title: Antidepressant-associated mood elevations in bipolar II disorder compared with bipolar I disorder and major depressive disorder: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Antidepressant-associated manic and hypomanic episodes have been reported in bipolar I disorder but are rare in major depressive disorder (MDD). Several lines of evidence suggest that bipolar II disorder is a distinct illness from bipolar I disorder and MDD. The risk of antidepressant-associated mood elevations (AAME) in bipolar II disorder relative to bipolar I disorder and MDD is unknown.
  
  
  METHODS
  We conducted a computer-aided MEDLINE search encompassing the dates 1949 to February 2008, using the keywords antidepressant and mania, antidepressant and hypomania, antidepressant and bipolar, fluoxetine and bipolar, fluvoxamine and bipolar, sertraline and bipolar, paroxetine and bipolar, citalopram and bipolar, escitalopram and bipolar, venlafaxine and bipolar, mirtazapine and bipolar, bupropion and bipolar, monoamine oxidase inhibitor and bipolar, phenelzine and bipolar, tranylcypromine and bipolar, tricyclic and bipolar, imipramine and bipolar, amitriptyline and bipolar, nortriptyline and bipolar, and desipramine and bipolar.
  
  
  METHODS
  All prospective English-language studies, including randomized, controlled trials (RCTs), open-label studies, and naturalistic treatment reports, were eligible for inclusion. We located 13 studies, including 7 RCTs, that reported rates of antidepressant-associated mood elevations in bipolar I disorder versus bipolar II disorder, and 5, including 4 RCTs, that reported rates in bipolar II disorder versus MDD.
  
  
  METHODS
  Data were combined to estimate mean switch rates and subjected to meta-analysis to determine the relative risks of antidepressant-associated mood elevations in bipolar I disorder versus bipolar II disorder and in bipolar II disorder versus MDD.
  
  
  RESULTS
  The mean rates of antidepressant-associated mood elevations in studies comparing bipolar I disorder and bipolar II disorder were 14.2% and 7.1%, respectively, in acute trials (less than 16 weeks), and 23.4% and 13.9%, respectively, in maintenance studies. The mean rates in reports comparing bipolar II disorder and MDD were 8.1% and 1.5%, respectively, in acute trials, and 16.5% and 6.0%, respectively, in maintenance studies. The relative risk (RR) of antidepressant-associated mood elevations was greater in bipolar I disorder than bipolar II disorder (RR = 1.78, 95% CI = 1.24 to 2.58, p = .002), and higher in bipolar II disorder than MDD (RR = 2.77, 95% CI = 1.26 to 6.09, p = .01). Mood elevations occurred almost exclusively into hypomania in MDD and bipolar II disorder, while patients with bipolar I disorder experienced manias and hypomanias with similar frequencies.
  
  
  CONCLUSIONS
  The risk of antidepressant-associated mood elevations in bipolar II disorder is intermediate between that in bipolar I disorder and MDD.
authors.affiliation: Research and International Affairs, Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Room 2C7, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1 Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bond
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Noronha
authors.forename: Marcia
authors.initials: M
authors.lastname: Kauer-Sant'Anna
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Lam
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
mesh_terms: D000342:Affective Symptoms / Q000139:chemically induced* / Q000453:epidemiology; D000928:Antidepressive Agents / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D012306:Risk
chemical_list: D000928:Antidepressive Agents