Trigeminal nerve stimulation in major depressive disorder: first proof of concept in an open pilot trial

Epilepsy Behav. 2011 Nov;22(3):475-8. doi: 10.1016/j.yebeh.2011.06.026. Epub 2011 Aug 4.


Modulation of brain activity via trigeminal nerve stimulation is an emerging therapy in drug-resistant epilepsy. This cranial nerve also projects to structures implicated in depression (such as the nucleus tractus solitarius and locus coeruleus). We examined the effects of external trigeminal nerve stimulation in major depressive disorder as an adjunct to pharmacotherapy. Five adults (mean age 49.6, SD 10.9, three females and two males) participated in an 8-week open-label outpatient trial; all had persistent symptoms despite adequate pharmacotherapy, with a mean score on the 28-item Hamilton Depression Rating Scale of 25.4 (SD=3.9) at entry. Nightly stimulation over the V(1) branch was well tolerated. Both the clinician-rated 28-item Hamilton Depression Rating Scale (P=0.006) and the self-rated Beck Depression Inventory (P=0.0004) detected significant symptomatic improvement. This novel neuromodulation approach may have use as an adjunct to pharmacotherapy in major depressive disorder. Additional larger trials are needed to delineate efficacy and tolerability with greater reliability.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Depressive Disorder, Major / therapy*
  • Electric Stimulation Therapy / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Reproducibility of Results
  • Treatment Outcome
  • Trigeminal Nerve / physiology*
  • Young Adult