Posted by SLS on October 1, 2006, at 11:00:19
In reply to Re: SSRI dopamine issues. » fca, posted by ace on September 30, 2006, at 22:42:21
This is about as good as it gets. This looks like a great literature review. (Please see below).
I'll let this one sit for awhile until I can collect my energies. Obviously, the SSRIs are driving the dopaminergic pathways indirectly towards producing EPS (extrapyramidal symptoms). This might not be a problem if once removed the EPS stops. This is a different situation entirely from the direct action of neuroleptic antipsychotics on the dopaminergic neurons. Unfortunately, the reversibility of these EPS could not be assessed in the study.
I would like to know in how many different ways prodromal serotonin syndrome can present. I was once given trazodone, a weak to moderate serotonin reuptake inhibitor, while taking clorgyline, a potent MAO-A inhibitor. I could not get my legs to move in order to walk. They would not go when given the usual command. It sure looked like a dystonic reaction. However, if I pretended that I was performing an exercise on a Nautilus machine, I could produce the movements necessary to walk. This was not a dopaminergic dystonia. This was determined at the NIH to be a serotonergic reaction. So, I wonder how many of these reports of EPS are actually manifestations of serotonin syndrome.
Excess serotonergic activity often begins near the head and moves downward. It is no wonder that some of the reports were of "tardive dyskinesia". As you or I would experience bruxism, some of these people probably experienced dystonic movements of the neck and jaw and cheek. If these people had true TD, the cases would have been reported as being persistent after drug discontinuation. No such comments were made in the abstract. I think it is possible that much of the dystonia and parkinsonian symptoms were actually serotonin syndrome reactions. Serotonin syndrome is very variable in its presentation.
That an SSRI can make Parkinsons worse does not mean that an SSRI can cause Parkinsons. Again, the application of an SSRI produces changes that indirectly affect the dopaminergic pathways that have deteriorated due to the disease process. That is about all that can be concluded. In a healthy brain, does applying this same change along the same pathways induce the irreversible disease processes of Parkinsons? That is too large a leap to make as far as I'm concerned. If you have an open sore on your right arm and I apply firm pressure with my index finger, you will recoil in pain. If I apply the same pressure to your other healthy arm, there is no harm done and no pain is experienced.
I have to believe that many of the reports of EPS are genuine EPS. The incidence is very low, though. I also share your concern about the possible effects of long-term administration of the SSRIs. One must remember, though, that the TCAs and MAOIs have been out for over 40 years, and many people have been on them for decades. They too, have been known to produce EPS reports (Please see below), although the more recent reporting for the SSRIs have produced greater numbers. TCAs and MAOIs can therefore be added to the SSRIs in the category of potential offenders. After 40 years, I don't know that they have demonstrated the induction of Parkinsons, or any other movement disorders. One would think that some associations and reports would have surfaced by now.
Yes, the SSRIs look suspicious.
I would just offer that
1) many of the cases of dystonia reported as EPS might have been serotonin syndrome and
2) that driving activity of dopaminergic pathways in the wrong direction indirectly with an SSRI such that it exacerbates Parkinsons is not the same as inducing the neurodegenerative disease process in a healthy person.
- Scott
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=Display&DB=pubmed
J Clin Psychiatry. 1996 Oct;57(10):449-54. Related Articles, LinksComment in:
* J Clin Psychiatry. 1997 Sep;58(9):403-4.
* J Clin Psychiatry. 1998 Mar;59(3):133.
Movement disorders associated with the serotonin selective reuptake inhibitors.Leo RJ.
Department of Psychiatry, School of Medicine, State University of New York at Buffalo 14215, USA.
BACKGROUND: To review the case reports and case series of movement disorders ascribed to the use of serotonin selective reuptake inhibitors (SSRIs). METHOD: Reports of SSRI-induced extrapyramidal symptoms (EPS) in the literature were located using a MEDLINE search and review of bibliographies. RESULTS: Among the 71 cases of SSRI-induced EPS reported in the literature, the most common side effect was akathisia (45.1%), followed by dystonia (28.2%), parkinsonism (14.1%), and tardive dyskinesia-like states (11.3%). Among patients with Parkinson's disease treated with SSRIs, there were 16 cases of worsening parkinsonism. Patients who developed dystonia, parkinsonism, or tardive dyskinesia were older on average than patients with akathisia; 67.6% of affected patients were females. Fluoxetine, the most commonly prescribed SSRI to date, was implicated in 53 (74.6%) of cases of SSRI-induced EPS. Several reports (57.7%) were confounded by the concomitant use of other medications that can contribute to the development of EPS. CONCLUSION: SSRI-induced EPS are probably related to agonism of serotonergic input to dopaminergic pathways within the CNS. Several patient-dependent and pharmacokinetic variables may determine the likelihood that EPS will emerge. Although these side effects are infrequent, clinicians should be alert to the possibility of their occurrence.
Publication Types:
* Review
PMID: 8909330 [PubMed - indexed for MEDLINE]
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9315989&query_hl=18&itool=pubmed_docsum
J Clin Psychopharmacol. 1997 Oct;17(5):377-89. Related Articles, Links
Click here to read
Extrapyramidal symptoms associated with cyclic antidepressant treatment: a review of the literature and consolidating hypotheses.
Gill HS, DeVane CL, Risch SC.
Department of Psychiatry, Medical University of South Carolina, Charleston 29425-0742, USA.
Extrapyramidal symptoms (EPS) including parkinsonism, akathisia, dystonia, and tardive dyskinesia have commonly been associated with acute or chronic administration of neuroleptic drugs. A review of the medical literature reveals a substantial number of cases with similar clinical characteristics associated with the tricyclic antidepressants, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). Although the data are not sufficient to make definitive pharmacoepidemiologic conclusions, the available number of case reports suggests the SSRIs may be more common offenders in producing these adverse drug effects. The exact mechanism is elusive but likely involves complex interactions of dopamine, serotonin, and norepinephrine between cortical structures and the basal ganglia. The final common pathway for production of EPS seems to be indirect modulation of dopaminergic function. Predictors of patients at risk for antidepressant-induced EPS are not established, but a greater awareness of the potential for these drug side effects to occur may increase their recognition and decrease antidepressant-induced morbidity.
Publication Types:
* Review
PMID: 9315989 [PubMed - indexed for MEDLINE]
poster:SLS
thread:690091
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