Skip to main content Accessibility help
×
Home

Antidepressant effects of augmentative transcranial magnetic stimulation: Randomised multicentre trial

  • Uwe Herwig (a1), Andreas J. Fallgatter (a2), Jacqueline Höppner (a3), Gerhard W. Eschweiler (a4), Martina Kron (a5), Göran Hajak (a6), Frank Padberg (a7), Angela Naderi-Heiden (a8), Birgit Abler (a9), Peter Eichhammer (a10), Nicola Grossheinrich (a11), Birgit Haya (a12), Thomas Kammer (a9), Berthold Langguth (a10), Christoph Laske (a4), Christian Plewnia (a4), Melany M. Richter (a13), Merten Schulz (a3), Stefan Unterecker (a2), Antonia Zinke (a3), Manfred Spitzer (a14) and Carlos Schönfeldt-Lecuona (a14)...

Abstract

Background

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new treatment option for depression. Previous studies were performed with low sample sizes in single centres and reported heterogeneous results.

Aims

To investigate the efficacy of rTMS as augmentative treatment in depression.

Method

In a randomised, double-blind, sham-controlled multicentre trial 127 patients with moderate to severe depressive episodes were randomly assigned to real or sham stimulation for 3 weeks in addition to simultaneously initiated antidepressant medication.

Results

We found no difference in the responder rates of the real and the sham treatment groups (31% in each) or in the decrease of the scores on the depression rating scales.

Conclusions

The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Antidepressant effects of augmentative transcranial magnetic stimulation
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Antidepressant effects of augmentative transcranial magnetic stimulation
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Antidepressant effects of augmentative transcranial magnetic stimulation
      Available formats
      ×

Copyright

Corresponding author

Dr U. Herwig, Psychiatric University Hospital, University of Zürich, Lenggstr. 31, CH-8032 Zürich, Switzerland. Tel: +41 44 384 3375; fax: +41 44 383 4456; email: uwe.herwig@puk.zh.ch

Footnotes

Hide All

Declaration of interest

None.

Footnotes

References

Hide All
Abler, B., Walter, H., Wunderlich, A., et al (2005) Side effects of transcranial magnetic stimulation biased task performance in a cognitive neuroscience study. Brain Topography, 17, 193196.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). APA.
Amini, H., Aghayan, S., Jalili, S. A., et al (2005) Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized tria. Journal of Clinical Pharmacy and Therapeutics, 30, 133138.
Anderson, I. M., Delvai, N. A., Ashim, B., et al (2007) Adjunctive fast repetitive transcranial magnetic stimulation in depression. British Journal of Psychiatry, 190, 533534.
Avery, D. H., Holtzheimer, P. E., Fawaz, W., et al (2006) A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biological Psychiatry, 59, 187194.
Beck, A., Ward, C., Mendelson, M., et al (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561571.
Berton, O. & Nestler, E. J. (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nature Reviews. Neuroscience, 7, 137151.
Burt, T., Lisanby, S. H. & Sackeim, H. A. (2002) Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. International Journal of Neuropsychopharmacology, 5, 73103.
Couturier, J. L. (2005) Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis. Journal of Psychiatry and Neuroscience, 30, 8390.
First, M. B., Spitzer, R. L., Gibbon, M., et al (1998) Structured Clinical Interview for DSM–IV Axis I Disorder – Patient Edition. New York State Psychiatric Institute.
Fitzgerald, P. B., Benitez, J., de Castella, A., et al (2006) A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression. American Journal of Psychiatry, 163, 8894.
George, M. S., Nahas, Z., Molloy, M., et al (2000) A controlled trial of daily left prefrontal cortex TMS for treating depression. Biological Psychiatry, 48, 962970.
Grunhaus, L., Schreiber, S., Dolberg, O. T., et al (2003) A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Biological Psychiatry, 53, 324331.
Hamilton, M. (1960) Arating scale for deprssion. Journal of Neurology, Neurosurgery and Psychiatry, 23, 5662
Herwig, U., Lampe, Y., Juengling, F. D., et al (2003a) Add-on rTMS for treatment of depression: a pilot study using stereotaxic coil-navigation according to PET data. Journal of Psychiatric Research, 37, 267275.
Herwig, U., Satrapi, P. & Schonfeldt-Lecuona, C. (2003b) Using the international 10–20 EEG system for positioning of transcranial magnetic stimulation. Brain Topography, 16, 9599.
Kozel, F. A. & George, M. S. (2002) Meta-analysis of left prefrontal repetitive transcranial magnetic stimulation (rTMS) to treat depression. Journal of Psychiatric Practice, 8, 270275.
Lisanby, S. H., Gutman, D., Luber, B., et al (2001) Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Biological Psychiatry, 49, 460463.
Loo, C. K. & Mitchell, P. B. (2005) A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. Journal of Affective Disorders, 88, 255267.
Loo, C. K., Taylor, J. L., Gandevia, S. C., et al (2000) Transcranial magnetic stimulation (TMS) in controlled treatment sudies: are some sham forms active? Biological Psychiatry, 47, 325331.
Loo, C. K., Mitchell, P. B., Croker, V. M., et al (2003) Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. Psychological Medicine, 33, 3340.
Lopez, A. D. & Murray, C. C. (1998) The global burden of disease, 1990–2020. Nature Medicine, 4, 12411243.
Martin, J. L. R., Barbanoj, M. J., Schlaepfer, T. E., et al (2003) Repetitive transcranial magnetic stimulation for the treatment of depression: systematic review and meta-analysis. British Journal of Psychiatry, 182, 480491.
Miniussi, C., Bonato, C., Bignotti, S., et al (2005) Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: an efficacious therapy for major drug-resistant depression? Clinical Neurophysiology, 116, 10621071.
Montgomery, S. A. & Asberg, M. (1979) Anew depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.
Mosimann, U. P., Schmitt, W., Greenberg, B. D., et al (2004) Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients. Psychiatry Research, 126, 123133.
Nahas, Z., Kozel, F. A., Li, X., et al (2003) Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disorders, 5, 4047.
Padberg, F., Zwanzger, P., Keck, M. E., et al (2002) Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity. Neuropsychopharmacology, 27, 638645.
Pascual-Leone, A., Rubio, B., Pallardo, F., et al (1996) Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet, 348, 233237.
Pogarell, O., Koch, W., Popperl, G., et al (2006) Striatal dopamine release after prefrontal repetitive transcranial magnetic stimulation in major depression: preliminary results of a dynamic [(123)I] IBZM SPECT study. Journal of Psychiatric Research, 40, 307314.
Post, A. & Keck, M. E. (2001) Transcranial magnetic stimulation as a therapeutic tool in psych atry: what do we know about the neurobiological mechanisms? Journal of Psychiatric Research, 35, 193215.
Poulet, E., Brunelin, J., Boeuve, C., et al (2004) Repetitive transcranial magnetic stimulation does not potentiate antidepressant treatment. European Psychiatry, 19, 382383.
Praeg, E., Herwig, U., Lutz, K., et al (2005) The role of the right dorsal premotor cortex in visuomotor learning: a transcranial magnetic stimulation study. Neuroreport, 16, 17151718.
Rossini, P. M., Barker, A. T., Berardelli, A., et al (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalography and Clinical Neurophysiology, 91, 7992.
Rossini, D., Magri, L., Lucca, A., et al (2005) Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in patients with major depressive disorder? A double-blind, randomized, sham-controlled trial. Journal of Clinical Psychiatry, 66, 15691575.
Rumi, D. O., Gattaz, W. F., Rigonatti, S. P., et al (2005) Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biological Psychiatry, 57, 162166.
Shelton, R. C., Haman, K. L., Rapaport, M. H., et al (2006) A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. Journal of Clinical Psychiatry, 67, 16741681.
World Health Organization (1992) The ICD-10 Classfication of Mental and Behavioural Disorders. WHO.

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Antidepressant effects of augmentative transcranial magnetic stimulation: Randomised multicentre trial

  • Uwe Herwig (a1), Andreas J. Fallgatter (a2), Jacqueline Höppner (a3), Gerhard W. Eschweiler (a4), Martina Kron (a5), Göran Hajak (a6), Frank Padberg (a7), Angela Naderi-Heiden (a8), Birgit Abler (a9), Peter Eichhammer (a10), Nicola Grossheinrich (a11), Birgit Haya (a12), Thomas Kammer (a9), Berthold Langguth (a10), Christoph Laske (a4), Christian Plewnia (a4), Melany M. Richter (a13), Merten Schulz (a3), Stefan Unterecker (a2), Antonia Zinke (a3), Manfred Spitzer (a14) and Carlos Schönfeldt-Lecuona (a14)...
Submit a response

eLetters

Trans-cranial magnetic stimulation treatment -emergent mania in a patient with obsessive compulsive disorder

Sujita Kumar Kar, Assistant Professor, Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
Adarsh Tripathi, Associate Professor, Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
13 July 2016

Trans-cranial magnetic stimulation (TMS) is a newer modality of brain stimulation used for various neuropsychiatric disorders. The electromagnetic stimulus produces therapeutic effect by means of depolarization of neurons, neuro-modulation as well as neuroplasticity (Rossi et al., 2009). Evidences suggest beneficial role of TMS in depression (approved by US FDA), schizophrenia, mania, anxiety disorder, Obsessive Compulsive Disorder (OCD), substance use disorders, dystonia, Parkinson’s disease, tinnitus, post stroke neuro-rehabilitation and tics (Rossi et al., 2009).

TMS is a relatively safe modality of treatment. Treatment emergent mania and hypomania has been earlier reported in various case reports (Sakkas et al., 2003, Philip and Carpenter, 2013, Xia et al., 2008, Ozten et al., 2013). This is a rare side effect of TMS. In all these cases patients were treated with TMS for depression over the dorsolateral prefrontal cortex (DLPFC) high frequency along with the on-going antidepressant treatment. We report here a case of OCD with depression where low frequency rTMS was used in supplementary motor area which is having inhibitory properties was given and patient developed mania.

A 32 year old male diagnosed with obsessive compulsive disorder (OCD) since 14 years was hospitalized in our hospital for his complaints of low mood, hopelessness, worthlessness, death wishes, decreased energy and decreased sleep for past six months. At the time of hospitalization, he was receiving escitalopram 20mg/day for more than two months. He also had a suicidal attempt a week prior to hospitalization. Considering active suicidal behaviour, electroconvulsive therapy had been started along with the on-going antidepressant treatment, with which his depressive symptoms improved. Patient had withdrawn his consent for ECT due to adverse effect to anesthetic agents as result of which ECT was stopped prematurely. However, the symptoms of OCD persisted. He had history of receiving, adequate trials of pharmacotherapy (Fluoxetine upto 80mg/day, Fluvoxamine 300mg/day, Clomipramine 225mg/day, augmentation with risperidone upto 4mg/day) previously and unwilling for cognitive behaviour therapy. Considering this augmentation with repetitive trans-cranial magnetic stimulation (rTMS) was planned. Low-frequency (1Hz) rTMS at 100% resting motor threshold was delivered over supplementary motor cortex using the figure 8 coil. 1200 pulses per session were given for 20 sessions in one session per day fashion. His OCD symptoms improved significantly (more than 60% reduction in Y-BOCS score). The patient had no past or family history of psychiatric illness. His hormonal and neuroimaging findings were within normal limits.

At the end of 18th session, increased talkativeness, increased sociability, reduced and irritability has been observed, which worsened with two subsequent sessions of rTMS for which his antidepressant as well as rTMS was stopped. Quetiapine has to be started upto 100mg/day dose. There was complete resolution of these symptoms in next 10days. Subsequently Escitalopram was restarted at a dose of 10mg/day. He was maintained well with this treatment in follow up of upto 6 months.

Our patient had some unique features like – development of manic features following low-frequency TMS over supplementary motor cortex is not reported earlier in comparison to unlike DLPFC in already published case reports (Sakkas et al., 2003, Philip and Carpenter, 2013, Xia et al., 2008, Ozten et al., 2013) and development of manic symptoms after 18 sessions of TMS (delayed response). Mostly patients with OCD receive a relatively higher daily dose of antidepressants then patients suffering from depression. Use of higher daily dose of antidepressants possesses a risk for switch to mania. Our patient was receiving 20mg/day dose of escitalopram and received ECT, which might have produced a priming effect for the action of TMS and caused development of mania. The other possibility may be exclusive effect of TMS in augmenting the antidepressant response through underlying intricate neuro-modulatory mechanism. Stoppage of antidepressant and TMS resulted in resolution of symptoms. Though the patient had received quetiapine, the dose was sub-optimal and after 10 days, again escitalopram was restarted without further development of manic symptoms.

The above explanations suggest the possibility of treatment emergent mania mediated by TMS. The clinicians need to aware of such events and further studies are required to understand this neuro-biologic mechanism.

References:

OZTEN, E., SAYAR, G. H. & KARAMUSTAFALIOGLU, O. 2013. Hypomanic shift observed during rTMS treatment of patients with unipolar depressive disorder: four case reports. Ann Gen Psychiatry, 12, 12.

PHILIP, N. S. & CARPENTER, S. L. 2013. Repetitive transcranial magnetic stimulation induced hypomanic symptoms in a woman with a history of electroconvulsive therapy induced mania: a case report. F1000Res, 2, 284.

ROSSI, S., HALLETT, M., ROSSINI, P. M. & PASCUAL-LEONE, A. 2009. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol, 120, 2008-39.

SAKKAS, P., MIHALOPOULOU, P., MOURTZOUHOU, P., PSARROS, C., MASDRAKIS, V., POLITIS, A. & CHRISTODOULOU, G. N. 2003. Induction of mania by rTMS: report of two cases. Eur Psychiatry, 18, 196-8.

XIA, G., GAJWANI, P., MUZINA, D. J., KEMP, D. E., GAO, K., GANOCY, S. J. & CALABRESE, J. R. 2008. Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. Int J Neuropsychopharmacol, 11, 119-30.

... More

Conflict of interest: None Declared

Write a reply

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *