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.

Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance: A Case Study.

We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers.

Trigeminal nerve stimulation (TNS) protocol for treating major depression: an open-label proof-of-concept trial.

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). DISCUSSION: 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. CONCLUSION: 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.

Safety of repeated transcranial direct current stimulation in impaired skin: a case report.

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique based on the application of a weak, direct electric current via 2 or more electrodes (anode and cathode) over the scalp. One concern when applying tDCS is skin burn. It has been suggested that skin lesions are related to changes in the local dermal homeostasis, and therefore, caution is warranted in patients with skin diseases (Loo et al [Int J Neuropsychopharmacol. 2011;14:425-426]). In this context, we believe that it would be useful for this emerging field of tDCS to report the preliminary safety of repeated application of tDCS in a patient with vitiligo, an autoimmune disorder characterized by depigmentation sites of the skin or mucous membranes. We report the case of a 31-year-old male patient with schizophrenia who underwent 10-daily tDCS sessions. He has had generalized vitiligo since childhood, and despite previous treatment, no current dermatologic follow-up was being carried out. Depigmentation sites were evident in different areas, particularly under the anodal area. We found that repeated anodal tDCS in 1 patient did not lead to skin lesions when applied over a vitiligo skin area. Some of the procedures that we used to buffer changes in skin temperature may have contributed to prevent tDCS-induced skin damage. Nevertheless, the exact conditions that lead to skin lesion are still unknown. Given the growing use and testing of tDCS, continuous assessment and reporting of local adverse effects are still warranted especially in conditions with increased risk of skin lesions such as in dermatologic conditions, skin burns, and previous skin damage.