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Can a Low Dosage of Aripiprazole Modify Incentive Salience in Naive Bipolar Patients Who Gamble?

Carbone, Manuel G. MD*; Pagni, Giovanni MD*; Tagliarini, Claudia MD*; Maremmani, Icro MD, FISAM†,‡,§

Addictive Disorders & Their Treatment: September 2019 - Volume 18 - Issue 3 - p 134–139
doi: 10.1097/ADT.0000000000000163
Case Report

Gambling disorder is a pathologic condition, resulting from the interaction of multiple risk factors. Among these, dopamine neurotransmission is known for playing a significant role, as seen, for example, in patients using dopamine replacement therapy prescribed for Parkinson disease, in which gambling is considered to be iatrogenic. Considering this, together with the general mechanism of action of antipsychotic drugs, growing attention has recently been dedicated to Aripiprazole and to its partial dopaminergic agonism (reducing D2-receptor hyperactivation in the mesolimbic pathway and improving D2-receptor stimulation in the mesocortical and nigrostriatal pathway). In fact, Aripiprazole has been noticed in several cases to worsen preexisting pathologic gambling and also, in some cases, to precipitate pathologic gambling in those without preexisting pathologic gambling when used at therapeutic doses (10 to 15 mg). Mr F, a bipolar patient under treatment without either personal or family history of gambling, following a low-dose Aripiprazole administration, began displaying gambling behaviors, which immediately ceased after suspension of the drug. Subsequently, after the reintroduction of Aripiprazole, this time at standard dosage, the patient resumed additive behavior of gambling, which in this case also ceased at the time of suspension. It is possible to hypothesize that the dopaminergic agonist activity of low-dose Aripiprazole has influenced the physiological process of salience, leading the patient to give particular attention, through reward circuits, to a specific stimulus, otherwise not relevant. More difficult to explain, on the other hand, is how the standard dosage anti-D2 activity of Aripiprazole, has reactivated gambling behaviors again. According to our hypothesis, it is possible that the administration of standard dose of Aripiprazole has triggered a reward-deficiency syndrome, recalling the gratifying action of the recently experimented gambling to the patient’s memory, bringing him to the relapse.

*Department of Experimental and Clinical Medicine, School of Psychiatry

§Department of Specialty Medicine, Vincent P. Dole Dual Diagnosis Unit, 2nd Psychiatric Unit, Santa Chiara University Hospital, University of Pisa

G. De Lisio Institute of Behavioral Sciences, Pisa

Association for the Application of Neuroscientific Knowledge to Social Aims (AU-CNS), Pietrasanta, Lucca, Italy

I.M., served and/or currently serves as Board Member/Consultant for Indivior, Molteni, Mundipharma, D&A Pharma, CT Sanremo, Lundbeck, Gilead, Merck & Co, and Angelini. The remaining authors declare no conflict of interest.

Reprints: Manuel G. Carbone, MD, Department of Experimental and Clinical Medicine, School of Psychiatry, University of Pisa, Via Roma 67 56100, Pisa, Italy (e-mail:

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