Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder

Aimee M Hunter, Michael J Minzenberg, Ian A Cook, David E Krantz, Jennifer G Levitt, Natalie M Rotstein, Shweta A Chawla, Andrew F Leuchter, Aimee M Hunter, Michael J Minzenberg, Ian A Cook, David E Krantz, Jennifer G Levitt, Natalie M Rotstein, Shweta A Chawla, Andrew F Leuchter

Abstract

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS.

Methods: Medications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks.

Results: Use of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02).

Conclusions: Concomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome.

Keywords: Major Depressive Disorder; adrenergic; benzodiazepines; gamma-aminobutyric acid (GABA); psychostimulants; repetitive transcranial magnetic stimulation (rTMS); treatment outcome.

Conflict of interest statement

Dr. Minzenberg owns stock in Elan Pharmaceuticals and has received investigator‐initiated support from Shire. Dr. Cook reports he has received research support from Covidien (formerly Aspect Medical Systems), National Institutes of Health, and NeoSync, Inc. within the past three years; he has been an advisor/consultant/reviewer for Arctica Health, Cerêve, HeartCloud, NeuroDetect, NeuroSigma, NIH (ITVA), U.S. Departments of Defense and Justice, and the VA (DSMB); he is editor of the Patient Management section of the American Psychiatric Association's FOCUS journal; his biomedical intellectual property is assigned to the Regents of the University of California, and he has stock options in NeuroSigma, where he has served as Chief Medical Officer (on leave); he is employed by the University of California, Los Angeles and also has an appointment as a Staff Psychiatrist, Neuromodulation and Mood Disorders programs, Greater Los Angeles Veterans Administration Health System. Dr. Krantz discloses that within the past 36 months he has received research support from the National Institutes of Health. He currently serves as an investigator on a study sponsored by Neosync, Inc. Dr. Leuchter discloses that within the past 36 months he has received research support from the National Institutes of Health, Neuronetics, Department of Defense, CHDI Foundation, and NeuroSigma, Inc. He has served as a consultant to NeoSync, Inc., Ionis Pharmaceuticals, Inc., and ElMindA. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). Dr. Leuchter owns stock options in NeoSync, Inc. and has equity interest in BBA. Dr. Levitt, Dr. Hunter, Ms. Rotstein and Ms. Chawla do not have anything to disclose.

© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Data flow diagram of subject inclusion
Figure 2
Figure 2
Change in IDS total score (mean and standard deviation) at weeks 2, 4, 6 and rates of response and remission, for users versus non‐users of benzodiazepines (a) and psychostimulants (b)

References

    1. Berlim, M. T. , den Eynde Van, F. , & Daskalakis, Z. J. (2013). High‐frequency repetitive transcranial magnetic stimulation accelerates and enhances the clinical response to antidepressants in major depression: A meta‐analysis of randomized, double‐blind, and sham‐controlled trials. Journal of Clinical Psychiatry, 74, 122–129. 10.4088/JCP.12r07996
    1. Boroojerdi, B. , Battaglia, F. , Muellbacher, W. , & Cohen, L. G. (2001). Mechanisms underlying rapid experience‐dependent plasticity in the human visual cortex. Proceedings of the National Academy of Sciences of the United States of America, 98(25), 14698–14701. 10.1073/pnas.251357198
    1. Carpenter, L. L. , Janicak, P. G. , Aaronson, S. T. , Boyadjis, T. , Brock, D. G. , Cook, I. A. , … Demitrack, M. A. (2012). Transcranial magnetic stimulation (TMS) for major depression: A multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and Anxiety, 29(7), 587–596. 10.1002/da.21969
    1. Chen, S. , Huang, X. , Zeng, X. J. , Sieghart, W. , & Tietz, E. I. (1999). Benzodiazepine‐mediated regulation of alpha1, alpha2, beta1‐3 and gamma2 GABA(A) receptor subunit proteins in the rat brain hippocampus and cortex. Neuroscience, 93(1), 33–44. 10.1016/S0306-4522(99)00118-9
    1. Dubin, M. J. , Mao, X. , Banerjee, S. , Goodman, Z. , Lapidus, K. A. B. , Kang, G. , … Shungu, D. C. (2016). Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. Journal of Psychiatry & Neuroscience, 41(3), E37–45. 10.1503/jpn.150223
    1. Fitzgerald, P. B. , Benitez, J. , de Castella, A. , Daskalakis, Z. J. , Brown, T. L. , & Kulkarni, J. (2006). A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment‐resistant depression. American Journal of Psychiatry, 163(1), 88–94. 10.1176/appi.ajp.163.1.88
    1. George, M. S. , Lisanby, S. H. , Avery, D. , McDonald, W. M. , Durkalski, V. , Pavlicova, M. , … Sackeim, H. A. (2010). Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham‐controlled randomized trial. Archives of General Psychiatry, 67(5), 507–516. 10.1001/archgenpsychiatry.2010.46
    1. George, M. S. , Taylor, J. J. , & Short, E. B. (2013). The expanding evidence base for rTMS treatment of depression. Current Opinion in Psychiatry, 26(1), 13–18. 10.1097/YCO.0b013e32835ab46d
    1. Gilbert, D. L. , Ridel, K. R. , Sallee, F. R. , Zhang, J. , Lipps, T. D. , & Wassermann, E. M. (2006). Comparison of the inhibitory and excitatory effects of ADHD medications methylphenidate and atomoxetine on motor cortex. Neuropsychopharmacology, 31(2), 442–449. 10.1038/sj.npp.1300806
    1. Gouzer, G. , Specht, C. G. , Allain, L. , Shinoe, T. , & Triller, A. (2014). Benzodiazepine‐dependent stabilization of GABAA receptors at synapses. Molecular and Cellular Neuroscience, 63, 101–113. 10.1016/j.mcn.2014.10.004
    1. Gu, Q. (2002). Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity. Neuroscience, 111(4), 815–835. 10.1016/S0306-4522(02)00026-X
    1. Guo, T. , Xiang, Y.‐T. , Xiao, L. E. , Hu, C.‐Q. , Chiu, H. F. K. , Ungvari, G. S. , … Wang, G. (2015). Measurement‐based care versus standard care for major depression: A randomized controlled trial with blind raters. American Journal of Psychiatry, 172(10), 1004–1013. 10.1176/appi.ajp.2015.14050652
    1. Hu, S.‐H. , Lai, J.‐B. , Xu, D.‐R. , Qi, H.‐l. , Peterson, B. S. , Bao, A.‐M. , … Xu, Y. I. (2016). Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: A randomized, double‐blinded, control study. Scientific Reports, 6, 30537 10.1038/srep30537
    1. Impagnatiello, F. , Pesold, C. , Longone, P. , Caruncho, H. , Fritschy, J. M. , Costa, E. , & Guidotti, A. (1996). Modifications of gamma‐aminobutyric acidA receptor subunit expression in rat neocortex during tolerance to diazepam. Molecular Pharmacology, 49(5), 822–831.
    1. Kobayashi, B. , Cook, I. A. , Hunter, A. M. , Minzenberg, M. J. , Krantz, D. E. , & Leuchter, A. F. (2017). Can neurophysiologic measures serve as biomarkers for the efficacy of repetitive transcranial magnetic stimulation treatment of major depressive disorder? International Review of Psychiatry, 29(2), 98–114. 10.1080/09540261.2017.129769
    1. Korchounov, A. , & Ziemann, U. (2011). Neuromodulatory neurotransmitters influence LTP‐like plasticity in human cortex: A pharmaco‐TMS study. Neuropsychopharmacology, 36(9), 1894–1902. 10.1038/npp.2011.75
    1. Levkovitz, Y. , Isserles, M. , Padberg, F. , Lisanby, S. H. , Bystritsky, A. , Xia, G. , … Zangen, A. (2015). Efficacy and safety of deep transcranial magnetic stimulation for major depression: A prospective multicenter randomized controlled trial. World Psychiatry, 14(1), 64–73. 10.1002/wps.20199
    1. McClintock, S. M. , Reti, I. M. , Carpenter, L. L. , McDonald, W. M. , Dubin, M. , Taylor, S. F. , Krystal, A. D. (2018). Consensus recommendations for the clinical application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. The Journal of Clinical Psychiatry, 79(1), 35–48. 10.4088/JCP.16cs10905
    1. McDonald, W. M. , Durkalski, V. , Ball, E. R. , Holtzheimer, P. E. , Pavlicova, M. , Lisanby, S. H. , … George, M. S. (2011). Improving the antidepressant efficacy of transcranial magnetic stimulation: Maximizing the number of stimulations and treatment location in treatment‐resistant depression. Depression and Anxiety, 28(11), 973–980. 10.1002/da.20885
    1. Meintzschel, F. , & Ziemann, U. (2005). Modification of practice‐dependent plasticity in human motor cortex by neuromodulators. Cerebral Cortex, 16(8), 1106–1115. 10.1093/cercor/bhj052
    1. O’Reardon, J. P. , Solvason, H. B. , Janicak, P. G. , Sampson, S. , Isenberg, K. E. , Nahas, Z. , … Sackeim, H. A. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry, 62(11), 1208–1216. 10.1016/j.biopsych.2007.01.018
    1. Pehrson, A. L. , & Sanchez, C. (2015). Altered γ‐aminobutyric acid neurotransmission in major depressive disorder: A critical review of the supporting evidence and the influence of serotonergic antidepressants. Drug Design, Development and Therapy, 9, 603–624. 10.2147/DDDT.S62912
    1. Perera, T. , George, M. S. , Grammer, G. , Janicak, P. G. , Pascual‐Leone, A. , & Wirecki, T. S. (2016). The clinical TMS society consensus review and treatment recommendations for TMS therapy for major depressive disorder. Brain Stimulation, 9(3), 336–346. 10.1016/j.brs.2016.03.010
    1. Pesold, C. , Caruncho, H. J. , Impagnatiello, F. , Berg, M. J. , Fritschy, J. M. , Guidotti, A. , & Costa, E. (1997). Tolerance to diazepam and changes in GABAA receptor subunit expression in rat neocortical areas. Neuroscience, 79(2), 477–487. 10.1016/S0306-4522(96)00609-4
    1. Plewnia, C. , Bartels, M. , Cohen, L. , & Gerloff, C. (2001). Noradrenergic modulation of human cortex excitability by the presynaptic α2‐antagonist yohimbine. Neuroscience Letters, 307(1), 41–44. 10.1016/S0304-3940(01)01921-8
    1. Roth, B. L. , Sheffler, D. J. , & Kroeze, W. K. (2004). Magic shotguns versus magic bullets: Selectively non‐selective drugs for mood disorders and schizophrenia. Nature Reviews Drug Discovery, 3(4), 353 10.1038/nrd1346
    1. Rush, A. J. , Gullion, C. M. , Basco, M. R. , Jarrett, R. B. , & Trivedi, M. H. (1996). The inventory of depressive symptomatology (IDS): Psychometric properties. Psychological Medicine, 26(3), 477–486. 10.1017/S0033291700035558
    1. Schulze, L. , Remington, G. , Giacobbe, P. , Kennedy, S. H. , Blumberger, D. M. , Daskalakis, Z. J. , & Downar, J. (2017). Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta‐burst stimulation for refractory depression. Journal of Psychopharmacology, 31(3), 312–319. 10.1177/0269881116675516
    1. Tegenthoff, M. , Cornelius, B. , Pleger, B. , Malin, J. P. , & Schwenkreis, P. (2004). Amphetamine enhances training‐induced motor cortex plasticity. Acta Neurologica Scandinavica, 109(5), 330–336. 10.1046/j.1600-0404.2003.00235.x
    1. Uusi‐Oukari, M. , & Korpi, E. R. (2010). Regulation of GABA(A) receptor subunit expression by pharmacological agents. Pharmacological Reviews, 62(1), 97–135. 10.1124/pr.109.002063
    1. Wardenaar, K. J. , van Veen, T. , Giltay, E. J. , den Hollander‐Gijsman, M. , Penninx, B. W. , & Zitman, F. G. (2010). The structure and dimensionality of the Inventory of Depressive Symptomatology Self Report (IDS‐SR) in patients with depressive disorders and healthy controls. Journal of Affective Disorders, 125(1–3), 146–154. 10.1016/j.jad.2009.12.020
    1. Ziemann, U. (2004). TMS and drugs. Clinical Neurophysiology, 115(8), 1717–1729. 10.1016/j.clinph.2004.03.006
    1. Ziemann, U. , Reis, J. , Schwenkreis, P. , Rosanova, M. , Strafella, A. , Badawy, R. , & Müller‐Dahlhaus, F. (2015). TMS and drugs revisited 2014. Clinical Neurophysiology, 126(10), 1847–1868. 10.1016/j.clinph.2014.08.028
    1. Ziemann, U. , Tergau, F. , Bruns, D. , Baudewig, J. , & Paulus, W. (1997). Changes in human motor cortex excitability induced by dopaminergic and anti‐dopaminergic drugs. Electroencephalography and Clinical Neurophysiology, 105(6), 430–437. 10.1016/S0924-980X(97)00050-7

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