Real world transcranial magnetic stimulation for major depression: A multisite, naturalistic, retrospective study.

BACKGROUND: In 2008, the U.S. FDA approved rTMS as a treatment against medication-resistant depression. However, real-world rTMS outcomes remain understudied. This study investigates how rTMS for depression is delivered in routine clinical practice in France, and measures its effectiveness as well as its moderators. METHODS: Five centers provided retrospective data on patients who were treated with rTMS for treatment-resistant depression from January 2015 to December 2020. Patients were assessed twice using a hetero-questionnaire, with baseline and immediate post-treatment assessments. We conducted univariate analyses to study which factors were significantly associated with rTMS effectiveness. We then included age, gender, and significant factors in a multivariate model. RESULTS: We collected data from 435 patients with a mean age of 51.27 (14.91): 66 % were female, and 26 % suffered from bipolar depression. Stimulation was delivered using four different stimulation parameters: 1 Hz (7 % of the individuals), 10 Hz (43 %), 20 Hz (12 %), and 50 Hz (intermittent Theta Burst Stimulation, iTBS) (38 %). The mean improvement of depressive symptoms was 33 % (p < 0.001, effect-size: 0.79). Response and remission rates were of 31 % and 22.8 %, respectively. In the multivariate analysis, improvement in depressive symptoms was associated with higher baseline symptoms. CONCLUSION: This is one of the largest studies that investigates, with careful clinician-rated scales by trained psychiatrists, the effect of rTMS in naturalistic settings. Repetitive TMS appears to be effective in routine clinical practice, although its efficacy could be improved by analyzing predictors of response, as well as personalized targeting of specific brain areas.

Prospective survey of psychiatric patients during the first confinement of the COVID 2019 pandemic.

In the early steps of an emerging infectious disease epidemic such as Covid-19, uncertainties about the nature of the disease, its spread and impact can lead to emotional distress. In addition, the studies on confinement during an epidemic have shown a psychological impact of this measure on the feelings of anxiety and depression in the general population. METHOD: We assessed the psychological health of 550 patients followed up in outpatient psychiatry, via a pandemic-related teleconsultation during the first confinement period between March and June 2020. Patients were assessed at the beginning and at the end of the confinement on their personal situation, social relationships, professional activity, anxiety and mood. We also evaluated patients' symptomatology and their quality of life. RESULTS: Patients were well informed about Covid-19 via the media and complied with the confinement and barrier procedures. They appreciated the phone-calls and the teleconsultation follow-up. A small proportion of patients were completely socially isolated mainly at the beginning of the confinement (10%). There was no difference between the beginning and the end of the confinement in terms of depressive and anxiety symptoms or quality of life. The women were more anxious and depressed than men. Only smoking was significantly increased during this period. CONCLUSION: The expected and feared health catastrophe in psychiatry during this first phase of the pandemic in 2020 did not occur. Will the psychiatric wave appear in the "post- pandemic", the future will tell.

Effect of Intermittent Theta Burst Stimulation on the Neural Processing of Emotional Stimuli in Healthy Volunteers.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that has shown to be effective in treatment-resistant depression. Through studying the effect of iTBS on healthy subjects, we wished to attain a greater understanding of its impact on the brain. Our objective was to assess whether 10 iTBS sessions altered the neural processing of emotional stimuli, mood and brain anatomy in healthy subjects. METHODS: In this double-blind randomized sham-controlled study, 30 subjects received either active iTBS treatment (10 sessions, two sessions a day) or sham treatment over the left dorsolateral prefrontal cortex. Assessments of mood, structural magnetic resonance imaging (MRI) and functional MRI (fMRI) were performed before and after iTBS sessions. During the fMRI, three different categories of stimuli were presented: positive, negative and neutral photographs. RESULTS: This study showed that, during the presentation of negative stimuli (compared with neutral stimuli), 10 sessions of iTBS increased activity in the left anterior insula. However, iTBS did not induce any change in mood, regional gray matter volume or cortical thickness. CONCLUSIONS: iTBS modifies healthy subjects' brain activity in a key region that processes emotional stimuli. (AFSSAPS: ID-RCB 2010A01032-37).

[Mood disorders: When should we use repetitive transcranial magnetic stimulation?] / Troubles de l'humeur : quand recourir à la stimulation magnétique transcrânienne ?

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians'knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders.

Gender-Related Brain Activations during an Emotional Task: An fMRI Study.

BACKGROUND: Women have twice the rate of depression and anxiety disorders as men. Some studies suggest that this could be caused by women's greater sensitivity to negative emotions. Few brain imaging studies have compared the brain activity of men to women during a presentation of emotional stimuli. Our objective was to investigate brain activations in men and women during an emotional task. We hypothesized that the pattern of brain activations would differ by gender and valence of the stimuli. METHODS: We conducted a functional magnetic resonance imaging study in 30 healthy participants (15 men and 15 women). Positive, negative and neutral photographs were presented to the subjects. Participants subjectively rated the valence and intensity of the stimuli. RESULTS: No significant gender-by-category interaction effect was observed for the intensity or valence of the stimuli. We found that, during the presentation of negative photographs, there was a higher activity in women's right fusiform gyrus compared to men's. CONCLUSION: Given the involvement of the fusiform gyrus in anxiety disorders, this study yields promising findings in order to better understand women's vulnerability to anxiety disorders.

Structural and functional brain biomarkers of clinical response to rTMS of medication-resistant auditory hallucinations in schizophrenia patients: study protocol for a randomized sham-controlled double-blind clinical trial.

BACKGROUND: The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia. METHODS: Forty-five schizophrenia patients with medication-resistant AVH will be enrolled in a double-blind randomized sham-controlled monocentric clinical trial. Patients will be assigned to a regime of 20 sessions of active or sham 1 Hz rTMS delivered twice a day, 5 days a week for 2 weeks over the left temporo-parietal junction. Response will be assessed after rTMS and patients will be classified in responders or non-responders to treatment. Magnetic resonance imaging (MRI) sessions including diffusion weighted imaging and resting-state functional MRI sequences will be recorded before the onset of the rTMS treatment and 3 days following its discontinuation. The primary outcome measure is difference in fractional anisotropy between responder and non-responder patients at baseline. Differences in resting-state functional MRI data at baseline will be also investigated between responder and non-responder groups. Clinical, neuropsychological, neurophysiological, and blood serum BDNF assessments will be performed at baseline, 3 days, 1 month, and 3 months following rTMS. DISCUSSION: The aim of this research project is to identify and assess the biomarker value of MRI-based structural and functional biomarkers predicting clinical response to rTMS for AVH in schizophrenia patients. The outcome of the trial should improve patient care by offering them a novel suitable therapy and deepen our understanding on how rTMS may impact AVH and develop more effective therapies adapted to individual patient needs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02755623 . Registered on 22 April 2016.

A randomized, sham-controlled study of maintenance rTMS for treatment-resistant depression (TRD).

A few open-labeled studies have investigated the use of maintenance rTMS to prevent relapse for treatment-resistant depression (TRD) after rTMS treatment. We aim to assess the benefits of maintenance rTMS treatment for TRD patients who respond to rTMS treatment using a randomized, double-blind controlled design. Fifty eight TRD patients received rTMS over one month in an open-labeled design study (phase I). Responder patients were then randomized into active and sham high-frequency rTMS groups for the subsequent eleven months (phase II). The regularity of sessions was gradually reduced. The antidepressant effect of rTMS was evaluated using the Hamilton Depression Rating Scale (HDRS). Intention-to-treat analysis was performed to assess the effectiveness of maintenance sessions. Of the 58 patients included, 35 patients were responders after one month of active rTMS (phase I), and 17 patients were randomized for the maintenance sessions (phase II). The delta HDRS scores demonstrated a significant improvement between the first month and the fourth month in active group in comparison with sham group (phase II). There was no significant difference between these two groups for other periods of time. Repetitive TMS could represent a novel strategy for preventing relapse in TRD patients who respond to rTMS treatment. These results should be confirmed in a larger sample.

Impact of reward on pain threshold and tolerance to experimental pain (Cold Pressor Task) in healthy subjects and patients with schizophrenia.

Reduced pain sensitivity is considered as a potential endophenotype of schizophrenia. Patient's motivation in pain experimental studies was neither assessed nor controlled. This study aimed to assess the effect of reward on pain in patients with schizophrenia compared to controls. Rewarded subjects showed higher pain threshold and tolerance compared to unrewarded subjects. Pain tolerance was significantly lower in patients than in controls when they were not rewarded. Reward resulted in an increase of pain tolerance with a higher manner in patients. This study suggests that better control of motivational aspects could improve assessment of pain sensitivity in schizophrenia.

Repetitive Transcranial Magnetic Stimulation to Supplementary Motor Area in Refractory Obsessive-Compulsive Disorder Treatment: a Sham-Controlled Trial.

BACKGROUND: Repetitive transcranial magnetic stimulation has been explored in patients with obsessive-compulsive disorder, but with negative or conflicting results. This randomized double-blind study was designed to assess the efficacy of 1-Hz repetitive transcranial magnetic stimulation over the presupplementary area. METHODS: Forty medication-resistant patients were assigned to 4 weeks of either active or sham repetitive transcranial magnetic stimulation targeting the presupplementary area with the help of a neuronavigation system. RESULTS: According to the Yale-Brown obsessive-compulsive scale, the baseline-week 4 evolution showed no significant differences between groups. Responder rates at week 4 were not different between groups (repetitive transcranial magnetic stimulation 10.5% vs sham 20%; P=.63). CONCLUSION: Low-frequency repetitive transcranial magnetic stimulation applied to the presupplementary area seems ineffective for the treatment of obsessive-compulsive disorder patients, at least in severe and drug-refractory cases such as those included in this study. Further research is required to determine profiles of responder patients and appropriate repetitive transcranial magnetic stimulation parameters for obsessive-compulsive disorder.

Effect of repetitive transcranial magnetic stimulation on mood in healthy subjects.

BACKGROUND: High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear. OBJECTIVE: Our aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects. DESIGN: In a randomised double-blind study, 20 subjects received 10 daily sessions of active (10 Hz frequency) or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales (VASs), and the Ekman 60 faces test. RESULTS: The 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTMS group presented a significant improvement in their adaptation to daily life, which was assessed through VAS. CONCLUSION: This study did not show any deleterious effect on mood and emotion recognition of 10 sessions of rTMS applied on the DLPFC in healthy subjects. This study also suggested a positive effect of rTMS on quality of life.

A double-blind sham controlled study of right prefrontal repetitive transcranial magnetic stimulation (rTMS): therapeutic and cognitive effect in medication free unipolar depression during 4 weeks.

BACKGROUND: Transcranial magnetic stimulation (TMS) has become a therapeutic tool in psychiatric diseases. METHODOLOGY: The objective was to evaluate the efficacy of TMS in unipolar depression: the percentage of responders (>50% HDRS reduction) and remission (HDRS score < or =8, after four weeks of active TMS treatment in depressed patients free of any antidepressive agent versus placebo-TMS. RESULTS: 27 patients were randomized in two groups: rTMS (N=11) versus sham TMS (N=16). Statistical differences were detected between sham and TMS treated groups on remission (0/16 versus 4/11 p=0.032, 1/16 versus 6/11 0.028 and 1/16 versus 7/11 p=0.011 at day 14, day 21 and day 28, respectively) and on response (2/16 versus 5/11 at day 14 (NS), 2/16 versus 7/11 p=0.0115 at day 21 and 1/16 versus 7/11 (p=0.025) day 28, respectively, using the exact Fisher test). Significant differences were observed between day 1 versus day 8 (p<0.01), day 15, day 21 and day 28 (p<0.001) in TMS group and only versus day 21 (p<0.01) and day 28 (p<0.05) for the sham group. ANOVA comparison between TMS and sham groups was significant at day 14 and day 28 (p<0.05). LIMITATIONS: The few number of patients. CONCLUSION: Our study has shown an efficacy of right rTMS in free medication unipolar depression over a month. Nevertheless, number of patients included is limited and multicentric studies will be necessary to specify the antidepressive action of TMS.

Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients.

The aim of this study is to assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) as an add-on therapy in the treatment of manic bipolar patients. Eight patients were enrolled in an open trial. They received fast rTMS (five trains of 15 s, 80% of the motor threshold, 10 Hz) over the right dorsolateral prefrontal cortex (DLPFC). They were evaluated using the Mania Assessment Scale (MAS) and the Clinical Global Impression (CGI) at baseline and at day 14. All patients were taking medication during the treatment trial. There was a significant improvement of manic symptoms at the end of the trial. No side effects were reported. The results show a significant improvement of mania when patients are treated with fast rTMS over the right DLPFC. However, these results have to be interpreted with caution since they derive from an open case series and all the subjects were taking psychotropic medication during rTMS treatment. Double-blind controlled studies with a sham comparison condition should be conducted to investigate the efficiency of this treatment in manic bipolar disorders.