title: Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: a phase II, sham-controlled, randomized clinical trial.
abstract: BACKGROUND
  Considering both the burden determined by major depressive disorder (MDD) itself and the high refractoriness and recurrence index, alternative strategies, such as trigeminal nerve stimulation (TNS), are the cutting edge instruments to optimize clinical response and to avoid treatment discontinuation and relapse of symptoms. 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 towards brain areas related to mood symptoms.
  
  
  METHODS
  The study was a phase II, randomized, sham-controlled trial with 40 patients with MDD. Patients with moderate or severe depressive symptoms as assessed by adequate clinical scales underwent a 10-day intervention protocol. Regarding main clinical outcome, analysis of variance (ANOVA) was performed to evaluate mean change scores in depressive symptoms as assessed by the HDRS-17 between baseline (t1), after intervention protocol (t2), and during one-month follow-up (t3).
  
  
  RESULTS
  There was a significant interaction between the mean percentage changes in depressive symptoms according to the HDRS in the two groups across the three assessments (F=6.38, df=2, p=0.0033). Post hoc analyses (Bonferroni method) demonstrated a statistically significant difference between depressive symptoms at baseline and t1 (p=0.01) and between depressive symptoms at baseline and t2 (p=0.009). No severe adverse effects were reported.
  
  
  CONCLUSIONS
  Our results in the present controlled trial highlight the possibility of more practical treatment protocols for clinical research, which are similar to those for different neuromodulation strategies such as transcranial direct current stimulation (tDCS). The in-office administration of TNS in our protocol is similar to the schedule for repetitive transcranial magnetic stimulation (rTMS), though over fewer treatment sessions.
  
  
  CONCLUSIONS
  Further controlled studies will contribute to the establishment of the clinical relevance of this new treatment strategy for MDD.
authors.affiliation: Clinical Neuromodulation Laboratory, Santa Casa de São Paulo School of Medicine, Brazil. Electronic address: pedroshiozawa@gmail.com.br.
authors.forename: Pedro
authors.initials: P
authors.lastname: Shiozawa
authors.affiliation: Clinical Neuromodulation Laboratory, Santa Casa de São Paulo School of Medicine, Brazil.
authors.forename: Mailu Enokibara
authors.initials: ME
authors.lastname: da Silva
authors.affiliation: Clinical Neuromodulation Laboratory, Santa Casa de São Paulo School of Medicine, Brazil.
authors.forename: Geraldo Teles Machado
authors.initials: GT
authors.lastname: Netto
authors.affiliation: Clinical Neuromodulation Laboratory, Santa Casa de São Paulo School of Medicine, Brazil.
authors.forename: Ivan
authors.initials: I
authors.lastname: Taiar
authors.affiliation: Clinical Neuromodulation Laboratory, Santa Casa de São Paulo School of Medicine, Brazil.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
mesh_terms: D000328:Adult; D000339:Affect; D000368:Aged; D003865:Major Depressive Disorder / Q000523:psychology / Q000628:therapy*; D004599:Electric Stimulation Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012449:Safety; D065908:Transcranial Direct Current Stimulation; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome; D014276:Trigeminal Nerve
keywords: Depression; Neuromodulation; Trigeminal nerve stimulation