Table 2: Summary of recent studies examining the risk of manic/hypomanic switch following the use of antidepressants in the treatment of acute bipolar depression.

Increased risk of switchNo increased risk of switch
StudyNo. of participantsDrugCommentsStudyNo. of participantsDrugComments

Antidepressants as Monotherapy
Amsterdam and Shults 2005 [13]34 ( , )Fluoxetine, olanzapine/fluoxetine combinationNo Placebo Control
Parker et al. 2006 [16]10 BPIIEscitalopramSmall sample size
Agosti and Stewart 2007 [21]70 BP IIImipramine, phenelzineNo valid tool used to assess switch
Amsterdam and Shults 2008 [17]83 BPIIVenlafaxineCompared to Lithium, no placebo control
McElroy et al. 2010 (EMBOLDEN II) [14]740 ( , )paroxetine
Amsterdam and Shults 2010 [15]148 BPIIFluoxetineNo placebo control, subsyndromal hypomania in 19.6%

Antidepressants with mood stabilizers
Post et al. 2006 [40]174Venlafaxine15%; no placebo controlSchaffer et al. 2006 [27]20CitalopramSmall sample size, no placebo control
Truman et al. 2007 [30]366 ( , )Paroxetine, bupropionBy self-report onlyFonseca et al. 2006 [28]20EscitalopramSmall sample size, no placebo control
Amsterdam and Shults 2010 [15]148 BPIIFluoxetineNo placebo control, subsyndromal hypomania in 19.6%Sachs et al. 2007 [29]366 ( , )Paroxetine, bupropion
Perlis et al. 2010 [45]410Olanzapine/fluoxetine combination, lamotrigineConducted by Lilly Research Laboratories
Sidor et al. 2011 [32]1,034 (Meta- Analysis)Fluoxetine, paroxetine, bupropion, imipramine