title: Manic switches induced by antidepressants: an umbrella review comparing randomized controlled trials and observational studies.
abstract: OBJECTIVE
  We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials (RCTs) compared to observational studies (OSs).
  
  
  METHODS
  Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence.
  
  
  RESULTS
  A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder.
  
  
  CONCLUSIONS
  Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies.
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France.|EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, Rennes, France.
authors.forename: N
authors.initials: N
authors.lastname: Allain
authors.affiliation: Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University, Rennes, France.|INSERM CIC-P 1414, Clinical Investigation Center, CHU Rennes, Rennes 1 University, Rennes, France.
authors.forename: C
authors.initials: C
authors.lastname: Leven
authors.affiliation: CESP, University of Paris-Sud, Université Paris-Saclay, UVSQ, INSERM U1178, Maison de Solenn, Paris Cedex, France.
authors.forename: B
authors.initials: B
authors.lastname: Falissard
authors.affiliation: Department of Internal Medicine, Rennes University Hospital, Rennes, France.
authors.forename: J-S
authors.initials: JS
authors.lastname: Allain
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France.|EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, Rennes, France.
authors.forename: J-M
authors.initials: JM
authors.lastname: Batail
authors.affiliation: Department of Pharmacology, Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France.|Pharmacoepidemiology Team (CTAD-PEPI), Rennes University Hospital, Rennes, France.
authors.forename: E
authors.initials: E
authors.lastname: Polard
authors.affiliation: Department of Medical and Clinical Pharmacology, Midi-Pyrénées Centre for Pharmacovigilance, Pharmacoepidemiology and Drug Information, INSERM U 1027 Pharmacoepidemiology Research Unit, Toulouse, France.
authors.forename: F
authors.initials: F
authors.lastname: Montastruc
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France.|EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, Rennes, France.
authors.forename: D
authors.initials: D
authors.lastname: Drapier
authors.affiliation: INSERM CIC-P 1414, Clinical Investigation Center, CHU Rennes, Rennes 1 University, Rennes, France.|Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Palo Alto, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Naudet
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000145:classification* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D064887:Observational Studies as Topic; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis
chemical_list: D000928:Antidepressive Agents
keywords: affective disorders; depression; meta-analysis; randomized controlled trial