title: Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review.
abstract: OBJECTIVE
  Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment-resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance.
  
  
  METHODS
  A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms.
  
  
  RESULTS
  Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2).
  
  
  CONCLUSIONS
  The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.
authors.affiliation: Department of Mood Disorders, University Psychiatric Center, Catholic University Leuven, Campus Kortenberg, Kortenberg, Belgium. pascal.sienaert@uc-kortenberg.be
authors.forename: Pascal
authors.initials: P
authors.lastname: Sienaert
authors.forename: Lore
authors.initials: L
authors.lastname: Lambrichts
authors.forename: Annemiek
authors.initials: A
authors.lastname: Dols
authors.forename: Jürgen
authors.initials: J
authors.lastname: De Fruyt
mesh_terms: D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D019317:Evidence-Based Medicine / Q000379:methods*; D006801:Humans
chemical_list: D018692:Antimanic Agents