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Hirnstimulationsverfahren zur Behandlung schizophrener Psychosen

Non-invasive brain stimulation for treatment of schizophrenic psychoses

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Zusammenfassung

Trotz der Verfügbarkeit vielfältiger pharmakologischer und psychosozialer Therapiemöglichkeiten gelingt bei Patienten mit schizophrenen Psychosen in vielen Fällen keine optimale Symptomkontrolle. Neben persistierenden akustischen Halluzinationen gilt dies zudem für die Negativsymptomatik sowie die kognitiven Symptome. Verschiedene Verfahren der nichtinvasiven Hirnstimulation werden derzeit als neue therapeutische Optionen zur Behandlung schizophrener Psychosen angesehen. Mit diesen Verfahren soll insbesondere die Verbesserung der Behandlung der zuvor genannten Symptome erreicht werden. Dabei ist das am längsten angewendete und in der Versorgung am besten etablierte Verfahren die Elektrokonvulsionsbehandlung (EKT). Neuere Verfahren, wie die repetitive transkranielle Magnetstimulation (rTMS) oder die transkranielle Gleichstromstimulation (tDCS), haben dagegen einen pathophysiologischen gezielteren Ansatz. Die folgende Übersichtsarbeit stellt verschiedene nichtinvasive Hirnstimulationsverfahren vor und diskutiert die aktuellen Studien zur therapeutischen Anwendung bei Schizophrenie. Insgesamt können die neuen Verfahren als klinisch relevante Zusatztherapie bei der Schizophrenie angesehen werden. Dabei ist die beste Evidenz bei der Anwendung der rTMS für die Behandlung der Negativsymptomatik und der persistierenden akustischen Halluzinationen vorhanden, wobei es auch für diese Indikationen entsprechende negative Studien gibt. Die anderen Hirnstimulationsverfahren zeigen in ersten Studien vielversprechende Ergebnisse und weitere Studien werden die Wirksamkeit weiter evaluieren müssen. Vor dem Hintergrund des wachsenden Wissens um die neurobiologischen Grundlagen der Schizophrenie bietet die nichtinvasive Hirnstimulation neue Therapieperspektiven für Patienten mit einer schizophrenen Psychose.

Summary

Despite many different available pharmacological and psychosocial treatment options, an optimal control of symptoms is only partly possible for most schizophrenia patients. Especially, persistent auditory hallucinations, negative symptoms and cognitive impairment are difficult to treat symptoms. Several non-invasive brain stimulation techniques are increasingly being considered as new therapeutic add on options for the management of schizophrenia, targeting these symptom domains. The technique which has been available for the longest time and that is best established in clinical care is electroconvulsive therapy (ECT). New stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) allow a more pathophysiological-based approach. This review article introduces various non-invasive brain stimulation techniques and discusses recent treatment studies on schizophrenia. In total, the novel brain stimulation techniques discussed here can be considered relevant add on therapeutic approaches for schizophrenia. In this context, the best evidence is available for the application of rTMS for the treatment of negative symptoms and persistent auditory hallucinations; however, negative studies have also been published for both indications. Studies using other non-invasive brain stimulation techniques showed promising results but further research is needed to establish the clinical efficacy. Based on a growing pathophysiological knowledge, non-invasive brain stimulation techniques provide new treatment perspectives for patients with schizophrenia.

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Literatur

  1. Hasan A, Falkai P, Wobrock T et al (2012) World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry 13:318–378

    Article  PubMed  Google Scholar 

  2. Ziemann U, Paulus W, Nitsche MA et al (2008) Consensus: motor cortex plasticity protocols. Brain Stimul 1:164–182

    Article  PubMed  Google Scholar 

  3. Lefaucheur JP, Andre-Obadia N, Antal A et al (2014) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 125(11):2150–2206

    Article  PubMed  Google Scholar 

  4. Slotema CW, Blom JD, Lutterveld R van et al (2014) Review of the efficacy of transcranial magnetic stimulation for auditory verbal hallucinations. Biol Psychiatry 76:101–110

    Article  PubMed  Google Scholar 

  5. Pratt JA, Winchester C, Egerton A et al (2008) Modelling prefrontal cortex deficits in schizophrenia: implications for treatment. Br J Pharmacol 153(Suppl 1):S465–S470

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Shi C, Yu X, Cheung EF et al (2014) Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: a meta-analysis. Psychiatry Res 215:505–513

    Article  PubMed Central  PubMed  Google Scholar 

  7. Wobrock T, Guse B, Cordes J et al (2015) Left prefrontal high-frequency repetitive transcranial magnetic stimulation for the treatment of schizophrenia with predominant negative symptoms: a sham-controlled, randomized multicenter trial. Biol Psychiatry 77:979–988

    Article  PubMed  Google Scholar 

  8. Zhao S, Kong J, Li S et al (2014) Randomized controlled trial of four protocols of repetitive transcranial magnetic stimulation for treating the negative symptoms of schizophrenia. Shanghai Arch Psychiatry 26:15–21

    PubMed Central  PubMed  Google Scholar 

  9. Quan WX, Zhu XL, Qiao H et al (2015): The effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia and the follow-up study. Neurosci Lett 584:197–201

    Article  CAS  PubMed  Google Scholar 

  10. Harvey PD, Koren D, Reichenberg A, Bowie CR (2006) Negative symptoms and cognitive deficits: what is the nature of their relationship? Schizophr Bull 32:250–258

    Article  PubMed Central  PubMed  Google Scholar 

  11. Barch DM, Ceaser A (2012) Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn Sci 16:27–34

    Article  PubMed  Google Scholar 

  12. Lett TA, Voineskos AN, Kennedy JL et al (2013) Treating working memory deficits in schizophrenia: a review of the Neurobiology. Biol Psychiatry 75(5):361–370

    Article  PubMed  Google Scholar 

  13. Nuechterlein KH, Barch DM, Gold JM et al (2004) Identification of separable cognitive factors in schizophrenia. Schizophr Res 72:29–39

    Article  PubMed  Google Scholar 

  14. Guse B, Falkai P, Wobrock T (2010) Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review. J Neural Transm 117:105–122

    Article  PubMed Central  PubMed  Google Scholar 

  15. Oh SY, Kim YK (2011) Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry 35:1938–1943

    Article  PubMed  Google Scholar 

  16. Barr MS, Farzan F, Rajji TK et al (2013) Can repetitive magnetic stimulation improve cognition in schizophrenia? Pilot data from a randomized controlled trial. Biological Psychiatry 73:510–517

    Article  PubMed  Google Scholar 

  17. Wolwer W, Lowe A, Brinkmeyer J et al (2014) Repetitive transcranial magnetic stimulation (rTMS) improves facial affect recognition in schizophrenia. Brain Stimul 7:559–563

    Article  PubMed  Google Scholar 

  18. Mittrach M, Thunker J, Winterer G et al (2010) The tolerability of rTMS treatment in schizophrenia with respect to cognitive function. Pharmacopsychiatry 43:110–117

    Article  CAS  PubMed  Google Scholar 

  19. Dlabac-de Lange JJ, Bais L, Es FD van et al (2015) Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: results of a multicenter double-blind randomized controlled trial. Psychol Med 45:1263–1275

    Article  Google Scholar 

  20. Cordes J, Falkai P, Guse B et al (2009) Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study. European archives of psychiatry and clinical neuroscience. 259(Suppl 2):S189–S197

  21. Huang YZ, Edwards MJ, Rounis E et al (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206

    Article  CAS  PubMed  Google Scholar 

  22. Plewnia C, Zwissler B, Wasserka B et al (2014) Treatment of auditory hallucinations with bilateral theta burst stimulation: a randomized controlled pilot trial. Brain stimulation 7:340–341

    Article  PubMed  Google Scholar 

  23. Kindler J, Homan P, Flury R et al (2013) Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. Psychiatry Res 209:114–117

    Article  PubMed  Google Scholar 

  24. Nitsche MA, Cohen LG, Wassermann EM et al (2008) Transcranial direct current stimulation: state of the art 2008. Brain Stimul 1:206–223

    Article  PubMed  Google Scholar 

  25. Mondino M, Brunelin J, Palm U et al (2015) Transcranial direct current stimulation for the treatment of refractory symptoms of schizophrenia. Current evidence and future directions. Current pharmaceutical design. Curr Pharm Des (Epub ahead of print)

  26. Brunelin J, Mondino M, Gassab L et al (2012) Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 169:719–724

    Article  PubMed  Google Scholar 

  27. Fitzgerald PB, McQueen S, Daskalakis ZJ, Hoy KE (2014) A negative pilot study of daily bimodal transcranial direct current stimulation in schizophrenia. Brain Stimul 7:813–816

    Article  PubMed  Google Scholar 

  28. Brunelin J, Mondino M, Haesebaert F et al (2012) Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia. Brain Stimul 5:431–432

    Article  PubMed  Google Scholar 

  29. Kurimori M, Shiozawa P, Bikson M et al (2015) Targeting negative symptoms in schizophrenia: results from a proof-of-concept trial assessing prefrontal anodic tDCS protocol. Schizophr Res pii: S0920-9964(15)00286-8

    Google Scholar 

  30. Englot DJ, Chang EF, Auguste KI (2011) Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg 115:1248–1255

    Article  PubMed  Google Scholar 

  31. Martin JL, Martin-Sanchez E (2012) Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. Eur Psychiatry 27:147–155

    Article  CAS  PubMed  Google Scholar 

  32. Stefan H, Kreiselmeyer G, Kerling F et al (2012) Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia 53:e115–e118

    Article  PubMed  Google Scholar 

  33. Hein E, Nowak M, Kiess O et al (2013) Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm 120:821–827

    Article  PubMed  Google Scholar 

  34. Nemeroff CB, Mayberg HS, Krahl SE et al (2006) VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 31:1345–1355

    Article  PubMed  Google Scholar 

  35. Perez SM, Carreno FR, Frazer A, Lodge DJ (2014) Vagal nerve stimulation reverses aberrant dopamine system function in the methylazoxymethanol acetate rodent model of schizophrenia. J Neurosci 34:9261–9267

    Article  PubMed Central  PubMed  Google Scholar 

  36. Hasan A, Wolff-Menzler C, Pfeiffer S et al (2015) Transcutaneous Non-invasive Vagus Nerve Stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized-controlled pilot study. Eur Arch Psychiatry Clin Neurosci (Accepted for Publication)

  37. Bundesärztekammer (2003) Stellungnahme zur Elektrokrampftherapie (EKT) als psychiatrische Behandlungsmaßnahme. Dtsch Ärztebl 3:141–143

    Google Scholar 

  38. DGPPN (2012) Elektrokonvulsionstherapie: Psychiatrische Fachgesellschaften aus vier Ländern empfehlen einen rechtzeitigen und adäquaten Einsatz. http://www.dgppn.de/fileadmin/user_upload/_medien/download/pdf/stellungnahmen/2012/stn-2012-06-07-elektrokonvulsionstherapie.pdf

  39. Tharyan P, Adams CE (2005) Electroconvulsive therapy for schizophrenia. Cochrane Database Syst Rev CD000076

  40. Sommer IE, Slotema CW, Daskalakis ZJ et al (2012) The treatment of hallucinations in schizophrenia spectrum disorders. Schizophr Bull 38:704–714

    Article  PubMed Central  PubMed  Google Scholar 

  41. Petrides G, Malur C, Braga RJ et al (2015) Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study. Am J Psychiatry 172:52–58

    Article  PubMed  Google Scholar 

  42. Rosa MA, Lisanby SH (2012) Somatic treatments for mood disorders. Neuropsychopharmacology 37:102–116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Sako W, Goto S, Shimazu H et al (2008) Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia. Mov Disord 23:1929–1931

    Article  PubMed  Google Scholar 

  44. Chang EF, Schrock LE, Starr PA, Ostrem JL (2010) Long-term benefit sustained after bilateral pallidal deep brain stimulation in patients with refractory tardive dystonia. Stereotact Funct Neurosurg 88:304–310

    Article  PubMed  Google Scholar 

  45. Hasan A, Falkai P, Wobrock T et al (2013) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 14:2–44

    Article  PubMed  Google Scholar 

  46. Plewnia C, Schober F, Rilk A et al (2008) Sustained improvement of obsessive-compulsive disorder by deep brain stimulation in a woman with residual schizophrenia. Int J Neuropsychopharmacol 11:1181–1183

    Article  PubMed  Google Scholar 

  47. Lehman AF, Lieberman JA, Dixon LB et al (2004) Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 161:1–56

    Article  PubMed  Google Scholar 

  48. DGPPN (2006) S3 Praxisleitlinien in Psychiatrie und Psychotherapie. Band 1 – Behandlungsleitlinie Schizophrenie. Steinkopff-Verlag, Darmstadt

  49. Buchanan RW, Kreyenbuhl J, Kelly DL et al (2010) The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 36:71–93

    Article  PubMed Central  PubMed  Google Scholar 

  50. Hasan A, Falkai P, Wobrock T et al (2015) World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia. Part 3: Update 2015 Management of special circumstances: Depression, Suicidality, substance use disorders and pregnancy and lactation. World J Biol Psychiatry 16:142–170

    Article  PubMed  Google Scholar 

  51. NICE (2009) Guidance on the use of electroconvulsive therapy. National Institute for Health and Care Excellence

  52. Wobrock T, Guse B, Cordes J et al (2015) Left prefrontal high-frequency rTMS for the treatment of schizophrenia with predominant negative symptoms – a sham-controlled, randomized multicentre tria. Biol Psychiatry 77(11):979–988

    Article  PubMed  Google Scholar 

  53. Dollfus S, Lecardeur L, Morello R, Etard O (2015) Placebo response in repetitive transcranial magnetic stimulation trials of treatment of auditory hallucinations in schizophrenia: a meta-analysis. Schizophr Bull pii: sbv076 (Epub ahead of print)

    Google Scholar 

  54. Rutherford BR, Pott E, Tandler JM et al (2014) Placebo response in antipsychotic clinical trials: a meta-analysis. JAMA Psychiatry 71:1409–1421

    Article  PubMed Central  PubMed  Google Scholar 

  55. Ridding MC, Ziemann U (2010) Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 588:2291–2304

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Strube W, Bunse T, Nitsche MA et al (2015) Smoking restores impaired LTD-like plasticity in schizophrenia: a transcranial direct current stimulation study. Neuropsychopharmacology 40:822–830

    Article  CAS  PubMed  Google Scholar 

  57. Hasan A, Nitsche MA, Rein B et al (2011) Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. Behav Brain Res 224:15–22

    Article  PubMed  Google Scholar 

  58. Li LM, Uehara K, Hanakawa T (2015) The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies. Front Cell Neurosci 9:181

    PubMed Central  PubMed  Google Scholar 

  59. Hamada M, Murase N, Hasan A et al (2013) The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 23:1593–1605

    Article  PubMed  Google Scholar 

  60. Homan P, Kindler J, Hauf M et al (2012) Cerebral blood flow identifies responders to transcranial magnetic stimulation in auditory verbal hallucinations. Transl Psychiatry 2:e189

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Eberle MC, Wildgruber D, Wasserka B et al (2010) Relief from chronic intractable auditory hallucinations after long-term bilateral theta burst stimulation. Am J Psychiatry 167(11):1410

    Article  PubMed  Google Scholar 

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Danksagung/Förderung

Wir bedanken uns bei Frau Drotohée Streb für die redaktionelle Unterstützung bei der Erstellung des Manuskripts.

Diese Arbeit wird unterstützt durch die Forschungsverbünde ESPRIT (Research project C2: „Efficacy and mechanisms of transcranial direct current stimulation (tDCS)-enhanced cognitive training in schizophrenia“ FKZ: 01EE1407H) und GCBS (German Center for Brain Stimulation), gefördert vom Bundesministerium für Bildung und Forschung (BMBF, Förderkennzeichen: 01EE1407H und 01EE1403).

Interessenkonflikte

A. Hasan erhielt Honorare für Referententätigkeiten von der Bundesapothekerkammer und der Landesapothekerkammern Rheinland-Pfalz/Niedersachsen, von Desitin, Lundbeck und von Otsuka. Er wurde zu wissenschaftlichen Kongressen von Janssen Cilag, Pfizer und Lundbeck eingeladen und erhielt ein Honorar für Mitarbeit im Advisory Board von Roche sowie Publikationsunterstützung von Roche. T. Wobrock erhielt Honorare für Referententätigkeit von AstraZeneca, Alpine Biomed, Bristol Myers Squibb, Janssen Cilag, Eli Lilly, Essex, Fa. I3G, Lundbeck, Novartis, Organon, Otsuka, Pfizer, Roche, Sanofi-Synthelabo/Aventis sowie für die Mitarbeit im Advisory Board Fa. Janssen-Cilag. Früher erhielt T.W. Unterstützung bei Reisekosten und Kongressen durch AstraZeneca, Bristol Myers Squibb, Eli Lilly, Essex, Janssen Cilag, Lundbeck, Sanofi-Synthelabo/Aventis. Des Weiteren bekam er finanzielle Unterstützung seiner Forschungsaktivitäten durch die DFG, das BMBF, AstraZeneca (investigatorinitiierte Studie, IIT), Fa. Cerbomed, Fa. I3G und dem AOK-Bundesverband/Landesverband Niedersachsen (Auftragsforschung). W. Strube erhiehlt Honorare für Referententätigkeiten von Mag&More. F. Padberg erhielt Honorare für Referententätigkeiten von der Mag&More GmbH sowie finanzielle und materielle Unterstützung für Studien von der neuroConn GmbH und Brainsway Inc. P. Falkai berichtet keine Interessenkonflikte in den letzten 3 Jahren. Zuvor erhielt er Honorare für Referententätigkeit sowie Unterstützung bei Reisekosten und Kongressen von AstraZeneca, Bristol Myers Squibb, GE Healthcare, GlaxoSmithKline, Janssen Cilag, Eli Lilly, Essex, Lundbeck, Otsuka, Pfizer, Servier und Takeda. A. Fallgatter, U. Palm und C. Plewnia geben an, dass kein Interessenkonflikt vorliegt.

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Hasan, A., Wobrock, T., Palm, U. et al. Hirnstimulationsverfahren zur Behandlung schizophrener Psychosen. Nervenarzt 86, 1481–1491 (2015). https://doi.org/10.1007/s00115-015-4323-8

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