title: Treatments of Negative Symptoms in Schizophrenia: Meta-Analysis of 168 Randomized Placebo-Controlled Trials.
abstract: Existing treatments for schizophrenia can improve positive symptoms, but it is unclear if they have any impact on negative symptoms. This meta-analysis was conducted to assess the efficacy of available treatments for negative symptoms in schizophrenia.
  
  
  
  All randomized-controlled trials of interventions for negative symptoms in schizophrenia until December 2013 were retrieved; 168 unique and independent placebo-controlled trials were used. Negative symptom scores at baseline and follow-up, duration of illness, doses of medication, type of interventions, and sample demographics were extracted. Heterogeneity was addressed with the I (2) and Q statistic. Standardized mean difference in values of the Negative Symptom Rating Scale used in each study was calculated as the main outcome measure.
  
  
  
  6503 patients in the treatment arm and 5815 patients in the placebo arm were included. No evidence of publication biases found. Most treatments reduced negative symptoms at follow-up relative to placebo: second-generation antipsychotics: -0.579 (-0.755 to -0.404); antidepressants: -0.349 (-0.551 to -0.146); combinations of pharmacological agents: -0.518 (-0.757 to -0.279); glutamatergic medications: -0.289 (-0.478 to -0.1); psychological interventions: -0.396 (-0.563 to -0.229). No significant effect was found for first-generation antipsychotics: -0.531 (-1.104 to 0.041) and brain stimulation: -0.228 (-0.775 to 0.319). Effects of most treatments were not clinically meaningful as measured on Clinical Global Impression Severity Scale.
  
  
  
  Although some statistically significant effects on negative symptoms were evident, none reached the threshold for clinically significant improvement.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK; OASIS team, South London and the Maudsley NHS Foundation Trust, London, UK;
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK; evangelos.e.papanastasiou@kcl.ac.uk.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Papanastasiou
authors.affiliation: Department of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK;
authors.forename: Daniel
authors.initials: D
authors.lastname: Stahl
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy;
authors.forename: Matteo
authors.initials: M
authors.lastname: Rocchetti
authors.affiliation: Department of Psychiatry and Pharmacology, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: William
authors.initials: W
authors.lastname: Carpenter
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK;
authors.forename: Sukhwinder
authors.initials: S
authors.lastname: Shergill
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK; OASIS team, South London and the Maudsley NHS Foundation Trust, London, UK;
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D006801:Humans; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000503:physiopathology / Q000628:therapy*
keywords: antipsychotics; negative symptoms; psychosis; schizophrenia; treatment