title: Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial.
abstract: BACKGROUND
  Long-term studies for patients with resistant schizophrenia are necessary to assess the effectiveness of combination strategies on persisting positive symptoms.
  
  
  OBJECTIVE
  This multicenter, naturalistic, randomized, superiority study (ClinicalTrials.gov identifier: NCT00395915) aimed to compare clinical efficacy and tolerability of haloperidol versus aripiprazole as combination treatment with clozapine in patients with resistant schizophrenia.
  
  
  RESULTS
  One hundred six patients were followed up for 12 months. After 12 months, the proportion of patients who discontinued treatment was not significantly different between aripiprazole and haloperidol (37% vs 28%, respectively; P = 0.431). The change in the Brief Psychiatric Rating Scale score was similar in the aripiprazole and haloperidol groups (-7.0 vs -7.9, respectively; P = 0.389), whereas the tolerability total score decreased significantly more in the aripiprazole group (-7.2 vs -2.3; P = 0.008).
  
  
  CONCLUSIONS
  While the effectiveness of clozapine augmentation with a second antipsychotic agent is not clearly demonstrated yet, results from this study suggest that augmentation with aripiprazole offers no substantial benefit over haloperidol in efficacy. Aripiprazole was perceived more tolerable than haloperidol, but it is uncertain how this finding may translate into the real world of clinical practice.
authors.affiliation: Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Italy. andrea.cipriani@univr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Cipriani
authors.forename: Simone
authors.initials: S
authors.lastname: Accordini
authors.forename: Michela
authors.initials: M
authors.lastname: Nosè
authors.forename: Marianna
authors.initials: M
authors.lastname: Purgato
authors.forename: Francesca
authors.initials: F
authors.lastname: Girlanda
authors.forename: Michele
authors.initials: M
authors.lastname: Tansella
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D015999:Multivariate Analysis; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D003024:Clozapine; D006220:Haloperidol