Posted by SLS on June 10, 2000, at 9:39:52
In reply to Incomplete recovery gaining attention, posted by JohnL on June 10, 2000, at 5:40:44
> My pdoc is head of psychiatry at two different institutions. And he has pretty much phased out private practice. As a result he spends most of his time in conferences, meetings, consultations, research, and stuff like that.
Cool. Mine too.
> He acknowledged that antidepressants are indeed wonder meds. He says 80% of patients who try 2 different antidepressants will improve. But he says recent focus has been on the recognition that of those 80% who improve, a substantial proportion of them do not indeed recover to complete normalcy. Or normal baseline as he called it.
Unfortunately, combining drugs early in the course of therapeutic trials still seems to be underutilized. I become extremely frustrated and angered when I read a post here of someone whose doctor has decided to switch them from an SSRI to Wellbutrin when they have already failed to respond to several other drugs monotherapeutically.
> This is why I believe that there are multiple chemical imbalances that can cause depression, and that low serotonin is just one of them. Obviously if doctors focus on serotonin meds--as evidenced by the universal popularity of SSRIs--then a whole lot of other guilty chemistries are being ignored. And thus considerable--yet incomplete--recovery. Antidepressants as a class only address three of ten possible causes.
Three only? Ten only?
It is way more than that - on both accounts.
Perhaps low serotonin is never the cause.
Just because an effective antidepressant works its magic by inhibiting the reuptake of serotonin does not lead to the logical conclusion that it is low serotonin that is responsible for the depression in the first place.
> In my case for example I experienced substantial improvement on any serotonin antidepressant. Yet I was still left with this crippling anhedonia thing. I never recovered to baseline. As it turns out, the chemistry guilty with me was not low serotonin, NE, or dopamine, but rather malfunction of something in the NE/dopamine relationship. My robust response to Ritalin was the tip-off, as my pdoc phrased it. Or, as I call it, an important clue. All along antidepressants were merely masking the symptoms of depression, but not fixing the cause. Adrafinil ended up being the molecule that hit a bullseye and fixed the problem right at the heart of the source.
This is very possible. But it may have nothing to do with a NE/DA relationship. NE alpha-1 agonism may not contribute to either its antidepressant effect or its antinarcoleptic effect. The package insert of Provigil (modafinil) makes no mention of NE and declines to offer a mechanism of action. It describes the ability of it to bind to DA transporter in vitro, but this is probably irrelevant, as so many drugs do at clinically irrelevant high concentrations.
> Anyway, no real point here. Just wanted to share what we talked about in case anyone's interested.
I think all of your points are crucial ones. The tendency for many people to attain only a partial remission from using only one drug is something that has been recognized and addressed by competent psychiatrists for a long time. The NIMH is a good barometer of current putative clinical observations and therapeutic modalities. They tend to be objective and conservative, trying to maintain a consistent level of accuracy. Their research teams have pleaded their case for polypharmacy for many years. They work to discover what treatments work, without necessarily determining with surety the reasons why they work. Of course, one of their ultimate goals is the latter. There is little justification for deeming a partial improvement as being satisfactory. For most people, a nearly complete recovery is possible using the tools that are currently available.
As far as to what extent the underlying physiological perturbations underlying psychiatric disorders are understood, I think it is bit premature to explain them. I imagine that if the brilliant minds in research who are trying to get us all well were willing to express a determination of depression as to its causes, dynamics, and the mechanisms by which successful treatments produce their therapeutic effects, they would have told us by now.
Perhaps dopaminergic drugs make a good bandage to compensate for the underactivity of glutaminergic neurons afferent to the thalamus and hippocampus that have been downregulated due to their chronic overactivity in response to stress. This would allow for a perturbation of the balance between glutaminergic and GABAergic activity there in favor of efferent GABAergic neurons leading to the nucleus accumbens, whereby dopaminergic neurotransmission in this healthy structure is thus inhibited. What do you think? Perhaps adrafinil addresses this by promoting an increase in the neurotransmission of these thalamic and hippocampal glutaminergic neurons. Of course, it could be that modafinil activates cortical function simply by increasing the release of glutamate there. Where's DA, NE, or 5-HT?
I just like to express this sort of caveat every now and then.
- Scott
poster:SLS
thread:36813
URL: http://www.dr-bob.org/babble/20000610/msgs/36822.html