Prospective Acceptability of Digital Therapy for Major Depressive Disorder in France: Multicentric Real-Life Study.

BACKGROUND: Major depressive disorder is one of the leading causes of disability worldwide. Although most international guidelines recommend psychological and psychosocial interventions as first-line treatment for mild to moderate depression, access remains limited in France due to the limited availability of trained clinicians, high costs for patients in the context of nonreimbursement, and the fear of stigmatization. Therefore, online blended psychological treatment such as Deprexis could improve access to care for people with depression. It has several advantages, such as easy accessibility and scalability, and it is supported by evidence. OBJECTIVE: This study aims to evaluate the real-life acceptability of Deprexis for people with depression in France outside of a reimbursement pathway. METHODS: Deprexis Acceptability Study Measure in Real Life (DARE) was designed as a multicenter cross-sectional study in which Deprexis was offered to any patient meeting the inclusion criteria during the fixed inclusion period (June 2022-March 2023). Inclusion criteria were (1) depression, (2) age between 18 and 65 years, (3) sufficient French language skills, and (4) access to the internet with a device to connect to the Deprexis platform. Exclusion criteria were previous or current diagnoses of bipolar disorder, psychotic symptoms, and suicidal thoughts during the current episode. The primary objective was to measure the prospective acceptability of Deprexis, a new digital therapy. Secondary objectives were to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on Deprexis before enrollment to ensure that they all had the same level of information and understanding of the program. RESULTS: A total of 245 patients were eligible (n=159, 64.9% were women and n=138, 56.3% were single). The mean age was 40.7 (SD 14.1) years. A total of 78% (n=191) of the patients had moderate to severe depression (according to the Patient Health Questionnaire-9 [PHQ-9]). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders, and suicidal ideation). A total of 33.9% (n=83) of patients accepted the idea of using Deprexis; the main reason for refusal was financial at 83.3% (n=135). Multivariate logistic regression identified factors that might favor the acceptability of Deprexis. Among these, being a couple, being treated with an antidepressant, or having a low severity level favored the acceptance of Deprexis. CONCLUSIONS: DARE is the first French study aiming at evaluating the prospective acceptability of digital therapy in the treatment of depression. The main reason for the refusal of Deprexis was financial. DARE will allow better identification of factors influencing acceptability in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use, and severity of depression.

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).

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.

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.

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.

Effect of two weeks of rTMS on brain activity in healthy subjects during an n-back task: a randomized double blind study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown significant efficiency in the treatment of several psychiatric disorders. In depressive disorders, the dorsolateral prefrontal cortex (DLPFC) is the main target for rTMS, but the effects of this stimulation on cognitive functions and their neural correlates are not well known. Previous works have established that the left DLPFC is reliably activated during the n-back working memory task. OBJECTIVE: The aim of this randomized double-blind study was to determine the impact of rTMS applied to the DLPFC on brain activity during an n-back task in healthy subjects. METHODS: After randomization, twenty subjects received either active treatment (10 sessions; 1 session a day; frequency = 10 Hz; intensity = 110% of motor threshold) or placebo treatment (sham coil). Subjects performed an n-back task during two functional magnetic resonance imaging sessions (one before stimulation, and one after 10 active or sham rTMS sessions). RESULTS: No significant changes, neither in mood nor in performance in the n-back task, were shown. A significant group-by-time interaction effect was found in the bilateral middle frontal gyrus and in the left caudate nucleus. CONCLUSIONS: These results show that rTMS applied on the left DLPFC had close and remote effects on brain areas involved in working memory.