Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. long-term trials of MG-101 prophylactic benefits have MG-101 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 MG-101 consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions 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. MG-101 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. The efficacy and MG-101 safety of antidepressant drug treatment in bipolar disorder is the subject of long-standing debate based on a scientific literature that is limited and inconsistent (1-6). The sparseness of high-quality clinical research hampers the formulation of sound clinical recommendations on the use of antidepressants in the treatment of bipolar disorder (7-12). We propose that a consensus formed by the experience and judgment of clinical and academic bipolar disorder experts guided by the available research findings may help in developing at least tentative treatment recommendations as additional research is awaited. Accordingly the International Society for Bipolar Disorders (ISBD) appointed Dr. Vieta to assemble a task force of international experts to review the evidence base for benefits and risks of antidepressant treatment in bipolar disorder and to formulate clinical recommendations based on the consensus development process. This report represents a consensus statement from this endeavor. Method Consensus Methods The ISBD Task Force was made up of a panel of global experts on bipolar disorder selected according to an objective procedure based on a Scopus search of citations on the specific topic of antidepressant use in bipolar disorder (number of citations per candidate during the past 3 years). The most cited authors (including several ISBD nonmembers) and some additional authors from key geographical areas were MG-101 identified and invited by e-mail to participate; 76% agreed to participate. An introductory meeting was held at the ISBD biennial congress (Istanbul March 2012) where task force procedures were reviewed and agreed upon. These procedures focused on the discussion and integration of findings from peer-reviewed published research findings on the topic including reviews and meta-analyses as well as clinical trial reports. An expert coauthor (I.P.) was appointed to develop a first draft of a systematic review to be circulated after initial review by the senior author (E.V.). The aims of the task force were to conduct a thorough and balanced review of research findings and to integrate them into an expert consensus based on clinical experience and judgment as well as research evidence and to provide a synthesis of current knowledge supporting clinical recommendations for this important and timely topic. The final section of this report which summarizes consensus statements was achieved through a face-to-face meeting personal and group e-mail correspondence and serial iterative revisions of the report in order to provide Cd33 a final guide on the use of antidepressants in bipolar disorder. Funding for this international project was provided solely by the Spanish government. Search Strategy We performed an extensive literature search on PubMed using the following search terms limited to human studies: antidepressant* AND (mania[ti] OR manic[ti]); antidepressant* AND (bipolar[ti] AND depressi*[ti]); antidepressant* AND (mixed [ti] AND state*[ti]); antidepressant* AND bipolar disorder AND maintenance[ti]; antidepressant* AND bipolar disorder AND comorbid*[ti]; antidepressant* AND switch AND (manic OR mania OR hypomani*); antidepressant* AND (cycle acceleration OR phase shift OR cycle frequen*); and antidepressant* AND (suicid*[ti] OR self-kill*[ti] OR.