title: Trigeminal nerve stimulation (TNS) protocol for treating major depression: an open-label proof-of-concept trial.
abstract: BACKGROUND
  Major depressive disorder (MDD) is an incapacitating mental disorder associated with significant personal, social, and economic impairment. Patients with MDD present lower quality of life and higher prevalence of medical conditions, including epilepsy. Noninvasive brain stimulation (NIBS) is a technique that might aid in overcoming some of the current challenges related to pharmacotherapy. Trigeminal nerve stimulation is an incipient, simple, low-cost interventional strategy based on the application of an electric current over a branch of the trigeminal nerve with further propagation of the stimuli toward brain areas related to mood symptoms.
  
  
  METHODS
  We performed an open-label proof-of-concept trial using TNS for MDD. To the best of our knowledge, we present a TNS interventional protocol that has not been evaluated for MDD hitherto.
  
  
  RESULTS
  A total of 11 patients were studied, with a mean age of 50.36 years (sd: 11.8 from 30 to 60). Only one patient was male. Regarding the main outcome, there was a reduction of depressive symptoms with a mean score of 5.72 (sd: 2.24) (p<0.001) on the HDRS-17. Considering a categorical analysis, all patients presented clinical response defined as a reduction of scores of at least 50%. Only one patient did not reach a remission score (defined as an HDRS score lower than 8).
  
  
  CONCLUSIONS
  In the current neuromodulation scenario, clinical results have been working as truly hypothesis-driven forces, i.e., empirical observation and data analysis from different studies have been highlighting possible mechanisms related to the neurobiological functioning of neuromodulation strategies. The present results, however significant, need to be taken as hypothesis-driven given the study design. Data generalization is jeopardized due to the present study lacking a control group. Our results, therefore, may be overestimated due to intrinsic characteristics such as the placebo effect and Hawthorne effect.
  
  
  CONCLUSIONS
  We present a proof-of-concept trial evaluating a new TNS protocol for depression. Data analysis underscores a significant participation of TNS in ameliorating depressive symptoms of patients with moderate or severe depressive episode. Further controlled studies will contribute to establish the clinical relevance of this new strategy for MDD.
authors.affiliation: The Clinical Neuromodulation Laboratory, Santa Casa Medical School, São Paulo, Brazil. Electronic address: pedroshiozawa@gmail.com.br.
authors.forename: Pedro
authors.initials: P
authors.lastname: Shiozawa
authors.affiliation: The Clinical Neuromodulation Laboratory, Santa Casa Medical School, São Paulo, Brazil.
authors.forename: Michel Silvio
authors.initials: MS
authors.lastname: Duailibi
authors.affiliation: The Clinical Neuromodulation Laboratory, Santa Casa Medical School, São Paulo, Brazil.
authors.forename: Mailu Enokibara
authors.initials: ME
authors.lastname: da Silva
authors.affiliation: The Clinical Neuromodulation Laboratory, Santa Casa Medical School, São Paulo, Brazil.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
mesh_terms: D000328:Adult; D002985:Clinical Protocols; D003865:Major Depressive Disorder / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D016896:Treatment Outcome; D014276:Trigeminal Nerve / Q000502:physiology*
keywords: Depression; Neuromodulation; Trigeminal nerve stimulation