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How come certain drugs (i.e. antidepressants) take days/weeks before they work?

Wow, both those posts seem like excellent info. But what exactly would you say are the academic prerequisites to being able to truly understand this stuff. I asked my psychiatrist the question in the first post and he answered that I'd have to take at least one pharmacology course to understand it. This thread has proven him correct.
 
When I had a lecture on the mechanisms of depression a few years ago at Edinburgh university my professors was in support of the HPA axis theory Zalo posted about. Now I've read, but not really looked in the literature, about ketamine (and possibly other dissociatives) causing near instant, and long lasting anti-depressant effects even after a single dose. Apparently it's not got nothing to do with it's blocking of NMDA receptors but more with how it activates intracellular signalling and caused changes in gene expression? Anyone know more about this?
 
red22 said:
Wow, both those posts seem like excellent info. But what exactly would you say are the academic prerequisites to being able to truly understand this stuff. I asked my psychiatrist the question in the first post and he answered that I'd have to take at least one pharmacology course to understand it. This thread has proven him correct.
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You just need to read a lot of primary lit and look up terms and concepts that you don't understand. Like any learning, a lot of it is just exposure to ideas until you start making connections on your own. Remember that a lot of this stuff is not well established experimentally, either, though; there's a lot of complexity to the brain.
 
Do SNRI's such as venleflaxine and desvenlflaxine follow the same down stream pharmacodynamics as SSRI's do? When taking my Effexor for the first time it felt oddly psychoactive and then the perceptible effects reduced to neglegible levels until about 3 weeks of treatment after which each dose is nearly immediately felt as a mild euphoriant.
 
All drugs take effect immediately upon entering the body! A lot of drugs take effect before even entering your bloodstream (usually side effects), e.g. due to irritations they cause on your skin or mucous membranes.

When someone says a drug takes a while to take effect, they are talking about the desirable/therapeutical effects. Just like it will take a while for some undesirable effects to kick in when you are using recreational drugs.

Usually we are talking about adaptive responsive the body undergoes when exposed to the chemical in question or to it's actual primary effects. These responses may then be the therapeutical desired effect itself or they may enable the drug in question to unfold it's desired effects.

These adaptive responses could e.g. be desensitation of a target receptor or it's downregulation, the former of which is the case for SSRI's afaik.

Tbh I hate hearing this crap, even if it is just wrong phrasing ("therapeutical effects" vs. "effects"). part of why I can't hear it anymore is that I get extremely hypomanic minutes after dropping an instant release SSRI (which ironically will wipe out depression). Most people will also get a shitload of side effects on day 1 if they are sensitive enough to the given dosage.

The God said:
What about an NDRI such as bupropion? I felt the effects about 1-2 hours after my first dose.
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The effects of bupropion have been outlined above, but again I'd like to stress that these statements (med x takes time span t to take effect) are not about when you feel a drug, they're about when the desired therapeutical effects kick in. For instance in the case of the lithium I am taking, this can be anywhere between a few days and a year (I think synaptogenesis is supposed to be involved here). Nonetheless most people will feel the drug fuck with your stomach on day 1, oh how they do.

Now there are other substances, e.g. long esters of (lipophilic) steroid hormones, that can take weeks to take effect because they are only released very gradually and even when they are released gradually, their effects are due to profound changes the cell undergoes after their (intracellular) binding to their target proteins, which in turn can mean inhibition or promotion of the synthesis of specific proteins. To finally see the both effects and side effects of e.g. testosterone enanthate manifest will therefore take weeks. Nonetheless side effects can manifest on day one (e.g. an inflammation at the injection site).

This is one example for a substance class directly interfering with "genetic transcription" (which your doctor mentioned). The substance binds to it's target proteins which in turn allows the proteins (if they aren't bound to it already) to bind to certain areas in the DNA. This often promotes or inhibits a process called "transcription", the synthesis of new RNA in this case directly from the respective DNA segment. RNA which is in turn used to synthesize proteins (a process called "translation").
 
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I too get immediate effects from venlafaxine (hypomania) and side effects from others when dosed high enough, eg 40mg fluoxetine, but it fades quickly and with time I became almost immune to SSRIs, getting little of either therapeutic nor side effects but strong discontinuation syndrome. Weird. Took them for anxiety, not depression. Somehow I think that initial hypomania should be seen as a warning sign not to continue or one will get dependent like I am currently and since years, taking SSRI just to avoid the abstinence brain zap dysphoria which doesn't fade for days or weeks..

Otherwise I fully agree to @cr00k above.
 
not true. some antidepressants can be quite quick, especially if you IV them, like ketamine. also sublingual works fine as well if you consider suboxone an antidepressant. but tianeptine is probably the only oral antidepressant that has 90% binding and works within 15 mins orally. its insane!
 
allone said:
not true. some antidepressants can be quite quick, especially if you IV them, like ketamine. also sublingual works fine as well if you consider suboxone an antidepressant. but tianeptine is probably the only oral antidepressant that has 90% binding and works within 15 mins orally. its insane!
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Ketamine is a whole different story than SSRI serotonergic antidepressant. It's used because it's so fast acting, IV is not necessary. The nasal route works as well.

Tianeptine weirdly does nothing at all for me in recommended dosages, only when taking like 100mg and more at once I get some effects but this is recreational use.
 
what do you mean recreational use? who else will use tianeptine at recommended dose? its 12.5mg three times a day at recommended amount. you take 500mg and you will see what i mean.
also as bonus as we are talking about SSRIs, take prozac at tripple the recommended dose, open the capsules and sublingually take em. you will feel it within minutes. makes you wanna dance. but because im a chronic masturbator, next day you cannot feel your dick which sucks.
 
Really, fluoxetine is different when used sublingually? Triple the recommended dosage of 20mg so 60mg is still within therapeutic range or do you speak about three times 60mg? Then it'd make more sense. I read before about abuse of venlafaxine but thought it was because of that's structure as a PEA having very weak releaser activity which becomes more pronounced in overdose.

Afaik a high therapeutic dosage of a SSRI will occupy almost all of SERT so upping the dosage doesn't make sense. With fluoxetine it might be the 5ht2c agonism becoming more effective at high dosages, 80mg certainly made me restless but nothing recreational.
 
They really are more advanced than drugs that get you high. They harness more sophisticated tracts to better trick the brain into thinking that the activity is natural. Wish I had more to say on this, but neuroscience is ever-expanding.
 
I found a cheap drug online called Amoxapine.

According to wikipedia: "Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment."
 
I don't think that all psychotropic drugs (including antidepressants) are drugs that work immediately after ingestion (like THC or paracetamol...). These drugs only create the conditions to be able to start a new life. But new life has to be learned. And that takes time.

The human psyche is not something that changes from today to tomorrow.
 
Isn't It a proven fact that TCA antidepressents work because there anticholinergic with SNRI stopping the bowels from crying on low non-CNS ACH. I've seen people on Reddit nootropic subs state on using DPH/Benadryl If they feel gross after eating something high in ACH.
 
There are still a few hypotheses regarding ssri effects.

I think the serotonin hypothesis is insufficient to describe all of the effects of ssris. The evidence that these drugs also work through the BDNF/TrkB pathway is too strong.

A popular and (to me) plausible explanation is that serotonin levels drive BDNF expression. This fits in well with the data regarding 5HT1 autoreceptors, and explains the lag in antidepressant effects.

I have seen a paper in Cell which proposes that a broad range of antidepressants directly bind to TrkB receptors. This paper claims that ssris have a very weak binding affinity, and that the delay in those drugs’ efficacy is due to the time it takes for brain concentrations to reach a level that binding occurs at. I haven’t really seen anybody else running with this hypothesis, but the findings are interesting.
 
Smyth2 said:
I found a cheap drug online called Amoxapine.

According to wikipedia: "Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment."
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Unsurprisingly it's not often prescribed for depression

Probably due to it's dopamine antagonism
 
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