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.

Local Alterations of Left Arcuate Fasciculus and Transcallosal White Matter Microstructure in Schizophrenia Patients with Medication-resistant Auditory Verbal Hallucinations: A Pilot Study.

Auditory verbal hallucinations (AVH) in schizophrenia (SZ) have been associated with abnormalities of the left arcuate fasciculus and transcallosal white matter projections linking homologous language areas of both hemispheres. While most studies have used a whole-tract approach, here we focused on analyzing local alterations of the above-mentioned pathways in SZ patients suffering medication-resistant AVH. Fractional anisotropy (FA) was estimated along the left arcuate fasciculus and interhemispheric projections of the rostral and caudal corpus callosum. Then, potential associations between white matter tracts and SZ symptoms were explored by correlating local site-by-site FA values and AVH severity estimated via the Auditory Hallucinations Rating Scale (AHRS). Compared to a sample of healthy controls, SZ patients displayed lower FA values in the rostral portion of the left arcuate fasciculus, near the frontal operculum, and in the left and right lateral regions of the rostral portion of the transcallosal pathways. In contrast, SZ patients showed higher FA values than healthy controls in the medial portion of the latter transcallosal pathway and in the midsagittal section of the interhemispheric auditory pathway. Finally, significant correlations were found between local FA values in the left arcuate fasciculus and the severity of the AVH's attentional salience. Contributing to the study of associations between local white matter alterations of language networks and SZ symptoms, our findings highlight local alterations of white matter integrity in these pathways linking language areas in SZ patients with AVH. We also hypothesize a link between the left arcuate fasciculus and the attentional capture of AVH.

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).

Intermittent Theta-Burst Stimulation Over the DorsoLateral PreFrontal Cortex (DLPFC) in Healthy Subjects Produces No Cumulative Effect on Cortical Excitability.

Background: Intermittent Theta Burst Stimulation (iTBS) is a design of repetitive Transcranial Magnetic Stimulation (rTMS) and could be a candidate to replace rTMS in the treatment of depression, thanks to its efficacy, shorter duration, and ease of use. The antidepressant mechanism of iTBS, and whether this mechanism is mediated by a modulation of cortical excitability, remains unknown. Methods: Using a randomized double-blind, sham-controlled trial, 30 healthy volunteers received either iTBS or a sham treatment targeting the left DorsoLateral PreFrontal Cortex (L-DLPFC), twice a day over 5 consecutive days. Cortical excitability was measured before and after the 5 days of stimulation. Results: No difference in cortical excitability was observed between active or sham iTBS. Conclusion: Our study does not support any effect on cortical excitability of repetitive iTBS targeting the L-DLPFC.

Use of Treprostinil in Pediatric Pulmonary Hypertension: Case Reports and Review of the Literature.

BACKGROUND: Add-on therapy with prostacyclin in pediatric refractory pulmonary hypertension (PH) poses a challenge, especially when considering continuous intravenous administration in younger children. A search for alternate routes of drug delivery has led to the clinical investigation of stable and long-acting prostacyclin analogues, such as subcutaneous treprostinil. We reported 2 pediatric cases of PH treated with subcutaneous treprostinil and reviewed the literature on treprostinil use in children. METHOD: The literature review used 3 electronic databases and a combination of terms (treprostinil, pediatric, PH, prostanoid, etc). We also searched for pediatric clinical trials on treprostinil registered on international clinical trial registries. RESULTS: The reported cases highlighted the multifactorial nature of PH in pediatrics: a female child with a giant omphalocele, and intracardiac and extracardiac shunts; and a male premature child with a congenital diaphragmatic hernia and long-term PH. The literature review identified 19 studies reporting treprostinil use in 421 children with various types of PH (groups 1 and 3). Subcutaneous treprostinil was the most administered formulation, at a mean dose of 40 ng/kg/min. Overall, 12 clinical trials on treprostinil for children with PH were registered on the clinical trial registries. Most authors concluded that subcutaneous treprostinil was effective, well tolerated, and represented an alternative to intravenous epoprostenol. CONCLUSIONS: Subcutaneous treprostinil may be a useful adjunct in the therapeutic algorithm for children with severe PH, refractory to oral drugs, and after a complete check-up for all PH etiologies.

Effects of a life-skills-based prevention program on self-esteem and risk behaviors in adolescents: a pilot study.

BACKGROUND: Risk behaviors among young people are a major social and public health issue. This study aims to assess the impact of a life-skills-based prevention program (called Mission Papillagou) on self-esteem, well-being, and risk behaviors among adolescents. METHOD: In a two-arm controlled study involving 520 school pupils aged between 10 and 15 years old, participants taking part in the prevention program (the Papillagou group) were compared to pupils who did not take part (the control group). Two assessment sessions were performed, one at baseline, and one after either the Mission Papillagou program (Papillagou group) or usual lessons (control group). Participants self-reported on their self-esteem, well-being, behaviors, interests and opinions. RESULTS: The Mission Papillagou program significantly improved Self-Esteem scores (ηρ2 = .035). Well-being (Cramér's V = .14) and mood ("feeling of depression": Cramér's V = .503; "feeling hopelessness about the future": Cramér's V = .357; "waking up at night": Cramér's V = .343) also improved in the Papillagou group compared to the control group. Regarding risk behaviors, the prevention program produced a decrease in the frequency of insults (Cramér's V = .267) and rumor-spreading (Cramér's V = .440), and a change of opinion toward the possibility of smoking an electronic cigarette in the future (Cramér's V = .372). CONCLUSION: This study suggests that life-skills-based risk prevention programs are effective.

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.

Unexpected Improvement of Hand Motor Function with a Left Temporoparietal Low-Frequency Repetitive Transcranial Magnetic Stimulation Regime Suppressing Auditory Hallucinations in a Brainstem Chronic Stroke Patient.

We here report paradoxical hand function recovery in a 61-year-old male tetra-paretic chronic patient following a stroke of the brainstem (with highly degraded right and abolished left-hand finger flexion/extension disabling him to manipulate objects) who experienced insidious auditory hallucinations (AHs) 4 years after such event. Symptomatic treatment for AHs was provided with periodical double sessions of low-frequency repetitive transcranial magnetic stimulation (rTMS) (daily 1 Hz, 2 × 1,200 pulses interleaved by 1 h interval) delivered to the left temporoparietal junction across two periods of 5 and 3 weeks, respectively. At the end of each stimulation period, AHs disappeared completely. Most surprisingly and totally unexpectedly, the patient experienced beneficial improvements of long-lasting impairments in his right-hand function. Detailed examination of onset and offset of rTMS stimulation regimes strongly suggests a temporal relation with the remission and re-appearance of AHs and also with a fragile but clinically meaningful improvements of right (but not left) hand function contingent to the accrual of stimulation sessions. On the basis of post-recovery magnetic resonance imaging structural and functional evidence, mechanistic hypotheses that could subtend such unexpected motor recovery are critically discussed.

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.

[Cognitive remediation and nursing care]. / Remédiation cognitive et prise en charge infirmière.

Therapies based on cognitive remediation integrate psychiatric care. Cognitive remediation helps to ease cognitive disorders and enable patients to improve their day-to-day lives. It is essential to complete nurses' training in this field. This article presents the example of a patient with schizophrenia who followed the Cognitive Remediation Therapy programme, enabling him to access mainstream employment.

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.