Pramipexole
in treatment-resistant bipolar
depression
Patients
with bipolar disorder runs a high risk of major
depressive episodes. It is not clear that
current antidepressants add significant benefit
to the therapeutic action of mood stabilizers
and there is concern that they may induce mania
and enhance cycle rhythm. Various studies have
suggested that dopamine may be involved in the
pathophysiology of depression and that some
antidepressants could be efficacious, because
they boost dopamine neurotransmission. The
dopaminergic D2/D3 receptor agonist,
pramipexole, has an efficacy similar to that of
fluoxetine in patients with major depression. A
recent study evaluated the antidepressant action
and safety of pramipexole in patients with
treatment-resistant bipolar depression.
Twenty two depressed outpatients with DSM-IV
non-psychotic bipolar disorder, whose current
episode had not responded to at least 2
treatments with standard antidepressants with
concomitant mood stabilizers were recruited to
participate in a randomized, placebo-controlled
trial. Patients were assigned to receive
pramipexole at a flexible dose (maximum dose of
1.7 mg/day) or placebo in addition to their
existing mood stabilizer therapy for 6
weeks.
Ten of 12 (83%) patients treated with
pramipexole completed the study compared to only
6 of 10 (60%) control patients. Eight of 12
(67%) pramipexole-treated patients whereas only
2 of 10 (20%) subjects receiving placebo had a
50% or greater improvement in their HDRS score.
The reduction from baseline of the HDRS score
was greaterfor the pramipexole group (48%) than
for the control group (21%). Greater
improvements in CGI were also observed with
pramipexole than placebo. One patient who had an
episode of mania during the pramipexole therapy
and discontinued. No other patient discontinued
the trial because of adverse events.
These findings show that pramipexole, which
wasshown to be safe and well tolerated, was an
effective antidepressant in patients suffering
from treatment resistant bipolar depression.
Larger trials are necessary to support these
promising preliminary results. Goldberg
JF, Burdick KE, Endick CJ. Preliminary
randomized, double-blind, placebo-controlled
trial of pramipexole added to mood stabilizers
for treatment-resistant bipolar depression. Am J
Psychiatry 161: 564-566, 2004.