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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by SLS on December 6, 2000, at 8:52:59
I thought I would repost my short treatise on drug-induced weight gain. Someone had asked about it this week, so I figured I would cease another opportunity to see my name appear on the board.
Oops. Was that a joke? :-)
- Scott
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SSRI-induced weight-gain is poorly understood. Weight-gain produced by SSRIs is considered to be a paradoxical reaction. That this paradoxical reaction is so frequently seen on Psycho-Babble may be an indicator of a bias towards an array of serotonergic (5-HT) dysregulations that is overrepresented in a population biased towards treatment-resistance and "poop-out".Serotonergic systemic and synaptic relationships are very complex and, in my way of thinking, vulnerable to a broader set of potential dysregulations.
In addition, despite their claimed selectivity, SSRIs still interact with various other important systems. The term "selective" was originally chosen to describe the tendency of these drugs to interact more exclusively relative to the three major monoamine neurotransmitters recognized as being important at the time (dopamine, norepinephrine, and serotonin). It is a misconception to think of SSRIs as being selective with respect to all other neurotransmitters and neuromodulatory systems.
The SSRIs is obviously the class of drug in the greatest demand for an understanding as to why they cause weight-gain. I apologize for not being able to more precisely report the mechanisms underlying this "unappetizing" side-effect.
---------------------------------------------------------
SOME MECHANISMS OF PSYCHOTROPIC-INDUCED WEIGHT-GAIN:
I. Increased secretion of prolactin by the pituitary gland.
Medications:1. The older typical neuroleptic antipsychotics: Haldol, Thorazine, Loxitane, Navane, Mellaril, etc.
2. Sulpiride and amisulpride
3. Paxil (paroxetine)
Mechanisms:1. The body thinks it's pregnant. It wants to store as much fat as possible for postnatal care. Got milk?
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II. Blockade of histamine H1 receptors (H1 antagonists):
Medications:1. The newer atypical antipsychotics: Clozaril, Zyprexa, Risperdal. Clozaril and Zyprexa are the highest.
2. Tricyclics
3. Remeron
4. Many other psychotropics
Mechanisms:1. Increased hunger and food intake.
2. Carbohydrate craving.
3. Lowered basal metabolism rate (BMR). The rate of energy burned through thermogenesis (heat production) is decreased in brown adipose tissue (BAT) and as well as white adipose tissue (WAT). Psychotropic medications prevent the H1-induced increase in the expression of energy-releasing uncoupling proteins (UCP) located in the inner mitochondria of these tissues.
4. Decreased insulin sensitivity in muscle and heart. More glucose winds up being metabolized and stored as fat.
----------------------------------------------------------------
III. Chronic NE-beta receptor stimulation.
Medications:1. Tricyclics
2. Ludiomil
3. Remeron
4. Effexor
Mechanisms:1. Decreased expression of uncoupling proteins (UCP) in skeletal muscle and heart muscle, resulting in higher energy efficiency; energy is burned more slowly. (NE-beta receptor downregulation?)
2. Reduced plasma levels of insulin and free fatty acids (FFA). This produces a reduced uptake of glucose (energy) by skeletal muscle and heart muscle. The extra energy is stored in adipose tissue (fat).
----------------------------------------------------------------
IV. Changed glucose / insulin dynamics. Influences how much energy
is stored.
Medications:1. Hydrazine MAOIs: Nardil and Marplan
2. Newer atypical neuroleptic antipsychotics: Clozaril, Risperdal, Zyprexa, Seroquel, and Zeldox. (I don't know to what extent each of these drugs affect glucose/insulin dynamics, but some are known to exacerbate diabetes).
Mechanisms:1. Decreased insulin sensitivity in muscle. Reduces the rate of glucose uptake by muscles. This extra glucose is stored as fat.
2. Inhibition of gluconeogenesis resulting in a decrease in the liberation of energy from protein reserves.
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Posted by shar on December 6, 2000, at 14:47:09
In reply to Drug-Induced Weight Gain - Some Mechanisms, posted by SLS on December 6, 2000, at 8:52:59
SLS,
I commend you on your courage to post so soon after that sense of humor fiasco... JKJKJKJK. 8-) ((SLS))I actually appreciate you reposting this info, because it is hard for me to remember some of the more technical info I see here.
This might not have anything to do with your treatise, but when I kept pressing my doctor on how a drug that is supposedly circulating in my brain and affecting receptors in my brain would cause constipation (not in my brain) and similar non-brain side effects, she finally said we have receptors all over our body.
So, if that is true, and the action of the AD isn't even mostly limited to our brains, but goes all over our bodies to receptors all over our bodies, who knows what is really happening? All of our systems could be affected.
I often wondered if she was exaggerating, just wanted to shut me up, or if that could really be happening. If so, it seems we haven't even begun to figure out the AD's "how do I affect thee" ?
Shar
> I thought I would repost my short treatise on drug-induced weight gain. Someone had asked about it this week, so I figured I would cease another opportunity to see my name appear on the board.
>
> Oops. Was that a joke? :-)
>
>
> - Scott
>
>
> ----------------------------------------------------------------
> ----------------------------------------------------------------
>
>
> SSRI-induced weight-gain is poorly understood. Weight-gain produced by SSRIs is considered to be a paradoxical reaction. That this paradoxical reaction is so frequently seen on Psycho-Babble may be an indicator of a bias towards an array of serotonergic (5-HT) dysregulations that is overrepresented in a population biased towards treatment-resistance and "poop-out".
>
> Serotonergic systemic and synaptic relationships are very complex and, in my way of thinking, vulnerable to a broader set of potential dysregulations.
>
> In addition, despite their claimed selectivity, SSRIs still interact with various other important systems. The term "selective" was originally chosen to describe the tendency of these drugs to interact more exclusively relative to the three major monoamine neurotransmitters recognized as being important at the time (dopamine, norepinephrine, and serotonin). It is a misconception to think of SSRIs as being selective with respect to all other neurotransmitters and neuromodulatory systems.
>
> The SSRIs is obviously the class of drug in the greatest demand for an understanding as to why they cause weight-gain. I apologize for not being able to more precisely report the mechanisms underlying this "unappetizing" side-effect.
>
>
> ---------------------------------------------------------
>
>
> SOME MECHANISMS OF PSYCHOTROPIC-INDUCED WEIGHT-GAIN:
>
>
> I. Increased secretion of prolactin by the pituitary gland.
>
>
> Medications:
>
> 1. The older typical neuroleptic antipsychotics: Haldol, Thorazine, Loxitane, Navane, Mellaril, etc.
>
> 2. Sulpiride and amisulpride
>
> 3. Paxil (paroxetine)
>
>
> Mechanisms:
>
> 1. The body thinks it's pregnant. It wants to store as much fat as possible for postnatal care. Got milk?
>
>
> ----------------------------------------------------------------
>
>
> II. Blockade of histamine H1 receptors (H1 antagonists):
>
>
> Medications:
>
> 1. The newer atypical antipsychotics: Clozaril, Zyprexa, Risperdal. Clozaril and Zyprexa are the highest.
>
> 2. Tricyclics
>
> 3. Remeron
>
> 4. Many other psychotropics
>
>
> Mechanisms:
>
> 1. Increased hunger and food intake.
>
> 2. Carbohydrate craving.
>
> 3. Lowered basal metabolism rate (BMR). The rate of energy burned through thermogenesis (heat production) is decreased in brown adipose tissue (BAT) and as well as white adipose tissue (WAT). Psychotropic medications prevent the H1-induced increase in the expression of energy-releasing uncoupling proteins (UCP) located in the inner mitochondria of these tissues.
>
> 4. Decreased insulin sensitivity in muscle and heart. More glucose winds up being metabolized and stored as fat.
>
>
> ----------------------------------------------------------------
>
>
> III. Chronic NE-beta receptor stimulation.
>
>
> Medications:
>
> 1. Tricyclics
> 2. Ludiomil
> 3. Remeron
> 4. Effexor
>
>
> Mechanisms:
>
> 1. Decreased expression of uncoupling proteins (UCP) in skeletal muscle and heart muscle, resulting in higher energy efficiency; energy is burned more slowly. (NE-beta receptor downregulation?)
>
> 2. Reduced plasma levels of insulin and free fatty acids (FFA). This produces a reduced uptake of glucose (energy) by skeletal muscle and heart muscle. The extra energy is stored in adipose tissue (fat).
>
>
> ----------------------------------------------------------------
>
>
> IV. Changed glucose / insulin dynamics. Influences how much energy
> is stored.
>
>
> Medications:
>
> 1. Hydrazine MAOIs: Nardil and Marplan
>
> 2. Newer atypical neuroleptic antipsychotics: Clozaril, Risperdal, Zyprexa, Seroquel, and Zeldox. (I don't know to what extent each of these drugs affect glucose/insulin dynamics, but some are known to exacerbate diabetes).
>
>
> Mechanisms:
>
> 1. Decreased insulin sensitivity in muscle. Reduces the rate of glucose uptake by muscles. This extra glucose is stored as fat.
>
> 2. Inhibition of gluconeogenesis resulting in a decrease in the liberation of energy from protein reserves.
>
>
> -----------------------------------------------------------------
Posted by Lisabet on December 6, 2000, at 18:02:16
In reply to Drug-Induced Weight Gain - Some Mechanisms, posted by SLS on December 6, 2000, at 8:52:59
Scott, what is the component/s of Wellbutrin that makes you lose weight? Does it have to do with metabolism?
-Lisa
Posted by Cam W. on December 7, 2000, at 14:07:48
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms, posted by Lisabet on December 6, 2000, at 18:02:16
> Scott, what is the component/s of Wellbutrin that makes you lose weight? Does it have to do with metabolism?
>
> -LisaLisa - It probably isn't what Wellbutrin has that prevents weight gain, it is probably what it doesn't have. Wellbutrin doesn't block serotonin receptors (5-HT2C, to be exact), histaminergic (H1) receptors or muscarinic/cholinergic (M1) receptors to any appreciable extent. All of these receptors have been implicated in weight gain caused by the tricyclics (TCAs) and SSRIs.
Hope this helps - Cam
Posted by Lisabet on December 8, 2000, at 19:30:32
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms » Lisabet, posted by Cam W. on December 7, 2000, at 14:07:48
Cam, thanks.
Thank you for the explanation. How then, does it suppress appetite? (Forgive me if I'm being ignorant.)
And, is there anything I can do (besides exercise- I'm saving this as a last resort), or take to continue losing weight? I've hit a plateau. I was losing weight before I took the Wellbutrin and then continued, but stopped. My energy has increased, therefore I am more active. And I eat much smaller meals. My interest for food has decreased.
Any suggestions? Thanks.
-Lisa
Posted by Cam W. on December 9, 2000, at 1:07:43
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms, posted by Lisabet on December 8, 2000, at 19:30:32
Lisa
>
> Thank you for the explanation. How then, does it suppress appetite?To tell you the truth, I dunno; or more precisely, Wellbutrin probably doesn't really cause appetite suppression. It probably has more to do with not interacting with serotonin or histamine receptors. Some people do gain weight when taking Wellbutrin, but not as many as is seen with most SSRIs or TCAs. I think that it just doesn't promote weight gain, rather than curbing appetite or causing weight loss.
> And, is there anything I can do (besides exercise- I'm saving this as a last resort).Exercise, even more than eating properly should be a first resort (sorry). Pills and diets are never as effective as exercise is in maintaining health.
- Cam
Posted by SLS on December 9, 2000, at 17:20:35
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms » Lisabet, posted by Cam W. on December 7, 2000, at 14:07:48
> Lisa - It probably isn't what Wellbutrin has that prevents weight gain, it is probably what it doesn't have. Wellbutrin doesn't block serotonin receptors (5-HT2C, to be exact), histaminergic (H1) receptors or muscarinic/cholinergic (M1) receptors to any appreciable extent. All of these receptors have been implicated in weight gain caused by the tricyclics (TCAs) and SSRIs.
Dear Cam,I double-checked my SSRI weight-gain information. Isn't the fact that weight-gain occurs during increased 5-HT2C receptor stimulation resulting from SSRIs paradoxical? I thought 5-HT2C stimulation produced weight-loss and reduced appetite rather than weight-gain and hyperphagia. Fenfluramine might be a paradigm of this effect. I believe this is why the drug manufacturers noted weight-loss as predominant over weight-gain in their clinical trials and noted such in their labelling. People do lose weight on these drugs. I would love to know the true statistics in a homogeneous population of unipolar depressives. I would then like to see a comparison of weight-gain vs weight-loss in five subpopulations:
1) treatment-resistant depression (TRD)
2) rapid poop-out
3) unambiguous, fully qualified atypical unipolar depression with reverse vegetative symptomology.
4) bipolar depression
5) dysthymiaI wonder if weight-gain is more likely to occur in these conditions. Perhaps they are indicative of a subsensitive 5-HT2C receptor polymorphism associated with depression or an idiosyncratic acceleration of 5-HT2C downregulation.
- Scott
Posted by Cam W. on December 9, 2000, at 22:35:08
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms » Cam W., posted by SLS on December 9, 2000, at 17:20:35
>
>
> > Lisa - It probably isn't what Wellbutrin has that prevents weight gain, it is probably what it doesn't have. Wellbutrin doesn't block serotonin receptors (5-HT2C, to be exact), histaminergic (H1) receptors or muscarinic/cholinergic (M1) receptors to any appreciable extent. All of these receptors have been implicated in weight gain caused by the tricyclics (TCAs) and SSRIs.
>
>
> Dear Cam,
>
> I double-checked my SSRI weight-gain information. Isn't the fact that weight-gain occurs during increased 5-HT2C receptor stimulation resulting from SSRIs paradoxical? I thought 5-HT2C stimulation produced weight-loss and reduced appetite rather than weight-gain and hyperphagia. Fenfluramine might be a paradigm of this effect. I believe this is why the drug manufacturers noted weight-loss as predominant over weight-gain in their clinical trials and noted such in their labelling. People do lose weight on these drugs. I would love to know the true statistics in a homogeneous population of unipolar depressives. I would then like to see a comparison of weight-gain vs weight-loss in five subpopulations:
>
> 1) treatment-resistant depression (TRD)
> 2) rapid poop-out
> 3) unambiguous, fully qualified atypical unipolar depression with reverse vegetative symptomology.
> 4) bipolar depression
> 5) dysthymia
>
> I wonder if weight-gain is more likely to occur in these conditions. Perhaps they are indicative of a subsensitive 5-HT2C receptor polymorphism associated with depression or an idiosyncratic acceleration of 5-HT2C downregulation.
>
>
> - ScottScott - This weight gain thing really has me baffled. You raise the same points that I have tried to resolve several times. I too, would like to see studies in this area (but who's going to fund it?). I do not really have a good grasp of what really regulates weight. With 50 to 100 neurotransmitter (or more precisely neurotransmitter-like substances - incl. nitric oxide, carbon monoxide, peptides, amino acids and several proteins, etc.) I really am finding the way the brain works to be quite facinating (so simple, yet so complex).
"If the brain were so simple that we could understand it, we would be so simple that we couldn't" - Emerson Pugh, 1997 (my addendum - "yet")
Here's another conundrum with Wellbutrin. It is a stimulating drug (esp. for the first couple of weeks, where it seems to act like a diet pill). After that, it isn't so much stimulating, but it still will keep many people awake at night, if taken too late. The wake sleep cycle is controlled (in part) in the midbrain reticular activating system. This is where the raphe nuclei are located, which contains the majority of serotonergic innervation. But Wellbutrin doesn't bind to serotonergic receptors. It is easy to say that the serotonin is affected in a round about way, but what about the converse. If you use the same logic, serotonergic antidepressants should increase stimulation of noradrenergic receptors.
It is too simplistic (reductionistic) to look at any of these neurotransmitters and receptors in isolation. The concentrations of all neurotransmitters and all receptors have to be taken into account at the same time. Since we don't know what they all are, we still can't do this. Using the analogy of building a car engine: we can fix the alternator, but the lights still don't come on.
I guess that the more I learn, the less I know. That means that I will be an expert when I convince myself that I know nothing.
In the meantime, all we can do is "Keep on Truckin'". Your pal - Cam
Posted by SLS on December 10, 2000, at 9:56:28
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms » SLS, posted by Cam W. on December 9, 2000, at 22:35:08
Hi Cam.
> I guess that the more I learn, the less I know. That means that I will be an expert when I convince myself that I know nothing.
That's O.K. The more you learn, the less *I* know. Soon I will be a know-nothing too.
:-)
- Scott
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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