October 18, 2010

Why Zyprexa (And Other Atypical Antipsychotics) Make You Fat

annalynne_mccord_90210.jpg
this post does not apply to her, she only eats apples


Strange finding: Zyprexa makes free fatty acids level go down.

Wait, isn't that a good thing?

II.  Zyprexa's effects on glucose and insulin are bad.

In a rat study of rats, using rats, Zyprexa raised glucose levels by 20%, both in fed and fasting states.

It didn't much increase insulin in fed states (already high) but it kept insulin high even in fasting states: at 14h post meal, it was 140% higher than it should have been.  All that exposure to insulin, for so long.  At the coffee cart, we doctors would call that bad.

III.  Zyprexa's effect on triglycerides is... weird.

Zyprexa made circulating triglyceride levels fall-- it promoted the uptake of free fatty acids by various tissues:



zyprexa triglycerides.png
All those tissues taking up fatty acids-- what did they do with it?

IV.  Zyprexa Makes Your Body Use Fat, Not Carbs, As Fuel

Normally, after eating, your body uses carbohydrate as the main energy source.  After a long time hungry, it switches to fat.

Zyprexa made the body use fat all the time:


zyprexa rer.png

RER (respiratory exchange ratio) tells you what's being used: 1= carbs, 0.85= carb/fat mix, and .7 is all fat.  You eat, and your body uses carbs.  After a few hours, your body switches to fat utilization.

In graph A, in the first 3 hours the body should have been using carbs and fat; but with Zyprexa, it was preferring mostly fat.

In graph B, every time you got a Zyprexa dose, your body switched to fat utilization instead of carbs.

V.  Wait a second, why would increased utilization of fat be a bad thing?

If the body is churning through the fat, what do you think it is doing with all the sugar?  Answer: turning your arteries into Twizzlers.  Yum!

The typical thinking is that hyperglycemia leads to insulin resistance leads to increased fatty acid utilization.  But that might be the wrong direction: it seems that the increased fatty acid utilization means sugar is unused (hyperglycemia) and remains high well into the fasting state, with consequent high levels of insulin.  Insulin high too long becomes tolerance to insulin becomes insulin resistance becomes BKA.


VI.  SUMMARY: A class effect, to varying degrees; and eating less may not help.


1. Food intake was the same between controls and Zyprexaers.  You get these effects even if you eat the same.

2. This effect is shared by other atypicals, in a predictable fashion:


atypicals rer fed.pngIn the fed state, Zyprexa and Clozaril do a massive conversion to fat utilization, Risperdal a medium, and sulpiride minimal covnersion.

In the fasting state:

atypical rer fasting.pngGeodon has a lesser effect than Zyprexa, and appears to normalize; Abilify and Haldol seem close to normal.

3. These effects are consistent with Lilly's own studies that the majority of weight gain happens in the first month, and not suddenly after a year of use.

4.  There is still a hunger component to weight gain that is separate from the metabolic effect.  Some drugs will make you hungry, change your metabolism, or some mixture of the two.  Hunger appears to be a H1 mediated process (Seroquel, Zyprexa, Clozaril, Remeron, Paxil>Prozac, etc.)

5.  The immediate clinical consequence of this information is probably (paradoxically) to tell the patients to eat less sugar. 

Unless you dramatically cut fat out of your diet, the body will still churn through what fat you do eat at the expense of carbohydrate.  Better, and easier, to reduce the carb load that lingers in your body (and likely ultimately gets stored.)

VII.  Is that all the bad news?

No, of course not!

In another study (same authors, same topic, same time-- two completely different journals; thanks promotions committee, turning academics into bloggers one study at a time) they found that while there was increased lipogenesis (storage), the rats didn't have a change in body weight.

In other words, Zyprexa didn't make them heavier, it made them fatter.  It increased their body fat while decreasing the lean body mass. Bright side: now they can float!

Add to this that it though caloric intake was the same, it dramatically decreased locomotor activity.  So same calories, but less calorie need.

VIII.  Well thank God doctors are finally going to know the truth about Zyprexa!


From who(m)?

The reality is I found these two articles by accident, researching a blog post about something else entirely.  I would never have found this article, let alone the other article, on my own.  And I read a lot.

Ordinarily, this kind of information would have come to me through my Abilify rep: "see?  Zyprexa blows!"  But the FDA now forbids anti-competitor comparisons; and neither are the reps allowed to tell me that the study exists.  Promotional speakers can't mention this either.  So?  CME?  BWAHAHAHAHAHAHAHAHA!

Here's the bottom line, and it applies to all speech everywhere: either you permit all kinds of speech, and let the truth battle on its merits; or you permit only one line of speech-- and let the truth, if it was suppressed, come up like smoke through cracks.  But when you permit some speech and block others-- when you create gatekeepers of speech-- it creates the impression that the truth is in the permitted speech.  Most of the time, it's not.



POLL: What was the "other research" I was doing?

View results






Comments

Wait, weren't we trying for... (Below threshold)

October 18, 2010 4:11 PM | Posted by DaveInMaine: | Reply

Wait, weren't we trying for fat-dumb-and-happy in the first place (but maybe not in that order)?

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Do you think this is true f... (Below threshold)

October 18, 2010 4:12 PM | Posted by Anonymous: | Reply

Do you think this is true for zoloft too?

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For what it's worth, the fu... (Below threshold)

October 18, 2010 4:45 PM | Posted by Aron: | Reply

For what it's worth, the full text of the first study mentions light and dark cycles that were maintained for the rats. I imagine that's how Alone stumbled onto the study.
Considering how small and insignificant the light/dark information is in the study, it's kind of surprising if Alone really did find it while looking for information on the correlation of light and metabolism.

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That chick is HAWT!... (Below threshold)

October 18, 2010 5:30 PM | Posted by GT: | Reply

That chick is HAWT!

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I've been on Seroquel for o... (Below threshold)

October 18, 2010 11:35 PM | Posted by Mouse: | Reply

I've been on Seroquel for over a year now. I am using it at sub-therapeutic levels (100mg per night) for sleep. I want to get off of it but I simply cannot fall asleep without it. I also take zolpidem, clonazepam, doxepin AND gabapentin. I used to be able to sleep with just zolpidem. Then I needed the clonazepam. Then the doxepin. The gabapentin is for something unrelated. How can I get off of Seroquel? Just to note: I don't have bipolar or any type of schizo disorder. I was simply depressed (and I've never responded to any SSRIs) so one medicine led to another, I guess. I take 2mg of clonazepam (and have been at this dose for 2 years) and I feel nothing.

Also, when I first began taking Seroquel I found it beneficial because I was underweight and it did help me feel hungry and eat more (but then this awful side effect of feeling like I could not swallow has scared me into not eating after I take it). I am now at my normal weight and my BMI is still on the low side- 17.4. But this is normal for me.

How do I get off of the Seroquel? My psychiatrist has no answers. She just prescribes more meds.

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@GT:Yeah, if you'r... (Below threshold)

October 19, 2010 12:26 AM | Posted, in reply to GT's comment, by SteveBMD: | Reply

@GT:

Yeah, if you're into overbite.

(... but seriously, who's not, really?)

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Dopamine is a major metabol... (Below threshold)

October 19, 2010 1:59 AM | Posted by Anonymous: | Reply

Dopamine is a major metabolic controller. In animals dopamine along with melatonin is largely responsible for seasonal adaptation, i.e. hibernation. Human obesity is largely a hibernation response gone unchecked and chronically triggered by very high carbohyrate and abnormally decreased bright sun exposure combined with abnormal stressors (sleep deprivation and abnormal light exposure patterns - too much during sleep, not enough during wake).

In people taking zyprexa, blocking their dopamine receptors (and serotonin, and others) is making genes active that promote hibernation - they stop burning fat, stop storing fat, blood sugar increases, fertility shuts down, etc. It is no different than a hibernating animal.

In obese and diabetic humans it has been shown there is a paucity of dopaminergic signalling, and this is reversible upon glucose restriction. Downregulation of dopamine signalling is necessary to allow metabolic disorders to occur, why ? Because it is fundamentally a normal evolutionarily concerned hibernation tendency, it is only a disease in our modern society where tehse genes are being abnormally activated, chronically, year round.
Bromocriptine helps diabetes and obesity for this reason.


Regarding the observation that people on olanzapine are not using carbohydrate for energy, I would assume that is just the natural result of blocking multiple serotonin and dopamine receptors in the body - an inability, a debilitation, in using glucose for energy. This is a natural and evolutionarily conserved result of deficient neurotransmitter signaling, which again to the body signifies seasonal change and impending winter thus a hibernation-like response (metabolic conservation involving fat accrual, sleeping more, hunger, and shut down fertility).

It's been known for awhile that when the body switches to using fat for energy this will result in hyperglycemia and thus compensatory hyperinsulinemia, which leads to body fat gain. When the body insists on burning fat even in the presence of carbohydrate, it could mean any number of things... 1) pathological insulin resistance due to damaged /deficient mitochondria (glucose cannot get into the cells because the mitochondria are deficient, mitochondria therefore burn fat primariliy and glucose in the blood is elevated)... 2) someone is taking a drug that induces hibernation and transient metabolic conservation (with deficient dopamine and serotonin, the body refuses to accept glucose, uses fat instead as in hibernation, body fat and blood sugar increase as it might in early fall to prepare for winter. Fertility decreases in response to decreased dopamine and serotonin as well, and infertility is a major feature of winter adaptation/hibernation in animals as it is in humans on dopamine receptor blockers.)

Eating less carbohydrate, particularly sugar, is the obvious intervention to control obesity. Even though increased fat utilization occurs during metabolic disorder, it is ultimately the glucose portion of the diet that triggers the fat storage and diabetes... or at least the WORST of it. If the body wants to use fat, then feed it fat. If you try to feed it sugar, all that will happen is your pancreas will spew out insulin and your liver will convert it to fat which is efficiently stored in adipose. If you avoid eating glucose food, the worst of this hyperglycemic/hyperinsulinemic tendency is controlled.

Regarding getting the "truth" out there...It's well known receptor blockers for psych illness make you a hibernating animal that sleeps 14 hours a day and has no motivation and weighs 300 pounds. This is not breaking news. Perhaps it would eliminate the stigma against fat schizophrenics, but that's more about social status than science anyway... the poor, uneducated, mentally ill, overweight people, how unfortunate. NO one cares.

Maybe one day, in a land far away, we will treat schizophrenia and manic depression as biological illnesses and figure out what is causing them, and ultimately resolve them... rather than just shut the brain down with receptor blockers like a chemical lobotomy.

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Eli Lilly Zyprexa s... (Below threshold)

October 19, 2010 4:30 AM | Posted by Daniel Haszard: | Reply


Eli Lilly Zyprexa saga

They called it the *Five at Five* (5 mg at 5 pm to keep nursing home patients subdued and sleepy) and *VIVA ZYPREXA* (Zyprexa for everybody) campaigns to off label market Eli Lilly Zyprexa as a fix for unapproved usage.

A New York Times report reviews what has been accomplished by multiple civil
and criminal lawsuits against Big Pharma companies that have relied on fraud
to market industry's worst pharmaceuticals--antipsychotic drugs--which have
become industry's most profitable cash cow.
"The new generation of antipsychotics has also become the single biggest
target of the False Claims Act, a federal law once largely aimed at fraud
among military contractors. Hundreds of millions of
dollars or is currently under investigation for possible health care fraud."
---
Daniel Haszard Zyprexa victim activist

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"...and criminal lawsuits a... (Below threshold)

October 19, 2010 9:13 AM | Posted, in reply to Daniel Haszard's comment, by Anonymous: | Reply

"...and criminal lawsuits against Big Pharma companies that have relied on fraud to market industry's worst pharmaceuticals--antipsychotic drugs..."

Wait a sec, "antipsychotic" is a problematic category, as is "worst pharmaceuticals." Are you including Compazine? Reserpine? Moban?

Antipsychotics do seem to help a lot of people and not everyone gets fat. For some, getting fat is actually preferable to other available options, including no treatment.

Go get the bad guys for failing to fully disclose information regarding adverse effects of a particular drug. But don't over-generalize and demonize big fuzzy categories like "antipsychotic" or "BigPharma." I don't see the point in that --well, unless you're an attorney or you're pimping some alt med thing.

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"But the FDA now forbids an... (Below threshold)

October 19, 2010 9:18 AM | Posted by Question: | Reply

"But the FDA now forbids anti-competitor comparisons; and neither are the reps allowed to tell me that the study exists. Promotional speakers can't mention this either."

Really? Drug reps can't say, "Here's a copy of a journal article that shows..."?

I'm kinda Google lazy, so if you have a link to the FDA rule, that would be cool.

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@SteveBMD:All cats... (Below threshold)

October 19, 2010 2:00 PM | Posted, in reply to SteveBMD's comment, by GT: | Reply

@SteveBMD:

All cats are grey in the dark.

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But that might be the wr... (Below threshold)

October 19, 2010 2:52 PM | Posted by Reader: | Reply

But that might be the wrong direction: it seems that the increased fatty acid utilization means sugar is unused (hyperglycemia) and remains high well into the fasting state, with consequent high levels of insulin. Insulin high too long becomes tolerance to insulin becomes insulin resistance becomes BKA.
The next question is...why is carb metabolization being shut off? If other science is to be believed [questionable], the body gobbles up carbs first due to the deleterious effects of high BG and circulating insulin. Low-carb dieters replicate this by, well, not eating carbs and forcing the body to rely on fatty acids protein->glucose. Most humans switch into a ketogenic state during sleep (hibernation re:anon @ 1:39). So...where's the switch that's being flipped to make this switch immediately?

Question 2: Do these increase the risk of ketoacidosis if the patients continue to follow the "officially recommended" low-fat, high-carb diet? Refusal to uptake circulating BG in accordance to circulating insulin seems like it would only lead to T2D, a flood of ketones and a massive spike in BG.

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@Mouse:First thing... (Below threshold)

October 19, 2010 7:50 PM | Posted by Anonymous: | Reply

@Mouse:

First thing for sleep is good sleeping habits, google "sleep hygiene" and really follow it all.
Also, sounds like serious benzo tolerance. Consider asking your doc about a slow taper or inpatient detox as benzo withdrawal can be life threatening. Stick with sedating antidepressants like doxepin or remeron if you are depressed (there's an old post on this blog if you search). If you don't think your doc is good, you should go somewhere else. Also, you shouldn't take medical advice from random people on the Internet.

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They don't give zyprexa for... (Below threshold)

October 20, 2010 1:57 AM | Posted, in reply to Daniel Haszard's comment, by Anonymous: | Reply

They don't give zyprexa for dementia. They give very low dose risperdal or seroquel but 5 mg of zyprexa is way too heavy for your average geri.

The only time I've seen zyprexa used in an elderly patient is when there is a history of manic depression or schizophrenia. Dementia psychosis is not treated with zyprexa.

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I developed hyperglycemia... (Below threshold)

October 21, 2010 11:28 AM | Posted by Harry Horton: | Reply

I developed hyperglycemia from 1 milligram of risperdal usage in 2001. In 2006, November mid part of the month, after the months of spring, summer and fall's: long daytime sunlight hours, my fastings flickered mysteriously back into normal range. They came in at 92, where they ran previously 130 to 145. I could not keep them there but for only four weeks. December they came up mysteriously. Don't know what to make of this.
Further articles on the metabolic dysregulation from the atypicals:
"Atypical antipsychotics rapidly and inappropriately switch preipheral fuel utilization to lipids, impairing metabolic flexibility in rodents" Excerpt: ...rapid suppression of the respiratory exchange ratio (RER) during the dark cycle. Normal rises in RER following refeeding, a sign of metabolic flexibility were severely blunted by olanzapine, increased lipid oxidation in muscle could be explained by - 50% lower concentrations of the negative cytoplasmic regulator of carnitine palmitoytransferase I, malonyl CoA. This was associated with loss of analeurotic metabolites and citric acid cycle precursors of malonyl-CoA synthesis rather than adenosine monophsophate activated kinase activation or direct ACC1/2 inhibition. The ability of antipsychotics to lower dark cycle RER in mice corresponded to their propensities to cause metabolic side effects. Our studies indicate that lipocentric mechanisms or altered intermediary metabolism could underlie FFA lowering hyperglycemia (Randle cycle) as well as some of the other side effects of atypical antipsychotics, thereby suggesting strategies for alleviating them.

The October 2010 'journal': Diabetes, carries several interesting articles on AMPK related subjects as well as an article on olanzapine. THe following are some of the articles from that edition:
"Central Nervous system delivery of the antipsychotic olanzapine induces hepatic insulin resistance"--excerpt: "Conclusions - acute central nervous system exposure to OLZ induces hypothalamic AMPK and hepatic insulin resistance, pointing to a hypothalamic site of action for the metabolic dysregulation of atypical antipsychotics." end quote. Compare thses research findings to the Johns Hopkins studies on AMPK quadrupled activity with olanzapine's use and the histamine receptor 1 blockading as the main culprit for weight gain. Proceedings of the National Academy of Sciences February 2007 carried this Johns Hopkins study. Solomon Snyder was a researcher in the study.
Another article from October 2010 Diabetes journal: "Hypothalamic AMP- Activated Protein kinase regulates glucose production"
A third article from the Diabetes journal centered on leucine comprised biological products along with its effects on glucose production with involvement with AMPK also.

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Perhaps in november, those ... (Below threshold)

October 21, 2010 1:40 PM | Posted by Anonymous: | Reply

Perhaps in november, those 4 weeks, you were taking expired risperdal, or the pharmacy screwed up? That it occurred in november suggests it probably isn't related to increased light or temp exposure... that it only occurred 4 weeks sounds about the length of time where one's prescription bottle might be filled and emptied via use.

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Actually, I was not takin... (Below threshold)

October 21, 2010 2:01 PM | Posted by Harry Horton: | Reply

Actually, I was not taking risperdal in November 2006. I took myself off the drug in October 2001. THe mysterious return to normal of fastings in November of 2006, for about four weeks, occured five years after the last time I took risperdal. I only conjecture that the sunlight hours could have been a factor for why the fastings returned to normal, since that was the only major feature I could deduce that could result to lower the fasting glucose levels. But I do admit basically I do not know the actual factual reason why the fastings returned to normal in November 2006. No diet change, no exercise change---even my diet during that month was pizza and other carbohydrate replete foods. So nothing happened there that could have been therapeutic. Perhaps someone could run an experiment and expose people to ultraviolet light for extended periods of time, people that have AAP induced hyperglycemia and altered lipid metabolism, and see if there is any improvement.

In any case, people who take over the counter anti histamines experience weight gain. Possibly the same mechanism roughly is at work with the atypical antipsychotics. Except, as with the case of clozaril and zyprexa, where the histamine receptor 1 is blocked so heavily, and the weight comes on profusely, sometimes in some patients over one hundred pounds---this strong complete blocking of the histamine 1 receptor by the AAPs could just simply throw a switch, for the body to stay on fat utilization. Since the histamine 1 receptor metabolism and subsequent free fatty acid and lipid metabolism has gotten deranged. Clozaril and zyprexa block the histamine 1 receptor at around the very strong level of 1.0-2.0. Risperdal blocks it at a lesser 19. The smaller number indicates the greater the blockage.

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The above zyprexa article... (Below threshold)

October 21, 2010 3:14 PM | Posted by Harry Horton: | Reply

The above zyprexa article listed on Last Psychiatrist, the info from the above article made note of the supression of the RER during the darkness part of the light dark cycle. THe utilization of fat burning and ignoring carbohydrate burning initially was also a condition expounded upon to some length in the article. I found three more articles on the fat and sugar burning activities and darkness's role in characterizing these metabolic functions.

(1) "Lipids of Light and Dark treated plastids" Daniel Brandon author https://kb.osu.edu/dspace/bitstream.

(2) "Daily rhythms of serum lipids in Dogs: influences of Lighting and..."

(3) "Darkness unveils vital meatbolic switch between sugar and fat"
http://www.sciencedaily.com/releases/2006/01/060125084012.htm.

excerpt from the science daily article, number (3), that is from above.--:
Constant darkness throws a molecualr switch in mammals that shifts the body's fuel consumption from glucose to fat and includes a state of torpor in mice, a research team led by scientists at the Univeristy of Texas Medical School at Houston reports in the Jan. 19 edition of Nature.
further down the article...a series of experiments pinpointed 5-prime adenosine monophosphate (5'-AMP)as the key molecular mediator of the constant darkness effect, switching mice from glucose burning, fat storing state to a fat burning, glucose conserving letahrgy....
further in the article: Mice do not hibernate but they can slip into similar short term states of torpor. Lee and colleagues started with a microarray analysis of gene expression in the livers of mice subject to the light dark cycle and those kept in the dark for 48 hours.
One gene fired up in the dark --procolipase which produces an enzyme (CLPS) required for degrading dietary fat. Expression of the gene previously was thought to be restricted in the pancreas and gastrointestioanl tract. Yet messenger RNA for CLPS (mClps) was found in the livers of the mice exposed to prolonged dark, an unexpected finding.... the article later went on: This is the first example of a gene that is turned on by darkness, where darkness itself is the signal..." end quote.

Hence with the mysterious return to normal fastings in November 2006, for only four weeks, the extended previous months of long daytime sunlight amounts , which could over ride any malfunction in the darkness switch, could possibly have been at play for return to normal fastings, possibly. this supposition combined with the above Science Daily info, in consideration also. THough its hard to factually elucidate such a situation. The Science Daily article date of publication: January 25,2006.

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THe October 21 2010 post ... (Below threshold)

October 21, 2010 4:18 PM | Posted by Harry Horton: | Reply

THe October 21 2010 post of mine, 11:28 a.m.in consideration concerning 'the inappropriate switch of peripheral fuel utilization to lipids'....article. The following facts could be pointed out from that post's quote. anapleurotic meatbolites disappear, affecting the kreb's cycle funtions, that is the loss of citirc acid precursors of malonyl Coa synthesis. The possibility the biological compound Triheptanion could be a therapeutic agent could be considered possibly, though I don't know much about the biology of that agent. The wikipedia article: Triheptanion supplies this excerpt: "Triheptanion is triglyceride that is composed of three seven carbon fatty acids. These odd carbon fatty acids are able to provide anapolerotic substrates for the TCA cycle. Triheptanion is used clincially in humans to treat inherited diseases.
Five carbon ketones produced from triheptanion are beta-ketopentanoate and beta-hydroxypentanoate. The fact that triheptanion can be an anapleurotic substrate for the TCA cycle is significant for the AAP induced metabolic syndrome condition. Since this area needs to be refortified at least in substantial part for relieving the metabolic syndrome conditions from AAP usage, perhaps.

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Harry,I completely a... (Below threshold)

October 21, 2010 6:07 PM | Posted, in reply to Harry Horton's comment, by Anonymous: | Reply

Harry,
I completely agree that sunlight and temp suppress the hibernation response (thus important for diabetes and obesity which are related to hibernation response), but I just cannot reasonably see how your experience is related to light/temp... if it was, it would have been observed june, july, august, september... november is rather far away from spring and summer.

By any chance were you given risperdal for manic depression? If you are noticing substantial physiological changes during seasonal shifts, I would suspect you might be. Manic depressives are very, very sensitive to seasonal shift light and temp and hormone changes. I have a mild bipolar disorder and my manic symptoms first began in june when I was in my early 20s, and they generally only occur between late spring to late summer. Prior to that day in july when I went a little nuts, I had zero manic symptoms. After that day, it was like "oh so now this is some new shit to deal with, great". Sucks, considering prior to that point in time all I had to deal with was depression (which I have had since the peri-pubertal years, but became notably problematic by preteens and was in full swing at 15).

My depressive symptoms can occur any time but are notably more common and worse in late fall to late winter. I have had manic symptoms in the dark cold months but not by natural means. Last year I began using bright light therapy to treat the horrible depression I was in... it was effective but I began having manic symptoms, as I expected might happen. Speaking personally, my mood shifts are controlled by many things (hormones, sleep, stress) but the most powerful is probably light and temperature (season). Stress sleep and hormones seem to only modulate.


In some ways I feel as if my mood disorder gives me special insight into the power light and temperature has on physiology. All people experience an easier time with weight control and energy and mood when the temp is higher and the light is brighter, and all people get a bit demotivated and foggy and eat more in darkness (mild hibernation response)... but the highs and lows I go through and the profound changes in energy and appetite and my whole entire body in general really make it quite clear that these things are powerful. This is another important point: my mood disorder is not simply affecting my mood, it affects my entire body, my whole physiology. I have profound changes in appetite and energy, motivation, the workings of my mind, weight and reproductive status all shift. Even my blink rate and facial gestures change. When I am high, I blink rapidly, and have lots of spontaneous facial gestures, laugh often, sing, dance, talk to myself. When I am low, my face is mask-like, and I have few spontaneous facial gestures or movements. Moving my arms hurt, my body feels like lead. My body aches and I am very pain sensitive when low. WHen I am high, I feel far less pain and can injure myself and hardly feel it. It's like being cracked out on drugs.

I view my mood disorder as an extreme, exaggerated hibernation tendency... as if my brain doesn't have the capacity to regulate how much it turns on or turns off in response to shifts in light and temp (or stress or sleep or hormone shifts).

I see many peopole who struggle with obesity and down moods and depression who avoid the sun, are exposed to lots of light at night during sleep, I can't help but wonder if they would do better if they were aware of the impact of these things. We are animals, we are not so much different from chimps and wolves and bears and birds, all animals have shifts in physiology in response to light and temp, all animals live by the seasons... humans are alone in that we are our own god and nature, we have eliminated the seasons, invented light and invented food (agriculture) and live independently from the world which otherwise shaped our genes... genes that still control us, whether we like it or not.

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As someone who took both th... (Below threshold)

October 21, 2010 10:30 PM | Posted by Milo: | Reply

As someone who took both those drugs and suffered the consequences (including the fat jokes from my psychiatrist himself... that bastard son of a bitch)
I think you are a criminal

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TLP, maybe you should post ... (Below threshold)

October 22, 2010 12:07 AM | Posted by Termm: | Reply

TLP, maybe you should post pubmed/whatever links to the articles you describe, so those who are interested can read it? Not that I would read this study, but it would be nice in general.

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In response to the last a... (Below threshold)

October 22, 2010 2:24 PM | Posted by Harry Horton: | Reply

In response to the last anonymous October 21 2010 post, on the sunlight temperature issue. It was really unusual back in November 2006. I walked into the doctor's office for the typical bi weekly blood sugar check, fasting level that is, and it came in at a surpirsing 92. It had dropped nearly fifty points from a previous 140 or so, that occured at 'doctor's office visited time' for fasting reading tht occured two weeks earlier. The next reading two weeks after the 92, it was still low, though rising a bit---at 102. I struggled on a strict wheat, green bean spinach diet, in previous years, to get it down to 110. But with the November 2006 fasting, the fastings fell on their own for some mysterious reason. Once December came around, and the way I figured it,I was beginning to lose 'daily long length sunlight hours' that comprise a day, typical of the summer and early fall, generally. There was no change in diet, exercise, with the low November 2006 fasting readings and the only factor that could approach, (and I agree with you that certainly the sunlight factor cannot be factually validated), was the fact November here in North Carolina, which is the last faint warm month of the summer fall season, the last bit of momentum of any benefical effects of long hours of sunlight, that would carry over from spirng, summer and early fall, could have potentially eked on into early and mid November. Even though November's days were relatively short with shorter sunlight hour duration than say early July. With the fasting information, even tightening the diet in early january or late December the A1c would still jump to 7.6, and stay around 7.0 into April and May. However by August with longer daylight hours it would fall back into the 6.7-6.9 range, even with no strict diet--i.e. I could eat carbs and sugars and fats without restrictions and still get the under 7.0 a1c in August, which has long sunlight hours in the day. THis under 7.0 a1c effect of August lasts into late November. And when finally----it seems---the short daylight hours, with its cold day temperatures, requiring more clothing to cover my body leaving little skin exposure to sunlight, in December days that is; in early December the a1c will shoot up close to one point higher than at other times of the years.

In regard to the zyprexa article research additional articles;
"Acute Effects of Atypical Antipsychotics on Whole body insulin resistance in rats: Implications for adverse metabolic effects" Houseknecht et al. Neuropsychopharamacology

"Atypical antipsychotic drugs directly impair insulin action in adipocyted: Effects on Glucose transport, lipogenesis, and antilipolysis" ---Letter to the Editor- (2007) - 32, 2431,2432. doi.10.1038/sj.npp.1301366.

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Other articles on lipid m... (Below threshold)

October 22, 2010 4:07 PM | Posted by Harry Horton: | Reply

Other articles on lipid metabolism with implications for fasting the suppression of the RER features of the dark period of the light and dark cycle, with zyprexa usage in play.

"Connections Between Circadian and Metabolic Systems Described" Science Daily: November 17, 2009.
Excerpts: "Given that the liver is a key organ associated with energy metabolism, the researchers were not surprised that several biologic pathways associated with the daily rhythm in lipid and glucose homeostasis were affected by the absence of Id2. In particular were genes associated with the regulation of lipid storage and biochemical processes favoring energy generation from fat." end quote.

Other articles: "Serum concentration of calcium, phosphate and 1,25 dihydroxyvitamin - D3 in goats (Capra Hyrcus): Daily rhythms" Giuseppe Piscone.
"Circadian clock coordinated hepatic lipid metabolism: only transcriptional regulation" excerpt: "THe absence of the circadian clock peturbs this secondary clock, provokes dysregulation of endoplasmic reticulum localized enzymes, and leads to impaired lipid metabolism". end quote
"Effect of hyperlipidemia on expression of circadian genes in apolipoprotein E. Knock out atherosclerotic mice." Hou et al. Lipids in Health and Disease.
"Clock is important for food and circulation regulation of macronutrient absorption in mice."

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Hi there again This ... (Below threshold)

October 25, 2010 2:45 AM | Posted, in reply to Harry Horton's comment, by Anonymous: | Reply

Hi there again
This is the anon who questioned you regarding the fasting sugar in november.

It seems like you have observed more than one occasion that your sugar has been easier to control during the warm months. I am not at all surprised by this, as I stated before dopamine receptor sensitivity is controlled by temp, and dopamine is more active when an organism is exposed to bright light. Speaking personally I have reactive hypoglycemia (not diabetes, but similar) and my blood sugar problems ALWAYS are worse when it's cold out and I don't get as much light. My weight fluctuates seasonally as well... I gain weight starting circa october, reach a high of mid 120s, and then start loosing again circa march, and reach a low weight of the low 110's. Yes, my weight fluctuates that much and is entirely controlled by temp and light.
I also mentioned the mild bipolar I have. My manic sx are pretty much confined to june-early september, although there are exceptions. I start feeling the craziness circa april but I don't get those cracked out and crazy episodes until that june-sept window.

If your a1c is decreasing in august, that means the effect took hold circa june (a1c is a measurement of the amount of glucose that attaches to a hemoglobin molecule, on average it measures glucose for the past 3 months). If your a1c increases in december, that means it begins in october. This is EXACTLY the pattern I observe with my weight and my reactive hypo (which as stated, reactive hypo is a variant of glucose intolerance related to diabetes).

I do totally believe you as your experiences mirror mine (with hypo/weight/my craziness).

It's a shame medicine and science don't seem to know as much as us fragmented crazies and patients. Obesity, diabetes, and many mood disorders are clearly related to the genetically concerned pro-hibernation traits gone awry. Obesity and diabetes and atypical depression are an exaggerated hibernation tendency, mania/bipolar may be an exaggerated seasonal opportunism seeing as so many bipolar and manic patients have sx on the break of light and spring.

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Yep, you're right in a al... (Below threshold)

October 25, 2010 12:43 PM | Posted by Harry Horton: | Reply

Yep, you're right in a alot of the points you make----this post in response to the last posting by anonymous. Even though spring around April and May being present with longer days than November and December, the A1c still retains a 'in part character' of the winter months, because the April and May months are close to the --previous--winter months, such moths that would drive the a1c up. October and November however, the months previous to these months are April to September, a good seven months of longer daylight hours and warmer temperatures that would begin and eventually drive down the a1c.
THe circadian rhythm is most likely the most basic and fundamental energy system in the body with everything else tied into it, fat amounts, bi polar with its wintertime depressive states and manic wild out of control thoughts with its springtime character. In medieval Europe people would stay in their huts all winter long followed with a frenetic breaking out with spring to get the planting season going, or else the population would starve. The circadian rhythm was present in this pattern of moving out from winter time hibernation to spring time manic like frenetic activity.

But in my own case, I wonder if the longer daylight temperatures and several months of skin exposure to larger amounts of sunlight could have been the reason to possibly switch the energy systems back to carbohydrates from the fat burning energy system and the lower fastings of november 2006. Along these lines in this the above article on zyprexa and why zyprexa makes you fat, the last psychiatrist noted at the end of his article ----that the other research that he was doing was on light and metabolism. As if to suggest the dynamics of light and its alternation with darkness could be connected to the facts on how zyprexa makes one fat. And those facts include the burning of fat initially and skipping over the carbohydrate mode of activation which should come first before fat burning. But gets reversed with zyprexa usage as well as with other atypical antipsychotics.

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Ketoacidosis has been rec... (Below threshold)

October 26, 2010 12:07 PM | Posted by Harry Horton: | Reply

Ketoacidosis has been recognized as an unusual development in atypical antipsychotic induced metabolic syndrome ailments. Ketone bodies circulating in the body have been found in ketoacidosis leaving the following issue. Are the ketone bodies of ketoacidosis in AAP ailemnts, be therapeutically treated with triheptanoin and a ketogenic diet, since ketpgenic diet, since ketogenic diet's name is relevant and associable to ketoacidosis. If ketoacidosis develops in AAP induced conditions---the disappearance of anapleurotic metabolites and the malonyl Coa synthesis disturbance feature could be the major dysfunction which creates ketoacidosis in AAP metabolic syndrome conditions. THus leaving the issue, would triheptanoin and a ketogenic diet be beneficial for treating AAP induced metabolic syndrome conditions.

(1) Triheptanoin oil and ketogenic diet pepck - and - the - ketogenic diet.
(2) Tri heptanoin overview - references, advice, news, videos, .... www. righthealth.com/topic/
(3) Clinical trials and studies November - December 2008.
(4) Manipulation of the 'Nutrient Sensors" AMPK/TOR with Anapleurotic Diet Therapy (Trihepatanoin)
i. oxidative sequence for heptanoate (liver)
ii. Effects of AMPK in "LC" - Fat [0] Disorders
THese latter two listings i,ii.,---being subsectins of the (4) Manipulation of AMPK....ect. article.

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Harry - Just a sug... (Below threshold)

October 27, 2010 4:08 AM | Posted by Anonymous: | Reply

Harry -

Just a suggestion but if your diabetes is amenable to light, this indicates your blood sugar control is sensitive to seasonal variation (hibernation tendency) and can probably significantly improve with low dose bromocriptine. Bromocriptine is safe, around for decades, dirt cheap, and a great deal of evidence suggests by augmenting the D2 receptor (the opposite of what zyprexa does), then you suppress the hibernation response, thus helping control obesity and diabetes. Bromocriptine is rather effective for diabetes and it dramatically improves outcomes in a weight reducing diet.

If antipsychotics trigger hibernation (obesity, diabetes, infertility, sleeping 20 hrs a day, apathy and anergia), and if research in animals show that dopamine d2 augmentation with bromocriptine can prevent the hibernation response in non-tropical animals (these non-tropical animals are the ones with the most pronounced hibernation adaptation)... it only stands to reason that d2 augmentation in humans can also greatly benefit diabetes and obesity. The research supports this.

Unfortunately no one gives a shit because bromocriptine is dramatically unprofitable. A drug that dramatically helps menopausal women, diabetics, and fatties? Cool! Where's the patent! Oh, you say it is dirt cheap and old? Forget it then, back to the drawing board.

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I am vaguely familiar wit... (Below threshold)

October 27, 2010 1:16 PM | Posted by Harry Horton: | Reply

I am vaguely familiar with bromocriptine, but I'll look into it. One thing that is intersting about the dopamine augmentation theory. In February 2007 the PNAS study from Johns Hopkins stated that they thought the weight gain and other metabolic syndrome features that came from atypical antipsychotics blockading the histamine 1 receptor. On the other hand in 1975 I had weight gain with haldol that was similar to the weight gain I had with risperdal. I don't think haldol blockades histamine 1 receptor. So another factor had to create the haldol weight gain. And the question is, is there a non histamine 1 receptor factor creating risperdal weight gain. and whtever this factor is, is it the same as haldol weight gain creation. As was the case with haldol. Yet I am relying on the John Hopkins study for understanding the weight gain with risperdal as H1 Receptor intitiated.
As for the light initiated conditions that make diabetes amenable, there is another study on the interent by a Boston doctor Richard Fiddian Green, who wrote an article: Poikilothermic default mechanism in diabetes cases. The body becomes sensitive to variations in environmental temperature ranges with a developed diabetes case. If such sensitivity to temperature variances are present in diabetes, then sensitivity to dark and light cycles also logically would be present. Temperature and its nature on the earth emerges from the alternation of daylight and night time darkness.

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In a rat study of rats, ... (Below threshold)

October 27, 2010 7:41 PM | Posted by Jack Coupal: | Reply

In a rat study of rats, using rats, Zyprexa raised glucose levels by 20%, both in fed and fasting states.

Sounds like Alone may correctly be questioning why rats were used in that study. Rats are rodents and nocturnal (more active at night than during day). Humans other than Charlie Sheen are not called nocturnal. Maybe a better test animal - like people - should have been studied.

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Rats are the most readily a... (Below threshold)

October 28, 2010 1:06 AM | Posted, in reply to Jack Coupal's comment, by Anonymous: | Reply

Rats are the most readily available and commonly used test animals. They are actually rather similar to humans, which is amazing considering all the differences.

It is true you cannot just extrapolate findings from a rat study to human beings - that is not the point. The point of rat study is preliminary research to get the baring to figure out how stuff sorta works, to better illuminate old questions and possibly identify new, more specific questions. It's sorta the equivalent of an artist drawing a rough sketch.

With that said, if something in rats causes their glucose to go up 20%, it is a reasonable assumption that hyperglycemia will also result in humans as well under those same conditions... perhaps not 20%, and perhaps not as often, but the underlying physiological mechanisms will be the same. The metabolism of a rat is not that severely different.
It is particularly true if we already observe the condition results in the outcome noted int he rat study - it wa soriginally observed that zyprexa users become fat anergic hypersomniac diabetic hyperprolactinemic/infertile hibernating bears. The rat study just gives us clues as to what is going on. It appears that blocking serotonin and dopamine receptors switches the body into hibernation, metabolically things change so that mitochondria refuse to accept glucose as fuel, because they use fat instead, which results in hyperglycemia, which results in hyperinsulinemia, which results in both IGT/DIABETES/OBESITY/FEELING LIKE A PILE OF CRAP.

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The following studies are... (Below threshold)

October 28, 2010 7:19 PM | Posted by Harry Horton: | Reply

The following studies are further explorations into lipid abnormalities with atypical antipsychotics. Also other metabolic areas are evaluated: cholesterol, tri glycerides, glucose, and leptin ect.
(1) Risk of lipid abnormality with haloperideol, olanzapine, quetiapine, and risperidone in a Veterans Affairs population.
2009 July Int. Clin. Psychopharmacology.
2) Weight gain related to treatment with atypical antipsychotics due to activation of PKC-B Pavan et al. Pharmacogenics Journal.
(3)Antipsychotics cause weight gain in children, teens. Psych central News Edition

(4)Metabolic disturbances associated with atypical antipsychotics. Morie Bronee Romainian journal of Psychopharmacology. This study supports the centrality of histamien 1 receptor involvement in AAP induced metabolic disturbances and weight gain.

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anonymous at 1:06AM,<... (Below threshold)

October 28, 2010 7:54 PM | Posted, in reply to Anonymous's comment, by Jack Coupal: | Reply

anonymous at 1:06AM,

Do you have some evidence that the underlying physiological (more likely, pharmacological) mechanism for increased serum glucose after Zyprexa in rats is the same as in humans?

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1) pharmacology does not ex... (Below threshold)

October 29, 2010 12:19 AM | Posted, in reply to Jack Coupal's comment, by Anonymous: | Reply

1) pharmacology does not exclude physiology, merely informs it.
2) Of course not. However, we know this:

Humans on zyprexa get hyperglycemia.
Rats on zyperxa get hyperglycemia.
Humans on zyprexa have a change in metabolism, which is causing hyperglycemia.
Rats on zyprexa have their mitochondria switch so that they prioritize fat oxidation, which results in hyperglycemia and hyperinsulinemia as a secondary effect.
In humans not on zyprexa, but with genetic tendency to aquire T2DM/ hyperglycemia, it is noted they have genetic traits which make their mitochondria prioritize burning fat for fuel first, which then makes them more insulin resistant. So, it is known that this zyprexa induced metabolic change does occur in humans under other circumstances (genetically), which makes them at risk to develop T2dm.

Considering the above, it is simple deduction to say that as of now it is a good hypothesis that human hyperglycemia post zyprexa is related to a switch to a primary fat burning state resulting in secondary glucose intolerance, hyperglycemia, and hyperinsulinemia, which results in diabetes and obesity (from hyperinsulinemia/increased appetite). It is not yet PROVEN but it is a reasonable hypothesis at this point in time.

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The switching to fat oxid... (Below threshold)

November 1, 2010 2:14 PM | Posted by Harry Horton: | Reply

The switching to fat oxidation and skipping over carbohydrate burning mechanisms, in zyprexa application, has been detailed in the 'why zyprexa makes you fat' article. One significant additional facet to this information from the article is: does significant insulin resistance subclinically be a prerequisite condition for developing glucose impairment. That is people that stay on fat oxidation, in chronically developed cases of AAP induced hyperglycemia possibly must have a substantial amount of insulin resistance underway in their metabolism. This fact is detailed in the February 2004 edition of the "Journal of American Psychiatry" with the Jonathan Howes article on clozaril and its impairment of glucose control without changes in insulin resistance study from February 2004 edition of the Journal of American Psychiatry. A small study it is, but introduces a very important feature of insulin resistance status as being a necessary feature for developing these energy burning disturbances in the metabolism. Along with this article and other info from the zyprexa makes you fat article: Richard Fiddian Green's 'rapid response piece' from the British Medical Journal: 'Schizophrenia and adverse effects of its treatments on mitochondrial metabolism'---genetic alterations in the mitochondria also could have occured with AAP usage. R.F. Green's ATP hydrolysis exceeding ATP resynthesis phenomena could be present or the vulnerability to this, could be present in the psychiatric disorders.

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<a href="http://www.asics-u... (Below threshold)

November 2, 2010 2:01 AM | Posted by coach handbags: | Reply

asisc shoes

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oh my god, i take so much m... (Below threshold)

November 2, 2010 8:22 PM | Posted by William: | Reply

oh my god, i take so much medication, and zyprexa included! shit! should i quit everything?

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^^ Crazy person.... (Below threshold)

November 2, 2010 8:57 PM | Posted by Anonymous: | Reply

^^ Crazy person.

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no, i'm not crazy. :)... (Below threshold)

November 2, 2010 11:51 PM | Posted by William: | Reply

no, i'm not crazy. :)

but shit, i noticed that when i take zyprexa i just want to eat everything all the time, eat eat eat! i don't know what to do :(

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Being crazy is like being g... (Below threshold)

November 3, 2010 3:47 AM | Posted, in reply to Anonymous's comment, by Anonymous: | Reply

Being crazy is like being gay. The rest of the world pretends to tolerate you to be politically correct, when in secret they find you creepy and would actively discriminate against you if only it were socially acceptable to do so.

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i'm not crazy, i said, my h... (Below threshold)

November 3, 2010 1:51 PM | Posted by william: | Reply

i'm not crazy, i said, my humor just flutuates too much, too too much. i just hate this zyprexa, because it makes me chubby. and i'm also gay, so, i know what you mean. :)

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Another dimension to the ... (Below threshold)

November 3, 2010 2:07 PM | Posted by Harry Horton: | Reply

Another dimension to the atypical antipsychotics induced hyperglycemia is the fact for a first year or so of AAP usage, 70% of the recipitent patients of the drugs have no hyperglycemia. 30% have some form of elevations of glucose levels (hyperglycemia). 1 to 5% have wildly out of control high levels of hyperglycemia. The issue is, is the overriding fat burning energy process (at the expense of carbohydrate fuel burning) present and active in the above cited 70% of the people or patients on the drugs, that have no hyperglycemia. If the carbohydrate channel is in non use for fuel utilization in these 70% of the patients, why is the nonhyperglycemic? So this is a major question to answer and further elucidate along with the data from the Last Psychiatrist's article: "Why does zyprexa make you fat". The data from the article leaves one with the impression that the predominance of fat burning fuel channel is present in----all---zyprexa usage cases. But if this fact is true why do 70% of the zyprexa users have no hyperglycemia.

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Continuing thoughts from ... (Below threshold)

November 3, 2010 2:36 PM | Posted by Harry Horton: | Reply

Continuing thoughts from previous post subject material...If the nonhyperglycemic 70% of the zyprexa users are experiencing fat burning fuel utilization, that is skipping over the carbohydrate fuel utilization, this latter mode of energy burning, that should come first (fat utilization burning comes later after carbohydrate fuel burning depletion occurs) returning to original thought in this sentence---and if in the 70% of zyprexa users are experiencing fat fuel utilization initially ---why are they not experieincing hyperglycemia, or what is controlling and reducing the excess sugar and carbohydrate amounts in the 70% nonhyperglycemic zyprexa users. One theory is a marked and high degree of underlying subclinical insulin resistance could be present for the hyperglycemic conditions to actualize. Oliver Howes February 2004 American Psychiatry Journal study---his article on "impairment of glucose control without changes in insulin resistance" is the study that carries the significant information. He found insulin resistance was in "the normal range" but its amount of IR was in the last quintile (20%) of the healthy
range, and this was the condition which his study group of patients
experienced loss of glucose control. In other words the patients in the Howes small group were coming close to pre diabetic status. The patients had already used up 80% or more of their 'healthy range of insulin resistance presence'--a point in their medical history that made them vulnerable to the hyperglycemia brought on by clozaril.

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The study: "Weight gain r... (Below threshold)

November 5, 2010 3:03 PM | Posted by Harry Horton: | Reply

The study: "Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-B" C. Pavan Pharmacogenics Journal. Excerpts from the article: "Regarding the signals driving this differentiation program, our data suggest a crucial role for PKC-B as revealed by the strongly inhibitory effect of histidine and siRNA leading to the neo-formation of adipose cells through metabolic pathways and not in cell proliferation. THis event was confirmed by morphological evaluation in which a clear translocation of PKC-B from cytosol to plasma membrane, in which it is then activated, occured only in presence of APD's. THis event was strongly related to the well known cellular response to high glucose that induces an increase in reactive oxygen species production. In fact, reactive oxygen species, through downstream effectors and in particularly through PKC-B lead to the neoformation of adipose cells.

In the end, in light of the results presented in this study we can conclude that:

a. clozaril induces a strong lipid increase activating adipogenesis through PKC-B activation and then through reactive oxygen species;
b. olanzapine, quetiapine and risperidone induce weight gain by means of both activation of adipocyte proliferation and adipogensis activation (also in this case by PKC-B reactive oxygen species);
c. aripiprazolo is the AAPD showing less activation on adipogenic event; and
d. THe adipogenic event in MDSCs is strongly boosted by APD supplementation.

It could then inquire that the paralellel administration of PKC-B inhibitor to APDs could fight the related weight gain." End excerpt.

The above information in this comment entry could be compared to the Proceedings of National Academy of Science February 2007, study, by the Johns Hopkins researcher Solomon Snyder---centering on the role histamine receptor 1 plays in creating the metabolic syndrome features created by atypical antipsychotic usage.

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Furthe excerpted material... (Below threshold)

November 5, 2010 4:35 PM | Posted by Harry Horton: | Reply

Furthe excerpted material from previous post study on PKC-B activation for weight gain, that isw the Pavan study. Excerpt:
"Following our previous study, in which we showed that high glucose by means of PKC-B activtion drove stem cells from both adipose tissue and skeletal muscle toward an adipogenic potential, in this study also we have blocked its activities in the presence of APDs, provided that is involved into the signals that underlie this process.

In preadipocytes, the quetiapine, olanzapine, and risperidone treatment induced an increase in both cell number (Figures 1b and c) and in adipose metabolism (detected with oil red staining and gene expression for glucose transporter -4 and lipoprotein lipase marker). Clozapine treatment induced only an increase in lipid production and not in cell number, whereas apriprazole was shown to have no effect on either proliferation of metabolism.

Subsequently, attention was focused on the transdifferentiation of muscle progenitors to an adipogenic lineage, given that myopathic skeletal muscle is characterized by the replacement of myofibers by adipose tissue. As in hyperglycemia, high glucose concentrations upregualte sterol regulatory element binding protein 1c, resulting in de novo lipogenesis and intracellular lipid accumulation in contracting myotubes.

In this study we show that when MDSC's are exposed to external stimuli of an adipogenic lineage, such as the presence of a high glucose environment, the APD exposure induces a remarkable increase in adipogenic transformation. Interestingly, APD treatment affected only transdifferentional events of MDSC's and not cell number. This APD -activated adipogenic differentiation program leading to a conversion of muscle stem cells into adippocytes as verified by molecular criteria, has never been described." end of excerpted quoted material from the Pavan article.

The last sentence is interesting, in that muscle cell stem cells converting to adipocytes has never been described in medical literature, ---not exactly clear on what the sentence exactly means. Muscle stem cells in general converting to adipocyte cells has never been documented. Is That what the sentence means. OR rather, in atypical antipsychotic usage, muscle stem cells converting to adipocytes have never been described. Its one or the other, though.

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Further studies on atypic... (Below threshold)

November 9, 2010 4:09 PM | Posted by Harry Horton: | Reply

Further studies on atypical antipsychotic induced hyperglycemia and diabetes. And related areas.
(1) Does lipid lowering therapy enhance ATP resynthesis? (19 August 2004) Richard Fiddian Green.
(2) The anti anapleuritic action of Statins. (19 August 2004) Richard Fiddian Green.
(3) Do statins cause Parkinsons disease.
(4) Life threatening hyperglycemia and acidosis related to olanzapine: a case report and review of literature Journal of Intensive Care Med.
(5) Monitoring of tissue pH, the critical measurement. Richard Fiddian Green

ATP hydrolysis exceeding ATP resynthesis has been deemed a metabolic condition that gives rise to tissue energetics impariment. This info listed in other articles by R.F. Green. That is diabetes also as an expression of such tissue energetics impairment. And the above article on lipid powering enhancing ATP resynthesis has relevance to the the 'Why zyprexa makes you fat' article, since hyperglycemia, diabetes and other metabolic syndrome conditions develop with the increase in lipid accumulation in cells, and other lipid abnormalities, as well as lipid increases in general. With atypical antipsychotic usage. And such lipid alterations in AAP usage could further have detrimental affects on mitochondrial metabolism ATP resynthesis functions. Particularly if such ATP resynthesis functions were weak or present to begin with in schizophrenics, before atypical antipsychotic applications.

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Psych drug dependence is a ... (Below threshold)

November 15, 2010 3:35 AM | Posted, in reply to Mouse's comment, by serouser: | Reply

Psych drug dependence is a vicous circle and it can be difficult to get off them.

Recommendations: get rid of psychiatrist and try to find neurologist who is specialized for sleeping problems. They maybe able to help with withdrawal.

Seroquel: read wikipedia insomnia article and try all substances mentioned in it (melatonin, L-Glycine, agomelatonin). Reduce seroquel gradually and use benzos to help with withdrawal.

Also read:

http://bipolarblast.wordpress.com/

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Further articles and medi... (Below threshold)

November 15, 2010 3:21 PM | Posted by Harry Horton: | Reply

Further articles and medical studies that center on atypical antipsychotic metabolic syndrome aide effects, as well as, related issues:

THe PNAS February 2007 study on weight gain with clozapine and zyprexa in consideration involving the histamine 1 receptor: (1) Antipsychotic drug induced weight gain mediated by histamine 1 receptor-linked activation by hypothalamic AMP-kinase" Solomon Snyder
(2) New DNA Repair Pathway" Science Daily November 13, 2010.
(3)Histamine in the nervous system Physiol: REv. 2008 88.
(4) Antipsychotic induced obesity histamine may be the key Jwatch Psychiatry.
(5) Hyperlipidemia following treatment with antipsychotic medications
(6) Eckankar web site. most likely the best information for addressing psychological problems and the roots of emotional conflicts--i.e. past life phenomena. Soul travellers of the Far Country - by Sri harold Klemp is one sampling book of the Eckankar philosophy. Other areas of Eckankar are contained in the web site.


The above scientific studies and articles address primarily AAP induced side effect conditions.

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The following info. is al... (Below threshold)

November 18, 2010 1:55 PM | Posted by Harry Horton: | Reply

The following info. is also asociable to a Last Psychiatrist May 2006 post on antipsychotics: glucose transporters being the subject of that post, that is the subject, that was expounded upon. The article here though is by Edward Ojuka: "Role of Calcium and AMP kinase in the regulation of mitochondrial biogenesis and Glut 4 levels in muscle." An excerpt from the article:"The present paper reviews the evidence, which indicates that the decrease in levels of high-energy phosphates, leading to activation of AMP kinase (AMPK), and the increase in cytosolic Ca2+, which activates Ca2+/calcmodulin - dependent protein kinase (CAMK), are signals that initiate these adaptive responses. Although the events downstream of AMPK and CAMK have not been well
characterized, these events lead to activation of various transcription factors, including nuclear respiratory factors (NRF) 1 and 2, which cause increased expression of proteins of the respiratory chain; PPAR-a, which upregulates the levels of enzymes of B oxidation; mitochondrial transcription factor A, which activates expression the mitochondrial genome; myocyte-enhancing factor 2A, the transcription factor that regulates GLUT 4 expression." End quote.

THe above quote covers some interesting terrain of biological phenomena that could be altered and changed with AAP induced use. THe AMPK with AAP's has been addressed by numerous medical studies, perhaps one of the most prominent being the Proceedings of National Academy of Sciences,February 2007, relating the Johns Hopkins research on quadrupled AMPK activity along with histamine 1 receptor centrality for weight gain cuase. Solomon Snyder being one of the investigators for that study.
Additonally, since diabetes, hyperglycemia and other metabolic syndrome disturbances occur with olanzapine, clozaril, and risperidone, and seroquel, and perhaps to lesser degree with ablify, the above Ojuka study draws another interesting player into the mix as a potential major biological force for creating the metabolic side effects found in the AAP cases. The element calcium. Calcium metabolism is interwoven with AMPK activity, for creating metabolic side effects most likely with AAPs. And co joining this fact with the Anastassiois Pittas June 2007 scientific study on vitmain D and calcium supplementation as potential potent preventative regime for steering off diabetes development, the calcium metabolism and its alterations in AAP usage could be more clearly elucidated in future studies for better understanding AAP induced metabolic syndrome features that crop up as side effects with these neuroleptic agents. Finally, if GLut 4 processes are altered in AAP usage, the histamine 1 receptor along with the calcium metabolism alterations and altered AMPK activity could be proceeding steps for creating disruptions in GLUT 4 action in AAP usage cases. In any case, the Ojuka study quote in this post relates the role of clacium and AMPK activity in coordination with other biological factors that in a downstream manner can determine the presence of GLUT 4 activity and processing(of a healthy nature) in the body's cells.

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William, honey, shop around... (Below threshold)

November 19, 2010 12:59 PM | Posted, in reply to william's comment, by Mary: | Reply

William, honey, shop around as much as you can afford to until you find a good pharmacologist to review your meds and make recommendations. My GP did this for me, though I also got lucky and got a psychiatrist who knows everything about darn near every drug there is. Seroquel has given me insulin resistance, and I chose to treat the insulin resistance rather than give up seroquel, cause seroquel made me well. My point is that there may be a way to treat your illness(es) using fewer drugs or at least not zyprexa. But if it is working for you and hasn't given you diabetes and you are not overweight, you may want to stay on it. It doesn't cause weight gain and diabetes in everyone. Good luck to you and I shall keep you in my (pitiful) prayers.

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The following article: "Nu... (Below threshold)

November 22, 2010 3:18 PM | Posted by Harry Horton: | Reply

The following article: "Nutrient and Energy Supply-dependency" Richard Fiddian Green. British Medical Journal The following excerpt: "The tissue pH is much more meaningful because it is directly related to the protonmotive force needed to drive ATP resynthesis by oxidative phosphorylation in accordance with the Nobel Laureate Ptere Mitchell's hypothesis The tissue pH is also related to the function of enzymes, which is pH and temperature dependent. [Like tissue pH the temperature is intimately dependent upon mitochondrial function and changes are indicaive of pathologic perturbations of mitochondrial functions]

It makes sense to aim to restore tissue pH and temperature to normality for provided they stay normal, a normal pH in an afebrile pateint accurately predicitve of an excellent prognosis...." end quote.

The above infomration is an illustrative display of mitochondrial processes that can contribute to diabetes and hyperglycmeia, when such processes are dysfunctional. Protonmotive force being dimninshed from a healthy status. Alerations in oxygen and nutrient supply to the mitochondria. And the all important roles of pH and temperature and their departure from healthy stature, and presence of function in the body. THe above information is supplemental to "the zyprexa makes one fat" article's main points presented in the October 18 2010 Last Psychiatrist entry. Since anapleuritic metabolites are dimisnished off in this zyprexa metabolic disturbance and the malonyl CoA regulatory status for fatty acid functions is also unravelled too. Leading to this fat burning function initially and metabolic inflexability.

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I developed hyperglycemia... (Below threshold)

December 28, 2010 2:30 PM | Posted by Harry Horton: | Reply

I developed hyperglycemia from risperdal usage in 2001, and have had the fuel utilization problem described in this article about zyprexa. The following article on the internet centers on a legal case involving a law suit against Johnson and Johnson (maker of risperdal) in West Virginia. The internet site: "Judge imposes 4.5M fine on Johnson and Johnson/West Virginia Record". An excerpt from the article: "Wellsburg-Circuit judge Martin Gaughan has imposed a penalty of nearly 4.5 million on drug maker Johnson and Johnson for false and misleading promotion of antipsychotic drug risperdal and painkiller Duragesic.
Attorney Gneral David McGraw originally sought more than 20 million." End quote. Its an interesting case that occured over the past few years, and I am not quite clear on actually who were the basic propounders of the suit. The psychiatrists I thought originally were the group (and could have been) that wished to bring the suit because of misleading information given by Johnson and Johnson that distorted dangerously prescribing procedures. Possibly the patients were the ones who brought the suit. In anycase, one interesting feature about the case, was the private law firm TOriseva and Hill acted in the capacity of attorney general while prosecuting the case, that took place in West Virginia.

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I like these research resu... (Below threshold)

January 25, 2011 10:26 AM | Posted by Dr.Mohammed Shafiqul Kabir: | Reply

I like these research results,i am a psychiatrist.

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Are the metabolc changes re... (Below threshold)

January 29, 2011 12:08 AM | Posted by Sandy: | Reply

Are the metabolc changes reversible? /will the fat cells go sway?
I was taking 30 mg pd Zyprexa for 1 mo and gained
20 lbs
and won't come off after stopping the Zypreda for 3 'mos
a

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A couple more studies cen... (Below threshold)

February 10, 2011 5:14 PM | Posted by Harry Horton: | Reply

A couple more studies centering on olanzapine and related areas to the drug and its use in psychiatric patients.
"Zonisamide prevents olanzapine - associated hyperhagia, weight gain, and elevated blood glucose in rats." excerpt: "An OLZ associated development of hyperphagia, weight gain, and elevated blood glucose in the rats was also found. THese outcomes were attenuated and reversed in the presence of concommitant ZNS. these results suggest the hypothesis, that ZNS may effectively treat or prevent weight gain or metabolic changes associated with SGAs." End excerpt from the study's abstract.

"Psychosis following Initiation of zonisamide" American Journal of Psychiatry.

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SOme further thoughts on ... (Below threshold)

March 8, 2011 5:53 PM | Posted by Harry Horton: | Reply

SOme further thoughts on weight gain and its implications with atypical antipsychotics (AAP's). The atypical antipsychotic blockage of the histamine receptor 1 results in weight gain and thus this biological activity most likely is central to initially the deleterious metabolic syndrome side effects in patients with these neuroleptics. Simply comparing this AAP induced weight gain to the excessive amounts of fat on the bodies of hibernating mammals for example burrowed away in their burrows and holes during wintertime could elucidate the problem more substantially. Constant darkness 24 hours a day for several months at a time is present with such buirrows that the hibernating mammals occupy. THis constant darkness occurs with substantial abdomina viscera like fat the comprises the burrowing mammal's body. WIth darkness and substantial fat together for the body's fuel consumption in these hibernating situations, these conditions keeps fat burning modes in operation initially and glucose burning as secondary as a subsequent mode of fuel utilization. Since the atypical antipsychotics create fat via the h1 receptor blockading, the drugs evidently also create within the patient's bodies, the hibernating situation where fat is burned initially and glucose is burned in a secondary manner in fuel consumption processes. A hibernating mammal and an AAP usage patient evidently approximate to having the same metabolic functions at the cost of losing present day evolved energy homeostasis functions that have diminished with AAP application.

"Darkness unveils vital metabolic switch between sugar and fat" Science Daily study. The above content is relevant to the above Science Daily article.

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Also found some other int... (Below threshold)

March 24, 2011 6:17 PM | Posted by Harry Horton: | Reply

Also found some other interesting information on risperdal here on March 24, 2011. Risperdal news on google, had an article that a lawsuit in Spartanburgh South Carolina, is once again going after Janssen and Janssen for fraudulent practices for marketing the drug. Interestingly, the article cited the Toriseva and Hill West Virginia lawsuit outcome, where 4.5 million dollars penalty was ordered for Janssen to cough up. Evidently Janssen and Janssen managed to get a reversal of that verdict in an appeals case. The judge decided state did not have enough evidence to successfully prosecute Janssesn and Janssen on misleading prescribing information. The South Carolina case appears to be leaning more against Janssen and Janssen, though as of this March 24 2011 recent media report on the internet.

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Zyprexa and fat has a good ... (Below threshold)

July 3, 2011 8:08 PM | Posted by Eman: | Reply

Zyprexa and fat has a good side - the drug has shown success in treating people with anorexia.

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This is what most obese sta... (Below threshold)

February 13, 2012 5:28 PM | Posted by ST: | Reply

This is what most obese states are -- and can be resolved with eating less total carbohydrates (from any source) and not worrying about fat intake.

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metformin. tards.... (Below threshold)

March 28, 2012 4:23 AM | Posted, in reply to Reader's comment, by Anonymous: | Reply

metformin. tards.

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Spiking people with anti-ps... (Below threshold)

June 19, 2012 6:26 AM | Posted by IceSmoker: | Reply

Spiking people with anti-psychotics is funny as hell.

What I've seen is anywhere from instant knockout all the way to the person becoming hyperactive(most common) and then the rare case of someone who will display behavior which is out of character and gets easily enraged while on a dose.

No one for one moment suspected they had been spiked and all of them were monitored closely in a safe environment. Medical history, etc was asked well in advance of the dose.

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A further update on the a... (Below threshold)

November 3, 2012 3:18 PM | Posted by Harry Horton: | Reply

A further update on the atypical antipsychotic induced weight gain phenomena and other side effects, particularly insulin resistance. THis, November 3 2012 communique thus updates the novel insulin sensitizer drug BGP-15 that possibly could be out in the market in the months ahead. The medical study from Hungary found in the journal: Cell Stress & Chaperones (2012) 17: 517-521; is presented below.

"The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics" Zsuzsanna Literati - Nagy.

A quote from the abstract: "Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process." end quote.

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Good to know. There are man... (Below threshold)

July 5, 2013 5:05 AM | Posted by Texas Gun Trust: | Reply

Good to know. There are many drugs that can make us gain weight as side effect. We should be aware what those drugs are so we can manage weight gain.

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You never want to be on an ... (Below threshold)

September 30, 2013 3:13 PM | Posted, in reply to Mouse's comment, by Michael10: | Reply

You never want to be on an antipsychotic for insomnia (take imovane instead) or depression. The risks of diabetes and tardive dyskinesea mainly make these drugs a bad bet. Try an antidepressant that doesnt cause impotence (post ssri sexual dysfunction)

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All these information is us... (Below threshold)

October 4, 2013 9:12 AM | Posted by Elena: | Reply

All these information is useful but my main question is what can people who take zyprexa do (meaning following a certain diet) NOT to gain weight? I would love to read something about this.

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I'm trying to absorb fat by... (Below threshold)

October 20, 2013 1:18 AM | Posted, in reply to DaveInMaine's comment, by Anonymous: | Reply

I'm trying to absorb fat by using zyprexa. I have crohns. I am over six feet tall and weight 124

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I find this article very in... (Below threshold)

April 21, 2014 4:16 PM | Posted by Ian: | Reply

I find this article very interesting. I have never taken any of these meds, however I do have really low triglycerides (37), relatively high FBG (100) and an RER of 0.72.

My question is: would it be better to cut the fat and go straight carbs/protein or to go low carb? I have done low carb in the past and all of my numbers crashed...

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My son takes Zyprexa 20mg (... (Below threshold)

April 25, 2014 11:49 AM | Posted by Anonymous: | Reply

My son takes Zyprexa 20mg (for 9 mos so far). It has stabilized his moods and thinking (which started with head trauma), but he has gained about 55 pounds and counting. I am confused about whether to encourage a high carb or low carb diet. Of course, he consumes lots of carbs and sugars but he says they make him feel good, so I have little influence. I know this is a temporary feeling, but the high carb people say this helps serotonin production. I wish there was a supplement to help offset this since the medication is helping him and going off it isn't an option. Calcium and D3? It is a terrible trade-off.

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psychiatry sadists will pay... (Below threshold)

June 9, 2014 5:00 PM | Posted, in reply to Anonymous's comment, by anon: | Reply

psychiatry sadists will pay dearly for the crimes and damages knowingly inflicted from these medications, the devil's cohorts will perish together

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