Posted by Jonathan on June 23, 2000, at 22:38:19
In reply to Re: Pramipexole (Mirapex) For Depression, posted by verac on June 23, 2000, at 12:26:00
> > > I would like to try the new drug Pramipexole for my depression, just a small amount to see if it might work for me. Can it be ordered from overseas pharmacies? Does anyone out there have a small, unused supply they'd like to get rid of?
> > > The same with Amisulpride (Solian), another D2/D3 drug. Any suggestions?
> >
> > I have been aggresively checking for Mirapex from an overseas pharmacy. No one seems to offer it (without a prescription). If they do, they aren't advertising it.
> > Bruce
>
> For your reference, Pramipexole is available just north of you here in Canada -called Mirapex. The data available however is only Parkinsons related with no reference whatsoever to depression. Has anyone any data at all on its use for major unipolar depression?
> Thanks very much, veracWow, this is _very_ interesting. I hope you get to try it, Bruce. Please let us know how you get on.
Below is the abstract of a recent paper which includes dosage details and a comparison with Prozac for major unipolar depression.
As a general rule with many exceptions, drugs for which the clinically effective daily dose is 100 mg/day are often best avoided unless there's no 'cleaner' alternative. Pramipexole, it seems, is no exception to this rule.
Another 'rule' of arguably dubious validity, which pramipexole could change, is: don't mess with dopamine (DA) until all other alternatives have failed, because DA has so many different actions and receptor subtypes. On the other hand, antidepressants which act on DA systems indirectly, via serotonergic and/or noradrenergic systems, are so slow.
What's interesting about pramipexole (and not clear from this abstract) is that at low doses it's an agonist at D2, D3 and (probably) D4 receptors, with the highest affinity for D3; this D3 selectivity is what makes it different from other DA receptor agonists that I've heard of.
If I remember correctly, some D2 receptors (but not all) are presynaptic and modulate synaptic dopamine levels, thus affecting all postsynaptic receptor types: the antidepressant amisulpride, a D2 antagonist (the opposite of pramipexole!) stimulates all postsynaptic DA receptors, including D3, indirectly by raising DA levels: pramipexole, however, lowers DA levels but stimulates D3 receptors directly and therefore more selectively.
I'd be grateful if anyone can add to and/or correct this; in particular, which DA receptor types are likely to be involved in which types of depression?
Jonathan.
Here's the abstract:
TI: Comparison of pramipexole, fluoxetine, and placebo in patients
with major depression
AU: Corrigan_MH, Denahan_AQ, Wright_CE, Ragual_RJ, Evens_DL
NA: PHARMACIA & UPJOHN INC,GLOBAL CLIN RES,MS 7278-NJ-260,95 CORP
DR,POB 6995,BRIDGEWATER,NJ,08807
PHARMACIA & UPJOHN INC,CNS DEV,KALAMAZOO,MI,49001
PHARMACIA & UPJOHN INC,CLIN BIOSTAT 2,KALAMAZOO,MI,49001
UNIV PENN HLTH SYST,DEPT PSYCHIAT,PHILADELPHIA,PA
JN: DEPRESSION AND ANXIETY, 2000, Vol.11, No.2, pp.58-65
IS: 1091-4269
DT: Article
AB: Pramipexole, a dopamine D-2 receptor agonist, was tested in 174
patients with major depression, with or without melancholia and
without psychotic features. Three daily dose bevels (0.375 mg,
1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20
mg and placebo in a randomized, double-blind, parallel-group
study. After a 1 week placebo ran-in period patients were
treated for 8 weeks, had a post-study follow-up (week 9), and
were evaluated primarily with the Hamilton Psychiatric Rating
Scale for Depression (HAM-D), the Montgomery-Asberg Depression
Rating Scale (MADRS), and the Clinician's Global Impressions-
Severity of Illness scale (CGI-SI), All patients who received
one nose of study medication were included in the observed-case
analysis (no missing data were replaced), Results indicated
that by endpoint (week 8), patients receiving pramipexole at
the 1.0 mg per day dose had significant improvement over
baseline compared to the placebo group by measure of the HAM-D,
MADRS, and CGI-SI, Significant improvement in this nose group
was seen at other timepoints as well. The most obvious
improvement was seen in the pramipexole 5.0 mg group, although
a substantial dropout rate for this group precluded statistical
tests vs, placebo late in the study. Patients taking fluoxetine
also showed significant improvements at endpoints on the MADRS
and earlier in the study on the HAM-D, No new or unusual safety
concerns were generated during this study. Pramipexole helped
safely alleviate the symptoms of depression at 1.0 mg per day
and especially in those patients who could tolerate the
escalation to 5 mg per day, (C) 2000 Wiley-Liss, Inc.
poster:Jonathan
thread:11831
URL: http://www.dr-bob.org/babble/20000619/msgs/38223.html