title: Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis.
abstract: BACKGROUND
  Cognitive impairment in schizophrenia is disabling, but current treatment options remain limited.
  
  
  OBJECTIVE
  To meta-analyze the efficacy and safety of adjunctive antidepressants for cognitive impairment in schizophrenia.
  
  
  METHODS
  PubMed, MEDLINE, PsycINFO, and Cochrane Library databases were searched until 12/2013 for randomized controlled trials comparing antidepressant augmentation of antipsychotics with placebo regarding effects on cognitive functioning in schizophrenia.
  
  
  METHODS
  Two authors independently extracted data. Standardized mean differences (SMDs) were calculated for continuous outcomes and risk ratios for categorical outcomes. SMDs of individual cognitive tests were pooled on a study level within domains (primary outcome) and across domains. When results were heterogeneous, random instead of fixed effects models were used.
  
  
  RESULTS
  We meta-analyzed 11 studies (duration = 8.7 ± 3.7 weeks) including 568 patients (mean age = 39.5 ± 6.9 years, males = 67.2%, illness duration = 12.5 ± 8.0 years). Antidepressants included mirtazapine (4 studies; n = 126), citalopram (2 studies; n = 231), fluvoxamine (1 study; n = 47), duloxetine (1 study; n = 40), mianserin (1 study; n = 30), bupropion (1 study; n = 61), and reboxetine (1 study; n = 33). Statistically significant, but clinically negligible, advantages were found for pooled antidepressants compared to placebo in executive function (Hedges' g = 0.17, p = 0.02) and a composite cognition score (Hedges' g = 0.095, p = 0.012). Depression improved with serotonergic antidepressants (p = 0.0009) and selective serotonin reuptake inhibitors (p = 0.009), but not with pooled antidepressants (p = 0.39). Sedation was more common with pooled antidepressants (p = 0.04).
  
  
  CONCLUSIONS
  Adjunctive antidepressants do not demonstrate clinically significant effects on cognition in schizophrenia patients, however, larger studies, preferably in euthymic schizophrenia patients and using full neurocognitive batteries, are needed to confirm this finding.
authors.affiliation: New York Medical College, Valhalla, NY, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Vernon
authors.affiliation: The Zucker Hillside Hospital, Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Grudnikoff
authors.affiliation: The Zucker Hillside Hospital, Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Seidman
authors.affiliation: Center for Autism, Pediatric Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Frazier
authors.affiliation: Atlanta VA Medical Center, Decatur, GA, USA.
authors.forename: Mani Sandhya
authors.initials: MS
authors.lastname: Vemulapalli
authors.affiliation: New York Medical College, Valhalla, NY, USA.
authors.forename: Priyanki
authors.initials: P
authors.lastname: Pareek
authors.affiliation: The Zucker Hillside Hospital, Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
authors.affiliation: The Zucker Hillside Hospital, Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.affiliation: The Zucker Hillside Hospital, Psychiatry, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: ccorrell@lij.edu.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents
keywords: Alpha 2 antagonists; Antidepressants; Augmentation; Cognition; Cognitive impairment; Schizophrenia; Selective serotonin reuptake inhibitors