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Re: Thoughts, Inositol...

Posted by Adam on December 13, 1999, at 13:09:51

In reply to Thoughts, posted by Zeke on December 13, 1999, at 9:49:10

Hey, Zeke,

> The one obvious thing to me is that you're in a study and your OCD is flaring up. Is this a drug study?

I am in a drug study for transdermal selegiline. There was a double-blind portion of the study, followed by an open-label portion
with all subjects getting the active agent. I am currently in that phase of the study, and have been for about 2 1/2 months.

> I think that even if you're on a high dose of selegiline and thus non-selective MAO inhibition, that augmenting other 5-HT active meds should be a RELATIVE contraindication, not an absolute one. Cautious addition of such a drug should at least be considered.

That may be true, and what I have read in the literature indicates actual cases of serotonin syndrome from such a combo. are quite
rare. However, I'm not sure if my doctors would suggest it, and though I would be willing to try it under close supervision, I'm
sure all parties would be happier with a safer solution.

> On the other hand, there's another path that will likewise drive your psychiatrists nuts. In place of Eldepryl, tramadol(Ultram) might be considered as it has efficacy in OCD and possibly affective disorders. The catch is that it acts on the mu-opioid system as well as 5HT. It is a analgesic by indication but isn't a controlled substance. You might look over at Dr. Bob's psychopharm tips for more about it. One issue is that it may (or may not) produce tolerance in re OCD. To move further down this path, if Eldepryl helps but you face these roadblocks, what about an amphetamine? This should improve mood and possibly OCD symptoms, and would be reasonable if Eldepryl -- an amphetamine congener -- helped.

I have read about tramadol and its effects on the serotonin system. It seems it is an SRI, though many publications also refer to its
ability to induce 5-HT release. It apparently can cause rapid remission of OCD. I've thought about it, but I've done so well on
selegiline as an antidepressant I'm reluctant to switch, or at least, I'm reluctant to give up on an MAOI. As for amphetamines, the
role of dopamine in OCD is obviously complex. There is mounting evidence that genetic polymorphisms of the dopamine D4 receptor are
associated with risk of OCD in individuals with tics, though I've not seen any functional explanations. There is also evidence that
dopamine receptor antagonists are helpful to those with OCD and tics or a family history of tics. There is one paper I am aware of
showing efficacy of d-amphetamine for OCD. However, it generally appears that pscychostimulants and dopamine receptor agonists can
aggravate OCD or induce OCD-like symptoms in animal models. This is of obvious concern to me. The major metabolite of l-deprenyl is
l-methamphetamine, which is in turn metabolised to l-amphetamine. These weakly induce dopamine release, and there is additional
evidence that selegiline (or a metabolite) has other effects on dopamine not related to MAO-inhibition, perhaps as a dopamine re-uptake
blocker. My guess is that while these properties make selegiline a great antidepressant and contribure to its lack of adverse
sexual effects, it might not be the greatest drug for OCD. I have to weigh that against the profound effects it has had on depression
for me.

> I'm not well versed on the inositol issue. However, if it precipitates insulin release, that's a good reason to suppose it will increase central 5HT by virtue of increased tryptophan levels in the brain. That by virtue of decreasing competing amino acids for entry.

I hadn't heard that inositol precipitates insulin release, but rather was involved with mediating insulin-receptor-driven metabolic
processes, in much the same way it mediates signalling from other receptors (ultimate production of the second messenger inositol-
triphosphate). I also was unaware of this insulin-tryptophan connection. Whatever the means inositol might potentiate insulin
signalling, I suppose this could be another beneficial property. I'll read up on that. Maybe this has something to do with the
carbohydrate/serotonin connection I keep hearing about (where hyperphagia and carbo. cravings as a symptom of depression are tantamount
to seeking a serotonin fix).






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