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Abstract

Objective:

Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, little is known about the comparative effectiveness of rTMS and other treatment options, such as antidepressants. In this multicenter randomized controlled trial, rTMS was compared with the next pharmacological treatment step in patients with treatment-resistant depression.

Methods:

Patients with unipolar nonpsychotic depression (N=89) with an inadequate response to at least two treatment trials were randomized to treatment with rTMS or to a switch of antidepressants, both in combination with psychotherapy. Treatment duration was 8 weeks and consisted of either 25 high-frequency rTMS sessions to the left dorsolateral prefrontal cortex or a switch of antidepressant medication following the Dutch treatment algorithm. The primary outcome was change in depression severity based on the Hamilton Depression Rating Scale (HAM-D). Secondary outcomes were response and remission rates as well as change in symptom dimensions (anhedonia, anxiety, sleep, rumination, and cognitive reactivity). Finally, expectations regarding treatment were assessed.

Results:

rTMS resulted in a significantly larger reduction in depressive symptoms than medication, which was also reflected in higher response (37.5% vs. 14.6%) and remission (27.1% vs. 4.9%) rates. A larger decrease in symptoms of anxiety and anhedonia was observed after rTMS compared with a switch in antidepressants, and no difference from the medication group was seen for symptom reductions in rumination, cognitive reactivity, and sleep disorders. Expectations regarding treatment correlated with changes in HAM-D scores.

Conclusions:

In a sample of patients with moderately treatment-resistant depression, rTMS was more effective in reducing depressive symptoms than a switch of antidepressant medication. In addition, the findings suggest that the choice of treatment may be guided by specific symptom dimensions.

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Supplementary Material

File (appi.ajp.20230556.ds001.pdf)

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry

History

Received: 14 July 2023
Revision received: 30 November 2023
Revision received: 23 January 2024
Accepted: 27 February 2024
Published online: 7 August 2024

Keywords

  1. Antidepressants
  2. Cognitive Reactivity
  3. Expectations
  4. Depressive Disorders
  5. Neurostimulation
  6. Repetitive Transcranial Magnetic Stimulation

Authors

Affiliations

Iris Dalhuisen, Ph.D. [email protected]
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Iris van Oostrom, Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Jan Spijker, M.D., Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Ben Wijnen, Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Eric van Exel, M.D., Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Hans van Mierlo, M.D., Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Dieuwertje de Waardt, M.D., Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Martijn Arns, Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Indira Tendolkar, M.D., Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).
Philip van Eijndhoven, M.D., Ph.D.
Department of Psychiatry, Radboud University Medical Center, and Donders Institute for Brain, Cognition, and Behavior, Centre for Medical Neuroscience, Nijmegen, the Netherlands (Dalhuisen, Tendolkar, van Eijndhoven); Neurocare Clinics, Nijmegen, the Netherlands (van Oostrom); Depression Expertise Centre, Pro Persona Mental Health Care, and Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands (Spijker); Center for Economic Evaluation, Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands (Wijnen); GGZ inGeest Specialized Mental Health Care, and Department of Psychiatry, Amsterdam University Medical Center, Amsterdam (van Exel); Department of Psychiatry and Psychology, St. Antonius Hospital, Utrecht/Nieuwegein, the Netherlands (van Mierlo); Department of Psychiatry, Elisabeth-TweeSteden Ziekenhuis Hospital, Tilburg, the Netherlands (de Waardt); Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands (Arns); Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands (Arns).

Notes

Send correspondence to Dr. Dalhuisen ([email protected]).

Competing Interests

The Netherlands Trial Register: NL7628 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON24799).
The data sets that were used for this study are available in the Radboud Repository (https://repository.ubn.ru.nl/).
Dr. Arns holds equity or stock in Neurocare and Sama Therapeutics; he has served as a consultant for Neurocare, Roche, Sama Therapeutics, and Synaeda; and he is a named inventor on patents and intellectual property. The other authors report no financial relationships with commercial interests.

Funding Information

Supported by the Netherlands Organization for Health Research and Development (project 852001925 to Dr. van Eijndhoven).

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