Girardi P1, Rapinesi C, Chiarotti F, Kotzalidis GD, Piacentino D, Serata D, Del Casale A, Scatena P, Mascioli F, Raccah RN, Brugnoli R, Digiacomantonio V,Ferri VR, Ferracuti S, Zangen A, Angeletti G. ...Read More
This is BrainsWay’s global website. The website includes information on clinical indications that were not cleared by the FDA and are considered investigational by the U.S. medical device regulations. BrainsWay D treatment is FDA cleared for patients with MDD who failed to respond to one or more anti-depressants in the current episode.
Shalvata Medical Health Center, Hod-Hasharon, Israel
14 February, 2008
This study evaluated the safety and feasibility of H- coil rTMS in the treatment of patients suffering from treatment-resistant MDD at the Shalvata Mental Health Center, Tel Aviv University, Israel. The study begun in 2006 and was completed in the beginning of 2008.
Three different H-coil designs were tested (H1 coil, H2 coil and H1L coil). 64 patients were enrolled and assigned as follows: 23 to receive H1 stimulation, 22 to receive H2 stimulation and 21 to receive H1L stimulation. Out of the 64 enrolled patients, 53 have completed the study and 11 were dropouts.
The treatment protocol consisted of a drug taper-down period of 10 to 14 days, followed by the subjects receiving daily prefrontal rTMS (20 Hz, 2 sec on 20 sec off, for 20 minutes, i.e., 1680 stimuli) each day for 4 consecutive weeks (i.e. 20 treatment sessions), at 120% of the individual motor threshold (MT). Eight of the 18 patients who completed the study with the H1L coil, received treatment at 110% of MT. Applicants who were partially responsive to their medications and who would likely worsen significantly with a medication taper were not enrolled. There was a follow-up visit one week after the end of TMS treatment. Tolerability, safety measures, specific depressive and cognitive tests were conducted.
The Primary Study Endpoints were the:
Safety of the H-Coil designs as defined by maintained subject baseline, pre treatment, physical and neurological status.
Clinical antidepressant response at the end of the treatment, defined as a decline in Hamilton depression rating scale from the baseline rating by 50%.
The H-Coil design safety was assessed using the following measures and tests:
Clinical inspection of the scalp area near the location of the stimulating coils, immediately after each stimulation session for possible skin lesion.
Clinical assessment evaluated immediately after each stimulation session, with focus on headache, visual disturbances, weakness, paresthesisas, instability, vertigo, tinnitus, changes in hearing or other bodily sensations.
Measure of blood pressure and pulse rate before and after stimulation. Neurological examination before and immediately after each treatment session. Self-graded possible headaches 5 minutes after stimulation using a Visual Analog Scale.
The antidepressant response was assessed using the following measures and tests: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), Beck Depression Inventory (BDI) score), Short clinical assessment.
The H coil TMS treatment was found to be efficacious in both treatment groups with almost all patients having some response to the treatment. HDRS scores significantly improved from baseline to study endpoint during Brainsway® Deep rTMS treatment (p<0.05 for H1, H2 and H1L coils). Reduction of 50% in the Hamilton Depression Rating Scale (HDRS) was observed in 45% of the patients treated with H1, 44.4% in patients treated with H2 and 37.5% in patients treated with H1L (fig.1). Remission was reached by 45% of the patients treated with H1, 15% of the patients treated with H2 and 28% of patients treated with H1L (fig.2). When we examined the patients treated with H1L at only 110% MT, we found that none of them had a significant response. In contrast, 50% of the patients treated with H1L at 120% MT reached remission (fig.2). Overall, approximately, 97% of the patients demonstrated some response to the treatment and approximately 40% of the patients had a significant response and experienced >50% improvement in their Hamilton scores.
The HDRS score showed that the deep TMS effected a statistically significant improvement at study endpoint relative to baseline (p<00001, for the H1 H2 and H1L coils). This improvement was also evident in the patients’ CGI-S score and in their self-report (using the Beck Depression Inventory- BDI), which showed a significant improvement from baseline to endpoint (p<0.05, for both H1 and H2 coils) (fig. 3). The improvement became evident in most cases between the first and second week of treatment. The cognitive evaluations showed that patients treated with H1 coil improved in the following fields: attention, working memory, learning, planning and problem solving. Patients treated with the H2 coil showed improvement in memory, planning and problem solving abilities.
Patients did not report any pain or discomfort as a result of the deep TMS treatment. Patients did not encounter side effects, such as changes in blood pressure, seizures or neurological problems. Some patients reported mild headaches. These were relieved by mild analgesia.
Figure 1. The effect of Deep TMS on HDRS score
Notes: * p<.05; ** p<.01 (all comparisons with H1L-110%)
Figure 2. Treatment response and remission
Notes: p<.05 (for H1L-110%-coil compared to H1L-120%-coil in response rates)
Figure 3. The effect of Deep TMS on BDI score
Notes: *** p<.05 (all comparisons with H1L-110%)