Posted by Cam W. on January 4, 2001, at 17:13:06
In reply to Cam...what say you., posted by stjames on January 4, 2001, at 16:09:31
James, buddy - I thought you might drag me into this one ;^)
You know that I totally back the 8 week rule. Man, if I could maintain the "start-up" side effects of Wellbutrin past the first couple of weeks, I'd be a happy man.
Unfortunately, all antidepressants have "start-up" side effects. This is because of the neurochemical changes that have occurred due to the breakdown of the body's stress defence system (in particular, but not exclusively, the HPA axis).
A breakdown of the HPA axis (hypothalamus-pituitary-adrenal axis) results in the symptoms we call depression. At the same time, the body is producing less serotonin (let's stick to this one subtype of depression for simplicity sake) as evinced by low levels of serotonin's metabolite in the CSF (cerebral spinal fluid - spinal taps = ouch; but a fairly funny mockumentary; not as good as Hardcore Logo, though....but I digress). Other neurotransmitters try to compensate for this lack of serotonin by altering their concentrations and the number of their receptors (the number of serotonin receptors also change). These other neurotransmitters (eg dopamine, norepinephrine, nitric oxide, glutamate, etc.) do not totally compensate for the lack of serotonin and the symptoms that we associate with depression are the result of this lack of compensation.
Now, when one starts taking a serotonergic antidepressant (SSRI - remember, for simplicity sake, we are talking about a subtype of depression that responds to a serotonergic antidepressant) the amount of serotonin in the brain (between nerve cells) increases. This causes a chain reaction of events to occur. Beta-receptors are downregulated; postsynaptic serotonin receptors are changed; amounts of different neurotransmitters begin to return to normal, etc. These changes take time to occur, as the body readjusts to a more "normal" complement of serotonin. In the meantime, the serotonin added to the system acts like excess serotonin, due to the compensatory changes of the other neurotransmitter systems, as well as changes to the complement of various serotonin receptors. The start-up side effects are caused by serotonin being added to a compensated (depressed) system (kinda like throwing gasoline on a fire - throw enough on and the fire goes out - I know it's a bad analogy, but I hope you get the picture). As time passes (2 to 8 weeks), the neurotransmitter systems readjust to pre-depressive levels and hopefully the depression has resolved. Then you need to stay on the antidepressant for another 9 months to retrain the body to work at this "normal" level, again.
The variation in time periods for these events to occur depends on how fast one's body can make these changes to the neurotransmitter systems. Everyone's neurochemistry is different, some being much slower than others. Therefore, it is unwise to give up too soon on an antidepressant. Research has shown that, if after 8 weeks, there is no noticeable improvement, perhaps a different class of antidepressants should be tried (in our example, a trial of a noradrenergic antidepressant or a dual action antidepressant may be in order). If there is partial response to an antidepressant by 8 weeks, augementation should be considered before changing classes (eg lithium, raising the dose, lowering the dose, etc.).
Full effect of an antidepressant, depending on one's body chemistry can take a long time. I believe that everyone taking an antidepressant will have ongoing improvement past the point of what is considered response, or even remission. Where this improvement stops is, at this point unknown (except that it is probably very individual in every person).
I will us an analogy from the treatment of tardive dyskinesia (TD). Treating TD with Clozaril can take from 6 months to a year to notice any substantial differences. I have seen Clozaril work in this manner. I encouraged the guy to keep taking the Clozaril after 5 months, but in my heart of hearts, I never expected it to work (if I was him I probably would have quit taking the med). Surprizingly, after 8 months the guy was riding his bicycle around town and you wouldn't know he has TD. At five months of Clozaril therapy he could even keep a hat on his head. The movements would only stop when he was in a deep sleep. I now have a much better appreciation for the body's biochemistry. It is absolutely facinating. So simple, yet so extremely complex. Let's not even start talking about second messenger systems and gene transcription.
I'm sorry, what was your question, again?
Start-up side effects do have both an upside (sedation in an agitated person) and a downside (nausea), but as the neurotransmitter systems adjust, these symptoms usually dissipate; but sometimes not completely. There are also longterm side effects that do not seem to resolve with time (lets pick on Paxil - insidious weight gain at 4-5 months and sexual dysfunction). If the drug is working to control depression, it is a shame to have to stop it due to longterm side effects. Most depressions (ie one's that are not chronic) will resolve, so one may have to put up with side effects for a year; at which point the body has retrained the neurotransmitter system to work at a certain level.
Also, during that year psychotherapy (which I also think is essential in "curing" a depression) can actually work because one is able to understand what the therapy is trying to do. Depression affects attention and cognition. In most cases, antidepressants are need to "put the floor under one's feet" (as was so aptly said by someone on this board) so that the depressed person is able to work with the therapist on what caused the depression in the first place.
That's enough for now. Sorry, I'm getting tired of typing. I hope this helps James - Cam
poster:Cam W.
thread:50902
URL: http://www.dr-bob.org/babble/20001231/msgs/50906.html