Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial
- PMID: 29726344
- DOI: 10.1016/S0140-6736(18)30295-2
Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial
Erratum in
-
Department of Error.Lancet. 2018 Jun 23;391(10139):e24. doi: 10.1016/S0140-6736(18)31323-0. Epub 2018 Jun 11. Lancet. 2018. PMID: 29903431 No abstract available.
Abstract
Background: Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.
Methods: In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782.
Findings: Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208).
Interpretation: In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness.
Funding: Canadian Institutes of Health Research.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Comment in
-
Transcranial magnetic stimulation for depression.Lancet. 2018 Apr 28;391(10131):1639-1640. doi: 10.1016/S0140-6736(18)30863-8. Epub 2018 Apr 26. Lancet. 2018. PMID: 29726325 No abstract available.
-
Commentary: Effectiveness of theta burst vs. high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomized non-inferiority trial.Front Hum Neurosci. 2018 Jun 25;12:255. doi: 10.3389/fnhum.2018.00255. eCollection 2018. Front Hum Neurosci. 2018. PMID: 29988538 Free PMC article. No abstract available.
-
Repetitive transcranial magnetic stimulation for depression.Lancet. 2019 Feb 2;393(10170):403. doi: 10.1016/S0140-6736(18)32760-0. Lancet. 2019. PMID: 30712895 No abstract available.
-
Considerable evidence supports rTMS for treatment-resistant depression.J Affect Disord. 2020 Feb 15;263:549-551. doi: 10.1016/j.jad.2019.11.017. Epub 2019 Nov 6. J Affect Disord. 2020. PMID: 31727396 No abstract available.
Similar articles
-
Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression: The FOUR-D Randomized Noninferiority Clinical Trial.JAMA Psychiatry. 2022 Nov 1;79(11):1065-1073. doi: 10.1001/jamapsychiatry.2022.2862. JAMA Psychiatry. 2022. PMID: 36129719 Free PMC article. Clinical Trial.
-
Current Updates on Newer Forms of Transcranial Magnetic Stimulation in Major Depression.Adv Exp Med Biol. 2021;1305:333-349. doi: 10.1007/978-981-33-6044-0_18. Adv Exp Med Biol. 2021. PMID: 33834408 Review.
-
Novel Augmentation Strategies in Major Depression.Dan Med J. 2017 Apr;64(4):B5338. Dan Med J. 2017. PMID: 28385173 Review.
-
Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.Trials. 2017 Jan 13;18(1):17. doi: 10.1186/s13063-016-1764-8. Trials. 2017. PMID: 28086851 Free PMC article. Clinical Trial.
-
rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation.Brain Stimul. 2015 Mar-Apr;8(2):208-15. doi: 10.1016/j.brs.2014.11.002. Epub 2014 Nov 6. Brain Stimul. 2015. PMID: 25465290
Cited by
-
Can Intermittent Theta-Burst Stimulation of Dorsolateral Prefrontal Cortex Relieve Executive Dysfunction in Patients With Late-Life Depression?Alpha Psychiatry. 2024 Jan 1;25(1):115-117. doi: 10.5152/alphapsychiatry.2024.231485. eCollection 2024 Jan. Alpha Psychiatry. 2024. PMID: 38799492 Free PMC article. No abstract available.
-
Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.Sci Rep. 2024 May 24;14(1):11847. doi: 10.1038/s41598-024-61404-9. Sci Rep. 2024. PMID: 38782921 Free PMC article.
-
Brain stimulation therapeutics.Addict Neurosci. 2023 Jun;6:100080. doi: 10.1016/j.addicn.2023.100080. Epub 2023 Mar 5. Addict Neurosci. 2023. PMID: 38770029 Free PMC article.
-
Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.Nat Med. 2024 May;30(5):1276-1283. doi: 10.1038/s41591-024-02940-9. Epub 2024 May 20. Nat Med. 2024. PMID: 38769431 Free PMC article. Clinical Trial.
-
Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial.BMJ Open. 2024 May 15;14(5):e081847. doi: 10.1136/bmjopen-2023-081847. BMJ Open. 2024. PMID: 38754874 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous