Brexpiprazole in patients with schizophrenia with or without substance use disorder: an observational study

Abstract

BackgroundPartial 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.MethodsWe 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.ResultsThe 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.ConclusionTreatment 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.

Investigating the Effectiveness of Brexpiprazole in Subjects with Schizophrenia Spectrum Illness and Co-Occurring Substance Use Disorder: A Prospective, Multicentric, Real-World Study

“…Our findings align with a recent Italian observational study including 85 adult patients with a diagnosis of schizophrenia with either a comorbid SUD (55.8%) or no SUD (44.2%) treated with brexpiprazole at 4 mg/day for 6 months, which showed improvements over the course of the study for CGI-S, the Brief Psychiatric Rating Scale (BPRS), and PANSS in both the SUD and non-SUD groups and the entire sample, and in the SUD group, there was a statistically significant reduction in substance craving [42]. Supporting this, an animal study by Nickols et al (2023) offered preclinical support for the effectiveness of brexpiprazole as a dopamine partial agonist in modulating behaviors dependent on dopamine during both opioid use and withdrawal, e.g., pathological drug-seeking behavior and other symptoms associated with opioid withdrawal following drug discontinuation [43].…”

Investigating the Effectiveness of Brexpiprazole in Schizophrenic Patients with Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Study

“…A visual analogue scale may not be adequately comprehensive to capture this phenomenon. Indeed, an Italian observational study including 85 adult patients with a diagnosis of schizophrenia with either comorbid SUD (55.8%) or non-SUD (44.2%) treated with brexpiprazole 4 mg/day for 6 months showed 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 in the SUD group a statistically significant reduction of substance craving [36]. Supporting this, an animal study from Nickols et al (2023), offered preclinical support for the effectiveness of brexpiprazole as a dopamine partial agonist in modulating behaviors dependent on dopamine during both opioid use and withdrawal, e.g., pathological drug-seeking behavior and other symptoms associated with opioid withdrawal following drug discontinuation [37].…”