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Dr. Bob is Robert Hsiung, MD,
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Posted by Iansf on February 8, 2006, at 19:45:30
Psychomotor Speed May Predict Responsiveness to Fluoxetine
News Author: Laurie Barclay, MD
Jan. 27, 2006 — Testing psychomotor speed can determine responsiveness of patients with depression to fluoxetine, according to the results of a study reported in the January issue of the American Journal of Psychology.
"The potential benefits of discovering predictors for individual antidepressants are considerable because patients could be matched to a medication to which they are most likely to respond," write Bonnie P. Taylor, PhD, from the New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons in New York, and colleagues. "Because the first choice of treatment for the majority of depressed patients is a selective serotonin reuptake inhibitor (SSRI), it would also be useful to prospectively identify patients who are likely to be unresponsive to SSRI monotherapy because they could be given some alternative.... The authors hypothesized that since psychomotor slowing in depressed patients has been linked to reduced dopaminergic neurotransmission, patients with slowing would be unresponsive to fluoxetine, an SSRI."
After baseline neuropsychological testing, 37 outpatients with depression completed a 12-week trial of open-label fluoxetine.
Compared with the 25 patients who responded to fluoxetine, the 12 patients who did not respond had significantly poorer verbal fluency on the Controlled Oral Word Association Test FAS (COWAT FAS) and in color naming on the Stroop Color and Word Test. Compared with the responders, the nonresponders also tended to perform worse on the Stroop Color and Word Test reading subtest and on the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III) digit symbol subtest. Both groups had similar performance on tasks of executive functioning, attention, visuospatial functioning, and verbal intelligence, suggesting that differential treatment response was specific to psychomotor speed.
"Psychomotor slowing may identify a subgroup of depressed patients who have a dopaminergic deficit that is unresponsive to fluoxetine monotherapy and who should therefore receive an alternative treatment," the authors write.
Study limitations include open-label design with no placebo control group, lack of generalizability to SSRIs other than fluoxetine, and flexible-dose design possibly leading to an underestimation of the predictive value of psychomotor slowing.
"Prospectively identifying patients who are unlikely to respond to one of the most frequently prescribed antidepressants would guide physicians to initiate treatment with an alternative medication," the authors conclude. "This is critical because it can potentially reduce the time to symptom relief and increase treatment compliance. Furthermore, it can prevent the premature discontinuation of treatment that often results from feelings of hopelessness, helplessness, and frustration due to an ineffective therapeutic response."
Eli Lilly and Co, the maker of fluoxetine, supported this study.
Am J Psychol. 2006;163:73-78
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
Posted by linkadge on February 9, 2006, at 9:15:34
In reply to Re: Psychomotor Speed Prozac Responsiveness, posted by SLS on February 9, 2006, at 8:56:50
Its funny, the authors suggest an alternative treatment for those who don't respond to the prozac, but they don't seem to suggest what other treatment might be best.
Like SLS pointed out, we really do not have an abundance of alternative drugs. If you don't respond to an SSRI, all you really have is a SNRI or an NRI to try.
We do know that parkinsons and depression often go hand in hand.
I would personally like to see a ballanced serotonin/dopamine uptake inhibitor.
Linkadge
Posted by zeugma on February 9, 2006, at 18:52:13
In reply to Re: Psychomotor Speed Prozac Responsiveness, posted by linkadge on February 9, 2006, at 9:15:34
hi,
I'm making a very naive point, but Ritalin is a pretty clean dopamine reuptake inhibitor and could be combined with an SSRI easily.
I didn't find Ritalin antidepressant at all.
-z
Posted by linkadge on February 10, 2006, at 9:37:54
In reply to Re: Psychomotor Speed Prozac Responsiveness » linkadge, posted by zeugma on February 9, 2006, at 18:52:13
No, I didn't find ritalin an antidepressant either. By itself it made me kinof depressed. If I combined it with an SSRI, in the magnatude of 10mg CR once daily, it did augment SSRI's.
I think there is a critical ballance between serotonin and dopamine. Some doctors have noted that if 20mg of fluoxetine doesn't work, oftentimes *reducing* the dose helps (possably because it may restore that ballance)
Linkadge
Posted by theo on February 10, 2006, at 21:56:43
In reply to Re: Psychomotor Speed Prozac Responsiveness, posted by SLS on February 9, 2006, at 8:56:50
Hello Scott,
Are you still taking Abilify and/or Keppra?
This is the end of the thread.
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