Ivan Taiar

Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: A phase II, sham-controlled, randomized clinical trial

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. METHOD 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. DISCUSSION 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. CONCLUSION Further controlled studies will contribute to the establishment of the clinical relevance of this new treatment strategy for MDD.

Transcutaneous Vagus Nerve Stimulation (taVNS) for Major Depressive Disorder: An Open Label Proof-of-Concept Trial

Despite recent advances in pharmacological treatments, Major Depressive Disorder (MDD) remains an incapacitating psychiatric condition with increasing prevalence and economic burden [1]. New therapeutical strategies such as vagus nerve stimulation (VNS) are being studied [2]. Different brain sites can be modulated by using electrical currents, which can theoretically restore balance to impaired circuits leading to clinical amelioration of symptoms. VNS involves the direct stimulation of the vagus nerve leading to further modulation of impaired brain areas related to psychiatric disorders [3,4]. Target stimulated areas include solitary tract nucleus, dorsal raphe, locus coeruleus, parabrachial area, amygdala, nucleus accumbent, hippocampus and the dorsolateral prefrontal cortex (DLPFC) [5]. Non-invasive VNS stimulation protocols have been assessed with promising results [6]. In fact, our group and others have recently proposed a hypothetically safer non-invasive approach for transcutaneously stimulating the vagus nerve in the ear, transcutaneous auricular VNS (taVNS) [7]. There are also methods for noninvasively stimulating the vagus nerve in the neck, or cervical region, called transcutaneous cervical VNS (tcVNS).We undertook this proofof-concept study to evaluate both the safety and potential clinical efficacy of this new experimental protocol with taVNS for treating patients with MDD. The present protocol had approval from institutional review board. Patients diagnosed with MDD according to the DSM-V criteria were recruited in an outpatient university hospital clinic. Symptom severity was assessed by the 17-itemHamilton Depression Rating Scale (HDRS). Exploratory analyses assessed depressive symptoms through the Beck Depression Inventory (BDI), anxiety symptoms through the Hamilton Anxiety Rating Scale (HAMA) and the Beck Anxiety Inventory (BAI), sleep quality through the Pittsburgh Sleep Quality Index (PSQI), and somatic symptoms through the Somatic Symptom Inventory (SSI) and the Somatoform Disorders Screening Instrument-7 days (SOMS-7). We also assessed cognitive functions with the Montreal Cognitive Assessment instrument (MoCA). Inclusion criteria were as follows: (1) 18to 59-year-old patients, (2) patients diagnosed with MDD following DSM-V criteria, (3) agreement to participate in the trial with written informed consent. Exclusion criteria were the following: (1) imminent need for psychiatric hospitalization, (2) any other [current or lifetime] psychiatric diagnosis, (3) neurologic or other severe diseases such as neoplastic syndromes and neurodegenerative and uncompensated chronic comorbidities, and (4) pregnancy. Clinical assessment was performed by a trained psychiatrist at baseline, at the last day of the stimulation protocol and one month after. The primary outcome was assessed by the mean difference in HDRS scores between baseline and the last day of stimulation. Participants were required to have at least four weeks without a change in psychiatric medication before the beginning of taVNS stimulation until the end of the one-month follow-up period. All patients underwent a 10-session taVNS protocol during a twoweek period. Electrical stimulationwas performed using the Ibramed Neurodyn II external neurostimulator to deliver electric current through the auricular branch of the vagus nerve at 120 Hz with a pulse wave duration of 250 μs for 30 minutes per day. The intensity was set at 12mA, which provoked a nonpainful mild paresthesia without muscle contraction for all patients. We performed the stimulation placing the electrodes bilaterally over the mastoid process area (anode to the left and cathode to the right), juxtaposed to the ear, near the tympanomastoid fissure (see Fig. 1) [8]. We used 15 cm2 auto-adhesive rubber electrodes to deliver the current. The present work was performed at the Interdisciplinary Center for Clinical Neuromodulation, Santa Casa School of Medical Sciences, São Paulo, Brazil. Figure 1. Anode positioning over the mastoid process area, juxtaposed to the ear. The cathode was positioned in the same way over the right mastoid process area.

Trigeminal nerve stimulation (TNS) for social anxiety disorder: A case study

Social anxiety disorder (SAD) is a common psychiatric condition with a lifetime prevalence rate of around 10%. Patients diagnosed with SAD present with marked occupational and social impairments as well as high comorbiditywith other psychiatric disorders such as depression and drug abuse/addiction [1]. Studies of neuromodulation strategies for anxiety disorders are in initial stages, lacking robust evidence. To the best of our knowledge, no study has evaluated the use of a neuromodulation strategy for SAD. In this report, we describe a 33-year-old male patient diagnosed with SAD according to DSM-V who successfully underwent a trigeminal nerve stimulation (TNS) intervention protocol, with amelioration of his symptoms. “Mr. C.” described that since hewas a little boy, he suffered from SAD, being forced to undergo home schooling since he was ten. The patient reported significant distress and occupational impairment that led him to quit college and work in socially isolated jobs. Prior to the TNS stimulation protocol, the patient had undergone pharmacological therapywith sertraline and venlafaxine aswell as cognitive–behavioral therapy for one year with poor clinical response. His medical presentation was unremarkable. The patient did not present any other psychiatric disorder. His family history was positive for SAD (father). Considering the severity of his symptoms and lack of clinical improvement with pharmacotherapy and psychotherapy, we proposed experimental TNS and the patient provided written informed consent (IRB-approved). During the stimulation protocol, the patient was not under any pharmacological treatment or psychotherapy and had not been so for the previous three months. Ten consecutive daily TNS sessions were performed. Electric stimulation was performed at 120 Hz with a pulse wave duration of 250 μs, continuously for 30 min per day. We used square auto-adhesive rubber electrodes of 25 cm placed over supraorbital trigeminal branches (V1) bilaterally following our previously tested protocol [2]. To assess the symptoms of SAD, we used the Social Phobia Inventory (SPIN) and the Liebowitz Social Anxiety Disorder Scale (LSAS).We also assessed cognitive functions with the Montreal Cognitive Assessment (MOCA). Cognitive functions were unaltered (23 at baseline and 24 at final outcome). Symptoms of SAD substantially improved during the 10-day treatment course and remained stable at the three-month follow-up. The patient reported significant global clinical gains (see Fig. 1). During the tenday period of stimulation, the patient reported gradual improvements on fear and anxiety that enabled him to face in part the avoidance. By the three-month follow-up, the patient reported significant

Transcranial Magnetic Stimulation and the Urge to Eat: A Comment on Lowe, Vincent, and Hall (2017)

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Determining an effective rTMS protocol for treating chronic tinnitus: focus on inhibiting the left temporoparietal cortex

temporoparietal cortex for rTMS study protocols as a promising site for treating chronic tinnitus. Our hypothesis for targeting this particular brain area follows previous neuroimaging findings which indicate activation of the temporoparietal cortex specifically during tinnitus perception [4, 5]. We evaluated the pooled effect size of rTMS over the left temporoparietal cortex for treating tinnitus regarding all data up-to-date available. Our efforts relied on methodological principles recommended by the Cochrane group for running a systematic review and meta-analysis [6]. All analyses were performed using the statistical packages for meta-analysis of Stata 12 for Mac OSX. The Hedges’ g was used as the measure of effect size, which is appropriate for studies of small sample sizes. The pooled effect size was weighted by the inverse variance method and measured using the random-effects model. Heterogeneity was evaluated with the I2 and the χ2 test. Publication bias was evaluated using Egger’s regression intercept test and the funnel plot, which displays confidence interval boundaries to assist in visualizing whether the studies are within the funnel, thus providing an estimate of publication bias. Sensitivity analysis, which assesses the impact of each study in the overall results by excluding one study at a time, was also performed. Our systematic review initially yielded twenty-nine studies assessing rTMS for chronic tinnitus, we then excluded all studies which did not adopt the left temporoparietal cortex as stimulation site. A total of five studies fulfilled eligibility criteria and were included in final analysis [1, 7–10] (n = 200). Four studies assessed tinnitus amelioration with Tinnitus Handicap Inventory (THI) studies and one study used Visual Analogue Scale (VAS) to verify the same outcome. rTMS frequency adopted varied from 1 up to 25 Hz. Data were analyzed based on subgroup frequency analysis, i.e., studies assessing different frequencies were Dear Editor,

N-Acetylcysteine for Treating Compulsive Behavior: An Updated Meta-Analysis.

To the Editors: C ompulsive behavior disorders stand for a diagnostic cluster that involves repetitive and ritualized behaviors. Different psychiatric conditions such as obsessivecompulsive disorder, body dysmorphic disorder, trichotillomania, hoarding disorder, and excoriation disorder are some of the main disorders included under this diagnosis. Increasing research evidence demonstrating common threads running through different psychiatric conditions