Trajectories of suicidal ideation during rTMS for treatment-resistant depression.

BACKGROUND: rTMS is a safe and effective intervention for treatment-resistant depression (TRD). However, there is limited data on its specific impact on suicidal ideation (SI), and the trajectory of SI over the treatment course. OBJECTIVE: This open-label clinical trial investigated SI outcomes and trajectories in patients with TRD receiving low-frequency rTMS (LFR) to the right dorsolateral prefrontal cortex (DLPFC; N = 55). METHODS: A latent class mixed-effect model was used to identify response trajectories for SI as well as core mood symptoms. Logistic regression analyses investigated risk factors associated with identified trajectories. RESULTS: For each symptom domain, we identified two distinct trajectories during LFR, one tracking improvement (SI: n = 35, 60 %; mood: n = 29, 53 %) and the other tracking no improvement (SI: n = 20, 40 %; mood: n = 26, 47 %). Male sex, higher baseline anxiety, and higher baseline SI were risk factors for no improvement of SI; while higher baseline anxiety and benzodiazepine use were risk factors for no improvement of mood. Mediation analyses showed that anxiety was a risk factor for no improvement of SI and mood independent of benzodiazepine treatment. CONCLUSIONS: This is the first study to investigate trajectories of response to LFR to the right DLPFC. SI and mood improved with LFR in most patients but the severity of anxiety symptoms was a factor of poor prognosis for both. Nuanced characterization of SI response to rTMS may lead to critical insights for individualized targeting strategies.

Cognitive-affective processes and suicidality in response to repetitive transcranial magnetic stimulation for treatment resistant depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) can elicit 45-55 % response rates and may alleviate suicidality symptoms in treatment resistant depression (TRD). Blunted anticipatory reward sensitivity and negatively biased self-referential processing may predict trajectories of depressive and suicidality symptoms in rTMS for TRD and be modulated during treatment. METHODS: Fifty-five individuals with TRD received four weeks of low-frequency rTMS applied to the right dorsolateral prefrontal cortex (LFR-rTMS) and were followed until 17 weeks post-baseline. Participants completed behavioral measures of anticipatory reward sensitivity and self-referential processing at baseline and five weeks post-baseline (approximately one-week post-treatment). We examined whether baseline anticipatory reward sensitivity and self-referential processing predicted trajectories of depressive and suicidality symptoms from baseline to follow-up and whether these cognitive-affective variables showed change from baseline to week five. RESULTS: Anticipatory reward sensitivity and negative self-referential encoding at baseline were associated with higher overall depressive symptoms and suicidality from baseline to 17 weeks post-baseline. At week five, participants self-attributed a higher number of positive traits and a lower number of negative traits and had a lesser tendency to remember negative relative to positive traits they had self-attributed, compared to baseline. LIMITATIONS: The specificity of these results to LFR-rTMS is unknown in the absence of a comparison group, and our relatively small sample size precluded the interpretation of null results. CONCLUSIONS: Baseline blunted anticipatory reward sensitivity and negative biases in self-referential processing may be risk factors for higher depressive symptoms and suicidality during and after LFR-rTMS, and LFR-rTMS may modulate self-referential processing.

Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial.

OBJECTIVE: The study objective was to investigate the predictive value of functional connectivity changes induced by acute repetitive transcranial magnetic stimulation (rTMS) for clinical response in treatment-resistant depression. METHODS: Cross-sectional changes in functional connectivity induced by a single concurrent rTMS-fMRI session were assessed in 38 outpatients with treatment-resistant depression (26 of them female; mean age, 41.87 years) who subsequently underwent a 4-week course of rTMS. rTMS was delivered at 1 Hz over the right dorsolateral prefrontal cortex. Acute rTMS-induced functional connectivity changes were computed and subjected to connectome-based predictive modeling to test their association with changes in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) after rTMS treatment. RESULTS: TMS-fMRI induced widespread, acute, and transient alterations in functional connectivity. The rTMS-induced connectivity changes predicted about 30% of the variance of improvement in the MADRS score. The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus. CONCLUSIONS: Acute rTMS-induced connectivity changes in patients with treatment-resistant depression may index macro-level neuroplasticity, relevant to interindividual variability in rTMS treatment response. Large-scale network phenomena occurring during rTMS might be used to inform prospective clinical trials.

A patient-oriented analysis of pain side effect: A step to improve the patient's experience during rTMS?

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an efficacious and well-tolerated intervention for treatment-resistant depression (TRD). A novel rTMS protocol, intermittent theta burst stimulation (iTBS) has been recently implemented in clinical practice, and it is essential to characterize the factors associated to pain and the trajectory of pain of iTBS compared to standard rTMS protocols. OBJECTIVE: We aimed to characterize the side effect profile and the pain trajectories of High-Frequency Left (HFL) and iTBS in TRD patients in the THREE-D trial. We also investigated factors associated to pain and the relationship between pain and clinical outcomes. METHODS: 414 patients were randomized to either HFL or iTBS. Severity of pain was measured after every treatment. General Estimating Equation was used to investigate factors associated with pain. Latent class linear mixed model was used to investigate latent classes of pain trajectories over the course of rTMS. RESULTS: Higher level of pain was associated with older age, higher stimulation intensity, higher anxiety, female, and non-response. The severity of pain significantly declined over the course of treatments with a steeper decrease early on in the course of the treatment in both protocols, and four latent pain trajectories were identified. The less favorable pain trajectories were associated with non-response and higher stimulation intensity. CONCLUSIONS: HFL and iTBS were associated with similar factors and pain trajectories, although iTBS was more uncomfortable. Response to rTMS was associated with less pain and more favorable pain trajectories furthering the evince base of overlapping neurobiological underpinnings of mood and pain. We translated these results into patient-oriented information to aid in the decision-making process when considering rTMS.