Psycho-Babble Medication | about biological treatments | Framed
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Posted by Adam on December 9, 1999, at 1:09:25

As some of you may have read in my prior posts, I have contended with
with severe depression and comorbid OCD. I have tried a number of
serotinergic drugs (Anafranil, Zoloft, Effexor, Serzone, Celexa).
Anafranil was intolerable to me. Zoloft, Effexor, and Celexa all
seemed to help with obsessions somewhat, but did little or nothing
for depression and caused serious sexual dysfunction. While on serzone
I experienced a dramatic worsening of my condition and wound up in
the hospital. I'm not certain of the connection, but obviously
wasn't getting me what I wanted (I've wondered about it's
properties as a 5-HT2 antagonist related to this problem).

My only relief from depression has been selegiline, which has been a
lifesaver. Unfortunately, my OCD symptoms have been flaring up, and
this seems to be worsening. Behavioral therapy is helping, but an
effective way to augment selegiline with another drug would be nice.
Unfortunately, options appear to be few. While selegiline at low doses
is most-likely safe with SSRIs, I am taking it at a nonselective dose
for MAO, increasing the risk of serotonin syndrome with SSRI
coadministration, and likely ruling out such an approach. Other
drugs known to affect the serotonin system (litium, pindolol, bupirone)
that might be safely combined with selegiline have shown little or
no efficacy for OCD, either alone or in combination with other drugs.

An as-of-yet still mysterious connection between serotonin siganalling
and OCD had been clearly demonstrated. Recent work with agonistic
compounds specific for certain serotonin receptor subtypes have implicated
the 5-HT2C receptor in mediating the anti-obsessional effects of
increased serotonergic stimulation. Interestingly, 5-HTC receptors
specifically activate a distinct signal transduction pathway involving
phospholipase C (PLC). 5-HT2C activation leads to production of cyclic
GMP,a so-called "second messenger" molecule that activates PLC, which
in turn metabolises phosphotidyl inositol, a rare phospholipid in the
cell membrane. This releases inositol triphosphate, which in turn
mediates signalling via release of intracellular calcium stores.

It was also noted that administration of exogenous inositol (a sugar much
like glucose) leads to activation of PLC and intracellular signalling.
Recent studies have indicated that inositol is efficacious for some
psychiatric disorders, including OCD. Its efficacy in OCD is thought to
be related to its ability to trigger downstream events in the 5-HTC-
mediated signal-transduction cascade. This study (by Fux, et al., Am
J Psychiatry, 153:1219-1221, 1996) showed efficacy of inositol similar
to SSRIs, even in some patients who did not respond to SSRI or
Anafranil treatment.




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Psycho-Babble Medication | Framed

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