N100 as a response prediction biomarker for accelerated 1 Hz right DLPFC-rTMS in major depression.

BACKGROUND AND OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD); however, this treatment currently lacks reliable biomarkers of treatment response. TMS-evoked potentials (TEPs), measured using TMS-electroencephalography (TMS-EEG), have been suggested as potential biomarker candidates, with the N100 peak being one of the most promising. This study investigated the association between baseline N100 amplitude and 1 Hz right dorsolateral prefrontal cortex (R-DLPFC) accelerated rTMS (arTMS) treatment in MDD. METHODS: Baseline TMS-EEG sessions were performed for 23 MDD patients. All patients then underwent 40 sessions of 1 Hz R-DLPFC (F4) arTMS over 5 days and a follow-up TMS-EEG session one week after the end of theses arTMS sessions. RESULTS: Baseline N100 amplitude at F4 showed a strong positive association (p < .001) with treatment outcome. The association between the change in N100 amplitude (baseline to follow-up) and treatment outcome did not remain significant after Bonferroni correction (p = .06, corrected; p = .03, uncorrected). Furthermore, treatment responders had a significantly larger mean baseline F4 TEP amplitude during the N100 time frame compared to non-responders (p < .001). Topographically, after Bonferroni correction, F4 is the only electrode at which its baseline N100 amplitude showed a significant positive association (p < .001) with treatment outcome. LIMITATIONS: Lack of control group and auditory masking. CONCLUSION: Baseline N100 amplitude showed a strong association with treatment outcome and thus demonstrated great potential to be utilized as a cost-effective and widely adoptable biomarker of rTMS treatment in MDD.

Cardiovascular biomarkers of response to accelerated low frequency repetitive transcranial magnetic stimulation in major depression.

BACKGROUND AND OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD). rTMS is in need of a reliable biomarker of treatment response. High frequency (HF) dorsolateral prefrontal cortex (DLPFC) rTMS has been reported to induce significant changes in the cardiac activity of MDD patients. Low frequency DLPFC rTMS has many advantages over HF-DLPFC rTMS and thus this study aims to further investigate the effect of low frequency 1 Hz right hemisphere (R)-DLPFC rTMS on the cardiac activity of MDD patients, as well as the potential of using electrocardiogram (ECG) parameters as biomarkers of treatment outcome. METHODS: Baseline ECG sessions were performed for 19 MDD patients. All patients then underwent 40 sessions of accelerated 1 Hz R-DLPFC rTMS one week after the baseline session. RESULTS: Heart rate (HR) significantly decreased from the resting period to the first and third minute of the 1 Hz R-DLPFC rTMS period. Resting HR was found to have a significant negative association with treatment outcome. Prior to Bonferroni correction, HR during stimulation and the degree of rTMS-induced HR reduction were significantly negatively associated with treatment outcome. No significant changes were observed for the heart rate variability (HRV) parameters. LIMITATIONS: Sample size (n = 19); the use of electroencephalography equipment for ECG; lack of respiration monitoring; relatively short recording duration for HRV parameters. CONCLUSION: This novel study provides further preliminary evidence that ECG may be utilized as a biomarker of rTMS treatment response in MDD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04376697.

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series.

Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.

Support for health care workers and psychological distress: thinking about now and beyond the COVID-19 pandemic. / Soutien aux travailleurs de la santé et détresse psychologique : réflexion sur la situation actuelle et la période suivant la pandémie de COVID-19.

INTRODUCTION: This study explores the relationship between emotional support, perceived risk and mental health outcomes among health care workers, who face high rates of burnout and mental distress since the beginning of the COVID-19 pandemic. METHODS: A cross-sectional, multicentred online survey of health care workers in the Greater Toronto Area, Ontario, Canada, during the first wave of the COVID-19 pandemic evaluated coping strategies, confidence in infection control, impact of previous work during the 2003 SARS outbreak and emotional support. Mental health outcomes were assessed using the Generalized Anxiety Disorder scale, the Impact of Event Scale - Revised and the Patient Health Questionnaire (PHQ-9). RESULTS: Of 3852 participants, 8.2% sought professional mental health services while 77.3% received emotional support from family, 74.0% from friends and 70.3% from colleagues. Those who felt unsupported in their work had higher odds ratios of experiencing moderate and severe symptoms of anxiety (odds ratio [OR] = 2.23; 95% confidence interval [CI]: 1.84-2.69), PTSD (OR = 1.88; 95% CI: 1.58-2.25) and depression (OR = 1.88; 95% CI: 1.57-2.25). Nearly 40% were afraid of telling family about the risks they were exposed to at work. Those who were able to share this information demonstrated lower risk of anxiety (OR = 0.58; 95% CI: 0.48-0.69), PTSD (OR = 0.48; 95% CI: 0.41-0.56) and depression (OR = 0.55; 95% CI: 0.47-0.65). CONCLUSION: Informal sources of support, including family, friends and colleagues, play an important role in mitigating distress and should be encouraged and utilized more by health care workers.

Surviving SARS and living through COVID-19: Healthcare worker mental health outcomes and insights for coping.

OBJECTIVE: Explore how previous work during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak affects the psychological response of clinical and non-clinical healthcare workers (HCWs) to the current COVID-19 pandemic. METHODS: A cross-sectional, multi-centered hospital online survey of HCWs in the Greater Toronto Area, Canada. Mental health outcomes of HCWs who worked during the COVID-19 pandemic and the SARS outbreak were assessed using Impact of Events-Revised scale (IES-R), Generalized Anxiety Disorder scale (GAD-7), and Patient Health Questionnaire (PHQ-9). RESULTS: Among 3852 participants, moderate/severe scores for symptoms of post- traumatic stress disorder (PTSD) (50.2%), anxiety (24.6%), and depression (31.5%) were observed among HCWs. Work during the 2003 SARS outbreak was reported by 1116 respondents (29.1%), who had lower scores for symptoms of PTSD (P = .002), anxiety (P < .001), and depression (P < .001) compared to those who had not worked during the SARS outbreak. Multivariable logistic regression analysis showed non-clinical HCWs during this pandemic were at higher risk of anxiety (OR, 1.68; 95% CI, 1.19-2.15, P = .01) and depressive symptoms (OR, 2.03; 95% CI, 1.34-3.07, P < .001). HCWs using sedatives (OR, 2.55; 95% CI, 1.61-4.03, P < .001), those who cared for only 2-5 patients with COVID-19 (OR, 1.59; 95% CI, 1.06-2.38, P = .01), and those who had been in isolation for COVID-19 (OR, 1.36; 95% CI, 0.96-1.93, P = .05), were at higher risk of moderate/severe symptoms of PTSD. In addition, deterioration in sleep was associated with symptoms of PTSD (OR, 4.68, 95% CI, 3.74-6.30, P < .001), anxiety (OR, 3.09, 95% CI, 2.11-4.53, P < .001), and depression (OR 5.07, 95% CI, 3.48-7.39, P < .001). CONCLUSION: Psychological distress was observed in both clinical and non-clinical HCWs, with no impact from previous SARS work experience. As the pandemic continues, increasing psychological and team support may decrease the mental health impacts.

Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study.

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.

Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation for treatment-refractory major depressive disorder: A three-arm, blinded, randomized controlled trial.

BACKGROUND: Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. OBJECTIVE: The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. METHODS: 120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. RESULTS: Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians' treatment arm guesses were significantly above chance. CONCLUSION: DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.