Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder

Neuromodulation. 2016 Apr;19(3):299-305. doi: 10.1111/ner.12399. Epub 2016 Jan 28.


Objectives: External stimulation of the trigeminal nerve (eTNS) is an emerging neuromodulation therapy for epilepsy and depression. Preliminary studies suggest it has an excellent safety profile and is associated with significant improvements in seizures and mood. Neuroanatomical projections of the trigeminal system suggest eTNS may alter activity in structures regulating mood, anxiety, and sleep. In this proof-of-concept trial, the effects of eTNS were evaluated in adults with posttraumatic stress disorder (PTSD) and comorbid unipolar major depressive disorder (MDD) as an adjunct to pharmacotherapy for these commonly co-occurring conditions.

Materials and methods: Twelve adults with PTSD and MDD were studied in an eight-week open outpatient trial (age 52.8 [13.7 sd], 8F:4M). Stimulation was applied to the supraorbital and supratrochlear nerves for eight hours each night as an adjunct to pharmacotherapy. Changes in symptoms were monitored using the PTSD Patient Checklist (PCL), Hamilton Depression Rating Scale (HDRS-17), Quick Inventory of Depressive Symptomatology (QIDS-C), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

Results: Over the eight weeks, eTNS treatment was associated with significant decreases in PCL (p = 0.003; median decrease of 15 points; effect size d 1.5), HDRS-17 (p < 0.001; 42% response rate, 25% remission; d 2.1), and QIDS-C scores (p < 0.001; d 1.8), as well as an improvement in quality of life (Q-LES-Q, p < 0.01). eTNS was well tolerated with few treatment emergent adverse events.

Conclusions: Significant improvements in PTSD and depression severity were achieved in the eight weeks of acute eTNS treatment. This novel approach to wearable brain stimulation may have use as an adjunct to pharmacotherapy in these disorders if efficacy and tolerability are confirmed with additional studies.

Keywords: external stimulation of the trigeminal nerve; major depressive disorder; neuromodulation; non-invasive brain stimulation; posttraumatic stress disorder; trigeminal nerve stimulation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Depressive Disorder, Major / complications*
  • Depressive Disorder, Major / therapy*
  • Electric Stimulation Therapy / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • Stress Disorders, Post-Traumatic / complications*
  • Stress Disorders, Post-Traumatic / therapy*
  • Treatment Outcome
  • Trigeminal Nerve / physiology*
  • Young Adult