Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Obsessive-Compulsive Disorder: A Multi-Site Study

Emily R Hawken, Dancho Dilkov, Emil Kaludiev, Selcuk Simek, Felicia Zhang, Roumen Milev, Emily R Hawken, Dancho Dilkov, Emil Kaludiev, Selcuk Simek, Felicia Zhang, Roumen Milev

Abstract

Recently, strategies beyond pharmacological and psychological treatments have been developed for the management of obsessive-compulsive disorder (OCD). Specifically, repetitive transcranial magnetic stimulation (rTMS) has been employed as an adjunctive treatment in cases of treatment-refractory OCD. Here, we investigate six weeks of low frequency rTMS, applied bilaterally and simultaneously over the sensory motor area, in OCD patients in a randomized, double-blind placebo-controlled clinical trial. Twenty-two participants were randomly enrolled into the treatment (ACTIVE = 10) or placebo (SHAM = 12) groups. At each of seven visits (baseline; day 1 and weeks 2, 4, and 6 of treatment; and two and six weeks after treatment) the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was administered. At the end of the six weeks of rTMS, patients in the ACTIVE group showed a clinically significant decrease in Y-BOCS scores compared to both the baseline and the SHAM group. This effect was maintained six weeks following the end of rTMS treatment. Therefore, in this sample, rTMS appeared to significantly improve the OCD symptoms of the treated patients beyond the treatment window. More studies need to be conducted to determine the generalizability of these findings and to define the duration of rTMS' clinical effect on the Y-BOCS. Clinical Trial Registration Number (NCT) at www.clinicaltrials.gov: NCT00616486.

Keywords: Yale-Brown obsessive compulsive scale; low-frequency rTMS; sensory motor area.

Figures

Figure 1
Figure 1
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) mean scores (±SE) from baseline (Visit 1) to the end of repetitive transcranial magnetic stimulation (rTMS) treatment (Visit 5) with a significant difference (*) at Visit 5; * p < 0.05. Hedge’s g at Visit 5: 1.001.
Figure 2
Figure 2
Y-BOCS mean scores (±SE) from baseline (Visit 1), the end of rTMS treatment (Visit 5), at the two-week (Visit 6) and six-week (Visit 7) follow-ups. Numbers inset in the bars represent participants in each group. † ACTIVE vs. SHAM p < 0.001.

References

    1. Torres A.R., Prince M.J., Bebbington P.E., Bhugra D., Brugha T.S., Farrell M., Jenkins R., Lewis G., Meltzer H., Singleton N. Obsessive-compulsive disorder: Prevalence, comorbidity, impact, and help-seeking in the British National Psychiatric Morbidity Survey of 2000. Am. J. Psychiatry. 2006;163:1978–1985. doi: 10.1176/ajp.2006.163.11.1978.
    1. Horwath E., Weissman M.M. The epidemiology and cross-national presentation of obessesive-compulsive disorder. Psychiatr. Clin. N. Am. 2000;23:493–507. doi: 10.1016/S0193-953X(05)70176-3.
    1. Stein D.J. Obsessive-compulsive disorder. Lancet. 2002;360:397–405. doi: 10.1016/S0140-6736(02)09620-4.
    1. Heyman I., Mataix-Cols D., Fineberg N.A. Obsessive-compulsive disorder. BMJ. 2006;333:424–429. doi: 10.1136/bmj.333.7565.424.
    1. Abramowitz J.S., Taylor S., McKay D. Obsessive-compulsive disorder. Lancet. 2009;374:491–499. doi: 10.1016/S0140-6736(09)60240-3.
    1. Eisen J.L., Sibrava N.J., Boisseau C.L., Mancebo M.C., Stout R.L., Pinto A., Rasmussen S.A. Five-year course of obsessive-compulsive disorder: Predictors of remission and relapse. J. Clin. Psychiatry. 2013;74:233–239. doi: 10.4088/JCP.12m07657.
    1. Pallanti S., Quercioli L. Treatment-refractory obsessive-compulsive disorder: Methodological issues, operational definitions and therapeutic lines. Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2006;30:400–412. doi: 10.1016/j.pnpbp.2005.11.028.
    1. Rosa-Alcazar A.I., Sanchez-Meca J., Gomez-Conesa A., Marin-Martinez F. Psychological treatment of obsessive-compulsive disorder: A meta-analysis. Clin. Psychol. Rev. 2008;28:1310–1325. doi: 10.1016/j.cpr.2008.07.001.
    1. Fineberg N.A., Gale T.M. Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int. Clin. Psychopharmacol. 2005;22:2313–322. doi: 10.1017/S1461145704004675.
    1. Marazziti D., Consoli G. Treatment strategies for obsessive-compulsive disorder. Exp. Opin. Pharmacother. 2010;11:331–343. doi: 10.1517/14656560903446948.
    1. Fineberg N.A., Brown A., Reghunandanan S., Pampaloni I. Evidence-based pharmacotherapy of obsessive-complusive disorder. Int. J. Neuropsychopharmacol. 2012;15:1173–1191. doi: 10.1017/S1461145711001829.
    1. Berlim M.T., Neufeld N.H., van den Eynde F. Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): An exploratory meta-analysis of randomized and sham-controlled trails. J. Psychiatr. Res. 2013;47:999–1006. doi: 10.1016/j.jpsychires.2013.03.022.
    1. Figee M., Luigjes J., Smolders R., Valencia-Alfonso C.E., van Wingen G., de Kwaasteniet B., Mantione M., Ooms P., de Koning P., Vulink N., et al. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nat. Neurosci. 2013;16:386–387. doi: 10.1038/nn.3344.
    1. Mantovani A., Simpson H.B., Fallon B.A., Rossi S., Lisanby S.H. Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. Int. J. Neuropsychopharmacol. 2010;13:217–227. doi: 10.1017/S1461145709990435.
    1. Gomes P.V.O., Brasil-Neto J.P., Allam N., Rodrigues de Souza E. A randomized, double-blind trial of repetitive transcrainial magnetic stimulation in obsessive-compulsive disorder with three-month follow-up. J. Neuropsychiatry Clin. Neurosci. 2010;24:437–443. doi: 10.1176/appi.neuropsych.11100242.
    1. Figee M., Vink M., de Geus F., Vulink N., Veltman D.J., Westenberg H., Denys D. Dysfunctional reward circuitry in obsessive-compulsive disorder. Biol. Psychiatry. 2011;69:867–874. doi: 10.1016/j.biopsych.2010.12.003.
    1. Harrison B.J., Pujol J., Cardoner N., Dues J., Alonso P., López-Solà M., Contreras-Rodríguez Real E., Segalàs C., Blanco-Hinojo L., Menchon J.M., et al. Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder. Biol. Psychiatry. 2013;73:321–328. doi: 10.1016/j.biopsych.2012.10.006.
    1. Jang J.H., Kim J.H., Jung W.H., Choi J.S., Jung M.H., Lee J.M., Choi C.H., Kang D.H., Kwon J.S. Functional connectivity in fronto-subcortical circuitry during the resting state in obsessive-compulsive disorder. Neurosci. Lett. 2010;474:158–162. doi: 10.1016/j.neulet.2010.03.031.
    1. Min B.K., Kim S.J., Park J.Y., Park H.J. Prestimulus top-down reflection of obsessive-compulsive disorder in EEG frontal theta and occipital α oscillations. Neurosci. Lett. 2011;496:181–185. doi: 10.1016/j.neulet.2011.04.018.
    1. Park J.Y., Lee J., Park H.J., Kim J.J., Namkoong K., Kim S.J. α Amplitude and phase locking in obsessive-compulsive disorder during working memory. Int. J. Psychophysiol. 2012;83:1–7. doi: 10.1016/j.ijpsycho.2011.09.014.
    1. Stern E.R., Fitzgerald K.D., Welsh R.C., Abelson J.L., Taylor S.F. Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder. PLoS ONE. 2012;7:420. doi: 10.1371/journal.pone.0036356.
    1. Buzsaki G., Draguhn A. Neuronal oscillations in cortical networks. Science. 2004;304:1926–1929. doi: 10.1126/science.1099745.
    1. Basar E., Basar-Eroglu C., Karakas S., Schurmann M. γ, α, δ, and θ oscillations govern cognitive processes. Int. J. Psychophysiol. 2001;39:241–248. doi: 10.1016/S0167-8760(00)00145-8.
    1. Engel A.K., Fries P., Singer W. Dynamic predictions: Oscillations and synchrony in top-down processing. Nat. Rev. Neurosci. 2001;2:704–716. doi: 10.1038/35094565.
    1. Fuggetta G., Noh N.A. A neurophysiological insight into the potential link between transcranial magnetic stimulation, thalamocortical dysrhythmia and neuropsychiatric disorders. Exp. Neurol. 2013;245:87–95. doi: 10.1016/j.expneurol.2012.10.010.
    1. Van den Heuvel O.A., Veltman D.J., Groenewegen H.J., Cath D.C., van Balkom A.J.L.M., van Hartskamp J., Barkhof F., van Dyck R. Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Arch. Gen. Psychiatry. 2005;62:301–310. doi: 10.1001/archpsyc.62.3.301.
    1. Chamberlain S.R., Blackwell A.D., Fineberg N.A., Robbins T.W., Sahakian B.J. The neuropsychology of obsessive compulsive disorder: The importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neurosci. Biobehav. Rev. 2005;29:399–419. doi: 10.1016/j.neubiorev.2004.11.006.
    1. De Wit S.J., de Vries F.E., van der Werf Y.D., Cath D.C., Heslenfeld D.J., Veltman E.M., van Balkom A.J.L.M., Veltman D.J., van den Heuvel O.A. Presupplementary motor area hyperactivity during response inhibition: A candidate endophenotype of obsessive compulsive disorder. Am. J. Psychiatry. 2012;169:1100–1108. doi: 10.1176/appi.ajp.2012.12010073.
    1. Modirrousta M., Shams E., Mansouri B., Moussavi Z., Sareen J., Enns M. The efficacy of deep repetitive transcranial magnetic stimulation over the medial prefrontal cortex in obsessive compulsive disorder: Results from an open-label study. Depress Anxiety. 2015;32:445–450. doi: 10.1002/da.22363.
    1. Greenberg B.D., Ziemann U., Harmon A., Murphy D.L., Wassermann E.M. Decreased neuronal inhibition in cerebral cortex in obsessive-compulsive disorder on transcranial magnetic stimulation. Lancet. 1998;352:881–882. doi: 10.1016/S0140-6736(05)60009-8.
    1. Greenberg B.D., Ziemann U., Cora-Locatelli G., Harmon A., Murphy D.L., Keel J.C., Wassermann E.M. Altered cortical excitability in obsessive-compulsive disorder. Neurology. 2000;54:142–147. doi: 10.1212/WNL.54.1.142.
    1. Mantovani A., Lisanby S.H., Pieraccini F., Ulivelli M., Castrogiovanni P., Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette’s syndrome (TS) Int. J. Neuropsychopharmacol. 2006;9:95–100. doi: 10.1017/S1461145705005729.
    1. Russo M., Naro A., Mastroeni C., Morgante C., Terranova M.R., Muscatello R., Zoccali R., Calabro R.S., Quartarone A. Obsessive-compulsive disorder: A “sensory-motor” problem? Int. J. Psychophysiol. 2014;92:74–78. doi: 10.1016/j.ijpsycho.2014.02.007.
    1. Mantovani A., Rossi S., Bassi B.D., Simpson H.B., Fallon B.A., Lisanby S.H. Modulation of motor cortex excitability in obsessive-compulsive disorder: An exploratory study on the relations of neurophysiology measures with clinical outcome. Psychiatry Res. 2013;210:1026–1032. doi: 10.1016/j.psychres.2013.08.054.
    1. Simpson H.B., Huppert J.D., Petkova E., Foa E.B., Liebowitz M.R. Response versus remission in obsessive-compulsive disorder. J. Clin. Psychiatry. 2006;67:269–276. doi: 10.4088/JCP.v67n0214.
    1. Menzies L., Chamberlain S.R., Laird A.R., Thelan S.M., Sahakian B.J., Bullmore E.T. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited. Neurosci. Biobehav. Rev. 2008;32:525–549. doi: 10.1016/j.neubiorev.2007.09.005.
    1. Dold M., Aigner M., Lanzenberger R., Kasper S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistent obsessive-compulsive disorder: A meta-analysis of double-blind, randomized, placebo-controlled trials. Int. J. Neuropsychopharmacol. 2013;16:557–574. doi: 10.1017/S1461145712000740.
    1. Overbeek T., Schruers K., Vermetten E., Griez E. Comorbidity of obsessive-compulsive disorder and depression: Prevalence, symptom severity, and treatment effect. J. Clin. Psychiatry. 2002;63:1106–1112. doi: 10.4088/JCP.v63n1204.
    1. Chen J., Zhou C., Wu B., Want Y., Li Q., Wei Y., Yang D., Mu J., Zhu D., Zou D., et al. Left versus right repetitive transcranial magnetic stimulation in treating major depression: A meta-analysis of randomized controlled trials. Psychiatry Res. 2013;210:1260–1264. doi: 10.1016/j.psychres.2013.09.007.
    1. Drevets W.C., Price J.L., Furey M.L. Brain structural functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Struct. Funct. 2008;213:93–118. doi: 10.1007/s00429-008-0189-x.
    1. Remijnse P.L., van den Heuvel O., Nielen M.M.A., Vriend C., Hendriks G.J., Hoogendijk W.J.G., Uylings H.B.M., Veltman D.J. Cognitive inflexibility in obsessive-compulisve disorder and major depression is associated with distinct neural correlates. PLoS ONE. 2013;8:420. doi: 10.1371/journal.pone.0059600.
    1. Nauczyciel C., Le Jeune F., Naudet F., Douabin S., Esquevin A., Verin M., Dondaine T., Robert G., Drapier D., Millet B. Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive compulsive disorder: A double-blind, crossover study. Transl. Psychiatry. 2014;4:e436. doi: 10.1038/tp.2014.62.

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