Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive pramipexole in bipolar depression : acute versus long-term data

Bipolar depression represents the most difficult-to-treat phase of bipolar disorder, mood-stabilizing compounds and second-generation antipsychotics being only partially effective, whereas the use of antidepressants is highly controversial because of risks of inefficacy, switching, rapid cycling, and increased suicidality. Among various augmentative pharmacological treatments, compounds with dopamine-enhancing activity have been shown to be variably beneficial in the treatment of bipolar depression with drug-resistance features. In particular, pramipexole - a dopamine D2/D3 receptor agonist - showed antidepressant properties in bipolar depressed patients in both randomized-controlled trials and open acute and follow-up reports. The present review aims to provide an updated perspective on the use of adjunctive pramipexole in bipolar depression, taking into account randomized-controlled trials, as well as open naturalistic studies, with a specific focus on the evaluation of acute versus long-term data in terms of effectiveness and tolerability. Despite methodological differences, short-term studies support the acute efficacy and tolerability/safety of adjunctive pramipexole, whereas open extended observations seem to confirm the effectiveness of the compound, with some additional concern in terms of safety and tolerability issues. Adjunctive pramipexole may be a valid option in both the acute and the long-term treatment of drug-resistant bipolar depression, with possible superior tolerability in the short term.