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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Available from: Paul E Keck, Oct 13, 2015
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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.
    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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    ABSTRACT: While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD), recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability. Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review. Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy. Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted.
    Depression research and treatment 01/2012; 2012(6):684725. DOI:10.1155/2012/684725
    • "Although confirmatory evidence for antidepressant-induced hypomania/mania was not found through a meta-analysis and systematic reviews of antidepressant trials for bipolar depression,[37–39] the limitations in the designs of previous trials could make a substantial contribution toward these results. Both clinical characteristics of individuals and biochemical profile of antidepressants may be involved in affective instability led by antidepressant use.[4041] With regards to the risk of polarity switch and overdose, selective serotonin reuptake inhibitors are generally preferable to tricyclic antidepressants.[7] "
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    ABSTRACT: Patients with bipolar disorder spend more time in a depressed than manic state, even with individualized treatment. To date, bipolar depression is often misdiagnosed and ineffectively managed both for acute episodes and residual symptoms. This review attempts to summarize the current status of available treatment strategies in the treatment of bipolar depression. For acute and prophylactic treatment, a substantial body of evidence supports the antidepressive efficacy of lithium for bipolar disorders and its antisuicidal effects. Among numerous anticonvulsants with mood-stabilizing properties, valproate and lamotrigine could be first-line options for bipolar depression. Due to receptor profile, mood-stabilizing properties of second-generation antipsychotics have been explored, and up to date, quetiapine and olanzapine appear to be a reasonable option for bipolar depression. The usefulness of antidepressants in bipolar depression is still controversial. Current guidelines generally recommend the cautious antidepressant use in combination with mood stabilizers to reduce the risk of mood elevation or cycle acceleration. Results from clinical trials on psychosocial intervention are promising, especially when integrated with pharmacotherapy. Most patients with bipolar depression need individualized and combined treatment, although the published evidence on this type of treatment strategy is limited. Future studies on the utility of currently available agents and modalities including psychosocial intervention are required.
    Indian Journal of Psychological Medicine 03/2011; 33(1):11-7. DOI:10.4103/0253-7176.85390
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