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Re: Natural anticonvulsants? » desolationrower

Posted by SLS on February 24, 2009, at 6:48:00

In reply to Re: Natural anticonvulsants?, posted by desolationrower on February 23, 2009, at 23:11:10

> oh something else i'll throw out...most ADs are mildly epileptogenic...shouldn't withdrawl be anticonvulsive?

I hadn't thought of that. I don't know. The multitude of changes that occur after long-term exposure to these drugs would make it hard to determine which withdrawal effects dominate. Maybe the temporal lobes are protected while the amygdala is kindled.

I did find one interesting paper that reported SSRIs ameliorated alcohol withdrawal. This would make sense if the serotonergic pathways effected by these ADs are inhibitory upon glutamate neurons. Here, the SSRIs are acting more anticonvulsant than proconvulsant.

> i'm not up on epilepsy, are you thinking your kindling is analagous to epilepsy kindling or actually a subtype?

Yup.

You would know the dynamics better than I, but serotonin acts as an inhibitor of many glutamatergic pathways. My guess is the sudden drop in synaptic serotonin as a result of removing an SRI disinhibits these glutamate pathways and allows them to become hyperexcitable and leading to kindling. I think the kindling allows for the withdrawal severity to grow more intense over time, prevents some people from discontinuing entirely, and allows for a persistence of withdrawal symptoms long after the drug is discontinued. I also have a hunch that future withdrawal episodes from discontinuing successive SRIs produces more severe withdrawal syndromes.

- Scott


*******************************************

1: Alcohol Alcohol. 2008 Jan-Feb;43(1):15-24. Epub 2007 Oct 12.Click here to read Links
Serotonergic anti-depressants and ethanol withdrawal syndrome: a review.
Uzbay IT.

Gulhane Military Medical Academy, Faculty of Medicine, Department of Medical Pharmacology, Psychopharmacology Research Unit, Etlik 06018 Ankara, Turkey. tuzbay@gata.edu.tr

AIM: To review laboratory findings on the effects of anti-depressant agents that interact with the serotonergic system on signs of ethanol withdrawal syndrome in rats. METHOD: Adult Wistar rats received a modified liquid diet to produce ethanol dependence. Signs of ethanol withdrawal, locomotor hyperactivity, stereotyped behaviour, tremor, wet dog shakes, agitation, and audiogenic seizures, were evaluated for the first 6 h of ethanol withdrawal. The effects of the anti-depressants fluoxetine, venlafaxine, escitalopram, tianeptine, and extract of Hypericum perforatum (St. John's wort) (HPE) were examined. RESULTS: Some beneficial effects of fluoxetine, tianeptine, HPE, escitalopram and venlafaxine on ethanol withdrawal signs were observed, ranked as follows: fluoxetine = tianeptine > HPE > escitalopram > venlafaxine. CONCLUSIONS: Tianeptine and fluoxetine seem to be potent pharmacologically active agents on ethanol withdrawal syndrome in rats. Thus, these anti-depressants may be useful in treatment of ethanol withdrawal syndrome in patients with alcoholism. In addition to serotonergic effects, interactions with nitrergic, glutamatergic, and adenosinergic systems may also provide a significant contribution to the beneficial effects of these drugs on ethanol withdrawal syndrome.

PMID: 17934195 [PubMed - indexed for MEDLINE


 

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