title: Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine.
abstract: BACKGROUND
  Although clozapine (CLZ) is considered the best evidence-based therapeutic option for treatment of resistant schizophrenia patients, a significant proportion of CLZ-treated patients show a partial or inadequate response to treatment, leading to increased healthcare cost and poor quality of life for affected individuals.
  
  
  METHODS
  This paper comprises a review of main research in CLZ augmentation strategies for treatment-refractory schizophrenia, with a focus on research conducted between 1990 and 2014. Databases that were searched include: PubMed, CINAHL, EMBASE PsychINFO, AgeLine and Cochrane Database of Systematic Reviews. Primary search terms were 'clozapine augmentation', 'clozapine and add-on' and 'treatment-resistant schizophrenia', with cross reference to specific agents covered in this article. We reviewed the available evidence on CLZ augmentation with antipsychotics, antidepressants, mood stabilizers and other agents.
  
  
  CONCLUSIONS
  Many drugs have been evaluated as CLZ add-on therapies without demonstrating convincing efficacy in treating refractory schizophrenia symptoms. More research is needed to better define outcomes in schizophrenia, the topic of treatment-resistance and more well-designed trials are required to establish true efficacy and safety of CLZ augmentation strategies.
authors.affiliation: University of Messina, Department of Neurosciences , Policlinico Universitario Via Consolare Valeria - Messina 98125 , Italy +39 090 22212092 ; +39 090 695136 ; mmuscatello@unime.it.
authors.forename: Maria Rosaria A
authors.initials: MR
authors.lastname: Muscatello
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Fazio
authors.forename: Cristina
authors.initials: C
authors.lastname: Segura-Garcia
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pandolfo
authors.forename: Rocco
authors.initials: R
authors.lastname: Zoccali
mesh_terms: D000339:Affect / Q000187:drug effects; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D004565:Electroconvulsive Therapy; D017048:Health Care Costs; D006801:Humans; D011788:Quality of Life; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D012565:Schizophrenic Psychology; D017211:Treatment Failure
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003024:Clozapine
keywords: add-on; clozapine augmentation; refractory; treatment-resistant schizophrenia