Mood switch in bipolar depression: Comparison of adjunctive venlafaxine, bupropion and sertraline

Department of Health and Human Services, National Institute of Mental Health, Bethesda, Maryland, USA.
The British Journal of Psychiatry (Impact Factor: 7.99). 09/2006; 189(2):124-31. DOI: 10.1192/bjp.bp.105.013045
Source: PubMed


Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression.
To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers.
In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers.
A total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49-53%) and remission (34-41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline.
More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.

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    • "This is corroborated by preclinical evidence pointing to the arachidonic cascade as a target of drugs used to manage bipolar disorder (Rapoport and Bosetti, 2002; Bazinet, 2009), indicating that lithium (Galimberti et al., 2014), valproate (Kieseppa et al., 2014), carbamazepine (Lee et al., 2012), and antipsychotics (Cheon et al., 2011) decrease AA turnover in the brain. In contrast, the antidepressants imipramine and fluoxetine, which may induce mania, increase brain AA turnover, while bupropion, which may be at lower risk of inducing mania (Post et al., 2006), does not alter AA turnover (Lee et al., 2007, 2010). These findings have led to the formulation of the arachidonic acid theory of bipolar disorder (Bazinet, 2009). "
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    The International Journal of Neuropsychopharmacology 12/2014; 18(5). DOI:10.1093/ijnp/pyu101 · 4.01 Impact Factor
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    • "While a somewhat higher risk was associated with the use of the SNRI venlafaxine [40] or tricyclic antidepressants [22], data interpretation is difficult due to the lack of comparison to placebo [40], as well as the lack of use of objective clinical scales to assess an affective switch [22]. Indeed, considerable inconsistency exists between studies regarding the definition of such a switch, including the use of different scales, such as the Clinical Global Impression for Bipolar Disorder (CGI-BP) [40] or the Young Mania Rating Scale (YMRS), or using different cutoff scores for mania or hypomania on the scale, such as a YMRS score of 16 [14], 14 [31], 13 [40], 12 [29], or 8 [15]. The result is making data applicability to clinical practice difficult. "
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