Clozapine-Treatment-Resistant Schizophrenia Successfully Managed with Brexpiprazole Combination Therapy: Two Case Reports

Abstract

Introduction Clozapine has proven to have a unique efficacy on treatment-resistant schizophrenia (TRS). Nevertheless, studies show that 47%-63% of clozapine-treated patients may fail to respond after around 12-years of treatment (CRS). Several augmentation strategies have been proven to be effective in CRS. Objectives Hereby, we present two clinical cases of CRS successfully managed with brexpiprazole augmentation. Methods A 48-year-old man without comorbid substance use, treated with clozapine-brexpiprazole augmentation, and a 20-year-old man with comorbid substance use, treated with clozapine-brexpiprazole combination and subsequently with twice-injection aripiprazole (TIA). They were administered with the following assessments at t0, t1-3 (first month), t4-8 (monthly until 6-month follow-up): CGI, BPRS, PANSS, CDSS, Craving VAS, BARS, BIS-11, HRS-A, MADRS, YMRS, AIMS. Results At 1-month follow-up, both patients showed a considerable improvement (respectively 75% and 55.9% reduction of PANSS total score). At 6-month follow-up, reached only with the first patient, we noticed a further improvement (an overall 37.5% reduction of PANSS total score from the baseline). Conclusions The present work is the first report describing combination treatment strategies with clozapine and brexpiprazole which appear to give promising results. Disclosure No significant relationships.

Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

“…The same team reported in a short communication on two cases of brexpiprazole and clozapine association in two patients with URS, both patients being subsequently switched on clozapine plus aripiprazole LAI ( 53 ). After 1 month of treatment, the clinical evolution was favorable, reflected in the PANSS scores’ improvement (over 55% total score decrease) ( 53 ). Only one patient presented at the 6 months follow-up, and his clinical status continued to improve ( 53 ).…”

“…After 1 month of treatment, the clinical evolution was favorable, reflected in the PANSS scores’ improvement (over 55% total score decrease) ( 53 ). Only one patient presented at the 6 months follow-up, and his clinical status continued to improve ( 53 ).…”

“…It is metabolized by CYP3A4 and 2D6, thus leaving unoccupied the CYP1A2 isoform. Based on the reviewed data, which are very limited ( n = 3 case reports), this augmentative strategy could be efficient, but treatment adherence is challenging ( 52 , 53 , 61 ).…”