Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review

Abstract

We reviewed trigeminal nerve stimulation (TNS) and transcutaneous vagus nerve stimulation (tVNS). All techniques have shown preliminary promising results, although the results are mixed. Method: We performed a systematic review of the Medline and Embase databases, with no constraint to dates, through June 2013. The keywords were [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders. Results: We included four preclinical and clinical five studies on TNS. All clinical data were based on open-label studies with small samples, which diminished the external validity of the results, thus reflecting the modest impact of TNS in current clinical practice. Of the tVNS clinical trials, three assessed physiological features in healthy volunteers, and one examined patients with epilepsy. Conclusion: TNS and tVNS improve treatment of particular neuropsychiatric disorders such as depression.Keywords: transcutaneous nerve stimulation, trigeminal stimulation, neuropsychiatric disorders. RESUMO O uso de estimulação de nervos cranianos de maneira transcutânea tem sido uma estratégia em desenvolvimento recente. Diferentes estudos apontam para resultados clínicos favoráveis no tratamento de diferentes quadros neuropsiquiátricos. Método: Revisão sistemática da literatura com base nas bibliotecas eletrônicas Medline e Embase, sem restrição de data inicial, até agosto de 2013. Os termos de busca utilizados foram [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders. Resultados: Incluímos quatro estudos pré-clinicos e cinco estudos clínicos abordando estimulação do nervo trigêmeo. Todos os estudos foram abertos, com pequenas amostras, o que reduz a validade externa dos dados, refletindo a ainda incipiente atuação da técnica, apesar de promissora. Considerando-se a estimulação do nervo vago, três artigos avaliaram aspectos fisiológicos em voluntários saudáveis e um artigo estudou pacientes com epilepsia. Conclusão: As estratégias de estimulação transcutânea de nervos cranianos, apesar de incipiente, tem demonstrado resultados clínicos favoráveis no tratamento de distúrbios neuropsiquiátricos.Palavras-chave: estimulação transcutânea de nervos cranianos, estimulação do nervo trigêmeo, distúrbios neuropsiquiátricos.

Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans

“…Both LC and NTS are considered as nuclei which disseminate neuromodulatory compound (Fanselow 2012) in the CNS, since they profoundly affect its excitability at virtually all levels. In addition, the LC and the NTS are believed to play a key role in mediating the clinical benefits observed following TNS in several neurological and neuropsychiatric disorders such as epilepsy, depression, anxiety and migraine (Shiozawa et al 2014;Fanselow 2012). In addition to the indirect effects on the lateral reticular formation, TNS can also modulate the activity of interneurons in the lateral tegmental field.…”

Trigeminal Nerve Stimulation (TNS) for Post-traumatic Stress Disorder: A Case Study

“…According to this hypothesis, the propagation of electric stimuli follows an inverse path from peripheral nerves toward the brain stem and central structures. The centrifuges electric propagation throughout neurons contrasts with the well-known "top-down" mechanism of other modulation strategies, such as electroconvulsive therapy and transcranial magnetic stimulation, in which the stimulus acts first on central brain structures, with propagation later to peripheral sites [11].…”

Transcutaneous Vagus and Trigeminal Nerve Stimulation: A New Perspective in the Treatment of Psychiatric Disorders

“…Different brain sites can be modulated throughout the use of electrical currents, what could restaure balance to impaired circuits leading to clinical amelioration of symptoms [6,7]. The rational for using trigeminal or vagus nerves for delivering electric current toward specific brain areas is the anatomical correlation these nerves maintain with sites related to psychiatric symptoms such as the amygdala, insula, precentral gyrus, hippocampus, thalamus and prefrontal cortex (structures widely related to cognitive functioning and mood regulation).…”

“…The rational for using trigeminal or vagus nerves for delivering electric current toward specific brain areas is the anatomical correlation these nerves maintain with sites related to psychiatric symptoms such as the amygdala, insula, precentral gyrus, hippocampus, thalamus and prefrontal cortex (structures widely related to cognitive functioning and mood regulation). Therefore, both TNS and tVNS modulate brain structures throughout the "bottom-up" hypothesis, in which stimulation of these nerves would propagate to its cortical and subcortical projections [7]. Following this hypothesis, Cook et al have initially proposed transcutaneous stimulation of the supraorbitary branch of the trigeminal nerve (TNS) with interesting results for major depressive disorder [8,9].…”