that include substandard research investigators and the sponsor of these clinical trials, Eli Lilly, has the ability to alter aspects of such trials for their own benefit. This was done as they still encouraged children to consume Zyprexa- near a million of them due to an arrangement that Zyprexa will be promoted by the ADD drug Strattera.


As stated earlier, previously sealed and damaging documents got exposed at the end of 2006, and are accessible on the internet and some websites, such as www.furiousseasons.com, which is what this article is based upon entirely. Perhaps the documents should have been exposed immediately instead of being held from public view. Many facts that you have read in this article are from these authentic documents that are more disturbing than fiction. The information is accurate, and many others are finally informed instead of deceived or denied their right to know.

“Character is what a man is in the dark” --- Dwight Moody

Dan Abshear

Author’s note: What has been written is based upon information and belief..

The Shrink said...

Interesting. We know that in older adults, brain volume is lost at about 3mls/year through primary ageing (and 16mls a year in secondary ageing processes like Lewy Body Dementia) so I wonder what the extent of Andreason's work found cerebral atrophy to be?

Is it that antipsychotic Rx causes brain volume to diminish at a significantly higher rate? Or is it that antipsychotic Rx is used in patient populations who lose brain volume at a faster rate through functional or organic neurodegenerative processes?

CL Psych said...

Shrink,

An interesting question, though primate research (linked in post) suggests that we're talking about a drug effect, though there could be possibly be a natural neurodegenerative process at work in addition to the drug effect.

Anonymous said...

Shrink,

Thanks for looking at both sides of the what if but I'd like to tell you that my 10 year old is a living, brain damaged example of what Zyprexa does to the brain.

My daughter is now 10 with an deminished IQ of 46, it's sad to say but her IQ at the age of 4 was much higher than it is today.

Also repeat MRI's do show significant atrophy of the brain. She has been through genetics, metabolic as well as had mitochondrial disorders ruled out. Medically there is no explanation as to the loss of brain matter other than the long term use of Zyprexa.

The sad reality in all of this is the drug manufacturer is aware of this occurance and everytime I have called they have continued to deny such medical findings but yet when you search brain atrophy and Zyprexa you can easily find numerous amounts of reports that have been called in by physicians and patients.

I hope and pray that the work that Dr.Andreasen has done will help to protect others so they don't end up like my daughter.

sober living house said...

The use of antipsychotic drugs is really one of the alternative to treat certain deceases but the the question on how the drug was used will always be another issue.Drug abuse is always imminent.

AM said...

I am interested in hearing more from the anonymous poster who lost iq points due to antipsychotics. Have you had any follow-up tests? I took abilify at 15 mg for three years and just scored about 15% less on an iq test than I think I should have. I am currently tapering off (at about 2.5 mg). Thanks