Ginevra Lombardozzi

Background: Schizophrenia with comorbid substance use disorder (SUD) is associated with greater clinical severity, poorer adherence, and worse functional outcomes. Third-generation antipsychotics, through partial dopamine agonism, may represent a useful strategy in this complex population. This study compared the long-term efficacy of brexpiprazole and aripiprazole in patients with schizophrenia, with or without comorbid SUD. Methods: Patients (N = 243) with DSM-5/DSM-5-TR schizophrenia orally received 4 mg/day brexpiprazole or 30 mg/day aripiprazole for 12 months in a real-world clinical setting. Psychopathology was assessed at baseline and after 1, 3, 6, and 12 months using the Brief Psychiatric Rating Scale (BPRS) and the Positive And Negative Syndrome Scale (PANSS). Analyses were performed on 217 completers, excluding 26 drop-outs. Outcomes were compared according to drug and presence/absence of comorbid SUD. Results: Both brexpiprazole and aripiprazole were associated with psychotic symptom and global psychopathology improvement over 12 months (p < 0.01). In patients without SUD, the two treatments showed comparable efficacy. Among patients with comorbid SUD, brexpiprazole showed greater improvement in BPRS and PANSS outcomes than aripiprazole (p < 0.01). Treatment response to aripiprazole, but not to brexpiprazole, was diminished by substance use. Brexpiprazole was associated with better tolerability and lower rates of subjective agitation-related discontinuation. Conclusions: Both dopamine partial agonists were effective in treating schizophrenia; however, brexpiprazole was superior in patients with comorbid SUD. Findings suggest that brexpiprazole may represent a promising therapeutic option in dual-disorder patients.

The triazolopyridine derivative trazodone is approved for the treatment of major depressive disorder (MDD) in adults; according to the available literature, this molecule, through a specific dose-dependent profile of action, was found to be a potential therapeutic option in some neurological conditions. This systematic review aimed to synthesise the available evidence on the use of trazodone in neurological patients. PubMed was searched for articles published from inception until March 2025. Article reference lists were screened, and relevant articles were retrieved for consultation. Clinical trials specifically investigating trazodone in neurological populations were included, following PRISMA guidelines for systematic reviews. Out of 69 records initially retrieved, 14 studies met the inclusion criteria, comprising 13 randomised controlled trials and 1 retrospective study, with a total of 608 patients. Most of the included studies focused on individuals with dementia, while others explored its use in different neurological disorders. Despite being an older antidepressant, trazodone remains widely prescribed. Beyond treating depression in neurological patients, it may may be useful in the treatment of some neurological aspects. However, current evidence remains limited. Further high-quality research is necessary to better define the therapeutic potential of trazodone in the management of neurological conditions.

Aripiprazole as a long-acting injectable (LAI) is initiated in oral aripiprazole-stabilised patients and needs, after first injection, 14 days supplementation of oral aripiprazole (one-injection start, OIS). Recently, an alternative two-injection start (TIS) was advanced, involving two 400 mg injections with a single 20 mg oral supplementation of aripiprazole. We tested the two regimens in patients with schizophrenia (SCZ, n = 152, 90 men and 62 women) with (SUD⁺; n = 93) or without (SUD^–; n = 59) substance use disorders (SUDs), comparing OIS (n = 66) with TIS (n = 86) and SUD⁺ vs. SUD^–. For 26 patients, we measured weekly for one month, aripiprazole + dehydroaripiprazole (active moiety) levels. Patients were followed for three months after LAI with psychopathology and quality-of-life scales (BPRS, CGI-S, ACES, BIS-11, and WHOQOL). All groups improved in psychopathology with no differences between OSI and TIS and between SCZ–SUD⁺ and SCZ–SUD^–. The TIS group was associated with serum blood levels of the active moiety within the therapeutic window, while the OIS group showed peaks above the window, possibly exposing patients to toxicity. Treatments were well-tolerated. Here we showed no disadvantages for TIS vs. OIS and possibly increased safety. Shifting the initiation of aripiprazole LAIs to the TIS modality may be safe and pharmacokinetically advantageous.

Background: Partial dopamine D₂ receptor agonists are used for psychotic symptoms in adults with schizophrenia spectrum disorders. Recently, interest surged for partial dopamine D₂ receptor agonists in substance use disorders (SUDs). Since it is believed that SUDs decrease the efficacy of pharmacotherapy of underlying psychiatric disorders, we tested the efficacy of the partial D₂ agonist brexpiprazole in patients with schizophrenia who were either comorbid with a SUD (SUD group) or not comorbid (non-SUD) to assess treatment response and the effect of brexpiprazole on substance craving in SUD.Methods: We included patients with DSM-5/DSM-5-TR schizophrenia (using SCID-5-CV) aged 18–66 years with either comorbid SUD or non-SUD to treat with brexpiprazole 4 mg/day for 6 months during February–October 2022. Patients were assessed with the Clinical Global Impressions–Severity (CGI-S) scale, the 24-item Brief Psychiatric Rating Scale (BPRS), and the Positive And Negative Syndrome Scale (PANSS) at baseline, weekly for the first 2 months and monthly for the next four. Furthermore, we assessed substance craving in SUD with a visual analog scale for craving (VAScrav) at the same timepoints.Results: The total sample was 86 (85 analysable) 18- to 64-year-old (mean 39.32 ± 14.09) patients with schizophrenia [51 men (59.3%) and 35 women (40.7%)], of whom 48 SUD (55.8%) (37 men and 11 women) and 38 non-SUD (44.2%) (14 men and 24 women). No serious or persistent adverse events developed over the study period, but one patient dropped out for subjective akathisia. Results indicated the main effects of time with improvements over the course of the study for CGI-S, BPRS, and PANSS in both SUD and non-SUD groups and the entire sample, and for VAScrav in SUD. Brexpiprazole was associated with similar significant improvements in both groups at the 6 month endpoint compared to baseline.Conclusion: Treatment with brexpiprazole for 6 months improved psychotic symptoms in patients with schizophrenia, independently from whether they belonged to the SUD or the non-SUD group; hence, SUD comorbidity did not confer treatment resistance to brexpiprazole. Furthermore, in the SUD group, we observed reduced substance craving.

Adverse childhood experiences (ACEs), social–emotional impairments (SEIs), and neurodevelopmental disorders (NDs) are frequent in psychiatric disorders, including substance-use disorders. We aimed to determine the prevalence of ACE, SEI, or ND in individuals with cannabis-use disorder (CUD). We compared individuals with preCUD-onset ACE, SEI, or ND to those without. We crosssectionally studied 323 inpatients or outpatients with a history of past or current CUD, aged 12–35 years (mean age 22.94 ± 4.79), 64.5% of whom were male. The sample was divided into two groups: the non-premorbid (N = 52) and the premorbid ACE/SEI/ND group (N = 271). Within the premorbid group, further subgroups were based on ACEs, SEI, and NDs. We also analyzed other substance use and psychiatric symptoms/diagnoses based on the non-premorbid-premorbid dichotomy in the CUD sample. Pre-CUD ACE-SEI-ND had higher prevalence of bipolar, schizoaffective, borderline personality, and attention-deficit/hyperactivity disorders, and a history of agitation, hallucinations, and self-injury. The ACE group had higher rates of agitation, depression, delusions, hallucinations, eating disorders, and use of cocaine, amphetamines, and hallucinogens than the SEI or ND. Patients in the premorbid group initiated cannabis use at an earlier age, experienced the first comorbid psychiatric episode earlier, and were hospitalized earlier than those in the non- premorbid ACE-SEI-ND group. PreCUD-onset ACE, SEI, or ND conditions in individuals with CUDare linked to earlier onset of comorbid mental illness. Furthermore, ACEs contribute to significant and potentially severe clinical symptoms, as well as the use of substances other than cannabis.

Motivated behaviours are thought to lead to enhanced performances. In the neurorehabilitation field, motivation has been demonstrated to be a link between cognition and motor performance, therefore playing an important role upon rehabilitation outcome determining factors. While motivation-enhancing interventions have been frequently investigated, a common and reliable motivation assessment strategy has not been established yet. This review aims to systematically explore and provide a comparison among the existing motivation assessment tools concerning stroke rehabilitation. For this purpose, a literature search (PubMed and Google Scholar) was performed, using the following Medical Subject Headings terms: “assessment” OR “scale” AND “motivation” AND “stroke” AND “rehabilitation”. In all, 31 randomized clinical trials and 15 clinical trials were examined. The existing assessment tools can be grouped into two categories: the first mirroring the trade-off between patients and rehabilitation, the latter reflecting the link between patients and interventions. Furthermore, we presented assessment tools which reflect participation level or apathy, as an indirect index of motivation. In conclusion, we are left to put forth a possible common motivation assessment strategy, which might provide valuable incentive to investigate in future research.

Background: The Covid 19 pandemic might have impacted response to drug treatment in major depressive episode (MDE). We compared responses to three different antidepressant drugs, i.e., vortioxetine, sertraline, and trazodone, in outpatients with MDE during Major Depressive Disorder (MDD), Bipolar Disorder (BD), or schizophrenia and related psychoses (SSOPDs) during two time periods, i.e., prior to suffering Covid-19–related trauma and after suffering such trauma. Methods: We conducted an observational study on clinically stabilised for at least 6 months outpatients with MDE during the course of MDD (N=58), BD (N=33), or SSOPDs (N=51). Patients, whose baseline assessments of Montgomery-Åsberg Rating Scale (MADRS), Hamilton Anxiety Rating Scale (Ham-A), Brief Psychiatric Rating Scale (BPRS), Visual Analogue Scale for Craving (VAS-crav) and World Health Organization Quality of Life, Brief version (WHOQOL-BREF) were available, were recruited at the time they suffered Covid-19–related traumas. Fifty patients, prior to the pandemic, when they were clinically stable, were treated with 15 mg/die vortioxetine, 44 with 450 mg/die trazodone, and 48 with 150 mg/die sertraline. After experiencing a major Covid-19–related personal trauma, patients showed clinical worsening which required dosage adjustment (20 mg/day vortioxetine; 600 mg/day trazodone, and 200 mg/day sertraline) and, for a part of them, a month of hospitalisation. Scores on the MADRS, Ham-A, BPRS, VAS-crav and WHOQOL-BREF were compared drug-wise and gender-wise with Student’s t test for continuous variables and χ2 for categorical variables. Result: The sample consisted of 142 outpatients (age, mean 39.63 ± 16.84; 70 men and 72 women); women were older than men (mean age 43.18 ± 17.61 vs. 35.98 ± 15.30; p=0.01). The two genders did not differ on other variables). For all treatments, symptoms worsening was observed at the time of trauma, followed by slow recovery with treatment readjustment. Trauma-related worsening in patients on vortioxetine was less intense than patients on the other two antidepressants and recovery was faster. All drugs were associated with an improvement in QoL. The vortioxetine group showed a lower hospitalisation rate (24%) than sertraline (35.4%) and trazodone (38.6%), but this was not significant (p=0.27). Conclusion: All drugs improved symptoms after Covid-19 trauma in patients with MDE, with vortioxetine showing a small advantage. No differences between vortioxetine, sertraline and trazodone were found as concerns the need for hospitalisation.