Pramipexole for the Treatment of Depression: Efficacy and Mechanisms

Dopaminergic mechanisms are a plausible treatment target for patients with clinical depression but are relatively underexplored in conventional antidepressant medications. There is continuing interest in the potential antidepressant effects of the dopamine receptor agonist, pramipexole, with data from both case series and controlled trials indicating that this agent may produce benefit for patients with difficult-to-treat depression. Pramipexole's therapeutic utility in depression is likely to be expressed through alterations in reward mechanisms which are strongly influenced by dopamine pathways and are known to function abnormally in depressed patients. Our work in healthy participants using brain imaging in conjunction with computational modelling suggests that repeated pramipexole facilitates reward learning by inhibiting value decay. This mechanism needs to be confirmed in larger clinical trials in depressed patients. Such studies will also allow assessment of whether baseline performance in reward learning in depression predicts therapeutic response to pramipexole treatment.