Previously, we reported on the high affinity binding of aripiprazole (ARP), an antipsychotic drug, to human albumin and the role of the chlorine atom of ARP on this binding. In this study, we investigated the binding mode of ARP to human albumin in detail using ARP derivatives and several animal-derived albumins. ARP bound strongly to human and dog albumin. The CD spectra of ARP bound to human and dog albumin were also similar. Deschloro-ARP bound less strongly to all of the albumin species compared to ARP and the shapes of CD spectra were similar for all albumin species. CD spectra of dimethyl-ARP, for which chlorine atoms were substituted methyl groups, were quite similar to that of deschloro-ARP. In displacement experiments, competitive binding was observed between ARP and deschloro-ARP. These results suggest that the chlorine atoms in ARP are involved in the binding modes of ARP for human and dog albumins, whereas ARP and deschloro-ARP appear to share the same binding region in site II. The above results imply that compounds having a chlorine atom bind more strongly to plasma proteins, resulting in a long blood retention time. Therefore, findings reported here may provide the basically useful data for drug design.

Patients with severe psychotic disorders such as schizophrenia, schizoaffective, and bipolar disorders frequently suffer from concomitant substance use disorders (SUDs)-Dual Disorder (DD) patients. In order to better understand current practices for management of patients with psychotic episodes and concomitant SUD in Italy, we carried out a survey of psychiatrists on current routine practice among prescribers. These aspects can help to identify at-risk patients, improve current prescribing practices, and favor early intervention. An ad hoc survey of 17 questions was administered to psychiatrists via electronic polling and on-line distribution; 448 completed questionnaires were collected. Comorbid substance abuse was most frequently diagnosed within the context of anxiety disorder (46%), followed by bipolar disorder (25%), and schizophrenia/schizoaffective disorder (12%). The vast majority of respondents felt that patient management was becoming more complex due to substance abuse. The areas reported to be most affected in patients with SUD were functioning, interpersonal relations, and impulsivity, while sensory perception disorders, ideation, agitation, and impulsivity were the most frequently reported symptoms. In the acute setting, haloperidol was used as the first-line agent of choice followed by aripiprazole and olanzapine. In the maintenance phase, aripiprazole was the dominantly used first-line agent, followed by olanzapine. Almost half of respondents used long-acting agents, while about one-third did not. Among those prescribing long-acting agents, efficacy, control of impulsivity, and control of specific symptoms were cited as motivators, while in the maintenance phase, better adherence, and tolerability were mainly cited. From the responses to the present survey, it is clear that the respondents are aware of the problem of SUD in psychotic patients. While treatment be optimized in terms of the choice and formulation of antipsychotics, greater emphasis should be placed on efficacy, tolerability, and the negative metabolic consequences of some antipsychotics. When considering the ideal antipsychotic, long-acting agents were considered to be superior in reducing relapse, even if current treatment guidelines often give preference to oral formulations.

Although inappropriate sexual behavior in dementia is not common, it can be extremely troublesome for healthcare professionals and caregivers as well as patients themselves. There is paucity of data in the literature for the management of these behaviors, but the limited available data suggest efficiency of some commonly used treatment modalities. Herein, we present a 74-year old Alzheimer's disease (AD) patient, known to be heterosexual throughout her past life, presenting with a recent display of same-sex inappropriate sexual behavior six years after the initial diagnosis of her disease. This new clinical picture of hypersexuality responded well to aripiprazole and her symptoms gradually diminished and eventually disappeared after onset of medication. This report also constitutes the first reported case of an AD patient in the published literature presenting with hypersexuality of shifted sexual orientation during the course of the disease.