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
----------------------------------------------------------------
----------------------------------------------------------------
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.
-----------------------------------------------------------------
poster:SLS
thread:50044
URL: http://www.dr-bob.org/babble/20001130/msgs/50044.html