Priming stimulation, which involves high-frequency repetitive transcranial magnetic stimulation (rTMS) followed by low-frequency, has been shown to enhance neural response and is one of the novel paradigms found beneficial in adult patients with depression and has not been studied in late-life depression (LLD). This study aims to compare the effect of adjunctive priming vis-a-vis no priming rTMS over right dorso-lateral prefrontal cortex (DLPFC), on treatment of LLD.

This trial is registered in Clinical Trial Registry-India (CTRI) on www.ctri.nic.in. CTRI registration number: CTRI/2020/08/027230. Forty patients of LLD who are symptomatic after an adequate antidepressant trial will be randomized into 2 groups (active priming and sham priming rTMS); each receiving 10 sessions of rTMS over 2 weeks. Patients will remain blind to treatment allocation. Assessments will be done using Hamilton rating scale for depression, Geriatric Depression Scale, Hamilton rating scale for Anxiety, Somatic Symptom Severity Scale 8, Hindi Mental Status Examination, and Clinical Global Impression scale at baseline, week 1, 2, and 4. Side effect checklist will be applied after each session in both groups and at the end of 4 weeks.

Data will be analyzed using statistical software Statistical Package for Social Sciences. Both the groups (active and sham groups) will be compared at the four given timepoints. Also, the baseline characteristics will be compared with the 3 follow-up points for any change.

The findings of the study will give an insight to the possible role of priming to augment the effect of low-frequency rTMS in LLD.

Identifying the factors that mediate treatment response to rTMS in MDD patients can guide clinicians to administer more appropriate, reliable, and personalized interventions.

The present study aimed to investigate sex differences in response to repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) patients.

In this paper, we developed a novel pipeline based on convolutional LSTM-based deep learning (DL) to classify 25 female and 25 male subjects based on their rTMS treatment response.

Five different classification models were generated, namely pre/post-rTMS female (model 1), pre/post-rTMS male (model 2), pre-rTMS female responder vs. pre-rTMS female non-responders (model 3), pre-rTMS male responder vs. pre-rTMS male non-responder (model 4), and pre-rTMS responder vs. non-responder of both sexes (model 5), achieving 93.3%, 98%, 95.2%, 99.2%, and 96.6% overall test accuracy, respectively.

These results indicate the potential of our approach to be used as a response predictor especially regarding sex-specific antidepressant effects of rTMS in MDD patients.

No significant relationships.

Rapid cycling Bipolar disorder and mixed affective states are treatment resistant conditions. Standard treatments are ineffective. Homozygous polymorphism of DIO2 gene is associated 3.75-fold risk of bipolar disorder.

High Dose Levothyroxine combined with repetitive transcranial magnetic stimulation (rTMS) in Rapid cycling Bipolar disorder: Is it thyroid disease?

20 RCBPD with ICD-10criteria for bipolar disorder. All were severely symptomatic. TFTs and ECGs were monitored weekly with cardiology and endocrinology backup. Genetic testing was undertaken for DiO1/DiO2 status.

17 were female, average age 32.4 yrs. 19/20 had Single nucleotide polymorphisms (SNP) of either DIO1, DIO2 or both. All but two patients were treated with rTMS to induce cerebral neuroplasticity. Average pre-treatment fT4 was 17.0 pmol/L , and fT3 4.5 pmol/L Average post-treatment, fT4 was 59.7 pmol/L and fT3 5.3 pmol/L. Average fT4:fT3 ratio pre-treatment was 4:1, and post-treatment was 5:1. HDL range was 200-800 mcg daily for remission. Average dose 472 mcg daily. Discontinuation rate was 0%. All patients had ECG and cardiac review One patient required a dose reduction because of minimal side effects 12 patients needed one mood stabiliser All were in remission for a minimum of 6 months.

We speculate that BPD may be a form of cerebral hypothyroidism and that HDL helps to overcome the deficit while robust inactivating deiodinases in the periphery protect from systemic thyrotoxicosis. This is evidenced by findings of normal clinical examination and elevated rT3. rTMS exercises its well established neuroplastic effect, helping to achieve and maintain remission as an adjunct to HDL.

The London Psychiatry Centre (TLPC) has pending patents for the combined protocol of rTMS and/or Thyroid hormones depending on the territory: - Pending US Patent application: (and/or) US20200384279 - Pending European patent appl

Treatment-resistant depression (TRD) presents a significant challenge in clinical practice. Besides antidepressant medications, neurostimulation methods (ECT, rTMS) and ketamine are viable treatment options.

To objectively evaluate the real effectiveness of treatments within interventional psychiatry in the maintenance treatment.

The extensive literature review of the efficacy of ECT, rTMS, and ketamine treatment in the maintenance treatment of TRD and the author’s clinical and research experience will be included in this presentation.

Neurostimulation, particularly ECT and ketamine treatment are usually effective treatments for patients with TRD. However, both of these treatment modalities do not have sustained benefits and after discontinuing treatment the majority of patients relapse. Ketamine has rapid therapeutic effects in depression, but these effects are short-lived. Continuation treatment with ketamine in the form of intranasal ketamine is an option, but concerns over cognitive impairment, interstitial cystitis and significant addictive potential related to longer use of ketamine are significant limiting factors. rTMS is a first-line treatment option for patients with TRD according to the Canadian CANMAT guidelines. However, the majority of patients may relapse following the course of rTMS. The maintenance rTMS over an extended period of time is usually not feasible as it may significantly affect the waiting time for newly referred patients. Portable TMS machine for home use would be an alternative option for a limited number of patients.

Maintenance treatment has been always a big clinical challenge in mood disorder psychiatry. Only well-established multimodal treatment is a realistic option for getting long-term benefits in treating patients with TRD.

No significant relationships.

Vascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressants (AD) and electroconvulsive therapy on depression since it plays a significant role in the neurogenesis. However, the serum VEGF level has not been investigated so far in association with rTMS treatment in patients with major depressive disorder (MDD).

The aim of our study was to compare the effect of the antidepressants and of the repetitive transcranial magnetic stimulation on the serum vascular endothelial growth factor and its association with the responsiveness to the treatments.

A dataset of 50 patients with TRD who were treated with AD (n=33) and bilateral rTMS for 2x5 days (n=17) was analysed (sample ’rTMS&AD’). Montgomery-Asberg Depression Scale (MADRS) was used for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2) and on the 28th day (V3). The VEGF levels were measured by ELISA assay.

The baseline VEGF levels were significantly higher in non-responders both in the rTMS&AD (p=0.04) and AD samples (p=0.02) compared to responders. The MADRS reduction and the changes in VEGF levels between V1 and V3 were significantly associated in responders only in the AD&rTMS sample (p=0.03). The baseline VEGF level has been proven as a significant predictive factor of treatment response in the total sample (p=0.018).

The baseline VEGF level can be a predictive factor to be a non-responder to different treatments. Change of the VEGF level is associated with the improvement of depressive symptoms only due to rTMS.

This study was supported by the FK 131315 grant of the National Research, Development and Innovation Office, Hungary. Authors declare no conflict of interest.

Clinical studies demonstrated the efficacy of rTMS treatment in major depressive disorder. However, the results of meta-analyses are contradictory due to the heterogeneity of the included studies.

The aim was to analyse the effectiveness of rTMS for treatment-resistant major depression.

A systematic literature review of English-language articles published in the last 10 years was performed on PubMed and Scopus databases according to PRISMA guideline principles. To assess the effects of rTMS on response and remission rates, random-effects model and inverse variance method were used.

23 randomized double-blind sham-controlled studies met the inclusion criteria for quantitative analysis for response (n= 1020 patients) and 12 studies for remission (n= 846 patients). The relative risk for response and remission were 2.19 (95% CI: 1.68-2,86, p=0.000 n=912) and 2.65 (95% CI: 1.32-5,31, p=0.002, n=603), respectively using rTMS as add on treatment (in patients after two antidepressant treatment failures) compared to standard pharmacotherapy. I2analysis showed no considerable heterogeneity in the combined effect sizes neither for remission studies (I2=23.36%) nor for response studies (I2=0.00%).

Transcranial magnetic stimulation became an evidence-based, effective treatment for treatment-resistant major depressive disorder, either as a monotherapy or as an augmentation of pharmacotherapy. However, because of the lack of standardized protocol, a substantial methodological heterogeneity exists. According to our results, rTMS was significantly more effective than sham rTMS in both response and remission outcomes, which is consistent with previous meta-analyses, but the effect size was a bit smaller than what was reported previously.

No significant relationships.

Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD.

In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment.

After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests.

rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Introduciton: Repetetive transcranial magnetic stimulation (rTMS) is an effective and safety noninvasive technique for treatment of major depression disorder (MDD). There is a body of increasing evidences on the potential molecular mechanisms underlying its effectivity even in case of treatment resistant depression (TRD), however, the exact mechanism is still not clarified. Among multiple biological systems, inflammation can be a target of rTMS in MDD (Tian et al. 2020; Tateishi et al. 2020).

Here we analysed serum cytokine levels in TRD before and after rTMS interventions.

We used bilateral stimulation (15Hz for left DLPC and 1Hz on the right side) in 18 patients with TRD (5 men and 13 women; mean age=47.7±12.1 year) for 2x5 days. Blood samples were collected before the first (V1) and after the last inetrevntion (V2). Phenotypic changes were measured by Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Snaith–Hamilton Pleasure Scale (SHAPS), Insomnia Severity Index (ISI) and Stroop Color-Word Test (SCWT) modified by Golden. Inflammatory cytokines were assessed by ELISA assays.

Change of BDI and BAI scores between V1 and V2 is associated with difference of TNFalpha levels (p=0.043; adj.R2=0.42 p=0.011; adj R2=0.43). Decrease on SHAPS score has been depended on IL-6 level (p=0.027) and the interaction of TNFalpha and IL-10 (p=0.005; adj R2=0.63). Sleep disturbance and neurocognitive function was not associated with cytokine levels.

Our results confirmed the association between depressive, anxious and anhedonia symptom improvement and inflammatory mechansims during rTMS treatment. The study was supported by the OTKA 151513 grant.

Although there are very effective treatment approaches for Attention Deficit Hyperactivity Disorder (ADHD) available, the clinical management has its limits making new treatment modalities a necessity. Evidence suggests that low frequency repetitive transcranial magnetic stimulation (rTMS), improves hyperactivity, impulsivity, and attention deficit of individuals with ADHD.

The aim of this case study is to present the effectiveness of rTMS on hyperactivity, impulsivity, and attention deficit of an individual with ADHD.

This is a case study of a 22 year old male diagnosed with ADHD. The protocol applied was 2 weeks of daily rTMS sessions. This involved repetitive TMS to the right dorsomedial prefrontal cortex (10 Hz, 3.000 pulses, 120% motor threshold) to treat attention deficit, hyperactivity and impulsivity. Assessments were conducted using Adult ADHD Questionnaires, the Jasper and Goldberg questionnaire and WHO self- reported scale at baseline, 1 month and up to 3 months follow up.

The patient showed overall improvement in scores in both ADHD scales with scores dropping more than 50 % in both scales from pre treatment to 3 months follow up. No side effects were recorded during therapy

Our findings suggest that the use of rTMS therapy in individuals with ADHD, is an efficacious and safe therapeutic treatment option.

Australia has a universal health insurance scheme covering part costs for private mental health care and which supports the public system. The Medical Benefits Schedule (MBS) schedule provides a recommended fee for each service, the amount the Australian Government thinks the service should cost. Many patients still pay a gap fee for the service. Similarly a system for medications, the Pharmaceutical Benefits Scheme (PBS) subsidises the cost of medicines for most medical conditions. As new evidence emerges in the treatment of psychiatric conditions, it is important that the MBS and PBS are updated so patients receive subsidised best practice treatment.

To provide an overview of RANZCP efforts to expand treatment availability through evidence and advocacy to government.

The RANZCP made submissions to the independent Medical Services Advisory Committee (MSAC) requesting an MBS listing for repetitive transcranial magnetic stimulation (rTMS) for treatment of antidepressant medication-resistant major depressive disorder. Submissions were made to the independent Pharmaceutical Benefits Advisory Committee (PBAC) to request ability to prescribe quetiapine in 25mg ranges for maintenance therapy.

Following RANZCP submissions, the MSAC supported public funding for initial treatment with rTMS for adults with major depression who have tried antidepressant medicine or psychological therapy and remain unwell. The PBAC has recommended changes allowing prescription of 25mg quetiapine tablets for maintenance therapy for acute mania, bipolar 1 disorder and in the treatment of schizophrenia following RANZCP submission.

The RANZCP has achieved access to treatments to provide optimal symptom relief for people living with mental illness.

Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.

This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).

Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.

IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.

In the Federal Republic of Germany about 3 million people suffer from tinnitus/are hit by tinnitus, numerous of them depend on intensive medical care. The repetitive transcranial magnetic stimulation is considered to be an innovative and promising therapy in tinnitus treatment. Low frequency stimulation is meant to reduce the abnormal neural activity in the auditory cortex. This study focuses on the efficacy of rTMS with tinnitus patients in the course of a multi disciplinary / an interdisciplinary therapy concept.

From November 2008 to June 2009 29 outpatients with chronic tinnitus were treated by low frequency rTMS (1 Hz frequency, 2000 impulses, intensity 110%) for 10 proceedings, stimulating the sinistral auditory cortex with a figure-of-eight-coil. Prior to and afterwards the proceedings questionnaires and assessments of a psychologist took place, afterwards statistical analyses were conducted, the data was explored and systematically discussed.

The severity index of the tinnitus as well as the depression symptoms of the subjects improved significantly. The average reduction rate of the tinnitus score is set at 7 points. With a response criterion at the minimum of 5 points, 57% were declared as responder, 29% as non-responder and 4 patients (14%) described an increase of the tinnitus loudness/annoyance.

The results show that the rTMS works as a helpful treatment tool with tinnitus patients and should be considered as an option in the routine tinnitus treatment.

La stimulation magnétique transcrânienne répétée (rTMS) est une technique thérapeutique non invasive de stimulation du cerveau, utilisée pour le traitement de la dépression résistante. Les études ont montré son efficacité sur la diminution de l’intensité de la dépression [1]. Mais, à ce jour, peu d’études se sont intéressées à l’évolution au cours de ce traitement, de facteurs psychologiques tels que les schémas dysfonctionnels représentés par les attitudes dysfonctionnelles [2] et les schémas précoces inadaptés [3] et qui sont impliqués dans la dépression.

Déterminer s’il y a une évolution des schémas précoces inadaptés (Young, 1990, 1999) et des attitudes dysfonctionnelles [2] avec le traitement rTMS.

Vingt-trois patients dépressifs traités par rTMS au cours d’une cure de 10 jours, avec ou sans traitement médicamenteux. En début et en fin de cure, puis un mois après la fin de la cure rTMS, ils ont rempli une batterie de questionnaires composés du MINI, du BDI-13, de l’HDRS, de la HAD, du STAI, de la DAS, de l’YSQ-S1 et de l’ESDV-5.

La rTMS confirme son efficacité sur les symptômes anxio-dépressif. Les attitudes dysfonctionnelles diminuent significativement un mois après la cure rTMS. En revanche, les schémas précoces inadaptés restent stables. La qualité de vie n’augmente modestement qu’un mois après la cure rTMS.

Bien que la rTMS permette une diminution significative de l’intensité de la dépression et l’anxiété, une vulnérabilité psychologique est maintenue au travers de schémas dysfonctionnels. Une psychothérapie associée au traitement et visant le changement de ces pensées négatives semble nécessaire, notamment afin d’éviter les rechutes dépressives. D’autres études avec un plus grand échantillon devraient examiner l’impact de la rTMS sur certains facteurs psychologiques à court, moyen, et long terme.

The Clinic of Psychiatry and Psychotherapy of Nuremberg established rTMS as a standard tool in the treatment of patients with depressive disorder since 2001. The stimulation protocol was modified in October 2008 to match the current standard procedure reported in the literature. The pulse number was heightened form 800 to 2000 per proceeding. This study examines the effects of the modified stimulation protocol and contrasts the results with the former stimulation efficacy.

The authors compared patients suffering from depression, who were treated by rTMS with 800 pulses/day and with 2000 pulses/day. The results of psychological examinations (MADRS, HAMD, BDI, grading, cognitive screening) prior to and afterwards the three-weeks-rTMS-cycle were submitted. Variance analyses were used for statistical reason.

The subsamples were comparable by sex, age, premorbid intellectual level as well as by self- and other-rated depression severity at treatment beginning. Statistical analyses showed a significant reduction of the depression symptoms in both stimulation protocol groups. Solely the HAMD score reduction in the 2000 pulse sample exceeded the decrease in the 800 pulse sample. Analogically the grading of human functions partly differed depending on the sample affiliation. Concerning the screening of cognitive functioning neither group was impaired.

rTMS still seems to be a well-functioning tool in the treatment of depressive disorders in the bounds of daily psychiatric health care. Although the modified stimulation protocol didn’t show many advantages in respect to improving depression symptoms, the results indicate the continual adjustment of the stimulation parameter to meet the current standards.

La rTMS est une technique non invasive modulant l’excitabilité corticale. Elle peut améliorer les performances mnésiques des patients âgés souffrant de troubles cognitifs. L’objectif est de présenter l’évolution des fonctions mnésiques de patients traités par rTMS. Sujet 1 : 73 ans, patient inclus dans une étude ayant pour but d’évaluer l’impact de la rTMS sur les troubles cognitifs. Le critère principal est l’évolution de la MoCA.

Stimulation du cortex préfrontal dorso-latéral droit à 1 Hz. Le patient reçoit 20 séances sur 4 semaines, 8 séances le 2e mois, 4 séances le 3e mois puis 6 séances les 3 derniers mois.

MoCA pré-inclusion : 25/30. Augmentation progressive jusqu’à M6 pour atteindre 30/30 puis diminution entre M6 et M12 jusqu’à 27/30. Sujet 2 : 81 ans, patient atteint de la maladie d’Alzheimer depuis 5 ans, traité par Donepezil. Méthode : protocole iTBS, 600 pulses, sur cortex dorso-latéral préfrontal gauche, à 80 % du seuil moteur gauche. Quarante séances sur 4 semaines. Le MMSE initial est de 16/30. Le MMSE post-rTMS immédiat s’élève à 20/30 et le MMSE à 3 mois à 24/30. Sujet 3 : 73 ans, patiente présentant des plaintes mnésiques à type d’atteinte isolée de la mémoire épisodique verbale. Elle est traitée par Duloxétine 30 mg/j et Rivastigmine patch 4,6 mg/. Méthode : 30 séances d’iTBS, 600 pulses, à 80 % du seuil moteur appliqué sur le cortex dorso-latéral préfrontal gauche, sur 3 semaines, répétée à M3. La MoCA pré-stimulation est à 15/30 et augmente à 19/30 après la seconde série.

La rTMS a montré des résultats positifs et encourageants pouvant être une piste pour la future prise en charge des troubles mnésiques chez le sujet âgé.

La stimulation magnétique transcrânienne (rTMS) est un traitement efficace de la dépression résistante. Sa place relative par rapport aux ECT dans la stratégie thérapeutique est questionnée ainsi que leur possible complémentarité.

Nous avons procédé à une synthèse de la littérature sur Pubmed fin juin 2014 avec la combinaison des mots clés suivants : ECT, mECT, rTMS, versus, adjuvant, add-on, comparative, efficacy, maintenance treatment, relapse, longitudinal follow-up, depression.

La rTMS peut être aussi efficace que l’ECT à coût équivalent sous certaines conditions (durée > 4 semaines, plus de 1200 pulses par séance, moins d’échecs médicamenteux antérieurs, et surtout absence de symptômes psychotiques). Les mécanismes d’action sont en partie communs : neurogenèse, sécrétion de facteurs neurotrophiques, transmission monoaminergique, gabaergique et glutamatergique, régulation de l’axe hypothalamo-hypophysaire et régulation de l’activité cérébrale frontal et limbique. L’action rapide de la rTMS sur le risque suicidaire reste à démontrer mais elle présente probablement un meilleur profil de tolérance cognitive en cure initiale, voire un effet procognitif. Dans les deux cas le taux de rechute est estimé entre 40 et 50 % à 3 mois en l’absence de prophylaxie adéquate. Le traitement d’entretien par rTMS consiste le plus souvent en 2 séances sur une journée de façon hebdomadaire sans consensus actuellement sur cette question. Bien que les ECT de maintenance soient bien tolérées, certains patients fragiles du fait de co-morbidités, ou réticents à certains traitements psychotropes, ou craignant les anesthésies, pourraient bénéficier de rTMS en relais des ECT. Plusieurs séries de cas plaident en ce sens.

Des essais prospectifs longitudinaux avec présence de groupes contrôles sont souhaitables, contrôlant sur la durée les traitements et les aspects cognitifs de façon objective et comparative. La rythmicité, les sous-groupes cliniques éligibles, et les traitements associés restent à préciser.