Download PDF
Pharmacopsychiatry 2010; 43(3): 110-117
DOI: 10.1055/s-0029-1242824
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

The Tolerability of rTMS Treatment in Schizophrenia with Respect to Cognitive Function

M. Mittrach1 , J. Thünker1 , G. Winterer3 , M. W. Agelink2 , G. Regenbrecht1 , M. Arends1 , A. Mobascher1 , S.-J. Kim1 , W. Wölwer1 , J. Brinkmeyer1 , W. Gaebel1 , J. Cordes1
  • 1Department of Psychiatry and Psychotherapy, Heinrich-Heine University, Düsseldorf, Germany
  • 2Department of Psychiatry, Psychotherapy and Psychosomatic, Herford, Germany
  • 3Institute for Genetics, University of Cologne, Cologne, Germany
Further Information

Publication History

received 17.10.2008 revised 28.09.2009

accepted 06.10.2009

Publication Date:
02 February 2010 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: The purpose of this study was to assess tolerability and safety of high-frequency rTMS with regard to cognitive performance when conducted as “add-on” treatment in chronic schizophrenia in-patients (n=32).

Methods: Patients, who were on stable antipsychotic treatment, were randomly assigned to verum or sham condition (double-blind). In the verum group, ten sessions of 10 Hz rTMS with a total of 10 000 stimuli were applied over the left dorsolateral prefrontal cortex (PFC) at 110% of motor threshold over a period of two weeks. The sham group received corresponding sham stimulation. RTMS effects on cognitive performance were assessed with a neuropsychological test battery consisting of the following tests: trail making test A and B (TMT), Wisconsin card sorting test (WCST), D2 attention task and the “short test of general intelligence” (KAI).

Results: No statistically significant deterioration of cognitive performance was observed as a result of rTMS treatment. Moreover it was shown that in the verum group patients with a less favourable performance on the WCST at baseline tend to improve after rTMS treatment with regard to psychopathology as opposed to patients in the control group.

Discussion: The stability of cognitive function suggests good tolerability of rTMS treatment in schizophrenia. The absence of evidence for cognitive deterioration could be due to low and short stimulation parameters.

References

  • 1 Brickenkamp R. d2, Aufmerksamkeits-Belastungs-Test (8. Auflage). Göttingen: Hogrefe 1994
    PubMed
  • 2 Callicott JH, Mattay VS, Verchinski BA. et al . Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down.  Am J Psychiatry. 2003;  160 2209-2215
    CrossrefPubMedGoogle Scholar
  • 3 Callicott JH, Weinberger DR. Neuropsychiatric dynamics: the study of mental illness using functional magnetic resonance imaging.  Eur J Radiol. 1999;  30 95-164
    CrossrefPubMedGoogle Scholar
  • 4 Cohen E, Bernardo M, Masana J. et al . Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: a pilot study.  J Neurol Neurosurg Psychiatry. 1999;  67 129-130
    CrossrefPubMedGoogle Scholar
  • 5 Cordes J, Arends M, Mobascher A. et al . Potential clinical targets of repetitive transcranial magnetic stimulation treatment in schizophrenia.  Neuropsychobiology. 2006;  54 87-99
    CrossrefPubMedGoogle Scholar
  • 6 Cordes J, Thünker J, Agelink MW. et al . Effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) on clinical global impression in chronic schizophrenia.  Psychiatry Res. 2009;  accepted 
    PubMedGoogle Scholar
  • 7 Di Pietro NC, Seamans JK. Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.  Pharmacopsychiatry. 2007;  40 ((Suppl 1)) 27-33
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Egan MF, Goldberg TE, Gscheidle T. et al . Relative risk for cognitive impairments in siblings of patients with schizophrenia.  Biol Psychiatry. 2001;  50 98-107
    CrossrefPubMedGoogle Scholar
  • 9 Fitzgerald PB, Benitez J, Daskalakis JZ. et al . A double-blind sham-controlled trial of repetitive transcranial magnetic stimulation in the treatment of refractory auditory hallucinations.  J Clin Psychopharmacol. 2005;  25 358-362
    CrossrefPubMedGoogle Scholar
  • 10 Fitzgerald PB, Daskalakis ZJ. A review of repetitive transcranial magnetic stimulation use in the treatment of schizophrenia.  Can J Psychiatry. 2008;  53 567-576
    PubMedGoogle Scholar
  • 11 George MS, Ketter TA, Post RM. SPECT and PET imaging in mood disorders.  J Clin Psychiatry. 1993;  54 ((Suppl)) 6-13
    PubMedGoogle Scholar
  • 12 Grant DA, Berg EA. Wisconsin Card Sorting Test. Journal of General Psychology 1948. Computer Version 4, Research Edition by Heaton, RK and PAR Staff 1993
    PubMedGoogle Scholar
  • 13 Green MF, Nuechterlein KH. The MATRICS initiative: developing a consensus cognitive battery for clinical trials.  Schizophr Res. 2004;  72 1-3
    Google Scholar
  • 14 Guy W. ECDEU Assessment manual for psychopharmacology. Rockville, MD, US Department of Health and Human Services publication (ADM) 1976: 218-222
    PubMed
  • 15 Hiller W, Zaudig M, Mombour W. Internationale Diagnose Checkliste für DSM-IV (IDCL). Göttingen: Hogrefe 1997
    PubMed
  • 16 Hoffman RE, Gueorguieva R, Hawkins KA. et al . Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample.  Biol Psychiatry. 2005;  58 97-104
    CrossrefPubMedGoogle Scholar
  • 17 Hoffman RE, Hawkins KA, Gueorguieva R. et al . Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations.  Arch Gen Psychiatry. 2003;  60 49-56
    CrossrefPubMedGoogle Scholar
  • 18 Holi MM, Eronen M, Toivonen K. et al . Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia.  Schizophr Bull. 2004;  30 429-434
    PubMedGoogle Scholar
  • 19 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia.  Schizophr Bull. 1987;  13 261-276
    CrossrefPubMedGoogle Scholar
  • 20 Klemm S, Schmidt B, Knappe S. et al . Impaired working speed and executive functions as frontal lobe dysfunctions in young first-degree relatives of schizophrenic patients.  Eur Child Adolesc Psychiatry. 2006;  15 400-408
    CrossrefPubMedGoogle Scholar
  • 21 Lehrl S, Gallwitz A, Blaha L. Kurztest für allgemeine Basisgrössen der Informationsverarbeitung KAI (3. Auflage). Ebersberg: VLESS Verlag 1992
    PubMed
  • 22 Lisanby SH. Electroconvulsive therapy for depression.  N Engl J Med. 2007;  357 1939-1945
    CrossrefPubMedGoogle Scholar
  • 23 Machii K, Cohen D, Ramos-Estebanez C. et al . Safety of rTMS to non-motor cortical areas in healthy participants and patients.  Clin Neurophysiol. 2006;  117 455-471
    CrossrefPubMedGoogle Scholar
  • 24 Marder SR, Davis JM, Chouinard G. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials.  J Clin Psychiatry. 1997;  58 538-546
    CrossrefPubMedGoogle Scholar
  • 25 McIntosh AM, Semple D, Tasker K. et al . Transcranial magnetic stimulation for auditory hallucinations in schizophrenia.  Psychiatry Res. 2004;  127 9-17
    CrossrefPubMedGoogle Scholar
  • 26 Meyer-Lindenberg AS, Olsen RK, Kohn PD. et al . Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia.  Arch Gen Psychiatry. 2005;  62 379-386
    Google Scholar
  • 27 Mogg A, Purvis R, Eranti S. et al . Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: A randomized controlled pilot study.  Schizophr Res. 2007;  93 221-228
    CrossrefPubMedGoogle Scholar
  • 28 Moos RH, McCoy L, Moos BS. Global assessment of functioning (GAF) ratings determinants and role as predictors of one-year treatment outcomes.  J Clin Psychol. 2000;  56 449-461
    CrossrefPubMedGoogle Scholar
  • 29 Nahas Z, DeBrux C, Chandler V. et al . Lack of significant changes on magnetic resonance scans before and after 2 weeks of daily left prefrontal repetitive transcranial magnetic stimulation for depression.  J ECT. 2000;  16 380-390
    PubMedGoogle Scholar
  • 30 Novak T, Horacek J, Mohr P. et al . The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results.  Neuro Endocrinol Lett. 2006;  27 209-213
    PubMedGoogle Scholar
  • 31 Padberg F, Grossheinrich N, Pogarell O. et al .In: Efficacy and Safety of Prefrontal Repetitive Transcranial Magnetic Stimulation in Affective Disorders, in Transcranial Brain Stimulation for Treatment of Psychiatric Disorders. Edited by Marcolin MA, Padberg F Adv Biol Psychiatr. Basel: Karger 2007 23: 53-83
    PubMedGoogle Scholar
  • 32 Qi Z, Miller GW, Voit EO. A mathematical model of presynaptic dopamine homeostasis: implications for schizophrenia.  Pharmacopsychiatry. 2008;  41 ((Suppl 1)) 89-98
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Rachid F, Bertschy G. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of depression: a critical appraisal of the last 10 years.  Neurophysiol Clin. 2006;  36 157-183
    CrossrefPubMedGoogle Scholar
  • 34 Reitan RM. A manual for the administrating and scoring of the Trail Making Test. Indianapolis. IN: Indiana University Press 1959
    PubMed
  • 35 Rollnik JD, Huber TJ, Mogk H. et al . High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients.  Neuroreport. 2000;  11 4013-4015
    CrossrefPubMedGoogle Scholar
  • 36 Rubin P, Vorstrup S, Hemmingsen R. et al . Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital: correlations with computerized tomography and regional cerebral blood flow findings.  Acta Psychiatr Scand. 1994;  90 385-390
    CrossrefPubMedGoogle Scholar
  • 37 Sachdev P, Loo C, Mitchell P. et al . Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: A pilot investigation.  Psychiatry Clin Neurosci. 2005;  59 354-357
    CrossrefPubMedGoogle Scholar
  • 38 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 Stimulation. 2008;  1 106-111
    CrossrefPubMedGoogle Scholar
  • 39 Stanford AD, Sharif Z, Corcoran C. et al . RTMS strategies for the study and treatment of schizophrenia: A review.  Int J Neuropsychopharmacol. 2008;  11 563-576
    PubMedGoogle Scholar
  • 40 Stip E. Cognition, schizophrenia and the effect of antipsychotics.  Encephale. 2006;  32 341-350
    CrossrefPubMedGoogle Scholar
  • 41 Tan HY, Callicott JH, Weinberger DR. Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia.  Cerbral Cortex. 2007;  17 171-181
    PubMedGoogle Scholar
  • 42 Tharyan P, Adams CE. Electroconvulsive therapy for schizophrenia.  Cochrane Database Syst Rev. 2009;  ((2)) CD000076
    PubMedGoogle Scholar
  • 43 Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: Report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7 1996 
    PubMed
  • 44 Winterer G, Musso F, Beckmann C. et al . Instability of prefrontal signal processing in schizophrenia.  Am J Psychiatry. 2006;  163 1960-1968
    CrossrefPubMedGoogle Scholar
  • 45 Wolkin A, Sanfilipo M, Wolf AP. et al . Negative symptoms and hypofrontality in chronic schizophrenia.  Archives Gen Psychiatry. 1992;  49 959-965
    PubMedGoogle Scholar

Correspondence

J. CordesMD 

Department of Psychiatry and Psychotherapy

Heinrich-Heine University of Düsseldorf

Bergische Landstraße 2

40629 Düsseldorf

Germany

Phone: +49/(0)211/922 3402

Fax: +49/(0)211/922 3615

Email: Joachim.cordes@lvr.de

      >