Antidepressants for the Acute Treatment of Bipolar Depression: A Systematic Review and Meta-Analysis

Department of Psychiatry, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9070, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 10/2010; 72(2):156-67. DOI: 10.4088/JCP.09r05385gre
Source: PubMed


The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression.
EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles.
Trials that compared acute (< 16 wk) antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch.
Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants.
Although antidepressants were found to be safe for the acute treatment of bipolar depression, their lack of efficacy may limit their clinical utility. Further high-quality studies are required to address the existing limitations in the literature.

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    • "For example, duloxetine (SNRI) is approved by the Food and Drug Administration (FDA) for the treatment of FM that may represent a hazard to a subset of individuals with undiagnosed comorbid BD (Hauser et al., 2009; Peritogiannis et al., 2009; Mustafa et al., 2010). Of note, however, the potential effects of antidepressant monotherapy in BD remains controversial, as numerous studies have also suggested that antidepressant therapy does not increase the risk of inducing mania, psychotic episodes, and/or rapid cycling (Sidor and Macqueen, 2011). In addition, tramadol, a commonly used drug in FM has been associated with the induction of mania (Watts and Grady, 1997). "
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    ABSTRACT: Background: Fibromyalgia (FM) is a chronic disorder with high morbidity and significant health service utilization costs. Few studies have reported on the phenotypic overlap of FM and bipolar disorder (BD). The aim of this review is to qualitatively and quantitatively summarize the results and clinical implications of the extant literature on the co-occurrence of FM and BD. Methods: A systematic search of PubMed/Medline, Cochrane, PsycINFO, CINAHL and Embase was conducted to search for relevant articles. Articles were included if incidence and/or prevalence of BD was determined in the FM sample. Results of prevalence were pooled from all studies. Pooled odds ratio (OR) was calculated based on case-control studies using standard meta-analytic methods. Results: A total of nine studies were included. The pooled rate of BD comorbidity in samples of FM patients was 21% (n=678); however, results varied greatly as a function of study methodology. Case-controlled studies revealed a pooled OR of 7.55 of BD co-morbidity in samples of FM patients [95% Confidence Interval (CI)=3.9-14.62, FM n=268, controls n=413] with low heterogeneity (I(2)=0%). Limitations: The current study was limited by the low number of available studies and heterogeneity of study methods and results. Conclusions: These data strongly suggest an association between BD and FM. Future studies employing a validated diagnostic screen are needed in order to more accurately determine the prevalence of BD in FM. An adequate psychiatric assessment is recommended in FM patients with suspected symptoms consistent with BD prior to administration of antidepressants in the treatment of FM.
    Journal of Affective Disorders 09/2015; 188:134-142. DOI:10.1016/j.jad.2015.08.030 · 3.38 Impact Factor
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    • "treatments are generally effective for the reversal of 60 manic episodes and preventing future episodes, these 61 medications have limited, if any, efficacy on their own in 62 the acute treatment of depressive episodes (McInerney 63 and Kennedy, 2014). Moreover, standard antidepressant 64 medications used either as monotherapies, or in conjunc- 65 tion with mood stabilizers or antipsychotics, are generally 66 ineffective for treating depressive episodes, and may 67 induce mood switching in a subset of patients with rapid 68 cycling BD (De Wilde and Doogan, 1982; Himmelhoch 69 et al., 1982; Gijsman et al., 2004; Amsterdam and 70 Shults, 2005; Sachs et al., 2007; McElroy et al., 2010; 71 Sidor and Macqueen, 2011; McInerney and Kennedy, 72 2014). Although there are a few studies suggesting ther- 73 apeutic efficacy of antidepressant monotherapy for bipo- 74 lar depression, current recommendations indicate 75 antidepressants be used only in combination with mood 76 stabilizers if those first-line medications fail (McInerney 77 and Kennedy, 2014). "
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    ABSTRACT: Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly 6 million (∼2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying 'mood' cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 08/2015; DOI:10.1016/j.neuroscience.2015.08.041 · 3.36 Impact Factor
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    • "Treatments for bipolar disorder : emphasis on bipolar depression Agents Indications in BD Status for bipolar depression References Antidepressants None for BD ; indication for 'major depression' widely assumed to include bipolar depression Clinically used Amit and Weizman (2012), Sidor and MacQueen (2011) (2012) Aripiprazole Mania, mixed-states and recurrences Mainly negative findings ; not approved for bipolar depression Thase et al. (2008) ; Cruz et al. (2010), De Fruyt et al. (2012) Asenapine Mania, mixed-states Experimental ; some evidence Cruz et al. (2010), De Fruyt et al. (2012) Carbamazepine Mania or mixed-states Not approved for bipolar depression Reinares et al. (2012) Deep brain stimulation Treatment-resistant depression Experimental ; some evidence Rizvi et al. (2011) Dopamine agonists a Proposed for bipolar depression Experimental ; some evidence Howland (2012) Divalproex Mania Not approved for bipolar depression Reinares et al. (2012) Electroconvulsive treatment Major and bipolar depression ; mania Clinically used ; FDA Class III medical device Dierckx et al. (2012) Gabapentin None for BD Not approved for bipolar depression Reinares et al. (2012) Glutamate NMDA-antagonists b Treatment-resistant & bipolar depression Experimental ; some evidence Owen (2012), Zarate et al. (2012) Lamotrigine Recurrences (mainly vs. depression) Not approved for bipolar depression Reinares et al. (2012) Levetiracetam None for BD Not approved for bipolar depression Saricicek et al. (2011) Light therapy (intensive) Depression, seasonal affective depression Experimental Poon et al. (2012) Lithium salts Mania, recurrences Not approved for bipolar depression Baldessarini (2013) Lurasidone Mania Not approved for bipolar depression De Fruyt et al. (2012) Modafinil, R-modafinil None for BD Experimental ; some evidence Frye et al. (2007) ; Calabrese et al. (2010) Olanzapine Mania, mixed-states, maintenance Some evidence ; approved in Japan Cruz et al. (2010), De Fruyt et al. (2012), Tohen et al. (2012) Olanzapine+Fluoxetine Treatment-resistant and acute bipolar depression FDA-approved Cruz et al. 2010, De Fruyt et al. 2012 Omega-3 fatty acids and other 'nutriceuticals' "

    03/2015; 13(1):102-112. DOI:10.1176/appi.focus.130119
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