Aripiprazole (ARI) is an atypical antipsychotic drug with D2 partial agonist properties, usually prescribed to treat mood disorders (major depression or bipolar disorder) and schizophrenic disorder (schizophrenia or schizoaffective disorder). Dopamine receptor agonists, as is ARI, have been implicated in some cases of impulse-control problems, such as gambling disorder (GD), increased spending, hypersexuality and compulsive eating.

Currently, it is hypothesized that aripiprazole may cause impulse-control problems because it can produce a hyperdopaminergic state in the mesolimbic pathway (reward system) through its predominant action on dopamine D3 receptors. We intend to do a non-systematic review of the scientific information regarding this subject.

The authors revised the published literature about this topic, selecting relevant articles, systematic reviews and case reports, with the topic words: “aripiprazol”, “gambling disorder” and “dopamine receptor” in scientific data base.

Overall, a few cases of ARI-induced pathological gambling as well as ARI-induced hypersexuality have been reported. In one study it was verified that comorbid psychiatric and substance use disorders were common among those who have experienced GD or worsened GD after beginning ARI treatment. In another study, it was verified that the group of patients who reported this alleged side-effect were mostly young (mean age, 33.6 years), mostly men (88.2%) and most lived alone.

Attributing to dopamine agonists the only factor that can explain the onset of GD is simplistic and dangerous. Many other potential risk factors, including individual vulnerability factors (temperament, genetics) as well as environmental factors, must be considered.

No significant relationships.

The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.

We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.

The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.

Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride.

Twenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory.

The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D2/3 receptor availability in the post-commissural caudate.

These results suggest that cognitive subtrait of impulsivity is associated with D2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control.