This drug has come up before on M&M, but some recent studies have considerably added to the amount of data available on the drug.
First of all, pramipexole is a non-ergoline dopamine D2/D3 agonist. It does not have the heart valve damage issues that its cousins cabergoline (Dostinex) and bromocriptine have. It also displays, somewhat interestingly, a higher affinity for D3 than D2, in contrast to bromocriptine (almost purely D2) and cabergoline (mixed D1/D2). It's Rx (non-scheduled) in the U.S., and studies are appearing about the drug at an impressive rate.
From personal experience, it has remarkable libido- and erection-improving capabilities and may indeed have some antidepressant properties, though I'm still testing the drug myself.
At any rate, the following make for some very interesting reading.
Major Depression In (PMID 10812530), (PMID 12479663), (PMID 15219473), and (PMID 14992985) pramipexole was tested as a lone antidepressant (first study), as an adjunct to an antidepressant (second study), or as an adjunct to a mood stabilizer (third and fourth studies). In all four, it showed considerable efficacy in major depression or bipolar depression. The first is probably most interesting, as it showed (relatively) high-dose pramipexole alone may be as effective as fluoxetine in the treatment of MDD.
Synergy With SSRIs In (PMID 16963794), data suggests that not only is pramipexole effective as an antidepressant, but it may actually synergize with SSRIs (at least setraline and fluoxetine) in a fairly interesting way. (See the study for details.)
Mechanism The study (PMID 18688211), though in rats, is probably the most interesting I've found. I'm going to simply quote the last portion of the abstract:
<div class='quotetop'>QUOTE </div><div class='quotemain'>After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%. It was also observed that sustained PPX administration produced desensitization of D(2)/D(3) and 5-HT(1A) cell body autoreceptors, as well as a decrease in sensitivity of alpha(2)-adrenergic cell body autoreceptors. These adaptive changes are implicated in long-term firing rate adaptations of DA, NE and 5-HT neurons after prolonged PPX administration. In conclusion, the therapeutic action of PPX in depression might be attributed to increased DA and 5-HT neurotransmission.</div>
In short, though pramipexole is a D2/D3 agonist, it rather dramatically increased the firing rate of 5-HT neurons and desensitized 5-HT(1A) and D2/D3 autoreceptors. The implication is that it should, with chronic use, improve D2 and 5-HT1A sensitivity and increase 5-HT neurotransmission. As all three of these factors have been implicated in major depression (among other psychiatric disorders), this seems absolutely enormous. And note that this study is from 2009, so it's implications have not yet filtered out.
This is pretty cool stuff. If it pans out, antidepressant sexual side effects may mean something very different a few years down the line...
EDIT: One last rather important detail. If you read the drug's entry on rxlist.com, it does not have many serious side effects, especially when the dose is titrated appropriately. (If you're going to try the drug, you really have to start at 0.25-0.5mg 2x/day and move up from there.) From personal experience, I got a little orthostatic hypotension, a little fatigue, and a little nausea at the start, but with continued treatment they went away. The last study in mice supports this - NE function declines initially, but recovers with chronic treatment. Fucking awesome.