Posted by SLS on February 9, 2006, at 8:56:50
In reply to Psychomotor Speed Prozac Responsiveness, posted by Iansf on February 8, 2006, at 19:45:30
This was a good study.
Personally, I fit the criteria of this proposed Prozac non-responder profile for depression. I had thought to return to Prozac and push the dosage to 60mg or higher. 20mg did not help at all. Now, I'm not so sure it is worth it. I began looking into dopaminergic drugs in 1983 because the predominant features of my depression were so retarded. This was back in the days when serotonin was a new word in psychiatrists' vocabulary and norepinephrine remained the focus of attention. I've been a dopamine pusher for over twenty years, long before the formation of Internet web forums. It was a novel idea at the time that my doctors were not not at ease to listen to coming from me. Discounting dopaminergic dysregulation seemed almost arbitrary to me. Perhaps it was not a popular idea because dopamine had already been assigned the role of culprit in schizophrenia. I was elated when I first found someone who agreed with my surmisals, a guy at the University of Chicago named Randrup. He was pretty much alone in expounding his ideas. I was certainly alone with mine in describing them to my doctors at Columbia Presbyterian in 1983. They refused to let me try the two drugs I suggested - bupropion and bromocriptine. It was a big joke to them at the time.
Of course, we now know that bupropion is not the potent dopamine reuptake inhibitor it was first thought to be. How it works still defies explanation. As a matter of fact, the workings of all antidpressants defy explanation at this point in human history.
There are really only two dopaminergic antidepressants around, and they are no longer around. That is to say, they are no longer being manufactured for human dispensation. Nomifensine and amineptine are powerful dopamine reuptake inhibitors. Of the two, I tried nomifensine while it was being sold as Merital in 1985. I experienced a robust response to it, but it appeared to be no better than the tricyclics I had tried. I remained improved for less than a week. I never got my hands on amineptine. I am very curious to know how I would have fared on it. It is noteworthy that nomifensine, like the tricyclics, is also a potent reuptake inhibitor of norepinephrine, and it is possible that it was through this mechanism that I gleaned a brief improvement of depression. Nomifensine is a good drug for retarded depressives nonetheless, and might still have a place on the shelves at our pharmacies if the manufacturer had not deemed the drug too dangerous for producing a potentially fatal condition known as hemolytic anemia. Its occurrence was rare. It is always difficult to judge such matters, but nomifensine was a very clean drug otherwise, cleaner than the tricyclics, and produced minimal side effects. I wish it could have served as at least a prototypic drug for more of its kind to be developed. We could probably use some powerful non-tricyclic mixed catecholaminergic drugs. But alas, the feverish and exclusive focus on serotonin reuptake inhibition had already begun.
Since then, my position on the roles of specific neurotransmitters in the etiology of affective disorders has become more moderate. I appreciate the complexity of the human brain and contest the simple-mindedness of many of the ideas that have been proposed to explain it. Dopaminergic drugs have helped me, but only briefly. Bromocriptine brings me a few days of relief from depression; amphetamine, a few hours to a few days. I think the least that can be said for dopaminergic pathways is that they might represent a secondary or tertiary site of dysregulation; a result of the primary pathologies located upstream or within a feedback loop.
Regardless of whether or not dopaminergic malfunction plays a role in producing the retarded symptomology of Prozac non-response, it is very useful that empirical studies such as this one be looked at carefully. My guess is that the association they observed between symptoms and responsivity is valid, and can help guide the clinician in making his initial choices of treatment. I would like to see the work done in this study replicated so that its validity can be confirmed. It would then be informative, I believe, for the non-responders to be placed on alternate medications to discover empirically which ones have a better than average chance of working for people with the retarded symptom profile.
- Scott
poster:SLS
thread:607677
URL: http://www.dr-bob.org/babble/20060205/msgs/607900.html