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Meta-Analysis
. 2024 May 1;7(5):e2412616.
doi: 10.1001/jamanetworkopen.2024.12616.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis

Michel Sabé  1   2 , Joshua Hyde  1 , Catharina Cramer  2 , Antonia Eberhard  2 , Alessio Crippa  3 , André Russowsky Brunoni  4 , André Aleman  5 , Stefan Kaiser  6 , David S Baldwin  7   8 , Matthew Garner  9 , Othman Sentissi  6   10 , Jess G Fiedorowicz  9   11 , Valerie Brandt  1   2 , Samuele Cortese  1   12   13   14   15 , Marco Solmi  9   16   17   18   19
Affiliations
Meta-Analysis

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis

Michel Sabé et al. JAMA Netw Open. .

Erratum in

  • Errors in Byline and Author Affiliations.
    [No authors listed] [No authors listed] JAMA Netw Open. 2024 Jul 1;7(7):e2424292. doi: 10.1001/jamanetworkopen.2024.24292. JAMA Netw Open. 2024. PMID: 38958984 Free PMC article. No abstract available.

Abstract

Importance: Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown.

Objective: To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders.

Data sources: Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge.

Study selection: Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older.

Data extraction and synthesis: Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Main outcomes and measures: The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS.

Results: A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings.

Conclusions and relevance: The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kaiser reported receiving personal fees from Boehringer Ingelheim outside the submitted work. Dr Baldwin reported receiving Research for Patient Benefit grants from the National Institute for Health and Care Research outside the submitted work. Dr Sentissi reported receiving lecture fees from Otsuka, Lundbeck, and OM Pharma and grants from Sunovion and Fondation privé des HUG outside the submitted work. Dr Cortese reported receiving grants from the European Research Commission and the National Institute for Health and Care Research and personal fees from Medice, the Association for Child and Adolescent Mental Health, the Canadian ADHD Resource Alliance, and British Association for Psychopharmacology outside the submitted work. Dr Solmi reported receiving honoraria from AbbVie, Angelini, Lundbeck, and Otsuka outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Dose-Response Curves of Transcranial Magnetic Stimulation (TMS) for Treating Schizophrenia
The dose-response curves represent the standardized mean difference reduction of symptoms for the treatment arm compared with the sham arm. Circles represent the number of individuals per dose included. The dotted lines are 95% CIs. Knot locations are at the 25th, 50th, and 75th percentiles to anchor the curves. A. The maximum reduction of negative symptoms (95% effective dose) was reached at 21 695 total pulses (95% CI, 10 071-23 531 total pulses; mean [SD] duration, 3.9 [2.0] weeks; 14 studies,,,,,,,,,,,,,; 909 participants; χ2 = 9.35; df = 2; P = .009; I2 = 83%). B. Although with very high uncertainty, this safety analysis found no effect on positive symptoms (mean [SD] duration, 3.9 [2.0] weeks; 14 studies,,,,,,,,,,,,,; 909 participants; χ2 = 0.05; df = 2; P = .98; I2 = 75%). C. Although with very high uncertainty for high dose, a bell-shape curve was obtained (mean [SD] duration, of 1.7 [0.5] weeks; 5 studies24,34, 53,91,122; 159 participants; χ2 = 36.52 df = 2; P < .001; I2 = 95%). AHRS indicates Auditory Hallucination Rating Scale.
Figure 2.
Figure 2.. Dose-Response Curves of Transcranial Magnetic Stimulation (TMS) for Treating Treatment-Resistant Depression
The dose-response curves represent the standardized mean difference reduction of symptoms for the treatment arm compared with the sham arm. Circles represent the number of individuals per dose included. The dotted lines are 95% CIs. Knot locations are at the 25th, 50th, and 75th percentiles to anchor the curves. A. Although with a moderate effect size, the maximum reduction of negative symptoms (95% effective dose) was reached at 12 374 total pulses (95% CI, 11 185-15 026 total pulses; mean [SD] duration, 2.8 [1.0] weeks; 26 studies,,,,,,,,,,,,,,,,,,,,,,,,,; 1166 participants; χ2 = 14.49; df = 2; P < .001; I2 = 90%). B. The maximum reduction of depressive symptoms (95% effective dose) was reached at 34 773 total pulses (95% CI, 32 256-36 521 total pulses; mean [SD] duration, 2.8 [0.5] weeks; 4 studies,,,; 178 participants; χ2 = 5.86; df = 2; P = .004; I2 = 95%).
Figure 3.
Figure 3.. Dose-Response Curves of Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) for Treating Major Depressive Disorder
The dose-response curves represent the standardized mean difference reduction of symptoms for the treatment arm compared with the sham arm. Circles represent the number of individuals per dose included. The dotted lines are 95% CIs. Knot locations are at the 25th, 50th, and 75th percentiles to anchor the curves. A. The maximum improvement of depressive symptoms (95% effective dose [ED95]) was reached at 14 054 total pulses (95% CI, 9522-19 235 total pulses; mean [SD] duration, 2.8 [0.5] weeks; 5 studies,,,,; 209 participants; χ2 = 1.46; df = 2; P = .48; I2 = 85%). B. The maximum improvement of depressive symptoms (ED95) was reached at 1835 total pulses (95% CI, 1721-1919 total pulses; mean [SD] duration, 2.8 [1.0] weeks; 2 studies,; 97 participants; χ2 = 25.67; df = 2; P = .001; I2 = 95%). C. The maximum improvement of depressive symptoms (ED95) was reached for a total of 48.2 coulombs (C) (95% CI, 35-55 C; mean [SD] duration, 3.1 [0.9] weeks; 6 studies,,,,,; 265 participants; χ2 = 14.56; df = 2; P < .001; I2 = 96%).
Figure 4.
Figure 4.. Dose-Response Curves for Transcranial Magnetic Stimulation (TMS) for Treating Obsessive-Compulsive Disorder (OCD) and Posttraumatic Stress Disorder (PTSD), Transcranial Direct Current Stimulation (tDCS) for Treating Methamphetamine Disorder (MUD) and Cocaine Use Disorder (CUD), and Intermittent Theta-Burst Stimulation (iTBS) for Treating MUD
The dose-response curves represent the standardized mean difference reduction of symptoms for the treatment arm compared with the sham arm. Circles represent the number of individuals per dose included. The dotted lines are 95% CIs. Knot locations are at the 25th, 50th, and 75th percentiles to anchor the curves. A. The maximum improvement of OCD symptoms (95% effective dose [ED95]) was reached at 18 923 total pulses (95% CI, 7837-19 543 total pulses; mean [SD] duration, 9.6 [1.8] weeks; 5 studies,,,,; 138 participants; χ2 = 20.65; df = 2l P < .001, I2 = 60%). B. The maximum improvement in Yale-Brown Obsessive-Compulsive Scale (Y-BCOS) scores (ED95) was reached at 13 679 total pulses (95% CI, 7117-14 734 total pulses; mean [SD] duration, 2.0 [1.0] weeks; 3 studies,,; 85 participants; χ2 = 15.19; df = 2; P < .001; I2 = 60%). C. The maximum improvement in Desires for Drug Questionnaire (DDQ) scores (ED95) was reached at 17 495 total pulses (95% CI, 16 596-18 523 total pulses; mean [SD] duration, 2.3 [1.3] weeks; 3 studies,,; 49 participants; χ2 = 54.15; df = 2; P < .001; I2 = 45%). D. The maximum improvement in DDQ scores (ED95) was reached for a total of 9.61 coulombs (C) (95% CI, 8.9-13.2 C; mean [SD] duration, 4.0 [2.1] weeks; 3 studies for MUD,, [151 participants], 3 studies for CUD,, [50 participants], and 1 study for alcohol use disorder [21 participants]; χ2 = 33.63; df = 2; P < .001; I2 = 60%). E. The maximum improvement DDQ scores (ED95) was reached at 9724 total pulses (95% CI, 7464-17 423 total pulses; mean [SD] duration, 3.5 [1.0] weeks; 4 studies,,,; 186 participants; χ2 = 92.82; df = 2; P < .001; I2 = 70%).
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