Thu, 09/09/2021 - 10:26
By Debra J. Stultz M.D.
46 posters were presented at the 9th Annual Clinical TMS Society meeting in West Palm Beach, Florida June 10-12th, with 29 sharing research on-line in a virtual format. These posters are available for 7.25 hours of CME depending on how many posters you review and can be found by going to the top of the Clinical TMS Society Dashboard, clicking on “Events” and then “On-Demand Webinars”. Next go down to the “2021 Poster Session”. The following is an outline of the posters presented, but by no means is an exhaustive review of the data presented. Please refer to the individual posters for additional details and to support the researchers contributing to the field of TMS knowledge.
Age/Gender
Posters referencing age and gender issues with TMS were presented by Pardell et al., Wyman et al., Goldman et al. and Stultz et al. “A retrospective outcome study comparing the effectiveness of rTMS therapy across Age and Gender” by Pardell et al. presented a retrospective chart review of 160 patients treated with the NeuroStar TMS device while measuring PHQ-9 scores. 109 patients were female and 51 were male. Comparing female vs male patients and those less than 50 years old as compared to those greater than 50 years of age while using a chi-square statistic for association; there was no statistical difference in sub-groups as to efficacy in PHQ-9 partial response, response, and remission. Higher numerical findings were demonstrated with increased partial responses and remission rates being found in females. Also, those less than 50 had higher remission rates. Comments from their poster suggested the lower remission rates for older males may be related to the length and severity of MDD illness.
Wyman et al. presented “Does Baseline Obsessive Compulsive Disorder (OCD) and Depression Scores, Age, and Gender Predict Remission in Patients Receiving Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of OCD?”. This was a study of 30 patients ages 17 – 40 years of age with a YBOCS score of greater than or equal to 14 and a clinical diagnosis of OCD receiving greater than or equal to 10 rTMS treatment sessions to the right dlPFC and supplementary motor area-FCz (SMA) [F4, cTBS, 40 seconds 80% and FCz, 1 Hz, 20 minutes at 100% rMT],while following the Yale-Brown Obsessive Compulsive Scale for OCD, the Patient Health Questionnaire 9-scale (PHQ-9), and The Hospital Depression and Anxiety Scale (HADS) depression sub-scale. The logistic regression model was not statistically significant in predicting remission based on the baseline YBOCS, PHQ-9, HADS, sex, or age.
“Transcranial Magnetic Stimulation Outcomes by Age: A Retrospective Chart Review in a Naturalistic Clinic Setting” by Goldman et al. described a retrospective chart review on 495 patients ages 15-78 with MDD following PHQ-9 and GAD-7 receiving bilateral rTMS with two different protocols based on the GAD-7 score. Age categories were 15-24, 25-34, 35-44, 45-54, and 55-78. Results revealed all age categories demonstrated improvement in depression with PHQ-9, rTMS response and remission rates did not differ across age categories, and higher baseline GAD-7 scores predicted a greater decrease in PHQ-9. Based on their report, advanced age should not be considered a poor prognostic indicator for rTMS efficacy (68 or the 495 patients were in the 55-78 age range).
“Repeat Transcranial Magnetic Stimulation (TMS) Treatment Cycles In An Elderly Patient with Recurrent Resistant Depression And A History Of Seizures: A Call For Maintenance Therapy” by Stultz et al. reported on a 70 year old female patient with a long history or recurrent resistant depression who received 4 different cycles of TMS from May 2019 until February 2021 using the Brainsway dTMS at 120% MT and 18 Hz to the LDPFC while following the Beck Depression Inventory (BDI) and the PHQ-9. The patient with a known seizure disorder was able to have benefit without a seizure in greater than 100 TMS sessions after failing multiple psychotropic medications, light therapy, the Fisher Wallace Stimulatory, synthroid augmentation, and psychotherapy. This study demonstrated repeated improvement in an elderly patient with very resistant depression. TMS in the elderly was also described below in Taylor’s TMS cognition study and adolescent studies were described by Croarkin et al. under the “Bilateral” heading.
Cognition
Cognitive issues with TMS were addressed by both Taylor et al. and Monira et al. Taylor et al. in “Network-targeted Prefrontal Transcranial Magnetic Stimulation (TMS) in Neuropsychiatric and Neurodegenerative Disorders” studied 27 patients ages 76 +/- 6.8 with mild cognitive impairments. They reported the L-DLPFC site had functional connectivity with the anterior cingulate, insular cortices, and supramarginal gyri. In addition to anticorrelated conncectiviety with the subgenual cingulate which is important in depression, prominent anticorrelated connectivity with the posterior cingulate which is important in mild cognitive impairment and Alzheimer’s was evident. “Evaluation of 1 Hz/20 Hz Bilateral rTMS Effects on Cognitive Performance in Patients with Major Depressive Disorder Using THINC-it” by Monira et al. was a naturalistic study of 943 patients with Major Depression using the THINC-it tool to detect changes in patients with MDD. Using 1 Hz right dlPFC 360 pulses and 20 Hz left dlPFC 1200 pulses for 30 – 36 sessions following the PHQ-9, GAD-7 and THINC-it surveys. Their study found mild-to moderate improvements in task performance and even larger improvements in subjective cognitive function with rTMS, independent of improvement of their clinical symptoms. rTMS did not worsen cognition, but slight improvement in executive functioning, working memory, attention, and processing speeds were seen.
Location
Growing interest in TMS research surrounds the location of TMS stimulation with respect to bilateral versus unilateral stimulation, as well as right versus left stimulation. This year posters were presented by Croarkin et al., Aaronson et al., Middleton et al., Monira et al, and Narwal et al. in reference to these topics. The Monira et al. study using bilateral stimulation was described above under cognition.
Bilateral/Unilateral
“Clinical Effectiveness of 1 Hz/20Hz Bilateral rTMS treatment in Adolescents with Major Depressive Disorder” by Croarkin et al. described a multi-site, naturalistic study in patients ages 12 -22 of bilateral rTMS stimulation using PHQ-9 and GAD-7 rating scales. In their study they used 1 Hz to right dlPFC for 360 pulses, and to the left dlPFC at 20 Hz for 1200 pulses. 43.3% of patients achieved remission for depression and 50.2% for anxiety. “Comparison of Left Unilateral TMS Treatment vs. Sequential Bilateral Treatment in a Large Registry Cohort” by Aaronson et al. compared 3,327 left-sided and 544 bilaterally treated patients from 107 treatment location sites of patients with primary major depressive disorder, age greater than 18, using the PHQ-9, and the Clinical Global Inventory-Severity scale. Population studies consisted of a modified intent to treat sample, completers, LUL or SBL only, or LUL only. They reported no superior outcome for the bilaterally treated group with statistically superiority of unilateral treatment for some CGI-S comparisons. Both HF-LUL only and SBL only TMS were highly effective in self- and clinician-ratings.
“Efficacy of Unilateral vs. Bilateral rTMS Treatment on Suicidal Ideation in Patients with Depression and Comorbid Anxiety” by Middleton et al. was a naturalistic study in patients with a primary diagnosis of Major Depressive Disorder and a secondary diagnosis of Generalized Anxiety Disorder following the PHQ-9, GAD-7, CHRT-Risk subscale where >3 indicates suicidal ideation is present. They used the MagVenture MagPro with B-65 coil 5 days/week of either unilateral 10 Hz (3000 Pulses) to the left dlPFC or bilateral sequential treatment of 1 Hz (360 pulses) to the right dlPFC then 20 Hz (1200 Pulses) to the left dlPFC. They found that overall there were large reductions in both anxiety and suicidality with rTMS treatment and demonstrated equally strong improvements with unilateral left treatment and bilateral treatment. Both unilateral and bilateral rTMS achieved remission from suicidality in > 70%, surpassing the overall remission rates of about 50% for depression and anxiety in general indicating even among those who do not achieve full remission from depression and anxiety symptoms, remission from suicidality is both possible and likely.
Left/Right
“The Outcomes & Comparative Efficacy of Left vs Right Sided TMS for Females with a Co-Diagnosis of MDD & GAD” by Karan Narwal MD involved 10 female patients ages 25-65 years of age with a diagnosis of major depression and generalized anxiety disorder. Using NeuroStar TMS on the left dorsolateral prefrontal cortex at 120% MT, 5-10 Hz for 3000 pulses in 5 patients and Neurostar Advanced therapy on the right dorsolateral prefrontal cortex of 120% MT, 1 Hz for 2000 pulses on the other 5, they treated patients 5 days per week for 6 weeks, with a taper of 3 weeks. While following the PHQ-9 and GAD-7, the results indicated high clinical impact on MDD in both left and right treatment, but greater clinical efficacy for anxiety on the left sided high frequency treatment. Singh et al in “A comparison of final Yale-Brown Obsessive-Compulsive Scale (YBOCS) in patients receiving either Repetitive Transcranial Magnetic Stimulation (rTMS) to the Right Dorsolateral Prefrontal Cortex + Supplementary Motor Area (rDLPFC + SMA) or Left Medial Orbiotfrontal Cortex (FP1) for the treatment of Obsessive-Compulsive Disorder (OCD)” studied 36 patients, with 29 receiving treatment over the rDLPC + SMA and 7 receiving treatment over the FPI studying YBOCS score comparison in the two groups at baseline and at the end of treatment. They concluded that the stimulation site did not predict treatment outcome.
Maintenance/Preservation/Relapse Prevention
Studies discussing maintenance, preservation, or relapse prevention were described by Wilson et al., Stultz et al., Mania et al. and Tirrell et al. Wilson et al. in “Systematic Review of Preservation TMS that includes Continuation, Maintenance, Relapse-Prevention, and Rescue TMS” performed a systematic review of publications on TMS after a successful acute course of treatment for major depression to review protocols, outcomes, risk of bias, and levels of evidence. After screening 542 records, 27 were ultimately included in the review. They reported that TMS approaches vary and more studies are critically needed. They introduced the term “Preservation TMS” to include all TMS protocols used after an acute course of treatment to replace the terms continuation, maintenance, relapse-prevention, re-introduction, and rescue TMS. The authors suggested that due to the lack of good alternatives, preservation TMS will be necessary to sustain wellness in some patients and is considered a safe option.
Stultz et al. in the previously mentioned poster entitled “Repeat Transcranial Magnetic Stimulation (TMS) Treatment Cycles In An Elderly Patient With Recurrent Resistant Depression And A History of Seizures: A Call For Maintenance Therapy” suggested their elderly patient with recurrent resistant depression requiring 4 TMS cycles in two years would have been more adequately treated with maintenance TMS if the insurance company would have allowed it preventing significant increase in depressive symptoms based on the Beck Depression Inventory and the PHQ-9 between treatment cycles. Mania et al. in “To continue or not – Case Report on TMS Maintenance” reported on a 39 year old female with resistant depression treated successfully with the H1-coil to the LDLPFC for 36 sessions followed by a 3 week taper while following the PHQ-9 and the HAM-D. After another recurrence in 3 months and treatment at the same above protocol, she then received maintenance TMS once a week for 3 months and every other week after that. Six months after her last session of the second treatment course she maintained benefit based on the PHQ-9 and the HAM-D.
Tirrell et al. in “Ecological Momentary Assessment (EMA)-Guided TMS Maintenance Therapy for Prevention of Depression Relapse: A Feasibility Pilot” placed patients who were TMS responders with PHQ-9 scores <10 in a 12 month open-labeled study with a target PHQ-9 score to trigger retreatment. Weekly evaluations were obtained and if the patient reached their target PHQ-9 score for two consecutive weeks, a 5 daily session “Cluster” TMS treatment protocol was initiated. Once stabilized, patients went back into the weekly monitoring program. 85% of Cluster TMS treatments generated a response and the patient returned to weekly monitoring. Five of the participants did not respond to a cluster TMS treatment and exited monitoring. Those with failed cluster TMS response had higher trigger PHQ-9 scores.
Military
A very large VA study was undertaken in “Transcranial Magnetic Stimulation in US Military Veterans: A Naturalistic Study in the Veterans Health Administration” by Madore et al. This was a multisite naturalistic study of TMS on 770 Veterans with MDD, the majority having comorbid PTSD while following the PHQ-9 and the PTSD symptom checklist for DSM-5 (PCL-5). Standard TMS parameters at local discretion were used and were typically High-frequency stimulation (10 Hz or iTBS) to the left dorsolateral prefrontal cortex at 120% MT of 3000 pulses for 36 sessions. 314 Veterans with MDD received TMS of adequate dose and 522 had threshold level PTSD symptoms severity with PCL-5 scores greater than 33. With respect to depression, patients demonstrated a reduction of 7.12 points (p<.001) on the PHQ-9, with 30.5% reaching clinical response, and 15.3% reaching clinical remission. In those with PTSD, a reduction of 18.49 on the PCL-5 (p <.001) was demonstrated with 57.5% meaningful improvement and 59.8% no longer meeting threshold severity. Very few serious side effects were noted in the 770 patients. Four veterans experienced unexpected side effects requiring significant medical intervention. One Veteran had a seizure and five were hospitalized for worsening of their psychiatric symptoms.
Another interesting veteran study was presented entitled “A retrospective review of patients with Post-Traumatic Stress Disorder (PTSD) treated by Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS) by Makale et al. used a MagPro R30 stimulator and B-65transducer 30 minutes per day, 5 days per week for 4-12 weeks. Prior to this, the patients had an EEG using CGX high impedance dry electrode headset initially prior to treatment and then once weekly and then Quantitative q EEG WELCH’s FFT power spectrum of amplitude versus frequency. Stimulus frequency aligned with the qEEG alpha band peak and magnetic field amplitude was 20 – 30% of machine power which equated to 50 – 60% of the individual motor threshold and was applied to several cortical areas along a frequency gradient. In their study, 84% of patients responded, and their mean PCL-5 score reduction was on average 23 PCL-5 points. Also, the EEG power spectrum dominant alpha peak migrated by up to 1 Hz toward the visual cortex dominant alpha frequency. They concluded that treating multiple cortical sites and the application of personalized rTMS showed promise in the refractory PTSD military veterans.
Therapy and TMS
Cruz et al. in “iTBS combined with Cognitive Behavioral Therapy for treatment resistance depression (TRD)” studied 14 TRD patients with 30 TMS theta burst TMS sessions. One-half were randomly assigned to receive CBT with their TMS. The patients were followed using the PHQ-9. The iTBS + CBT group had a remission rate of 85.71% and the iTBS alone group had a remission rate of 42.85%. Davila et al. in “Change in Reported Resilience After rTMS for Major Depressive Disorder at a Suburban Tertiary Clinic” studied 62 patients using the Brief Resilience Scale, the PHQ-9, and the Montgomery-Asberg Depression Rating Scale while using a Mag Venture machine at 120% MT 5 times per week for up to 6 weeks. Their conclusion was that rTMS for depression was associated with a significant increase in resiliency that correlated with mood change after 6 weeks of treatment.
Stimulation And Additional Substances
Yuan et al. in the “Effects of NMDA-R Partial Agonists on the Primary Motor Cortex Excitability” reported that considering prior studies have demonstrated that N-methyl-D-aspartic acid-receptor (NMDA-R) antagonists and anti-glutamatergic drugs like dextromethorphan, mamantine, and riluzole may attenuate intracortical facilitation and enhance intracortical inhibition, initiated a study demonstrating that two NMDA-R partial agonists (L-theanine and D-cycloserine) enhanced intracortical facilitation and attenuated intracortical inhibition in the primary motor cortex of healthy humans. In Ketamine Therapy Combined with Repetitive Transcranial Magnetic Stimulation (rTMS) for MDD at a Suburban Tertiary Clinic by Davila et al. patients were given rTMS with a MagVenture machine of 18-minute sessions over the left dorsal lateral prefrontal cortex and also received on average 6 IV Ketamine 1-2 weekly infusions of doses ranging from 0.5mg/kg to 1.25 mg/kg. PHQ-9 and BDI scales were followed. Of 29 patients ages 19-73, 15 patients completed the study. Combination rTMS with Ketamine demonstrated significant decrease in depression scales after 6 weeks, with the PHQ-9 decreasing from 17.5 +/-5 down to 9.6 +/- 7 and the BDI decreasing from a baseline of 30.3 +/- 12 to 18.4 +/- 12.
Specific Disorders/Symptoms
Anxiety/OCD
Pell et al. in “Deep TMS for the treatment of comorbid anxiety” used a principal rating scale of the HDRS Anxiety/Somatization factor score as well as post-marketing data using the Beck Anxiety Inventory while doing an evaluation of collated data from the pivotal RCT (Levkovitz et al.2015) of H1 vs Sham, a Head-to-head (Filipcic et al. 2019) H1 vs medication vs figure 8 study, a meta-analysis of 3 RCT’s, data from the 3 RCTs and 7 open-label trials as a meta-analysis, a meta-analysis of existing effect sizes in the literature for anxiolytic medication, and post-marketing Brainsway data. Their research indicated deep TMS treatment of depression demonstrated significant improvement in comorbid anxiety.
Tirrell et al. in “Mechanical Affective Touch Therapy (MATT) for Anxiety Disorders: Clinical Outcomes and EEG Biomarkers in an Open-Label Clinical Trial” enrolled 22 patients using the MATT device which stimulates C-tactile fibers through gentile vibration on bilateral mastoids twice daily for 4 weeks. The GAD-7, Perceived Stress Scale, Beck Depression Inventory, DASS-D Depression Scale, DASS-A Anxiety Scale, DASS-S Stress Scale and the MAIA Interoceptive Awareness scales were followed. Resting EEG evaluation was obtained before and after baseline and with the final MATT session. Anxiety and depressive symptoms improved significantly and mindfulness was enhanced at endpoint. Greater symptom improvement after a 4-week course of MATT was associated with reductions in occipital alpha power and increases in occipital theta power.
Zibman et al. in “Analysis of multi-center MDD trials indicates direct, polysymptomatic effect of rTMS on depression and anxiety with H-1 coil and delayed, indirect effect on anxiety with figure-8 coil” compared 165 patients from the Brainsway pivotal multicenter trial using the H1 coil compared to 174 from the OPT-TMS trial delivered with a figure 8 coil evaluating HDRS data. Their report suggested both treatment coils lead to improvement in depression and anxiety, but stated the improvement in anxiety with the figure 8 coil lagged behind depression, whereas the improvement was simultaneous with the H1- coil.
Multiple Sclerosis
Transcranial Magnetic Stimulation (TMS) Improvement in Depression, Insomnia, and Fatigue Associated with Multiple Sclerosis (MS) by Stultz et al. presented a case of a 60 year-old white female with a history of Secondary Progressive MS, recurrent depression, insomnia, and frequent suicidal ideation. She was treated using the Brainsway dTMS at 120% MT, 18 Hz to the LDLPFC while following the Beck Depression Inventory, Patient Health Questionnaire-9 (PHQ-9, Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI) and the Modified Fatigue Impact Scale (MFIS). The patient demonstrated an improvement in mood, fatigue, and insomnia. She had improvement on the Modified Fatigue Impact Scale overall, and specifically on the cognitive and physical components.
Pregnancy
Yee et al. in “Repetitive Transcranial Magnetic Stimulation in the Treatment of Major Depression during Pregnancy: A Case Series” reported on four pregnant patients, aged 31-37, treated with rTMS during the second or third trimester with rTMS of 36 sessions, 5 days a week, and included 5HZ continuous theta burst stimulation to the right DLPFC at 80% for 1200 pulses, 5 HZ intermittent theta burst stimulation to the left DLPFC at 80% MT for 200 pulses and 10Hz intermittent single pulse stimulation to the left DLPFC at 120% MT for 3000 pulses, totaling 4400 pulses. They followed the PHQ-9 and GAD-7 at baseline, and around 10, 20, and 30 sessions into treatment. All four patients responded with a greater or equal than 50% decrease in their PHQ-9 scores, two achieved remission. No adverse pregnancy or fetal outcomes were observed.
Pain
Aron Tendler MD in “Deep-TMS for Chronic Non-Cancer Pain Syndromes including CRPS” reported on dTMS for 13 chronic non-cancer pain patients including two with complex regional pain syndrome while following the comparative pain scale (CPS) using parameters of 20 Hz, 2.5 sec train, 20 second inter-train interval, 30 trains, 1500 pulses at 100% MT over the MC demonstrating meaningful non-pharmacologic analgesia. Eleven of the 13 improved with treatment.
Ramsay Hunt Syndrome
Hutton and Coombs in “Ramsay Hunt Syndrome Treated with TMS – A Case Report” wrote of treating a 45 year old male with Ramsay Hunt Syndrome, which is facial paralysis, hearing loss, tinnitus, and vertigo that co-occurs with shingles. The patient was given TMS via Neuronetics figure-of-eight and stimulated both vertically right behind the ear with the direction of the magnetic field oriented anteriorly and horizontally on the top of the ear with the magnetic pulse oriented ventrally. (A picture demonstrating the placement is available on the poster.) He was given 14 sessions of 10 Hz TMS at 140% MT for 1000 pulses at each location. Picture presentation on the poster demonstrated impressive improvement and the patient reported he could close his eye, had significant improvement in facial numbness, and reported a 20% improvement in hearing.
Schizophrenia
In “Deep-TMS for Negative Symptoms of Schizophrenia” Aron Tendler reported on 5 subjects with an average duration of schizophrenia of 7.2 years and an average of 4 failed antipsychotics treated with the H1 coil high-frequency TMS at 120% MT over the PFC demonstrating meaningful and significant reduction of negative symptoms and a significant reduction of the positive symptoms. Three of the five patients returned to work with treatment.
Smoking
Moeller et al. in “Deep Repetitive (drTMS) of the insula disrupts cigarette self-administration and modulates insula-centric brain function in smokers with schizophrenia” presented proof-of-concept data on rTMS for smoking cessation in 20 schizophrenic patients with dTMS of the insula. 20 patients were assigned to either active or sham dTMS and were studied 3 weeks using cigarette self-administration pre/post laboratory assessments and target engagement tested with arterial spin labeling with 3 MRI sessions during the trial. Their study demonstrated insula blood flow was lower after the first treatment than at baseline and the active TMS group smoked numerically fewer cigarettes after treatment than before treatment, a trend not seen for sham. Parameters were 20 minute daily morning session 5 days per week of 60 trains, each lasting 3s, interleaved with a 15 s delay, with a pulse strength building up to 120% MT by the 3rd session.
Suicide
As previously reported, Middleton et al. in “Efficacy of Unilateral vs. Bilateral rTMS Treatment on Suicidal Ideation in Patients with Depression and Comorbid Anxiety” stated both unilateral and bilateral rTMS achieved remission from suicidality in >70% in those with a primary diagnosis of major depressive disorder and a secondary diagnosis of generalized anxiety disorder.
In summary, the above mentioned poster presentations describe very exciting advances to our TMS treatment research! If you would like to view all 29 authors/presenters sharing their insight and research findings, click here to view the 2021 Poster Session: A Virtual Experience. The 2021 posters will be available for online viewing through December 31, 2021. As the window to view the posters are limited, we encourage everyone to register asap, to receive the max allotted time. Earn up to a max of 7.25 hours of CME depending on how many posters you choose to view.