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Effects - "Why Zyprexa (And other atypical antipsychotics) make you fat"

Discussion in 'Antipsychotics' started by EscapeDummy, Oct 22, 2010.

  1. EscapeDummy

    EscapeDummy Palladium Member

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    Swim has seen many, many people on antipsychotics complain of inordinate weight gain, he just read this article and thought it might be interesting and relevant to many here.



    October 18, 2010
    Why Zyprexa (And Other Atypical Antipsychotics) Make You Fat

    [​IMG]
    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:



    [​IMG]
    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:


    [​IMG]

    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:


    [​IMG]In the fed state, Zyprexa and Clozaril do a massive conversion to fat utilization, Risperdal a medium, and sulpiride minimal covnersion.

    In the fasting state:

    [​IMG]Geodon 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 is 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.

    http://thelastpsychiatrist.com/2010/10/zyprexa_and_fat.html



     
    Last edited: Oct 28, 2010
  2. Randomiiza

    Randomiiza Silver Member

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    This is about atypical anti-psychotics and it mentions Haloperidol...

    Still a lot better researched than most drug-related articles.
     
  3. EscapeDummy

    EscapeDummy Palladium Member

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    Well the article is saying that insulin levels on subjects on haloperidol returned to normal, not causing the problems that most atypicals do... plus, the graphs are from the journal articles he is discussing.
     
    Last edited: Jan 18, 2011
  4. Randomiiza

    Randomiiza Silver Member

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    thats true...I was just in a bad mood when I posted lol
     
  5. Boca Bitch

    Boca Bitch Newbie

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    Has anyone trialed individuals on atypicals on a ketogenic diet? I wonder if the same health problems would cease, or if new ones would arise.
     
  6. Mindless

    Mindless Gold Member

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    [FONT=Verdana, sans-serif]Murashita et al (2005) suggest that secretion of the neuropeptide ghrelin (other neuropeptides include insulin and leptin) may be increased by Olanzapine, leading to increased appetite and weight gain. [FONT=Verdana, sans-serif]Olanzapine increases plasma ghrelin level in patients with schizophrenia. [FONT=Verdana, sans-serif]Murashita M et al, [FONT=Verdana, sans-serif]Psychoneuroendocrinology.[FONT=Verdana, sans-serif] 2005 Jan;30(1):106-10.

    See Weight Gain, Schizophrenia and Antipsychotics ([FONT=Verdana, sans-serif][FONT=Verdana, sans-serif]Panariello et al 2011)
    [FONT=Verdana, sans-serif]for more detailed information on Olanzapine and other antipsychotic weight gain. Regular health checks are advisable in those prescribed this drug for psychosis, including weight. The underlying mechanism of weight gain may vary amongst individual antipsychotics, and each of us have our own genetic markers and other risk factors for obesity. More research is needed on how these individual risk factors can be avoided, including choice of medication, metabolic monitoring, and the development of new drugs[FONT=Verdana, sans-serif]. Weight gain is common with Olanzapine, and the associated obesity seems a highly under-rated side effect of this drug. This potential obesity damages health and reduces life expectancy.
     
    Last edited by a moderator: Apr 30, 2017
  7. Maxfrombx

    Maxfrombx Newbie

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    I was sure, reading only the intro, that it was from the last psychiatrist, lol.

    I like this guy's style, but sometimes it gets a bit too discouraging. I'm battling against fat gain, taking both quetiapine and cyamemazine. Despite working out 4 times a week and eating healthy, I still gain fat... well, almost healthy. Actually, with these meds, especially cyamemazine, I have the urge to eat a big meal of carbohydrates at least once a day.

    It should be added that APs tends to lower testosterone and raising prolactine, decreasing even more the lean mass.

    I think I'll discuss wednesday with my shrink the possibility to go back on aripiprazole instead of quetiapine.
     
  8. kailey_elise

    kailey_elise Gold Member

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    Max, yeah, I agree with you! I'm *still* battling all of the weight I put on while on Risperdal (risperidone) & Abilify (aripiprazole) a few years back. I gained a LOT of weight VERY quickly while taking Risperdal, which sucks, because otherwise, it's the best med I've taken in years. I switched to Abilify, but I was still gaining weight (albeit slower than the Risperdal gains).

    It's all well and good to say "reduce carbs/sugar" while taking AAPs, but that fails to take into account that they tend to make your body CRAVE those very things. My cravings for cereal/cookies/cake (especially at night, unfortunately) were often more powerful than cravings for cocaine once I quit. Yikes! People just didn't (& still don't!) understand that it wasn't just a willpower thing; I'd wake up multiple times a night with a painful gnawing in my belly that would ONLY be sated by, say, a bowl of cold cereal. I'd try other, healthier options first - yogurt, fruit, even a sandwich (usually ham & cheese), only to STILL not be able to go back to sleep because of the pain in my tummy! Then I'd have to eat the cereal anyway! Ugh, it was so freaking FRUSTRATING. After a while, I just started trying to eat the smallest bowl of cereal I could get away with, because I was eating more overall by trying to satisfy my hunger with other options. Meh.

    I wish you luck in your battle! Seroquel & Zyprexa seem to be the worst offenders regarding weight gain, but Risperdal's right up there too, and as I understand it, Risperdal seems to raise one's prolactin levels more than any of the other AAPs. I could squirt milk clear across the room while I was on Risperdal - and I've never had a child before! Even men can end up lactating while on AAPs! That's kind of scary, imo.

    Good articles, guys! Thanks for the info! :)

    ~Kailey
     
  9. Maxfrombx

    Maxfrombx Newbie

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    Thanks Kailey, yeah, it's a shame because Seroquel seems to really help too. I really don't know what to choose. I just come back from a stenuous work-out session only to not be able to look at myself in the mirror because this fat is just not me! Plus, gynecomastia tends to be visible behind my t-shirt!

    I experience just the same as you did, only a high carb meal allows me to be able to sleep, and it's about the worst time to have one...

    As many of my problems come from a poor self-image, it's really not a solution in the long term.
     
  10. kailey_elise

    kailey_elise Gold Member

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    *exactly*

    It sucks so so *SO* much that so many psych meds have either weight gain or bloating (to varying degrees) as a major side effect, because so many of us already have poor images of ourselves!

    ~Kailey
     
  11. Maxfrombx

    Maxfrombx Newbie

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    I think I have found the answer!

    While searching about solutions on how to lose weight on atypicals, I stubled upon this article:

    http://www.webmd.com/mental-health/news/20080108/fighting-antipsychotic-weight-gain

    Metformin side-effects are few. The only (rare) danger is lactic acidosis.

    I made myself a script for 500mg TID metformine for 3 months, in order to fight the fat I am gaining from cyamemazine.

    I just came back from the pharmacy and took my first 500mg. Hoping that it will normalize my glycemia (and my fat ratio).

    Maxfrombx added 752 Minutes and 38 Seconds later...

    Some more facts I discovered while searching about metformin:

    -It's sometimes used as a weight-loss aid, off-label.
    -Some anti-aging doctors advise all their patients to take metformin, as it normalize glycemia (never inducing hypoglycemia) and

    improve insulin sensitivity.
    -Many diabetic patients report weight loss as a side effect on the forums
    -Metformin works by increasing the number of insulin receptors, thus increasing insulin sensitivity.
    -The only dangerous side-effect, lactic acidosis, which is deadly 50% of the time, only occurs in 3 out 100 000 patients.

    Other side effects are mild and include for the most part gastro-instestinal disturbance (nausea, diarrhea).

    I'm associating it with a slow-carb diet (no white carbs/no carbs that can be white).

    The experiment will be a little biased because of the placebo effect, but as we know, this effect doesn't last long.
     
    Last edited: Oct 28, 2012
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