Sella Turcica17

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Why does it take up to 3-6 weeks before reaching the full clinical effects of antidepressants (esp. TCAs)? ..... Im sure the mechanism in more complicated than just waiting for blood levels to reach a certain level since blood levels correlate with efficacy and toxicity. Can anyone explain?

Also, if both first generation (typical) and second generation (atypical) antipsychotics work on D2 receptors, why don't the atypcal drugs have the same side effects (EPS) as the 1st generation drugs?

Thanks for your help!
 

BMBiology

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TCA: 3-4 wks to increase energy, 5-6 wks to change mood.
 

BMBiology

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2nd question: b/c in addition to blocking D2 receptors like typicals, atypicals also block serotonin.
 

Old Timer

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Why does it take up to 3-6 weeks before reaching the full clinical effects of antidepressants (esp. TCAs)? ..... Im sure the mechanism in more complicated than just waiting for blood levels to reach a certain level since blood levels correlate with efficacy and toxicity. Can anyone explain?

Also, if both first generation (typical) and second generation (atypical) antipsychotics work on D2 receptors, why don't the atypcal drugs have the same side effects (EPS) as the 1st generation drugs?

Thanks for your help!
The answer is, if we accept the amine hypothesis of depression, there is a net deficit of neurotransmitters in the synaptic space. Once you stop the re-uptake of these transmitters into the pre-synaptic neurons, it takes time to build these levels back up to normal.
 

rxlea

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I thought it had to do with downregulation of receptors and that atypical D2 antagonists are more specific than other antipsychotics...at least that is what I have read.
 

Ackj

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Also, if both first generation (typical) and second generation (atypical) antipsychotics work on D2 receptors, why don't the atypcal drugs have the same side effects (EPS) as the 1st generation drugs?
The atypicals are less potent for D2 (hit more 5-HT-2a), which means less occurrence of EPS. Comparing the First Gens, you'll also see this trend: Phenothiazines are less potent at D2 and have less EPS (however more side effects, since you're hitting more receptor types) while Butyrophenones are more potent at D2 and EPS is more common.


I thought I was going to take a break from studying for my schiz/bipolar/depression exam by logging in here, but it seems that I ended up doing a review anyway :D
 

rxlea

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The atypicals are less potent for D2 (hit more 5-HT-2a), which means less occurrence of EPS. Comparing the First Gens, you'll also see this trend: Phenothiazines are less potent at D2 and have less EPS (however more side effects, since you're hitting more receptor types) while Butyrophenones are more potent at D2 and EPS is more common.


I thought I was going to take a break from studying for my schiz/bipolar/depression exam by logging in here, but it seems that I ended up doing a review anyway :D
Thanks for the info :) and good luck on your exam! :)
 

Ackj

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The answer is, if we accept the amine hypothesis of depression, there is a net deficit of neurotransmitters in the synaptic space. Once you stop the re-uptake of these transmitters into the pre-synaptic neurons, it takes time to build these levels back up to normal.
Which is still imperfect, since amphetamines boost NE release, and aren't effective antidepressants. Also, there's really not a lot of evidence that the neurotransmitter systems are actually malfunctioning in the first place. When 5-HT and NE transporters are inhibited, the monoamines increase almost immediately, so we're still not really sure why it takes so long for the effect.
 

GreyFox2002

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It's not fully elucidated, but I believe it is thought that receptors are downregulated with lower levels of serotonin in the synapse. Therefore, it takes time for an upregulation of receptors to occur in response to an increase in cathecholamines.
 

tungsten87

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It's not fully elucidated, but I believe it is thought that receptors are downregulated with lower levels of serotonin in the synapse. Therefore, it takes time for an upregulation of receptors to occur in response to an increase in cathecholamines.
good answer fox.

-shalashaska.
 

eeyore spice

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Which is still imperfect, since amphetamines boost NE release, and aren't effective antidepressants.
Have you ever seen someone on amphetamines? Hell yes they're effective antidepressants. They just can't be taken on a regular basis without losing efficacy.
 

Old Timer

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It's not fully elucidated, but I believe it is thought that receptors are downregulated with lower levels of serotonin in the synapse. Therefore, it takes time for an upregulation of receptors to occur in response to an increase in cathecholamines.
But while the receptors down regulate in number they tend to increase in sensitivity....... So the real answer is we don't have a clue.....