Skip to main content
Log in

Anxiolytic effects of transcranial magnetic stimulation—an alternative treatment option in anxiety disorders?

  • Biological Psychiatry - Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

In contrast to major depression, only few studies are available so far on the effects of repetitive transcranial magnetic stimulation (rTMS) in anxiety disorders. In order to summarise available data concerning the putative anxiolytic action of repetitive rTMS, a systematic literature review was carried out. Although interpretation of the results is difficult because of a large variety of used treatment protocols and the lack of a placebo-controlled design in the majority of studies, there is evidence for anxiolytic action of rTMS both from preclinical trials and studies in humans. Based on the idea of interhemispheric imbalance and/or deficits in cortico-limbic control as a model for human anxiety, inhibitory rTMS of the prefrontal cortex has been shown to exert beneficial effects in a number of studies in healthy subjects, patients with PTSD and panic disorder. However, to further elucidate the putative anxiolytic action of rTMS in patients with anxiety disorders future studies have to be conducted addressing in particular the limitations of the studies mentioned above.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arai N, Okabe S, Furubayashi T, Mochizuki H, Iwata NK, Hanajima R, Terao Y, Ugawa Y (2007) Differences in after-effect between monophasic and biphasic high-frequency rTMS of the human motor cortex. Clin Neurophysiol 118:2227–2233

    Article  PubMed  Google Scholar 

  • Ballenger JC (1998) Panic disorder in primary care and general medicine. In: Rosenbaum JF, Pollack MH (eds) Panic disorder and its treatment. Dekker Inc, New York, pp 1–36

    Google Scholar 

  • Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ (2002) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. World J Biol Psychiatry 3:171–199

    Article  PubMed  Google Scholar 

  • Barker AT, Jalinous R, Freeston IL (1985) Non-invasive magnetic stimulation of human motor cortex. Lancet 1:1106–1107

    Article  PubMed  CAS  Google Scholar 

  • Barlow DH (2002) Anxiety and its disorders: the nature and treatment of anxiety and panic. The Guilford Press, New York

    Google Scholar 

  • Ben-Shachar D, Belmaker RH, Grisaru N, Klein E (1997) Transcranial magnetic stimulation induces alterations in brain monoamines. J Neural Transm 104:191–197

    Article  PubMed  CAS  Google Scholar 

  • Ben-Shachar D, Gazawi H, Riboyad-Levin J, Klein E (1999) Chronic repetitive transcranial magnetic stimulation alters beta-adrenergic and 5-HT2 receptor characteristics in rat brain. Brain Res 816:78–83

    Article  PubMed  CAS  Google Scholar 

  • Bishop S, Duncan J, Brett M, Lawrence AD (2004) Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli. Nat Neurosci 7:184–188

    Article  PubMed  CAS  Google Scholar 

  • Boshuisen ML, Ter Horst GJ, Paans AM, Reinders AA, den Boer JA (2002) rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest. Biol Psychiatry 52:126–135

    Article  PubMed  Google Scholar 

  • Bradwejn J, Koszycki D, Meterissian G (1990) Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder. Can J Psychiatry 35:83–85

    PubMed  CAS  Google Scholar 

  • Burt T, Lisanby SH, Sackeim HA (2002) Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol 5:73–103

    Article  PubMed  Google Scholar 

  • Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403

    PubMed  CAS  Google Scholar 

  • Cohen H, Kaplan Z, Kotler M, Kouperman I, Moisa R, Grisaru N (2004) Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study. Am J Psychiatry 161:515–524

    Article  PubMed  Google Scholar 

  • Couturier JL (2005) Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis. J Psychiatry Neurosci 30:83–90

    PubMed  Google Scholar 

  • d’Alfonso AA, van Honk J, Hermans E, Postma A, de Haan EH (2000) Laterality effects in selective attention to threat after repetitive transcranial magnetic stimulation at the prefrontal cortex in female subjects. Neurosci Lett 280:195–198

    Article  PubMed  Google Scholar 

  • Davidson RJ, Abercrombie H, Nitschke JB, Putnam K (1999) Regional brain function, emotion and disorders of emotion. Curr Opin Neurobiol 9:228–234

    Article  PubMed  CAS  Google Scholar 

  • Davis M (1992) The role of the amygdala in fear and anxiety. Annu Rev Neurosci 15:353–375

    Article  PubMed  CAS  Google Scholar 

  • Eser D, Schule C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, de la MS, Engel R, Kucher K, Rupprecht R (2007) Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study. Psychopharmacology (Berl) 192:479–487

    Article  CAS  Google Scholar 

  • Fischer H, Andersson JL, Furmark T, Fredrikson M (1998) Brain correlates of an unexpected panic attack: a human positron emission tomographic study. Neurosci Lett 251:137–140

    Article  PubMed  CAS  Google Scholar 

  • Fleischmann A, Prolov K, Abarbanel J, Belmaker RH (1995) The effect of transcranial magnetic stimulation of rat brain on behavioral models of depression. Brain Res 699:130–132

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Toro M, Salva CJ, Crespi FM, Andres TJ, Aguirre OI, Bosch CC (2002) Panic disorder and transcranial magnetic stimulation. Actas Esp Psiquiatr 30:221–224

    PubMed  CAS  Google Scholar 

  • Gorman JM, Kent JM, Sullivan GM, Coplan JD (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505

    Article  PubMed  CAS  Google Scholar 

  • Grisaru N, Amir M, Cohen H, Kaplan Z (1998) Effect of transcranial magnetic stimulation in posttraumatic stress disorder: a preliminary study. Biol Psychiatry 44:52–55

    Article  PubMed  CAS  Google Scholar 

  • Gross M, Nakamura L, Pascual-Leone A, Fregni F (2007) Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Acta Psychiatr Scand 116:165–173

    Article  PubMed  CAS  Google Scholar 

  • Hariri AR, Bookheimer SY, Mazziotta JC (2000) Modulating emotional responses: effects of a neocortical network on the limbic system. NeuroReport 11:43–48

    Article  PubMed  CAS  Google Scholar 

  • Hariri AR, Mattay VS, Tessitore A, Fera F, Weinberger DR (2003) Neocortical modulation of the amygdala response to fearful stimuli. Biol Psychiatry 53:494–501

    Article  PubMed  Google Scholar 

  • Heller W, Nitschke JB (1998) The puzzle of regional brain activity in depression and anxiety: the importance of subtypes and comorbidity. Cogn Emot 12:421–447

    Article  Google Scholar 

  • Herwig U, Fallgatter AJ, Hoppner J, Eschweiler GW, Kron M, Hajak G, Padberg F, Naderi-Heiden A, Abler B, Eichhammer P, Grossheinrich N, Hay B, Kammer T, Langguth B, Laske C, Plewnia C, Richter MM, Schulz M, Unterecker S, Zinke A, Spitzer M, Schonfeldt-Lecuona C (2007) Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial. Br J Psychiatry 191:441–448

    Article  PubMed  CAS  Google Scholar 

  • Hess G, Donoghue JP (1999) Facilitation of long-term potentiation in layer II/III horizontal connections of rat motor cortex following layer I stimulation: route of effect and cholinergic contributions. Exp Brain Res 127:279–290

    Article  PubMed  CAS  Google Scholar 

  • Hoffman RE, Cavus I (2002) Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. Am J Psychiatry 159:1093–1102

    Article  PubMed  Google Scholar 

  • Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206

    Article  PubMed  CAS  Google Scholar 

  • Isogawa K, Fujiki M, Akiyoshi J, Tsutsumi T, Horinouchi Y, Kodama K, Nagayama H (2003) Anxiety induced by repetitive transcranial magnetic stimulation is suppressed by chronic treatment of paroxetine in rats. Pharmacopsychiatry 36:7–11

    Article  PubMed  CAS  Google Scholar 

  • Isogawa K, Fujiki M, Akiyoshi J, Tsutsumi T, Kodama K, Matsushita H, Tanaka Y, Kobayashi H (2005) Anxiolytic suppression of repetitive transcranial magnetic stimulation-induced anxiety in the rats. Prog Neuropsychopharmacol Biol Psychiatry 29:664–668

    Article  PubMed  Google Scholar 

  • Kalisch R, Wiech K, Herrmann K, Dolan RJ (2006) Neural correlates of self-distraction from anxiety and a process model of cognitive emotion regulation. J Cogn Neurosci 18:1266–1276

    Article  PubMed  Google Scholar 

  • Kanno M, Matsumoto M, Togashi H, Yoshioka M, Mano Y (2003) Effects of repetitive transcranial magnetic stimulation on behavioral and neurochemical changes in rats during an elevated plus-maze test. J Neurol Sci 211:5–14

    PubMed  CAS  Google Scholar 

  • Keck ME, Welt T, Post A, Muller MB, Toschi N, Wigger A, Landgraf R, Holsboer F, Engelmann M (2001) Neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation in a psychopathological animal model are suggestive of antidepressant-like effects. Neuropsychopharmacology 24:337–349

    Article  PubMed  CAS  Google Scholar 

  • Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry 62:617–627

    Article  PubMed  Google Scholar 

  • LeDoux JE, Cicchetti P, Xagoraris A, Romanski LM (1990) The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning. J Neurosci 10:1062–1069

    PubMed  CAS  Google Scholar 

  • MacLeod C, Mathews A, Tata P (1986) Attentional bias in emotional disorders. J Abnorm Psychol 95:15–20

    Article  PubMed  CAS  Google Scholar 

  • Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S (2007) Repetitive transcranial magnetic stimulation (rTMS) in the treatment of panic disorder (PD) with comorbid major depression. J Affect Disord 102:277–280

    Article  PubMed  Google Scholar 

  • Martin JL, Barbanoj MJ, Schlaepfer TE, Thompson E, Perez V, Kulisevsky J (2003) Repetitive transcranial magnetic stimulation for the treatment of depression. Systematic review and meta-analysis. Br J Psychiatry 182:480–491

    Article  PubMed  Google Scholar 

  • McCann UD, Kimbrell TA, Morgan CM, Anderson T, Geraci M, Benson BE, Wassermann EM, Willis MW, Post RM (1998) Repetitive transcranial magnetic stimulation for posttraumatic stress disorder. Arch Gen Psychiatry 55:276–279

    Article  PubMed  CAS  Google Scholar 

  • Nyffeler T, Wurtz P, Luscher HR, Hess CW, Senn W, Pflugshaupt T, von Wartburg R, Luthi M, Muri RM (2006) Extending lifetime of plastic changes in the human brain. Eur J Neurosci 24:2961–2966

    Article  PubMed  Google Scholar 

  • O’Reardon JP, Cristancho P, Pilania P, Bapatla KB, Chuai S, Peshek AD (2007) Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion. Depress Anxiety 24:537–544

    Article  PubMed  Google Scholar 

  • Ochsner KN, Gross JJ (2005) The cognitive control of emotion. Trends Cogn Sci 9:242–249

    Article  PubMed  Google Scholar 

  • Post RM, Kimbrell TA, Frye M, George M, McCann U, Little J, Dunn R, Li H, Weiss SRB (1997) Implications of kindling and quenching for the possible frequency dependence of rTMS. CNS Spectr 2:54–60

    Google Scholar 

  • Prasko J, Zalesky R, Bares M, Horacek J, Kopecek M, Novak T, Paskova B (2007) The effect of repetitive transcranial magnetic stimulation (rTMS) add on serotonin reuptake inhibitors in patients with panic disorder: a randomized, double blind sham controlled study. Neuro Endocrinol Lett 28:33–38

    PubMed  Google Scholar 

  • Rosenberg PB, Mehndiratta RB, Mehndiratta YP, Wamer A, Rosse RB, Balish M (2002) Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. J Neuropsychiatry Clin Neurosci 14:270–276

    PubMed  Google Scholar 

  • Schutter DJ, van Honk J, d’Alfonso AA, Postma A, de Haan EH (2001) Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood. Neuroreport 12:445–447

    Article  PubMed  CAS  Google Scholar 

  • Taylor SF, Phan KL, Decker LR, Liberzon I (2003) Subjective rating of emotionally salient stimuli modulates neural activity. Neuroimage 18:650–659

    Article  PubMed  Google Scholar 

  • Tsutsumi T, Fujiki M, Akiyoshi J, Horinouchi Y, Isogawa K, Hori S, Nagayama H (2002) Effect of repetitive transcranial magnetic stimulation on forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry 26:107–111

    Article  PubMed  Google Scholar 

  • Van Honk J, Tuiten A, Van Den Hout M, Koppeschaar H, Thijssen J, De Haan E, Verbaten R (1998) Baseline salivary cortisol levels and preconscious selective attention for threat: a pilot study. Psychoneuroendocrinology 23:741–747

    Article  PubMed  Google Scholar 

  • Van Honk J, Tuiten A, Verbaten R, Van Den Hout M, Koppeschaar H, Thijssen J, De Haan E (1999) Correlations among salivary testosterone, mood, and selective attention to threat in humans. Horm Behav 36:17–24

    Article  PubMed  Google Scholar 

  • Van Honk J, Schutter DJ, d’Alfonso AA, Kessels RP, de Haan EH (2002) 1 Hz rTMS over the right prefrontal cortex reduces vigilant attention to unmasked but not to masked fearful faces. Biol Psychiatry 52:312–317

    Article  PubMed  Google Scholar 

  • Zwanzger P, Deckert J (2007) Angststörungen: Klinik, Diagnostik, Therapie. Nervenarzt 78:349–360

    Article  PubMed  CAS  Google Scholar 

  • Zwanzger P, Minov C, Ella R, Schule C, Baghai T, Moller HJ, Rupprecht R, Padberg F (2002) Transcranial magnetic stimulation for panic. Am J Psychiatry 159:315–316

    Article  PubMed  Google Scholar 

  • Zwanzger P, Eser D, Volkel N, Baghai TC, Moller HJ, Rupprecht R, Padberg F (2007) Effects of repetitive transcranial magnetic stimulation (rTMS) on panic attacks induced by cholecystokinin-tetrapeptide (CCK-4). Int J Neuropsychopharmacol 10:285–289

    Article  PubMed  CAS  Google Scholar 

  • Zyss T, Gorka Z, Kowalska M, Vetulani J (1997) Preliminary comparison of behavioral and biochemical effects of chronic transcranial magnetic stimulation and electroconvulsive shock in the rat. Biol Psychiatry 42:920–924

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Zwanzger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zwanzger, P., Fallgatter, A.J., Zavorotnyy, M. et al. Anxiolytic effects of transcranial magnetic stimulation—an alternative treatment option in anxiety disorders?. J Neural Transm 116, 767–775 (2009). https://doi.org/10.1007/s00702-008-0162-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-008-0162-0

Keywords

Navigation