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IntroductionTreating major depressive disorder (MDD) with transcranial direct current stimulation (tDCS) devices at home has various logistic advantages compared to tDCS treatment in the clinic. However, preliminary (controlled) studies showed side effects such as skin lesions and difficulties in the implementation of home-based tDCS. Thus, more data are needed regarding the feasibility and possible disadvantages of home-based tDCS.MethodsTen outpatients (23–69 years) with an acute depressive episode were included for this one-arm feasibility study testing home-based tDCS. All patients self-administered prefrontal tDCS (2 mA, 20 min, anodal left, cathodal right) at home on 30 consecutive working days supported by video consultations. Correct implementation of the home-based treatment was analyzed with tDCS recordings. Feasibility was examined by treatment compliance. For additional analyses of effectiveness, three depression scores were used: Hamilton depression rating scale (HDRS-21), Major Depression Inventory (MDI), and the subscale depression of the Depression-Anxiety-Stress Scale (DASS). Furthermore, usability was measured with the user experience questionnaire (UEQ). Tolerability was analyzed by the number of reported adverse events (AEs).ResultsEight patients did not stick to the protocol. AEs were minimal. Four patients responded to the home treatment according to the MDI. Usability was judged positive by the patients.ConclusionsRegular video consultations or other safety concepts are recommended regardless of the number of video sessions actually conducted. Home-based tDCS seems to be safe and handy in our feasibility study, warranting further investigation.

Abstract Background Low frequency repetitive transcranial magnetic stimulation (rTMS) is commonly used to inhibit pathological hyperactivity of the auditory cortex in tinnitus. Novel and supposedly superior and faster inhibitory protocols such as continuous theta burst stimulation (cTBS) were examined as well, but so far there is not sufficient evidence for a treatment application in chronic tinnitus. rTMS effects in general are dependent on the brain state immediate before stimulation. This feasibility study was designed based on the concept to shift the pathological intrinsic brain state of tinnitus patients via acoustic stimulation (“activate”) and induce inhibitory effects via cTBS (“fire”). Methods Seven tinnitus patients with response in residual inhibition received 10 consecutive daily sessions of a combinatory treatment comprised of 3-minute acoustic stimulation with white noise followed by 600 pulses of cTBS over the left temporo-parietal cortex (activate & fire). A control group of 5 patients was treated parallel to the activate & fire data collection with 10 sessions á 3000 pulses of 1 Hz rTMS over the left temporo-parietal cortex. Results The activate & fire protocol was well tolerated except in one patient with tinnitus loudness increase. This patient was excluded from analyses. No statistical superiority of the activate & fire treatment approach in alleviating tinnitus-related symptoms was evident. Power calculations showed an effect size of 0.706 and a needed sample size of 66 for statistical significant group differences. On a descriptive level the activate & fire group demonstrated a stronger decrease in tinnitus-related symptoms. Conclusion The present feasibility study showed that combining acoustic stimulation with magnetic brain stimulation may be well-tolerable in the majority of patients and represents a promising treatment approach for tinnitus by hypothetically alter the intrinsic state prior to brain stimulation.

IntroductionObsessive-compulsive disorder (OCD) affects 2–3% of the global population, causing distress in many functioning levels. Standard treatments only lead to a partial recovery, and about 10% of the patients remain treatment-resistant. Deep brain stimulation offers a treatment option for severe, therapy-refractory OCD, with a reported response of about 60%. We report a comprehensive clinical, demographic, and treatment data for patients who were treated with DBS in our institution.MethodsWe offered DBS to patients with severe chronic treatment resistant OCD. Severity was defined as marked impairment in functioning and treatment resistance was defined as non-response to adequate trials of medications and psychotherapy. Between 2020 and 2022, 11 patients were implanted bilaterally in the bed nucleus of stria terminalis (BNST). Patients were evaluated with YBOCS, MADRS, GAF, CGI, and WHOQOL-BREF. We performed the ratings at baseline (before surgery), after implantation before the start of the stimulation, after reaching satisfactory stimulation parameters, and at follow-up visits 3, 6, 9, and 12 months after optimized stimulation.ResultsOne patient has retracted his consent to publish the results of his treatment, thus we are reporting the results of 10 patients (5 males, 5 females, mean age: 37 years). Out of our 10 patients, 6 have shown a clear response indicated by a YBOCS-reduction between 42 and 100 percent at last follow-up. One further patient experienced a subjectively dramatic effect on OCD symptoms, but opted afterwards to stop the stimulation. The other 3 patients showed a slight, non-significant improvement of YBOCS between 8.8 and 21.9%. The overall mean YBOCS decreased from 28.3 at baseline to 13.3 (53% reduction) at the last follow-up. The improvement of the OCD symptoms was also accompanied by an improvement of depressive symptoms, global functioning, and quality of life.ConclusionOur results suggest that BNST-DBS can be effective for treatment-resistant OCD patients, as indicated by a reduction in symptoms and an overall improvement in functioning. Despite the need for additional research to define the patients’ selection criteria, the most appropriate anatomical target, and the most effective stimulation parameters, improved patient access for this therapy should be established.

Introduction: Depression in the elderly is an understudied condition. Psychopharmacological and psychotherapeutic approaches suffer from specific difficulties with this patient group. Brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a therapeutic alternative. rTMS remains understudied in this age group when compared with younger patients. Methods: A cohort of 505 patients with depression was analyzed in retrospect concerning their response to rTMS treatment. A total of 15.5% were 60 years old or older, defined as the elderly group of depressed patients. The majority of these were treated with high-frequency protocols over the left dorsolateral prefrontal cortex (DLPFC). For group comparisons, we used Student t-tests or chi-square-tests, depending on the scales of measurement. As measures for effect size, we used Cohen’s d for the relative and absolute change in the HDRS total score. Results: Groups did not differ significantly with respect to baseline depression severity or treatment parameters. In the group of elderly patients, a higher number of females were present. Groups did not differ significantly with respect to treatment efficacy, as indicated by the absolute and relative changes in the HDRS-21 sum score. Elderly patients tended to take higher numbers of mood stabilizers. Elderly patients showed a significantly superior reduction for the item “appetite” and a superior reduction tending towards significance for the item “work and interests”. Conclusions: Antidepressant rTMS treatment showed comparable efficacy for patients above 60 years to that in younger patients. Differences between the age groups concerning amelioration of distinct HDRS single items deserve further investigation.

Objective: To investigate whether a four-week course of neuronavigated intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is superior to the non-neuronavigated F3-EEG method of positioning. Methods: We conducted a single-center, two-arm, randomized and double-blinded study (clinicaltrials.gov NCT03953521). 37 inpatients with an at least moderate depressive episode were randomized to receive either neuronavigated or 10-20-EEG-system based F3 guided iTBS. Both groups received twenty week daily sessions of iTBS while continuing to receive standard-of-care treatment by their ward physicians. For navigated iTBS, we used magnetic resonance imaging to target the border between the anterior and middle third of the middle frontal gyrus considered to represent the left dorsolateral prefrontal cortex (lDLPFC).Differences in the treatment arms were blinded by completely mimicking the procedures of the respective other treatment group. Rating physicians were not involved in the treatment procedure.Primary outcome was defined as the change of the 21-item version of the Hamilton Depression Score (HAMD) from baseline to end of treatment at week 4. Secondary outcomes included HAMD score during the treatment, Patient Health Questionnaire-9, WHO Quality of Life-BREF and Clinical Global Impression. For primary outcome, we used a planned group comparison for the absolute change in the HAMD. For secondary outcome measures we calculated analyses of variance (ANOVAs) with the within-subjects factor time (primary: baseline vs. week 4; secondary: all visits) and the between-subjects factor group (navigated vs. F3 guided group). We also did planned contrasts between both groups for all variables and all treatment and follow-up visits with the aim not to oversee any group differences. For group contrasts we used Student T-tests for metric and chi-square tests for categorial variables. Significance threshold was set to 5% uncorrected for multiple comparisons. Results: Enrolment of 80 patients with interim analysis was planned. Interim analysis was performed after 37 patients (intention to treat). 6 patients dropped out, leaving 31 for analysis. With respect to primary outcome criteria, absolute change in the HAMD did not differ significantly between groups. In accordance, relative change and number of responders and remitters were not significantly different. Overall number of responders was 53% and of remitters was 60%. On a descriptive level, the results favor the clinical effects of the F3 group for the absolute and relative change in the HAMD and the number of responders. Number of remitters were exactly the same for both groups. Therefore, we decided to stop the trial due to the added burden of magnetic resonance imaging and neuronavigated treatment in relation to the effect. Secondary outcomes did also not differ significantly between groups. Patients did not differ in their baseline characteristics nor with respect to intake of medication during the trial period and all had access to the same therapeutic interventions. Conclusion: We noticed a high antidepressive effect of add-on iTBS treatment to standard inpatient treatment but failed to demonstrate a clinical superiority of neuronavigated localization. The non-navigated, F3 guided iTBS treatment used as a control group may be sophisticated enough to dilute potential added benefits, and the difference between the localization approaches is either negligible or too small to justify the additional efforts of navigation. The effects of concomitant treatment may mask effects, but our patient population reflects clinical reality in an inpatient setting. Further prospective studies are warranted to compare neuronavigated with surface-based approaches.

Repetitive transcranial magnetic stimulation (rTMS) is effective in the treatment of depression. However, for the subset of patients with bipolar disorder, less data is available and overall strength of evidence is weaker than for its use in unipolar depression. A cohort of 505 patients (of which 46 had a diagnosis of bipolar disorder) with depression who were treated with rTMS were analyzed retrospectively with regards to their response to several weeks of treatment. Hamilton Depression Rating Scale (HDRS) was assessed as main outcome. Unipolar and bipolar patients with depression did not differ significantly in baseline demographic variables or severity of depression. Both groups did not differ significantly in their response to treatment as indicated by absolute and relative changes in the HDRS and response and remission rates. On HDRS subitem-analysis, bipolar patients showed superior amelioration of the symptom “paranoid symptoms” in a statistically significant manner. In conclusion, depressed patients with a diagnosis of bipolar disorder benefit from rTMS in a similar fashion as patients with unipolar depression in a naturalistic setting. rTMS might be more effective in reducing paranoia in bipolar than in unipolar patients.

Background: Personalization of repetitive transcranial magnetic stimulation (rTMS) for tinnitus might be capable to overcome the heterogeneity of treatment responses. The assessment of loudness changes after short rTMS protocols in test sessions has been proposed as a strategy to identify the best protocol for the daily treatment application. However, the therapeutic advantages of this approach are currently not clear. The present study was designed to further investigate the feasibility and clinical efficacy of personalized rTMS as compared to a standardized rTMS protocol used for tinnitus. Methods: RTMS personalization was conducted via test sessions and reliable, sham-superior responses respectively short-term reductions in tinnitus loudness following active rTMS protocols (1, 10, 20 Hz, each 200 pulses) applied over the left and right temporal cortex. Twenty pulses at a frequency of 0.1 Hz served as a control condition (sham). In case of a response, patients were randomly allocated to ten treatment sessions of either personalized rTMS (2000 pulses with the site and frequency producing the most pronounced loudness reduction during test sessions) or standard rTMS (1 Hz, 2000 pulses left temporal cortex). Those participants who did not show a response during the test sessions received the standard protocol as well. Results: The study was terminated prematurely after 22 patients (instead of 50 planned) as the number of test session responders was much lower than expected (27% instead of 50%). Statistical evaluation of changes in metric tinnitus variables and treatment responses indicated only numerical, but not statistical superiority for personalized rTMS compared to standard treatment. Conclusions: The current stage of investigation does not allow for a clear conclusion about the therapeutic advantages of personalized rTMS for tinnitus based on test session responses. The feasibility of this approach is primarily limited by the low test session response rate.

Background: Suicide is a major public health problem. About 90% of suicide victims have one or more major psychiatric disorder, with a reported 20-fold increased risk for suicide in patients with affective disorders in comparison with healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective alternative or adjunctive treatment option for patients with depressive disorders, but little is known about its effects on suicide risk.Objective: For the assessment of the effectiveness of rTMS on suicidal ideation and behaviors, we performed a retrospective analysis of a large sample of patients with depressive disorders, who were treated with rTMS.Methods: We analyzed the records of 711 TMS in- and out-patients with depressive affective disorders in a tertiary referral hospital between 2002 and 2017. Out of these patients we were able to collect Hamilton depression rating scale (HAMD) data of 332 patients (180 females, 152 males; age range 20 to 79 years; mean age 47.3 ± 12.3) for which we analyzed the change of suicidal ideation by using item 3 (suicidality) of HAMD.Results: Out of all 711 patients treated with rTMS for their depression, one patient (0.1%) committed suicide during the TMS treatment. In the statistical analysis of the subsample with 332 patients there was an overall amelioration of depressive symptoms accompanied by a significant decrease in the suicidality item with a medium effect size. Decrease in suicidality was not inferior to changes in other items as indicated by effect sizes. Forty-seven percent of patients showed an amelioration in suicidality, 41.3% of patients did not show a change in their suicidality’s scores, and 11.7% of patients showed an increase in suicidality’s scores from baseline to final rating. Correlation of item 3 (suicidality) and item 7 (drive) demonstrated a significant positive association, revealing improved drive with a parallel decreased suicidality.Conclusion: Based on the proposed data, there is no evidence that rTMS increases the risk for suicide during the course of the treatment. Conversely, rTMS tends to reduce suicidal ideation. Our findings call for further rTMS controlled studies using large sample sizes and specific suicidality assessment measures to obtain more conclusive results.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization. Objective: The aim was to investigate the test–retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus. Methods: Three short verum (1, 10, 20 Hz; 200 pulses) and one sham (0.1 Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG), together with behavioral tinnitus loudness ratings. RTMS individualization was executed on the basis of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/gamma responders) in accordance with the prevalent neurophysiological models for tinnitus. Results: It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder), respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. On the contrary, test–retest correlation analyses per protocol at a group level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were found. Conclusion: RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability at the group level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies, as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.