Background: A recent evidence-based guideline demonstrated that bilateral repetitive transcranial magnetic stimulation (rTMS) over the motor cortex (M1) can improve motor symptoms of Parkinson's disease (PD). We conducted a randomized, double-blind, placebo-controlled study to evaluate the impact of bilateral M1 rTMS on depression in PD. Methods: Forty-six patients with PD and mild-to-moderate depression were randomly assigned to active (n = 23) and sham (n = 23) rTMS. Two patients in the sham group did not complete the protocol because of reasons unrelated to the study. High-frequency rTMS was applied over the primary motor cortex bilaterally for 10 days. An investigator blinded to the treatment performed three video-taped examinations on each patient: before stimulation (baseline), and 1 day (short-term effect) and 30 days after the treatment session ended (long-term effect). The primary end point was the changes in depression, while secondary end points included health-related quality of life scales and Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: In the actively treated group, not only did the severity of depression improve (from 17 to 7 points, Montgomery-Åsberg Depression Rating Scale, median values, p < 0.001), but also the health-related quality of life (from 25.4 to 16.9 points, PDQ-39 summary index, median values, p < 0.001). Besides, we could also demonstrate an improvement in MDS-UPDRS Motor Examination (from 26 to 20 points, median values, p < 0.05). In the sham-treated group, none of the examined tests and scales improved significantly after treatment. Conclusions: Our results demonstrate the beneficial effects of high-frequency bilateral M1 rTMS on depression and health-related quality of life in PD. However, this effect of rTMS should also be confirmed in patients with severe depression by further clinical trials.

Keywords:
Parkinson’s disease, Motor cortex, Transcranial magnetic stimulation, Depression, Health-related quality of life
1.
Janicak PG, O'Reardon JP, Sampson SM, Husain MM, Lisanby SH, Rado JT, Heart KL, Demitrack MA: Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry 2008;69:222-232.
2.
Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, et al: Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 2014;125:2150-2206.
3.
Arias-Carrion O, Machado S, Paes F, Velasques B, Teixeira S, Cardenas-Morales L, Piedade R, Ribeiro P, Nardi AE: Is rTMS an effective therapeutic strategy that can be used to treat Parkinson's disease? CNS Neurol Disord Drug Targets 2011;10:693-702.
4.
Pal E, Nagy F, Aschermann Z, Balazs E, Kovács N: The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: a randomized, double-blind, placebo-controlled study. Mov Disord 2010;25:2311-2317.
5.
Elahi B, Chen R: Effect of transcranial magnetic stimulation on Parkinson motor function - systematic review of controlled clinical trials. Mov Disord 2009;24:357-363.
6.
Vonloh M, Chen R, Kluger B: Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Parkinsonism Relat Disord 2013;19:573-585.
7.
Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK: Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 2003;18:467-486.
8.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4, text rev. Washington, American Psychiatric Publishing, 2000.
9.
Kaszas B, Kovács N, Balas I, Kallai J, Aschermann Z, Kerekes Z, Komoly S, Nagy F, Janszky J, Lucza T, Karadi K: Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease. Parkinsonism Relat Disord 2012;18:553-556.
10.
Volosin M, Janacsek K, Nemeth D: Hungarian version of the Montreal Cognitive Assessment (MoCA) for screening mild cognitive impairment (in Hungarian). Psychiatr Hung 2013;28:370-392.
11.
Kovács N, Aschermann Z, Acs P, Bosnyak E, Deli G, Komoly S: Levodopa-carbidopa intestinal gel infusion can improve the health-related quality of life. Mov Disord 2014;29:S162-S162.
12.
Lucza T, Karadi K, Kallai J, Weintraut R, Janszky J, Makkos A, Komoly S, Kovács N: Screening mild and major neurocognitive disorders in Parkinson's disease. Behav Neurol 2015;2015:983606.
13.
Lucza T, Karadi K, Komoly S, Janszky J, Kallai J, Makkos A, Kovács M, Weintraut R, Deli G, Aschermann Z, Kovács N: Neurokognitív zavarok diagnosztizálási és kezelési lehetőségei Parkinson-kórban. Orv Hetil 2015;156:915-926.
14.
Baron MS, Vitek JL, Bakay RA, Green J, Kaneoke Y, Hashimoto T, Turner RS, Woodard JL, Cole SA, McDonald WM, DeLong MR: Treatment of advanced Parkinson's disease by posterior GPI pallidotomy: 1-year results of a pilot study. Ann Neurol 1996;40:355-366.
15.
Pascual-Leone A, Hallett M: Induction of errors in a delayed response task by repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex. Neuroreport 1994;5:2517-2520.
16.
Beck AT, Steer RA, Ball R, Ranieri W: Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess 1996;67:588-597.
17.
Montgomery SA, Åsberg M: A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-389.
18.
Fazekas G, Kulmann L: Parkinsonos betegek életminőségét vizsgáló kérdőív (PDQ-39) magyarországi adaptációja. Ideggyogy Sz 2001;54:42-44.
19.
Horváth K, Aschermann Z, Ács P, Bosnyák E, Deli G, Pál E, Késmárki I, Horváth R, Takács K, Komoly S, Bokor M, Rigó E, Lajtos J, Klivényi P, Dibó G, Vécsei L, Takáts A, Tóth A, Imre P, Nagy F, Herceg M, Hidasi E, Kovács N: Validation of the Hungarian MDS- UPDRS: why do we need a new Parkinson scale? Ideggyogy Sz 2014;67:129-134.
20.
Hoehn MM, Yahr MD: Parkinsonism: onset, progression and mortality. Neurology 1967;17:427-442.
21.
Johns MW: A new method for measuring daytime sleepiness: The Epworth Sleepiness Scale. Sleep 1991;14:540-545.
22.
Kovács N, Pal E, Nagy F, Acs P, Bosnyak E, Faludi B: Parkinson's Disease Sleep Scale-2 is more specific for PD than the Epworth Sleep Scale. Mov Disord 2013;28:S224-S225.
23.
Horvath K, Aschermann Z, Acs P, Deli G, Janszky J, Karadi K, Komoly S, Faludi B, Kovács N: Test-retest validity of Parkinson's Disease Sleep Scale, 2nd version (PDSS-2). J Parkinsons Dis 2014;4:687-691.
24.
Schwab J, England A: Projection technique for evaluating surgery in Parkinson's disease; in Gillingham F, Donaldson M (eds): Third Symposium on Parkinson's Disease. Edinburgh, Livingston, 1969, pp 152-157.
25.
Duru G, Fantino B: The clinical relevance of changes in the Montgomery-Åsberg Depression Rating Scale using the minimum clinically important difference approach. Curr Med Res Opin 2008;24:1329-1335.
26.
Hiroe T, Kojima M, Yamamoto I, Nojima S, Kinoshita Y, Hashimoto N, Watanabe N, Maeda T, Furukawa TA: Gradations of clinical severity and sensitivity to change assessed with the Beck Depression Inventory-II in Japanese patients with depression. Psychiatry Res 2005;135:229-235.
27.
Horvath K, Aschermann Z, Acs P, Deli G, Janszky J, Komoly S, Karadi K, Kovács M, Makkos A, Faludi B, Kovács N: Minimal clinically important difference on Parkinson's Disease Sleep Scale, 2nd version. Parkinsons Dis 2015;2015:970534.
28.
Horvath K, Aschermann Z, Acs P, Deli G, Janszky J, Komoly S, Balázs É, Takács K, Karádi K, Kovács N: Minimal clinically important difference on the Motor Examination part of MDS-UPDRS. Parkinsonism Relat Disord 2015;21:1421-1426.
29.
Glass GV, Peckham P, Sanders J: Consequences of failure to meet assumptions underlying fixed effects analyses of variance and covariance. Rev Educ Res 1972;42:237-288.
30.
Harwell MR, Rubinstein E, Hayes W, Olds C: Summarizing Monte Carlo results in methodological research: the one- and two-factor fixed effects ANOVA cases. J Educ Stat 1992;17:315-339.
31.
Lix LM, JC K, Keselman H: Consequences of assumption violations revisited: a quantitative review of alternatives to the one-way analysis of variance F test. Rev Educ Res 1996;66:579-619.
32.
Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G, Dietrichs E, Fabbrini G, Friedman A, Kanovsky P, Kostic V, Nieuwboer A, Odin P, Poewe W, Rascol O, Sampaio C, Schupbach M, Tolosa E, Trenkwalder C, Schapira A, Berardelli A, Oertel WH: Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. Eur J Neurol 2013;20:5-15.
33.
Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C: The Movement Disorder Society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson's disease. Mov Disord 2011;26(suppl 3):S42-S80.
34.
Janicak PG, Dunner DL, Aaronson ST, Carpenter LL, Boyadjis TA, Brock DG, Cook IA, Lanocha K, Solvason HB, Bonneh-Barkay D, Demitrack MA: Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of quality of life outcome measures in clinical practice. CNS Spectr 2013;18:322-332.
35.
Schneider AL, Schneider TL, Stark H: Repetitive transcranial magnetic stimulation (rTMS) as an augmentation treatment for the negative symptoms of schizophrenia: a 4-week randomized placebo controlled study. Brain Stimul 2008;1:106-111.
36.
Boyer L, Dousset A, Roussel P, Dossetto N, Cammilleri S, Piano V, Khalfa S, Mundler O, Donnet A, Guedj E: rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic substrate. Neurology 2014;82:1231-1238.
37.
Litvinenko IV, Khalimov RR, Trufanov AG, Krasakov IV, Khaimov DA: New approach to gait disorders therapy in late stages of Parkinson's disease (in Russian). Adv Gerontol 2012;25:267-274.
38.
Horvath K, Aschermann Z, Acs P, Bosnyak E, Deli G, Pal E, Janszky J, Faludi B, Kesmarki I, Komoly S, Bokor M, Rigo E, Lajtos J, Klivenyi P, Dibo G, Vecsei L, Takats A, Toth A, Imre P, Nagy F, Herceg M, Kamondi A, Hidasi E, Kovács N: Is the MDS-UPDRS a good screening tool for detecting sleep problems and daytime sleepiness in Parkinson's disease? Parkinsons Dis 2014;2014:806169.
39.
Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N: Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008;23:2129-2170.
40.
Maruo T, Hosomi K, Shimokawa T, Kishima H, Oshino S, Morris S, Kageyama Y, Yokoe M, Yoshimine T, Saitoh Y: High-frequency repetitive transcranial magnetic stimulation over the primary foot motor area in Parkinson's disease. Brain Stimul 2013;6:884-891.
41.
Rektorova I, Sedlackova S, Telecka S, Hlubocky A, Rektor I: Dorsolateral prefrontal cortex: a possible target for modulating dyskinesias in Parkinson's disease by repetitive transcranial magnetic stimulation. Int J Biomed Imaging 2008;2008:372125.
42.
Sayin S, Cakmur R, Yener GG, Yaka E, Ugurel B, Uzunel F: Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson's disease. J Clin Neurosci 2014;21:1373-1376.
43.
Rihmer Z, Gonda X, Dome P: Depression in Parkinson's disease. Ideggyogy Sz 2014;67:229-236.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.