Q: Dopamine Agonists & Feeling Flat
Dear Dr. Phelps,
I hope you can help me with some strange questions. I have been diagnosed
as biplar II, with rapid cycling (about a week long cycle). I currently
take 750mg of Depakote, which slows the cycling. When I cycle up, I feel
like I'm itching inside, and I'm agitated. When I cycle down, I feel
inside myself and blunted, and I have a difficult time communicating.
Fortunately, .25 mg Risperdal seems to help the agitation, and was helping me
sleep. It hasn't done much for the depression that I dip into two days a
This is the problem: I have no emotions anymore. I don't feel
pleasure or sadness. I just feel completely apathetic with little or no
emotional responses. I've been through many meds, most of which i couldn't
tolerate (Lithium, Lamictal, Zyprexa, Trileptal, Wellbutrin, etc.). I'm
curious about trying Mirapex or other dopamine agonists in the hope of regaining
my emotions. Have you found them to be effective in a case such as this?
What next for me? I'm alive, but not living. I don't care enough to
Thanks for any input,
Dear Katy --
Hmm, tricky. I guess first we'd have to try to establish whether your "no
emotions" is your experience relative to where you used to live, which
was probably a great deal of emotion, not always good, but surely more intense
than where you live now; and whether your current experience is actually closer
to where people without bipolar disorder live -- or less than that, which sounds
like what you think is going on now (and may well be, I don't mean to say that's
not so, just that one would want to make sure first, before trying to "fix"
something like this, especially with things like dopamine agonists.
Next, you'd want to establish (I'm sure you've tried to
figure this out) whether it is primarily Depakote or risperidone that is doing
this, e.g. was this problem present even before the risperidone was added or
only afterward. Based on that you could wonder whether moving risperidone up,
e.g. to 1 or so, might have a little more antidepressant oomph, as it often
seems to; and whether you might even be able to taper off Depakote then, if that
was the primary suspect for the "no-emotion" problem.
If on the other hand risperidone was the primary
suspect, you could consider turning the Depakote up, though you may well already
have done that and discovered that some side effect limits that approach (after
all, you are still cycling, right? so you need more mood stabilizer influence
from somewhere, right? risperidone has not been really clearly shown to be able
to prevent cycling, though it can treat manic symptoms and also seems to
have this mild antidepressant effect in some folks). If you haven't tried going
higher with Depakote using their newer ER version, that's probably worth
a try; it really is quite a bit better, especially in terms of avoiding weight
gain through avoiding appetite increase.
Then, one could consider the new kid on the block,
aripiprazole (I am trying to refuse to dignify their trade name by repeating it
here). As you may know, it has dopamine agonist properties as well as dopamine
blocking properties (nifty trick), and there appear to be some people with
bipolar disorder out there who do really well on it, including at tiny doses (a
colleague of mine starts people at 1/2 the smallest pill they now make, 5 mg,
which is a 6th of the original starting dose, and goes up by that increment from
there). I haven't used it much yet but I definitely am hearing of occasional
superb outcomes. This medication comes to mind in part because of your having
wondered aloud about dopamine agonists, and in part because you have tried a lot
of other medications.
However, I didn't see a few other candidates on your
list (perhaps they were in the "etc"), such as Seroquel, which recently was
shown to have substantial antidepressant effects as well as more "Depakote-like"
effects, if you will; i.e. I would wonder if it too might represent a medication
which could be substituted for both of your current medications.
In general I'd try to keep the focus on stopping
cycling, and then, after that had been accomplished somehow, evaluating
whether this left you "too flat" in terms of mood capacity. Rarely I've had to
try adding a stimulant to get around this kind of problem. Something like
Ritalin (methylphenidate) would be more routine, and some folks have been using
modafinil (Provigil) in this role lately with some case reports of benefit.
As you may know, there are several studies of Mirapex (pramipexole)
for bipolar depression (check them out, especially the first three you'll
find if you do a
MED search using the terms "pramipexole bipolar".) Note that in two of
these studies, at least one of the small group of patients involved became
hypomanic (although so did two patients on placebo!). This is one of the common
risks of antidepressants, as you know. So from the data so far, it looks as
though adding pramipexole is rather like adding an antidepressant. And most
psychiatrists would agree that one should avoid adding an antidepressant when a
patient is cycling, as you now are. So again, I'd look to stop the
cycling first, then address the flatness part; if you do it the other way
around, you run the risk of continuing the cycling or making it require more
mood stabilizer to treat. (While you're on PUB MED, check out "modafinil
bipolar" also; less data thus far, but perhaps less risk of inducing
Finally, though I'm one of the only ones who seems to
worry about this, I'd be nervous about the possibility of somehow worsening the
bipolar disorder itself using pramipexole, though this is merely an extension of
my worry about doing the same thing using regular old antidepressants, as
discussed (see #2A) in the essay about
I hope you have good luck in your attempts to figure
this out (with your doctor, of course).
Published January, 2005