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

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

Cook IA1,2,3,4, Abrams M1,2, Leuchter AF1,2.

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Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences at UCLA, Los Angeles, CA, USA.
NeuroSigma, Inc, Los Angeles, CA, USA.



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.


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).


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.


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.


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

[Indexed for MEDLINE]

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