Treatment-resistant bipolar depression: towards a new definition

Acta Psychiatr Scand. 2009 Dec;120(6):429-40. doi: 10.1111/j.1600-0447.2009.01471.x. Epub 2009 Sep 9.


Objective: To summarize the conceptual and operational definitions of treatment-resistant bipolar depression and to review the evidence-based therapeutic options.

Method: Structured searches of PubMed, Index Medicus, Excerpta Medica and Psyclit conducted in December 2008.

Results: Criteria for treatment resistance in bipolar depression are commonly based on concepts stemming from treatment resistance as defined for unipolar depression, an approach that proved to be inadequate. In fact, the addition of an ad hoc criterion based on lithium and other mood stabilizer unresponsiveness after reaching adequate plasma levels appears to be a patch that attempts to take into account the uniqueness of bipolar depression but fails to become operational. Recent data from randomized clinical trials of new anticonvulsants and second-generation antipsychotics should lead to the development of a modern definition of treatment-resistant bipolar depression, and specific therapeutic algorithms.

Conclusion: We suggest a redefinition of resistant bipolar I and II depression. We propose different degrees of severity within bipolar depression in a stepwise manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / drug therapy*
  • Dibenzothiazepines / pharmacology
  • Dibenzothiazepines / therapeutic use
  • Drug Resistance / drug effects*
  • Evidence-Based Practice*
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use
  • Humans
  • Lithium / pharmacology
  • Lithium / therapeutic use
  • Olanzapine
  • Quetiapine Fumarate
  • Randomized Controlled Trials as Topic


  • Anticonvulsants
  • Antidepressive Agents
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Fluoxetine
  • Benzodiazepines
  • Quetiapine Fumarate
  • Lithium
  • Olanzapine