Nonpharmacologic treatments for treatment-resistant depression

Status: Decision completed

Policy context

Nonpharmacologic treatments for depression that does not respond to first line treatments was selected for review based on concerns about the safety, efficacy and cost of the treatments.  Depression is relatively common among adults and contributes to or is associated with higher rates of other disease processes, disability and reduced quality of life. This review will help to identify safe and effective evidenced-based care for TRD.

Primary criteria ranking

  • Safety = Medium
  • Efficacy = High
  • Cost = Medium

Assessment timeline

  • Draft Key Questions Published: September 19, 2013 
  • Public Comment Period: September 19 - October 3, 2013 
  • Draft Report Published: December 19, 2013 
  • Public Comment Period: Period: December 19 - January 17, 2014 
  • Final Report Published: February 24, 2014 
  • HTCC Public Meeting: March 21, 2014


According to a national U.S. survey conducted between 2001 and 2003, 16.6% of adults will experience a major depressive disorder (MDD) in their lifetime. Failure to respond to initial treatment plans involving psychotherapy and/or an antidepressant medication is common. Treatment-resistant depression or TRD, is a term used to describe MDD that does not respond to initial treatment with antidepressant medication, which is considered appropriate for moderate to severe MDD. A large multicenter study (STAR*D) found that approximately one third of MDD patients achieved remission with an initial antidepressant and approximately half achieved remission after a second antidepressant trial, provided the patients remained in treatment. Although a standard definition of TRD is not recognized, a recent evidence report prepared for the Agency for Healthcare Research and Quality (AHRQ) concluded that there is an emerging consensus that failure of ≥ 2 prior adequate pharmacologic trials is an appropriate definition. Treatment resistance may also occur in depression related to bipolar disorder.

Nonpharmacologic treatments are often tried when pharmacotherapy has failed or has proved intolerable to a patient. Such options include electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), transcranial direct current stimulation (tDCS), and vagus nerve stimulation (VNS).

The Centers for Medicaid & Medicare Services has no national policy on ECT, TMS, DBS, or tDCS. The FDA has approved ECT for depression and has approved TMS and VNS specifically for TRD. The FDA has not approved DBS or tDCS for depression.