title: Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials.
abstract: In epidemiological studies, statins appear to benefit mood, and there are now some randomized controlled trials examining the efficacy of statins. However, the role of statins in depression remains uncertain. Thus the aim of this paper was to assess the effect of statins on depressive symptoms by performing a meta-analysis of all double-blind, randomized, placebo controlled clinical trials (RCT) conducted in subjects with depression.
  
  
  
  A systematic search was executed using PubMed and ClinicalTrials.gov in November 30th, 2015 for all double-blind, RCT of statins versus placebo in persons with depressive symptoms. Sixty-seven potential articles were identified through search of electronic databases, of those three met inclusion criteria and were included in the meta-analysis. The outcome measure was change in Hamilton Depression Rating Scale (HDRS) scores associated with statin use. A meta-analysis was conducted and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. GRADE was used to assess study quality.
  
  
  
  The three articles included provided data on 165 participants with moderate to severe depression. Of these, 82 were randomized to statins as an adjuvant therapy to antidepressant treatment (i.e., citalopram or fluoxetine) and 83 to the placebo arm. All studies were double-blind RCTs, with a follow-up of 6-12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS (SMD=-0.73, 95% IC -1.04 to -0.42, p<0.001, 3 between-group comparisons, n=165). No serious adverse effects were reported.
  
  
  
  Our results suggest that adjunctive treatment with statins could be useful for the treatment of depressive symptoms. Additional double-blind, randomised, placebo-controlled trials are necessary to settle the matter.
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Hospital de la Santa Creu i Sant Pau, Servei de Psiquiatria, Barcelona, Spain. Electronic address: esalagre@gmail.com.
authors.forename: Estela
authors.initials: E
authors.lastname: Salagre
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: brisasf@gmail.com.
authors.forename: Brisa S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Department of Psychiatry, University of Melbourne, Parkville, Australia.
authors.forename: Seetal
authors.initials: S
authors.lastname: Dodd
authors.affiliation: Monash University, Faculty of Medicine, Nursing and Health Sciences, Melbourne, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brownstein
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, Department of Psychiatry and Orygen, The National Centre of Excellence in Youth Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D005473:Fluoxetine; D015283:Citalopram; D000069059:Atorvastatin; D019821:Simvastatin
keywords: Depression; Depressive symptoms; Inflammation; Meta-analysis; Randomized controlled trial; Statins; Systematic review; Treatment