Treatment-resistant and Multi-therapy resistant criteria for bipolar depression: A consensus definition

Diego Hidalgo-Mazzei, Michael Berk, Andrea Cipriani, Anthony Cleare, Arianna Di Florio, Daniel Dietch, John R Geddes, Guy Goodwin, Heinz Grunze, Joseph F Hayes, Ian Jones, Siegfried Kasper, Karine Macritchie, Hamish McAllister-Williams, Richard Morriss, Sam Nayrouz, Sofia Pappa, Daniel J Smith, Jair C Soares, Trisha SuppesPeter Talbot, Eduard Vieta, Stuart Watson, Lakshmi N Yatham, Allan H Young, Paul R A Stokes

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Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).
To reach consensus regarding threshold definitions criteria for TRBD and MTRBD.
Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method.
TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy.
The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.
Original languageEnglish
JournalBritish Journal of Psychiatry
Early online date6 Dec 2018
Publication statusPublished - 2018


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