Low-Dose Adjunctive Aripiprazole in the Treatment of Bipolar Depression: Double-Blind Placebo-Controlled Pilot Study
Status:
Terminated
Trial end date:
2013-06-01
Target enrollment:
Participant gender:
Summary
Aripiprazole is a new antipsychotic agent which possesses unique capabilities compared to
other antipsychotic agents, especially because of its partial dopaminergic agonistic
activity. Moreover, like the other atypical agents, aripiprazole is an antagonist of the
5-HT2a receptor, and an agonist of the 5-HT1a receptor. These pharmacological properties
should enable this molecule to provide antidepressant potentiating capabilities based on what
has been observed with other compounds sharing similar pharmacological profiles.
Aripiprazole is now well recognized for its capacity to potentiate antidepressants in the
treatment of unipolar depression. However, two randomized controlled trials of aripiprazole
in the treatment of bipolar depression were negative. This surprising result may stem from
the fact that the doses of aripiprazole used in these studies were rather high (17.6 ± 8.3
mg/d in study 1 and 15.5 ± 7.5 mg/d in study 2) and could have contributed to inhibit
dopaminergic activity in key brain areas involved in the modulation of rewards, motivation
and concentration. Bipolar depression is indeed heavily loaded with general symptoms of
psychomotor retardation including poor concentration, low energy level, hypersomnolence, and
hyperphagia. All these functions are modulated by dopamine and strategies aimed at improving
dopaminergic function are used frequently to resolve residual symptoms of bipolar depression.
It is expected that aripiprazole used at a more adequate lower dose than in previous studies,
should be efficacious in the treatment of bipolar type I depression.