title: Efficacy and safety of noradrenalin reuptake inhibitor augmentation therapy for schizophrenia: a meta-analysis of double-blind randomized placebo-controlled trials.
abstract: BACKGROUND
  We performed an updated meta-analysis of noradrenalin reuptake inhibitor (NRI) augmentation therapy in patients with schizophrenia treated with antipsychotics based on a previous meta-analysis (Singh et al.).
  
  
  METHODS
  PubMed, Cochrane Library databases, and PsycINFO citations were searched from their inception to June 10, 2013 without language restrictions. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing NRI augmentation therapy with placebo. The outcome measure for efficacy was the psychopathology of schizophrenia and the measures for safety were discontinuation rate and several side effects. We used standardized mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous variables, with their 95% confidence intervals (CIs). A random-effects model was used.
  
  
  RESULTS
  Nine studies (4 atomoxetine studies, 3 reboxetine studies, 1 reboxetine-betahistine combination study and 1 mazindol study, total n=298) were identified. No statistically significant effects of NRI augmentation therapy on overall (p=0.90), positive (p=0.81), and negative (p=0.89) symptoms were found. NRI augmentation therapy was marginally superior to placebo for efficacy of depressive symptoms (SMD=-1.08, p=0.05). Dropout due to all-cause (p=0.70), inefficacy (p=0.64), or adverse events (p=0.18) was similar in both groups. NRI augmentation therapy showed a significantly lower increase or larger reduction in body weight than placebo (SMD=-0.47, p=0.03). Reboxetine augmentation was associated with less weight gain that placebo in antipsychotic treated schizophrenia patients (SMD=-0.78, p=0.0001).
  
  
  CONCLUSIONS
  NRIs may exert an effect on depressive symptoms, and seem to be well-tolerated treatments.
authors.affiliation: Department of Psychiatry, Fujita Health University, School of Medicine, Toyoake, Aichi 470-1192, Japan. Electronic address: tarok@fujita-hu.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Mukai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriwaki
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D016208:Databases, Factual / Q000706:statistics & numerical data; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D014150:Antipsychotic Agents
keywords: Atomoxetine; Meta-analysis; Noradrenalin reuptake inhibitors; Reboxetine; Schizophrenia