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Dysthymia/Treatment Resistant Depressions

Posted by JohnB. on April 8, 1999, at 23:24:43

There's very promising information on a drug/neurotransmitter approach to treating chronic long term/ intractable depressive illness. The dopaminergic system has long been suspected as a biochemical part of the affective disorder problem (either directly or indirectly) and more evidence mounts that that dopamine receptors play a critical role not just in terms of mood state but just as critically in the prolongation/inescapability of this illness as it relates to memory, specifically emotional memory. It seems that what we call chronic, recurrent, or dysthymic depression may just be the mysteriously caused and tormentingly intrusive omnipresence of negative/stress related emotional memories. Somehow, the sufferer's perceptive awareness, or consciousness, is quite literally unable to break away from this unbearable onslaught of exclusively aversive emotive memories; the learned helplessness paradigm seems to fit in critically with this hypothesis.
At any rate, interesting things are happening in studies of a relatively new European "anti-psychotic" called Amisulpride (SOLIAN) as it relates to chronic depressive illness, not psychosis. This unique drug selectively blocks two subtypes of dopamine receptors (D2 and D3) and almost exclusively acts in the mesolimbic brain, unlike most other anti-psychotic meds. Intruigingly, amisulpride only blocks pre-synaptically, which means that in small doses, it actually increases dopaminergic (2 & 3) neurotransmission; this selectivity is amazing enough, but what makes this medication so potentially meaningful for treatment resistant and chronic depressives is the fact that it seems to potentiate D2 and D3 transmission primarily at certain sites WITHIN ONLY THE LIMBIC SYSTEM, the "birthplace" of emotional (mood) states and crucially implicated in memory storage and retreival. Unnecessary stimulation of dopaminergic receptors elsewhere in the brain involving locomotion and general attention/arousal seem to be larely bypassed, eliminating sleep disturbances, anxiety exascerbations, the jitters, and scattered and/or hyperattentiveness. Also, the extrapyramidal side effects (atkinesias and dyskinesias) are practically nonexistent at these non-pschotic doses. My guess is that drugs directed specifically for neuroaction in the limbic structures (whether dopaminergic, noradrenergic, serotonergic, or whatever) are going to be the critical links toward the most effective treatments for the core dysfunctions causing affective illness. Never use the word cure, but keep your eyes this and like-acting meds to come.




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