title: Risk factors for antidepressant-related switch to mania.
abstract: OBJECTIVE
  Treatment of bipolar depression with antidepressants is strongly debated on the basis of the methodologically poor and insufficient data supporting their use and the widely held belief that antidepressants can induce new episodes of abnormal mood elevation or accelerate the rate of cycling. The present study aimed at identifying clinical risk factors for switch into hypomania, mania, or mixed states, within 8 weeks after introduction of an antidepressant or after increasing its dosage, in a prospective, longitudinal design.
  
  
  METHODS
  221 consecutive DSM-IV-TR depressed bipolar I and II disorder patients were treated with antidepressants, which were added to previously prescribed mood stabilizers and/or atypical antipsychotics. No patient was on antidepressant monotherapy. The patients were enrolled from October 2005 through January 2010. The primary outcome was the assessment of switch to mania or hypomania within 8 weeks after the introduction or dose increase of an antidepressant. Both groups were compared with analysis of variance and χ² procedures.
  
  
  RESULTS
  Treatment-emergent affective switch was detected in 54 patients (24.4%) (switch group) while 167 patients (75.6%) (nonswitch group) did not experience a treatment-related switch. The main clinical differences significantly associated with the occurrence of an antidepressant-related switch, after performing logistic regression analysis, were higher rate of previous switches (P < .001) in the switch versus the nonswitch group, lower rate of responses to antidepressants (P < .001) in the switch versus the nonswitch group, and earlier age at onset (P = .026) in the switch versus the nonswitch group.
  
  
  CONCLUSIONS
  Bipolar patients with an earlier age at onset and an illness course characterized by lower rate of response to antidepressants and higher rate of switches into mania or hypomania were found to be the ones with higher switch risk. Nevertheless, a greater number of previous antidepressant exposures was not associated with the occurrence of an antidepressant-associated switch.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01503489.
authors.affiliation: Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Valentí
authors.forename: Isabella
authors.initials: I
authors.lastname: Pacchiarotti
authors.forename: C Mar
authors.initials: CM
authors.lastname: Bonnín
authors.forename: Adriane R
authors.initials: AR
authors.lastname: Rosa
authors.forename: Dina
authors.initials: D
authors.lastname: Popovic
authors.forename: Alessandra M A
authors.initials: AM
authors.lastname: Nivoli
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Goikolea
authors.forename: Andrea
authors.initials: A
authors.lastname: Murru
authors.forename: Juan
authors.initials: J
authors.lastname: Undurraga
authors.forename: Francesc
authors.initials: F
authors.lastname: Colom
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
mesh_terms: D017668:Age of Onset; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000928:Antidepressive Agents