This is to our knowledge the first report describing the beneficial symptomatic effects of the novel antipsychotic drug aripiprazole on motor, psychiatric, and cognitive symptoms in three patients affected by HD. The mechanism through which aripiprazole acted to improve patients’ chorea remains elusive. Aripiprazole is a dopamine neurotransmitter stabilizer acting as a functional antagonist in hyperdopaminergic and, conversely, as a functional agonist in hypodopaminergic states.19
In our small cohort of patients, the drug may have controlled the involuntary movements related to HD by antagonizing striatal D2
In agreement with several reports,14
aripiprazole also protected our patients from extrapyramidal side effects, probably owing to its pharmacodynamic profile – ie, partial agonist on dopaminergic D2
and on serotoninergic 5HT1A
receptors and antagonist on the 5HT2A
receptors – reducing the antagonist load at the nigrostriatal pathway level.12
Notably, the improvement in apathy, anxiety, and depression could depend on aripiprazole’s action in modulating central serotoninergic pathways.23
Our report also underlines another advantage of aripiprazole. In the first patient we treated in this series, switching to aripiprazole resolved the possible olanzapine-induced metabolic dysfunction. In agreement with our findings, previous reports have suggested that the risk of metabolic dysfunction is reduced in patients treated with aripiprazole compared to other atypical neuroleptics.11
Efficacy on cognitive functions is heralded but further clinical evidence is needed.
Despite normal fluctuations in motor symptoms occurring in HD along the course of the disease, the benefits we obtained in these three patients over the 12 months follow-up may be considered an indicator of the efficacy of aripiprazole in HD. Further evidence clearly awaits confirmation from a larger study. Notwithstanding this caveat, considering aripiprazole’s known dopamine stabilizing properties, the beneficial symptomatic effects we report on both motor and behavioural manifestations suggest investigating whether this drug might benefit voluntary movements, other than chorea. If so, considering that in one of our patients it improved apathy, a behavioural disturbance severely affecting patients’ independence in mild-to-advanced HD stages, aripiprazole might be an interesting novel symptomatic option that could be combined with other drugs specifically acting on chorea, such as tetrabenazine.27
In conclusion, our case reports suggest that aripiprazole is well tolerated, remarkably improving some of the motor and behavioral symptoms in patients affected by HD. Randomized, controlled, long-term studies are warranted to further investigate the effectiveness of this atypical neuroleptic in the symptomatic treatment in patients with HD.