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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by Edward on July 3, 2001, at 14:32:39
I don't understand this: whenever you take drugs constantly for a prolonged period of time, you become tolerant. You need more to produce the same effect until eventually you need to take the drug to be normal. This happens with any intoxicant. So why not with antidepressants? Surely if you take something that increases your serotonin levels for a long time you will become tolerant and it will lower your serotonin levels. Can anyone explain this to me?
Posted by PaulB on July 3, 2001, at 15:18:01
In reply to why do antidepressants work?, posted by Edward on July 3, 2001, at 14:32:39
> I don't understand this: whenever you take drugs constantly for a prolonged period of time, you become tolerant. You need more to produce the same effect until eventually you need to take the drug to be normal. This happens with any intoxicant. So why not with antidepressants? Surely if you take something that increases your serotonin levels for a long time you will become tolerant and it will lower your serotonin levels. Can anyone explain this to me?
Some drugs bind to the receptors that neurotransmitters latch onto in the brain like benzodiazepines and opiates and some drugs provide a massive release of neurotranmsitters like Amphetamine and MDMA. After exposure to these drugs for a while the no of receptors and their sensitivity will lessen causing tolerance like you mentioned. Antidepressants are different. They just allow the brain to make better use of what neurotransmitter is already present. They are not supposed to produce a high and that is why they take 2-4 weeks usually to start working so that the brian can adjust to a more normal level of neurotranmsitter. When they start working in a depressed person there is just an increase in neurotransmitter that locks into the receptor like in any healthy person. The re-uptake or MAO inhibition compensates for the faulty mechanism via which neurotransmitters are constantly recycled. Thats one theory anyway.
Posted by Elizabeth on July 3, 2001, at 16:27:19
In reply to why do antidepressants work?, posted by Edward on July 3, 2001, at 14:32:39
> I don't understand this: whenever you take drugs constantly for a prolonged period of time, you become tolerant.
That's often true, yes. With antidepressants, the adaptive changes that result from chronic use are thought to be responsible for the antidepressant effects. (Nobody is sure exactly how ADs work, but this general idea is consistent with everything we know about them.)
-elizabeth
Posted by Edward on July 4, 2001, at 14:12:46
In reply to Re: why do antidepressants work? » Edward, posted by Elizabeth on July 3, 2001, at 16:27:19
Thanx guys.
Posted by blackjack on July 4, 2001, at 14:50:31
In reply to why do antidepressants work?, posted by Edward on July 3, 2001, at 14:32:39
> I don't understand this: whenever you take drugs constantly for a prolonged period of time, you become tolerant.
That is not true of all drugs. Some drugs (marijuana comes to mind) actually produce a REVERSE tolerence, so the more you do it, the LESS you need to achieve the effect. Also, since many drugs affect several different systems, they sometimes create a tolerence to some of their effects, but not others. Most people will develop a tolerence to the euphoric effects of amphetamines, and to many of the peripheral side effects, like sweating and increased blood pressure, but the focus, enhancing and sleep-redcing effects are often sustained at the same dose for a person's entire lifetime. There are plenty of non-psychiaric drugs that people use for very extended periods of time that do not produce tolerence. It depends on the drug and, in part, the individual.
As has been stated by others, the process which often produces tolerence is one in which the brain adjusts its production of certain chemicals, or changes the number or nerve receptors for certain chemicals, in order to try to restore its previous ballance. It is thought, in the case of many antidepressants, that it is this very adjustment, not the immediate effects of the drugs, that is responsible for the sustained antidepressant effect. Prozac causes an almost immediate increas in seratonin levels (which is why the side effects start immediately) but it is not until several weeks later that the antideressant effects kick in. It is supposed (and, yes, there is a lot of guesswork) that this is because the increase in seratonin casues some other secondary changes in the brain over time.
Some people do develop a tolerence to some antidepressants, however. I began to develop withdrawal symptoms while still taking more than the maximum recommended dosage of the MAOI Parnate, and my depression returned. Increasing the dose did not help. I went off of it for a while, and when I went back on it, it worked as before for several months before the tolerence kicked in again. I have heard several other people who had simila experiences with MAOI's.
Likewise, there is a phenomenon called (technically :) "SSRI poop-out". People who have been taking an SSRI successfully for several months or even years will suddenly find that it no longer works. This may not be tolerence in the classic sense, but perhaps a reaction to a secondary change (e.g., decreased dopamine release) caused by chronic use of the SSRI in question.
Posted by Elizabeth on July 4, 2001, at 21:57:10
In reply to Re: why do antidepressants work? » Edward, posted by blackjack on July 4, 2001, at 14:50:31
> That is not true of all drugs. Some drugs (marijuana comes to mind) actually produce a REVERSE tolerence, so the more you do it, the LESS you need to achieve the effect.
"Sensitisation."
> Also, since many drugs affect several different systems, they sometimes create a tolerence to some of their effects, but not others. Most people will develop a tolerence to the euphoric effects of amphetamines, and to many of the peripheral side effects, like sweating and increased blood pressure, but the focus, enhancing and sleep-redcing effects are often sustained at the same dose for a person's entire lifetime.
People who take amphetamine for fatigue do sometimes develop tolerance (as do those who take it for appetite reduction). It's not so much a sleep-reducer as a REM sleep-reducer, and that effect persists (e.g., in narcolepsy). People with ADHD are often able to stay on the same dose for years, though.
> It is thought, in the case of many antidepressants, that it is this very adjustment, not the immediate effects of the drugs, that is responsible for the sustained antidepressant effect.
It clearly isn't the immediate effects, since they generally take several weeks to work. < g >
> Some people do develop a tolerence to some antidepressants, however. I began to develop withdrawal symptoms while still taking more than the maximum recommended dosage of the MAOI Parnate, and my depression returned.
I had a similar thing happen on Nardil, but I also began experiencing withdrawal symptoms -- mood swings, panic attacks, REM rebound. Increasing the dose didn't work for me either. I tried going off the Nardil for a few months; when I tried taking it again, the same thing happened. (This isn't "tolerance" as it's generally understood, although it has sometimes been described as tolerance.)
Sometimes people experience a sort of contentment bordering on apathy after taking SSRIs for a long time. This isn't poop-out, but an unwanted side effect.
-elizabeth
This is the end of the thread.
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