The hidden third: Improving outcome in treatment-resistant depression

Thomas E. Schlaepfer, Hans Ågren, Palmiero Monteleone, Cristobal Gasto, William Pitchot, Frederick Rouillon, David J. Nutt, Siegfried Kasper

Research output: Contribution to journalReview articlepeer-review


Treatment-resistant depression (TRD) presents many challenges for both patients and physicians. This review aims to evaluate the current status of the field of TRD and reflects the main findings of a consensus meeting held in September 2009. Literature searches were also conducted using PubMed and EMBASE. Abstracts of the retrieved articles were reviewed independently by the authors for inclusion. Evaluation of the clinical evidence in TRD is complicated by the absence of a validated definition, and there is a need to move away from traditional definitions of remission based on severity of symptoms to one that includes normalisation of functioning. One potential way of improving treatment of TRD is through the use of predictive biomarkers and clinical variables. The advent of new treatments may also help by focusing on neurotransmitters other than serotonin. Strategies such as the switching of antidepressants, use of combination therapy with lithium, atypical antipsychotics and other pharmacological agents can improve outcomes, and techniques such as deep brain stimulation and vagus nerve stimulation have shown promising early results. Despite consistent advances in the pharmacotherapy of mood disorders in the last decade, high rates of TRD are still a challenging aspect of overall management.

Original languageEnglish (US)
Pages (from-to)587-602
Number of pages16
JournalJournal of Psychopharmacology
Issue number5
StatePublished - May 2012
Externally publishedYes


  • Major depressive disorder
  • outcomes
  • remission
  • treatment resistance

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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