Pursuing personalized medicine for depression by targeting the lateral or medial prefrontal cortex with Deep TMS
Abraham Zangen, Samuel Zibman, Aron Tendler, Noam Barnea-Ygael, Uri Alyagon, Daniel M. Blumberger, Geoffrey Grammer, Hadar Shalev, Tatiana Gulevski, Tanya Vapnik, Alexander Bystritsky, Igor Filipčić, David Feifel, Ahava Stein, Frederic Deutsch, Yiftach Roth, Mark S. George
Abraham Zangen, Samuel Zibman, Aron Tendler, Noam Barnea-Ygael, Uri Alyagon, Daniel M. Blumberger, Geoffrey Grammer, Hadar Shalev, Tatiana Gulevski, Tanya Vapnik, Alexander Bystritsky, Igor Filipčić, David Feifel, Ahava Stein, Frederic Deutsch, Yiftach Roth, Mark S. George
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Clinical Research and Public Health Clinical trials Neuroscience

Pursuing personalized medicine for depression by targeting the lateral or medial prefrontal cortex with Deep TMS

Abstract

BACKGROUND Major depressive disorder (MDD) can benefit from novel interventions and personalization. Deep transcranial magnetic stimulation (Deep TMS) targeting the lateral prefrontal cortex (LPFC) using the H1 coil was FDA cleared for treatment of MDD. However, recent preliminary data indicate that targeting the medial prefrontal cortex (MPFC) using the H7 coil might induce outcomes that are as good or even better. Here, we explored whether Deep TMS targeting the MPFC is noninferior to targeting the LPFC and whether electrophysiological or clinical markers for patient selection can be identified.METHODS The present prospective, multicenter, randomized study enrolled 169 patients with MDD for whom antidepressants failed in the current episode. Patients were randomized to receive 24 Deep TMS sessions over 6 weeks, using either the H1 coil or the H7 coil. The primary efficacy endpoint was the change from baseline to week 6 in Hamilton Depression Rating Scale scores.RESULTS Clinical efficacy and safety profiles were similar and not significantly different between groups, with response rates of 60.9% for the H1 coil and 64.2% for the H7 coil. Moreover, brain activity measured by EEG during the first treatment session correlated with clinical outcomes in a coil-specific manner, and a cluster of baseline clinical symptoms was found to potentially distinguish between patients who can benefit from each Deep TMS target.CONCLUSION This study provides a treatment option for MDD, using the H7 coil, and initial guidance to differentiate between patients likely to respond to LPFC versus MPFC stimulation targets, which require further validation studies.TRIAL REGISTRATION ClinicalTrials.gov NCT03012724.FUNDING BrainsWay Ltd.

Authors

Abraham Zangen, Samuel Zibman, Aron Tendler, Noam Barnea-Ygael, Uri Alyagon, Daniel M. Blumberger, Geoffrey Grammer, Hadar Shalev, Tatiana Gulevski, Tanya Vapnik, Alexander Bystritsky, Igor Filipčić, David Feifel, Ahava Stein, Frederic Deutsch, Yiftach Roth, Mark S. George

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Figure 1

Timeline, assessments, enrollment, and randomization.

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Timeline, assessments, enrollment, and randomization. (A) Efficacy was a...
(A) Efficacy was assessed by Hamilton Depression Rating Scale (21-item version; HDRS-21), as well as by pre- and post-treatment Hamilton Anxiety Rating Scale (HARS) and Clinical Global Impression Severity and Improvement (CGI-S and CGI-I). In addition, patients completed self-report questionnaires on a weekly basis, including the Quick Inventory of Depressive Symptoms – Self Report (QIDS-SR) and the Patient Global Impressions Improvement (PGI-I). Daily functioning score (Global Assessment of Functioning, GAF) and quality-of-life measures (Quality of Life Enjoyment and Satisfaction Questionnaire, Q-Les-Q) were collected as well. Safety was assessed at pre- and posttreatment using the Scale for Suicide Ideations (SSI), Young Manic Rating Scale (YMRS), auditory threshold tests, physical and neurological examinations, and vital signs. Additional safety assessments included cognitive changes evaluations performed throughout the study, including the Mini-Mental Status Examination (MMSE) and the Buschke Selective Reminding Test (BSRT). Throughout the entire study patients were under the direct monitoring of a physician, and any adverse effects or subjective complaints were immediately recorded and treated. (B) Patients were outpatients aged 22 to 68 years who signed an informed consent form and had HDRS-21 ≥ 20 that was stable between screening and baseline assessments (±30%). Main exclusion criteria included comorbid psychiatric and neurological disorders, presence of psychosis, primary anxiety disorder causing higher distress than MDD, substance abuse within 6 months, prominent personality disorder causing higher distress than MDD, dysthymia, prior head trauma or seizures, and suicide attempt within 3 years. The intent-to-treat (ITT) analysis set included all patients enrolled in the study, and the completers (CO) analysis set included all patients randomized to the study who had no major protocol violations and completed the 6 weeks of treatment.