title: Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers.
abstract: BACKGROUND
  Bipolar patients with breakthrough major depressive episodes despite ongoing adequately-dosed mood stabilizer medication were randomized in a double-blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial.
  
  
  METHODS
  Subjects included 64 bipolar patients who participated at five sites in a 10-week double-blind trial for depression and a 1-year blinded continuation maintenance phase for responders. Nonresponders were re-randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health-Life Chart Methodology (NIMH-LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI-BP) and the occurrence of hypomania or mania.
  
  
  RESULTS
  Thirty-five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI-BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty-two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania.
  
  
  CONCLUSIONS
  In this randomized double-blind prospective study of three second-generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken.
authors.affiliation: Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20892-1272, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Post
authors.forename: L L
authors.initials: LL
authors.lastname: Altshuler
authors.forename: M A
authors.initials: MA
authors.lastname: Frye
authors.forename: T
authors.initials: T
authors.lastname: Suppes
authors.forename: A J
authors.initials: AJ
authors.lastname: Rush
authors.forename: P E
authors.initials: PE
authors.lastname: Keck
authors.forename: S L
authors.initials: SL
authors.lastname: McElroy
authors.forename: K D
authors.initials: KD
authors.lastname: Denicoff
authors.forename: G S
authors.initials: GS
authors.lastname: Leverich
authors.forename: R
authors.initials: R
authors.lastname: Kupka
authors.forename: W A
authors.initials: WA
authors.lastname: Nolen
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D018687:Antidepressive Agents, Second-Generation