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| quote: | Originally posted by NeoPhono
First off, MDMA has several routes of action, the most important is that it is a SERT competitive inhibitor. (SERT = serotonin transporter) It's the exact same class of transporters affected with traditional SSRIs. So, its primary mode of action is exactly the same as an SSRI; it leaves serotonin in the synaptic cleft for a longer period of time. It does cause an increase in release as well, but that, along with its effects on other neurotransmitters (specifically dopamine) are not as important as its SERT-inhibiting effect.
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Most antidepressents work on dopamine as well. But a release of seratonin presynaptically as well as reuptake inhibition makes the drug much more potent. Agreed here.
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Yes, there really is such a thing, as diagnosed by DSM-IV. I'm not talking about having a bad day every once in a while, but chronic, sometimes debilitating neurological disease. Sure, it's easy to "fake" clinical depression, but treatments tend to be cheap, effective and side-effect free, so for most it's better to be treated and not have the condition than to not be treated and have the condition. I agree that too many people are diagnosed with clinical depression, but I guess I'd rather have too many non-depressed people on medication than depressed people not getting the help they need.
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I agree to some extent, IF its so serious that psychotherapy can't work, then administer the drug. There is not enough stress on this. Chronic administration of the drugs can leave a person emotionless and numb, its true. So you have to wager either dealing with mental hardship or mental numbness. Thats for a psychotherapist do discern (i believe)
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For too long people have had stigmas against mental illness, but hopefully that is starting to change. If someone has diabetes, we realize it is due (simplistically) to a lack of natural insulin, so we treat them accordingly and we don't ostracize them because of their condition or treatment. If someone is hypothyroid, we realize that there is a defect in the thyroid hormone system and we treat them accordingly, without batting an eye. But for too long if someone has had a chemical unbalance that causes their mood to be altered, we put it in a different category than the previous two conditions. Mental illness is no different from the previous two. It's a physiological condition that can be treated and should be. Yes, the symptoms are psychological, but that doesn't mean it is any less of a disease or the person suffering from them are any less of a person. (end rant)
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Brain chemistry is not as well understood as body chemistry. The brain is plastic, it developes differently (synaptic connections) with every individual. if you compare science of the body related to science of the brain, we are still in the 1800's with psychopharmacology. I do agree however that there are always exceptions with depression and antidepressents should be administered to correctly diagnosed cases and patients to be monitored frequently.
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Upregulation of transporters is a slow process. It doesn't happen after acute exposure and even through chronic exposure is a slow process. Downregulation, in it's various forms, is much quicker as no new transmembrane proteins need to be assembled, just sequestered, destroyed or not produced. A neurotransmitter has its affect by receptor contacts per time on a postsynaptic membrane. The reason SSRIs and MDMA have their effect is because they increase the time portion of that equation. You have less receptors that can be activated, but you leave serotonin in the cleft for a longer period of time so you get more of an affect. Even with the SERT channels being blocked, biologic amines are still degraded and don't last indefinitely. It's not like we're going from serotonin being active from nanoseconds to days, we're going from nanoseconds to a few more nanoseconds. That is not enough time for upregulation of receptors, only for an increase in effect in postsynaptic neurons.
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Ill take your word for this, you seem to be well versed in this subject  But upregulation of receptors does occur! thats why people get those seizures or shocks when they have too many receptors and too little NT's. IF the body has too many NTS floating around, it will naturally create more receptors to deal with the excess over time. I may need to pull out a reference for this at some point if you disagree.
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Sure, withdraw symptoms can occur, usually in two forms. First, prior to the medicine you did have a natural chemical imbalance and coming off the medication returns you to this natural imbalance, leading to a return to depression. SSRIs are not a "cure" they're a treatment. They don't fix your natural "machinery" they simply alter how it works so it functions closer to normal. As soon as you stop taking it you return to how you were before taking the medication.
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Or worse... So whats the point of antidepressents not taken chronically? Perhaps just to deal with certain episodes that occur in your life.
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Second, you could have not had a problem before hand, so taking an SSRI, or MDMA in continuous doses, led to a downregulation of serotonin receptors, so that once you're off of the drug, your naturally made serotonin doesn't have the same affect as the large amounts of serotonin you had in your synaptic clefts while on the drug. Thus, you have rebound depression. Luckily, and unlike those with true serotonin defects, your transporters will return to normal and the symptoms will subside over time.
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not true here. you've over simplified the senario. Withdrawal effects could be so severe to lead to extreme manic episodes, anxiety attacks and even crazier psychological disorders. The brain is plastic and will adapt to antidepresent administration. By the time things may appear to be physiologically normal, the behavioral psychology maybe extremely off!
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DSM-IV is the best way we have to differentiating healthy from non-healthy. However, since we're dealing with subjective responses, and since depression itself is subjective, we'll always have some doubts when diagnosing depression. Monitoring someone on an antidepressive medication is extremely important and is done by all good physicians but it is also a big responsibility of the patient as well. There is no magic formula when it comes to SSRIs or any antipsychotic for that matter as far as dosage goes. Physiologies and tolerances are different so each patient has to have a tailor made drug regimen.
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The new version should be comming out soon. Its pretty outdated now i think that there are second generation antidepresents. I totally agree with monitoring, but its not being done enough. Totally agree with everything you said here.
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Downregulation occurs whenever there is overstimulation of receptors, and SSRIs can very well lead to this. It makes no difference where the receptor is located.
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gotcha
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No, the "trick" to antidepressants or any other drug is to use them to alleviate initial symptoms with as little side effect as possible. Severely depressed people aren't concerned with the possible effects of coming off a medication, they're worried about ending their daily fight with depression using a medication that causes as few ill-effects as possible. Going back to my first diatribe, a Type I diabetic isn't concerned with the withdraw effects of stopping insulin treatment, merely that the insulin works to control their diabetes. Someone with hypothyroid isn't concerned with what will happen when they stop taking synthroid, merely that their symptoms are controlled. In the same light, a clinically depressed patient only cares that their depression is relieved. Using your logic, I guess you're going to argue that the makers of artificial insulin or thyroid hormone are equally ruthless since their users are also "hooked for life?"
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The body is different then the brain. neural pathways are different for each individual. The brain is more complex then the body hence we are still very in the dark with alot of its workings. We still don't know exactly how ssris work with respect to other NTS and you have to realise that there are soo many seratonin receptors (probably up to 35 5HT's right now). Hard to compare but I agree SSRIs may be crucial in some instances. Hopefully the future leads to higher specificity and less side effects for the medications.
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Sure, there probably will be some negative side effects, with a decrease in libido being one. However, you as a patient have to ask yourself is a decrease in sex drive worth the alleviation of chronic depression? It's up to the patient to decide. I've never seen someone "forced" to take an antidepressive.
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agreed
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I'll agree that everyone is different and every drug behaves differently, but I won't agree that just because MDMA has multiple effects it is "better" than traditional SSRIs at treating depression.
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im not saying its better. im just saying that its more potent in relation to ssri's and shouldn't be considered soo bad in comparison.
Pretty much we have a concensus. I am in no means against antidepressents, just the politics behind diagnosis and administration.
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