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

University of Groningen, Groningen, Groningen, Netherlands
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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    ABSTRACT: Background: Disturbances related to the arachidonic acid cascade and prostaglandin metabolism may be involved in the pathophysiology of bipolar disorder, as supported by a recent genome-wide association study meta-analysis; however, evidence from clinical studies on a transcriptional level is lacking. Two enzymes in the arachidonic acid cascade are the prostaglandin D synthase (PTGDS), which catalyzes the conversion of prostaglandin H2 to prostaglandin D2 (PGD2), and the aldo-keto reductase family 1 member C3 (AKR1C3), which catalyzes the reduction of PGD2. We aimed to test the hypothesis that mRNA expression of PTGDS and AKR1C3 is deregulated in rapid-cycling disorder patients in a euthymic or current affective state compared with healthy control subjects, and that expression alters with affective states.
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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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    • "Whereas the use of antidepressants is well established in unipolar depression, their efficacy in bipolar depression is under dispute (Fountoulakis et al., 2008; Gijsman et al., 2004; Moller et al., 2001; Sachs et al., 2007). Recent evidence suggests that antidepressants, particularly if used as monotherapy, may have mood destabilizing properties and trigger manic episodes, named treatment emergent affective switches (TEAS), and may even induce rapid cycling courses (Ghaemi, 2008; Leverich et al., 2006; Post et al., 2006; Schneck et al., 2008). Lithium as an alternative, again, has been studied mostly in combined populations of unipolar and bipolar depression. "
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