The effect of deep repetitive transcranial magnetic stimulation with an H1 coil on hopelessness in patients with major depressive disorder: A randomized controlled trial.

OBJECTIVES: To assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) with an H1 coil as a treatment for hopelessness in patients with major depressive disorder (MDD). METHODS: We conducted a randomised controlled trial in a tertiary psychiatric institution in Croatia, including patients diagnosed with MDD without psychotic symptoms and with clinically relevant hopelessness. High-frequency (18 Hz) rTMS with an H1 coil was administered over four weeks on the left dorsolateral prefrontal cortex. We examined changes in the Beck Hopelessness Scale (BHS) scores. RESULTS: We randomly assigned 51 participants to the intervention group (rTMS plus standard therapy) and 52 to the control group (standard therapy). The mean (SD) ages were 50 (12.3) and 50 (10.4) years, and 47% and 52% of the participants were females in the intervention and control groups, respectively. Following treatment, the BHS scores decreased (unadjusted bivariate analysis, p = 0.043; false discovery rate (FDR) >5%). Multivariate analysis revealed that the BHS score was reduced by 10.8% (95% confidence interval (CI: -17.8% to -3.9%) in the rTMS group and 0.7% (95% CI: 7.5% -6.1%) in the control group (p = 0.037; FDR < 5%). CONCLUSIONS: rTMS with an H1 coil improved the symptoms of hopelessness in patients with MDD.

Current Status of Repetitive Transcranial Magnetic Stimulation (rTMS) in Croatia and in University Psychiatric Hospital Sveti Ivan.

This article reviews the history, evolution, and current status of repetitive transcranial magnetic stimulation (rTMS) in Croatia. University Psychiatric Hospital Sveti Ivan experts performed the first rTMS in 2015 as a first treatment and research group in Croatia. In addition to being a leading center for rTMS in clinical trials and in treating depression, University Psychiatric Clinic Sveti Ivan TMS center continues to research rTMS for depression and other neuropsychiatric disorders and conditions, exploring novel stimulation parameters and individualized treatment protocols. Since 2017 rTMS treatment for MDD in Croatia has been reimbursed by the National Insurance Fund and has been available to hospital and ambulatory patients by indication, and now is widely used in other health centers in Croatia, to treat depression and other neuropsychiatric disorders and conditions, especially when drugs are ineffective or produce harmful side effects.

Overview of Studies on the Efficacy of Repetitive Transcranial Magnetic Stimulation on the Severity of Symptoms of Major Depressive Disorder, Conducted in University Psychiatric Hospital Sveti Ivan 2016-2022.

This brief report presents the studies on HF rTMS efficacy on major depressive disorder (MDD) symptoms conducted in University Psychiatric Hospital Sveti Ivan from 2016 to 2022. We assessed the clinically relevant effects of rTMS delivered by H1-coil and the figure-8-coil on MDD symptoms severity in the pooled sample of patients. During the last seven years, we enrolled in the studies on MDD 336 patients with a median (interquartile range; IQR) age of 53 (45-61) years, 181 (54%) of them women. We performed interventions with two different coils (8-coil and H1-coil) at 120% of the motor threshold, approximately half with 10 and half with 18 Hz frequency, and > 90% with one daily session during 20 workdays. We offer considerations on how the bulk of our research informed the future direction of our laboratory's studies and clinical work.

A pilot investigation of accelerated deep transcranial magnetic stimulation protocols in treatment-resistant depression.

Accelerated repetitive transcranial magnetic stimulation (rTMS) protocols are being increasingly studied because of their potential to provide quicker and enhanced treatment efficacy. However, there is a lack of accelerated deep TMS with H1-coil (adTMS) treatment research. This randomized pilot study investigated the efficacy and safety of adTMS protocols. Twenty-eight TRD patients received 20-min sessions twice daily for 10 or 15 days. Primary outcomes were changes in Hamilton Depression Rating Scale (HDRS) scores and discontinuation because of adverse events (AE). Secondary outcomes were response, remission, daily changes in Beck Depression Inventory-II (BDI-II) scores, and AE incidence. HDRS scores decreased by 13 (95% CI 11-17; 59%, 95% CI 45-73%) and 13 (95% CI 11-14; 62%, 95% CI 54-69%) points in the 10- and 15-day protocols, respectively. The adjusted difference between the two protocols was not significant or clinically relevant. Remission was achieved by 38% and 42% after 10-day and 15-day protocols, respectively. The intervention was discontinued because of AEs in 3/33 (9%) patients. The BDI-II decreases were significant and clinically relevant during the first 8 days. Twice-daily adTMS for 10 days seems to be safe and effective, with rapid clinical benefits during the first week of treatment. These promising results warrant further investigation in larger randomized clinical trials comparing adTMS with the standard dTMS protocol.

Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-Coil in treatment of major depressive disorder; A randomized clinical trial.

Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment option for major depressive disorder (MDD). However, comparisons of efficacy between the two FDA-approved protocols of rTMS modalities are lacking. The aim of this industry-independent, randomized-controlled, single-blind trial was to evaluate clinical outcome of the two FDA-approved rTMS protocols delivered by H1-coil and the figure-8-coil, in MDD patients. A total of 228 MDD patients were randomized to 20 sessions of H1-coil or 8-coil as an adjunct to standard-of-care pharmacotherapy, or standard-of-care pharmacotherapy alone. Baseline MDD symptom severity was almost the same in the three groups. Hamilton depression rating scale (HAM-D17) mean score was 17 (5.3) in H1-coil, 17 (5.4) in 8-coil, and 19 (6.1) in control group. The primary outcome was the proportion of patients achieving remission defined as HAM-D17 score ≤7 at end-of-treatment at week-4. In the intention-to-treat analysis odds ratio for remission was 1.74 (CI95% 0.79-3.83) in H1-coil compared to the 8-coil group. The difference between two rTMS protocols was not significant. Remission rate was significantly greater in both HF-rTMS groups compared to the control: 60% (CI95% 48-71%), 43% (CI95% 31-55%) and 11% (CI95% 5-20%) respectively. The response was significantly better in H1-coil, than in 8-coil group OR = 2.33; CI95% 1.04-5.21 (P = 0.040). The HAM-D17 was lowered by 59% in the H1-coil, 41% in the 8-coil (P = 0.048), and 17% in the control group (P < 0.001 vs H1-coil; P = 0.003 vs 8-coil). Safety, tolerability, and the changes in quality of life were comparable. We confirmed the safety and efficacy of both FDA-approved protocols as adjunctive treatments of MDD. Better response rate and greater reduction of depression severity were observed in the H1-coil group, but without a significant difference in the remission rate between the two rTMS modalities. CLINICAL TRIALS REGISTRATION: Clinicaltrials.govNCT02917499.

Efficacy and safety of repetitive transcranial magnetic stimulation using an H1-coil or figure-8-coil in the treatment of unipolar major depressive disorder: A study protocol for a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique with few side effects that has been reported to be effective in the treatment of major depressive disorder (MDD). At present, no randomized controlled trials (RCT) have compared the efficacy and safety of rTMS delivered by the figure-8-coil and the H1-coil. We describe an industry-independent, randomized, controlled, single-blinded, single-center study protocol assessing the differences in efficacy and safety of rTMS for patients diagnosed with MDD with the H1-coil and figure-8-coil as an add-on to stable pharmacotherapy or pharmacotherapy alone. Stimulation protocols follow those that led to the FDA clearance of these treatments for MDD. The sample of 76 patents in each of the three groups will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is remission rate defined as Hamilton depression rating scale (HAM-D17) score ≤7 at the end of week-4. This clinical trial will address the efficacy and safety of rTMS modalities for MDD. The evaluation of biological markers will also help to elucidate the pathophysiology of MDD and the mechanisms of action of rTMS.

Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia.

BACKGROUND: An increasing body of research suggest that repetitive Transcranial Magnetic Stimulation (rTMS) is effective and safe treatment option for patients with major depressive disorder (MDD). The Psychiatric Hospital "Sveti Ivan" has the first TMS laboratory with rTMS and deep TMS (dTMS) in Croatia. The objective of this study was to assess the efficacy, safety and tolerability of augmentative rTMS treatment vs standard treatment in Croatian patients with major depressive disorder (MDD). SUBJECTS AND METHODS: Total of 93 MDD patients were enrolled; 41 of them were treated by augmentative rTMS and 52 were treated by standard (psychopharmacotherapy and psychotherapy) therapy only. We delivered rTMS to the left dorsolateral prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration), 3000 pulses per session using a figure-eight coil, minimum of 20 sessions during four weeks. Our key outcome was the change in Hamilton Depression Scale (HAM-D17) result from baseline to 4th week. Our secondary outcomes were changes in Hamilton Anxiety (HAM-A) and WHOQOL-BREF scales. RESULTS: After four weeks the changes of HAM-D17 and HAM-A results were significantly different between the group of patients treated by augmentative rTMS (48% and 53% decrease, respectively) and the group of patients treated by the standard therapy alone (24% and 30% decrease) (P=0.004, P=0.007). Absolute benefit increase defined as the difference between rates of remission (HAM-D17 ≤7) in rTMS and control group was 33% (P=0.001). Number of patients needed to treat with rTMS in order to achieve remission in one patient was NNT=3. In a group of patients treated with augmentative rTMS 21/41 (51%), and in control group 17/52 (33%) were responders (P=0.071). CONCLUSIONS: It seems that augmentative treatment with rTMS is more effective on depression and anxiety symptoms than standard therapy in MDD with equal safety and tolerability. Randomized, controlled studies are required to verify this finding.