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      Who will benefit from antidepressants in the acute treatment of bipolar depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q-learning

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          Abstract

          Background

          There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders.

          Methods

          Traditional randomized controlled trials and statistical methods are not designed to discover if, when, and to whom an intervention should be applied; thus, other methodological approaches are needed that allow for the practice of personalized, evidence-based medicine with patients with bipolar depression.

          Results

          Dynamic treatment regimes operationalize clinical decision-making as a sequence of decision rules, one per stage of clinical intervention, that map patient information to a recommended treatment. Using data from the acute depression randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime via Q-learning.

          Conclusions

          The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a mandatory mood stabilizer.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s40345-014-0018-5) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          Fully conditional specification in multivariate imputation

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            Optimal dynamic treatment regimes

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              The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.

              The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.
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                Author and article information

                Contributors
                fwu5@ncsu.edu
                eblaber@ncsu.edu
                Ilya.Lipkovich@quintiles.com
                Emanuel.Severus@uniklinikum-dresden.de
                Journal
                Int J Bipolar Disord
                Int J Bipolar Disord
                International Journal of Bipolar Disorders
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2194-7511
                3 April 2015
                3 April 2015
                2015
                : 3
                : 7
                Affiliations
                [ ]Department of Statistics, North Carolina State University, 2311 Stinson Drive, Raleigh, 27695 USA
                [ ]Quintiles, 4820 Emperor Blvd, Durham, 27703 USA
                [ ]Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden,, Fetscherstraße 74,, 01307 Dresden Germany
                Article
                18
                10.1186/s40345-014-0018-5
                4383759
                2029a4ae-ec7d-40cb-9f01-a5befdc51fb7
                © Wu et al.; licensee Springer. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 30 June 2014
                : 30 December 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                bipolar disorders,q-learning,antidepressant,dynamic treatment regimes

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