A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression

P. F.P. van Eijndhoven; J. Bartholomeus; M. Möbius; A. de Bruijn; G. R.A. Ferrari; P. Mulders; A. H. Schene; D. J.L.G. Schutter; J. Spijker; I. Tendolkar

doi:10.1016/j.jad.2020.05.055

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression

P. F.P. van Eijndhoven^*, J. Bartholomeus, M. Möbius, A. de Bruijn, G. R.A. Ferrari, P. Mulders, A. H. Schene, D. J.L.G. Schutter, J. Spijker, I. Tendolkar

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research Question: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? Method: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. Results: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. Conclusion: “Standard” 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

Original language	English
Pages (from-to)	444-449
Number of pages	6
Journal	Journal of Affective Disorders
Volume	274
DOIs	https://doi.org/10.1016/j.jad.2020.05.055
Publication status	Published - 1 Sept 2020

Bibliographical note

Funding Information:
We like to thank Moniek Munneke and Sasha Hulsken in the initial setup of the study and Jan Leijtens, Emma van den Berg, Lieke Martens, Eveline Ackermans and Edwin Schenkel for their assistance with data acquisition during the clinical trial.

Publisher Copyright:
© 2020

Funding

We like to thank Moniek Munneke and Sasha Hulsken in the initial setup of the study and Jan Leijtens, Emma van den Berg, Lieke Martens, Eveline Ackermans and Edwin Schenkel for their assistance with data acquisition during the clinical trial.

Keywords

Chronic depression
Repetitive transcranial magnetic stimulation
Treatment resistant depression

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

van Eijndhoven, P. F. P., Bartholomeus, J., Möbius, M., de Bruijn, A., Ferrari, G. R. A., Mulders, P., Schene, A. H., Schutter, D. J. L. G., Spijker, J., & Tendolkar, I. (2020). A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression. Journal of Affective Disorders, 274, 444-449. https://doi.org/10.1016/j.jad.2020.05.055

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abstract = "Background: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research Question: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? Method: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. Results: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. Conclusion: “Standard” 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.",

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note = "Funding Information: We like to thank Moniek Munneke and Sasha Hulsken in the initial setup of the study and Jan Leijtens, Emma van den Berg, Lieke Martens, Eveline Ackermans and Edwin Schenkel for their assistance with data acquisition during the clinical trial. Publisher Copyright: {\textcopyright} 2020",

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van Eijndhoven, PFP, Bartholomeus, J, Möbius, M, de Bruijn, A, Ferrari, GRA, Mulders, P, Schene, AH, Schutter, DJLG, Spijker, J & Tendolkar, I 2020, 'A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression', Journal of Affective Disorders, vol. 274, pp. 444-449. https://doi.org/10.1016/j.jad.2020.05.055

TY - JOUR

T1 - A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression

AU - van Eijndhoven, P. F.P.

AU - Bartholomeus, J.

AU - Möbius, M.

AU - de Bruijn, A.

AU - Ferrari, G. R.A.

AU - Mulders, P.

AU - Schene, A. H.

AU - Schutter, D. J.L.G.

AU - Spijker, J.

AU - Tendolkar, I.

N1 - Funding Information: We like to thank Moniek Munneke and Sasha Hulsken in the initial setup of the study and Jan Leijtens, Emma van den Berg, Lieke Martens, Eveline Ackermans and Edwin Schenkel for their assistance with data acquisition during the clinical trial. Publisher Copyright: © 2020

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Background: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research Question: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? Method: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. Results: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. Conclusion: “Standard” 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

AB - Background: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research Question: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? Method: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. Results: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. Conclusion: “Standard” 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

KW - Chronic depression

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ER -

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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