title: Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial.
abstract: This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.
authors.affiliation: World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Organization, Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Verona, Italy. corrado.barbui@univr.it
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
authors.forename: Simone
authors.initials: S
authors.lastname: Accordini
authors.forename: Michela
authors.initials: M
authors.lastname: Nosè
authors.forename: Scott
authors.initials: S
authors.lastname: Stroup
authors.forename: Marianna
authors.initials: M
authors.lastname: Purgato
authors.forename: Francesca
authors.initials: F
authors.lastname: Girlanda
authors.forename: Eleonora
authors.initials: E
authors.lastname: Esposito
authors.forename: Antonio
authors.initials: A
authors.lastname: Veronese
authors.forename: Michele
authors.initials: M
authors.lastname: Tansella
authors.forename: Andrea
authors.initials: A
authors.lastname: Cipriani
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D010054:Brief Psychiatric Rating Scale; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D003024:Clozapine; D006220:Haloperidol