Trigeminal Nerve Stimulation for Major Depressive Disorder: An Updated Systematic Review

Abstract

Context: Trigeminal nerve stimulation (TNS) is a promising non-invasive brain stimulation intervention. The TNS has been proposed for major depressive disorder (MDD) with auspicious results. The aim of this study was to review the literature on TNS for MDD. Evidence Acquisition: Systematic review, using MEDLINE and EMBASE, of first articles available until 22nd of April 2016. Results: We included seven studies; six of them were open-label studies and one sham-controlled randomized double-blinded trial. Most studies had small sample sizes. Two studies were on MDD with comorbid posttraumatic stress disorder and one study focused on the elderly population. Two different protocols of stimulation were reported. Studies had interesting positive results for treating MDD. Conclusions:The TNS was reported to be well tolerated, with no severe adverse effect reported, and had impressive results for MDD. This promising, safe and easy-to-use new neuromodulation technique could be a useful tool for MDD treatment. However, the results reported in the studies performed so far must be analyzed under the strict limitations of the study design. Most of the studies on TNS are case studies or open-label trials with very small sample sizes. We acknowledge that it is the time to initiate more rigorous sham-controlled trials to better understand the huge potential involved with this technique, which could lead to the development of more accessible, easy-to-use, safe and non-invasive technology.

Liking of salt is associated with depression, anxiety, and stress

“…Increased firing of VP neurons is also found in depression and silencing of VP neurons can ameliorate depressive-like behaviors ( Knowland et al 2017 ). Increased salt intake driven by liking of salt ( Hayes et al 2010 ; Pilic et al 2020 ) may lead to TN nerve stimulation ( Simon et al 2008 ; Bigiani, 2020 , 2021 ) which ameliorates depression ( Schrader et al 2011 ; Cook et al 2013 ; Paulino Trevizol and Cordeiro 2016 ; Generoso et al 2019 ) and anxiety ( Trevizol et al 2015 ; Freire et al 2020 ). Liking of salty foods can be reduced through exposure to lower sodium diets ( Riis et al 2021 ).…”

“…Therefore, there may be salt taste-associated changes to neurotransmitters, impacting mental health. High salt concentrations may modulate mood through stimulation of the trigeminal nerve (TN) ( Simon et al 2008 ; Bigiani 2020 , 2021 ) which also has an ameliorating effect on symptoms of depression ( Schrader et al 2011 ; Cook et al 2013 ; Paulino Trevizol and Cordeiro 2016 ; Generoso et al 2019 ) and anxiety ( Trevizol et al 2015 ; Freire et al 2020 ). Other studies have demonstrated increased neuronal activity in the ventral pallidum (VP), the center of hedonic liking in the brain ( Smith et al 2009 ; Root et al 2015 ), when salt liking increases under sodium depletion ( Tindell et al 2006 ) and in depression ( Knowland et al 2017 ).…”

Newer Neuromodulation Techniques for Psychiatric Disorders: A 2023 Update

“…Trigeminal nerve stimulation is a noninvasive neuromodulation technique that stimulates the peripheral cutaneous endings of the trigeminal nerve on the scalp, there by modulating the associated brain areas linked to trigeminal nerve nucleus. [44][45][46] Trigeminal nerve stimulation is safe, with no major side effects. 46 Existing evidence supports the potential role of trigeminal nerve stimulation in managing major depressive disorder, posttraumatic stress disorder, attention-deficit hyperactivity disorder (ADHD) and epilepsy.…”

“…[44][45][46] Trigeminal nerve stimulation is safe, with no major side effects. 46 Existing evidence supports the potential role of trigeminal nerve stimulation in managing major depressive disorder, posttraumatic stress disorder, attention-deficit hyperactivity disorder (ADHD) and epilepsy. [44][45][46][47][48]…”

“…Transcutaneous vagus nerve stimulation is a newer noninvasive neuromodulation technique that stimulates the auricular branch of vagus through electrode placement by modulating the activity of associated brain areas. [48][49][50][51] Transcutaneous vagus nerve stimulation is a safe technique and has been successfully used in managing refractory (drug-resistant) epilepsy 50,52 , depression 46 , and migraine. 49 Adverse effects of transcutaneous vagus nerve stimulation are often mild to moderate and may be manifested as erythema & pain at the stimulation site, headache, nausea, vertigo, fatigue.…”