Deep brain stimulation of the human reward system for major depression - Rationale, outcomes and outlook

Thomas E. Schlaepfer, Bettina H. Bewernick, Sarah Kayser, Rene Hurlemann, Volker A. Coenen

Research output: Contribution to journalReview articlepeer-review


Deep brain stimulation (DBS) as a putative approach for treatment-resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studies - all in relatively small patient populations and different target regions - have shown clinically relevant antidepressant effects in about half of the patients and very recently, DBS to a key structure of the reward system, the medial forebrain bundle, has yielded promising results within few days of stimulation and at much lower stimulation intensities. On the downside, DBS procedures in regions are associated with surgical risks (eg, hemorrhage) and psychiatric complications (suicidal attenuation, hypomania) as well as high costs. This overview summarizes research on the mechanisms of brain networks with respect to psychiatric diseases and - as a novelty - extrapolates to the role of the reward system in DBS for patients with treatment-resistant depression. It further evaluates relevant methodological aspects of today's research in DBS for TRD. On the scientific side, the reward system has an important yet clearly under-recognized role in both neurobiology and treatment of depression. On the methodological side of DBS research in TRD, better animal models are clearly needed to explain clinical effects of DBS in TRD. Larger sample sizes, long-term follow-up and designs including blinded sham control are required to draw final conclusions on efficacy and side effects. Practical research issues cover study design, patient tracking, and the discussion of meaningful secondary outcome measures.

Original languageEnglish (US)
Pages (from-to)1303-1314
Number of pages12
Issue number6
StatePublished - May 2014
Externally publishedYes


  • deep brain stimulation
  • major depression
  • medial forebrain bundle
  • neuromodulation
  • nucleus accumbens
  • reward system

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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