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Review
. 2025 Apr;151(4):485-505.
doi: 10.1111/acps.13768. Epub 2024 Nov 21.

More rTMS pulses or more sessions? The impact on treatment outcome for treatment resistant depression

E Oostra  1   2   3   4 , P Jazdzyk  5   6 , V Vis  2 , I Dalhuisen  7   8 , A W Hoogendoorn  1   3 , C H M Planting  1   3 , P F van Eijndhoven  7   8 , Y D van der Werf  2   9 , O A van den Heuvel  1   2   9 , E van Exel  1   3   4
Affiliations
Review

More rTMS pulses or more sessions? The impact on treatment outcome for treatment resistant depression

E Oostra et al. Acta Psychiatr Scand. 2025 Apr.

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment-resistant depression (TRD). Optimal rTMS parameters remain unclear, especially whether number of sessions or amount of pulses contribute more to treatment outcome. We hypothesize that treatment outcome depends on the number of sessions rather than on the amount of pulses.

Methods: We searched databases for randomized clinical trials (RCTs) on high-frequent (HF) or low-frequent (LF)-rTMS targeting the left or right DLPFC for TRD. Treatment efficacy was measured using standardized mean difference (SMD), calculated from pre- and post-treatment depression scores. Meta-regressions were used to explore linear associations between SMD and rTMS pulses, pulses/session and sessions for HF and LF-rTMS, separately for active and sham-rTMS. If these variables showed no linear association with SMD, we divided the data into quartiles and explored subgroup SMDs.

Results: Eighty-seven RCTs were included: 67 studied HF-rTMS, eleven studied LF-rTMS, and nine studied both. No linear association was found between SMD and amount of pulses or pulses/session for HF and LF-rTMS. Subgroup analyses showed the largest SMDs for 1200-1500 HF-pulses/session and 360-450 LF-pulses/session. The number of sessions was significantly associated with SMD for active HF (β = 0.09, p < 0.05) and LF-rTMS (β = 0.06, p < 0.01). Thirty was the maximal number of sessions, in the included RCTs.

Conclusion: More rTMS sessions, but not more pulses, were associated with improved treatment outcome, in both HF and LF-rTMS. Our findings suggest that 1200-1500 HF-pulses/session and 360-450 LF-pulses/session are already sufficient, and that a treatment course should consist of least 30 sessions for higher chance of response.

Keywords: meta‐analysis; meta‐regression; repetitive transcranial magnetic stimulation; treatment resistant depression.

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Conflict of interest statement

The authors report no biomedical financial interests or potential conflicts of interests.

Figures

FIGURE 1
FIGURE 1
Flowchart of our systematic literature search.
FIGURE 2
FIGURE 2
Meta‐regressions of the total amount of pulses or total amount of sessions as independent variable and SMD as dependent variable. (A): Meta‐regression of HF‐rTMS studies between total amount of pulses and SMD, corrected for total number of sessions. (B): Meta‐regression of HF‐rTMS studies between total number of sessions and SMD, corrected for total amount of pulses. (C): Meta‐regression of LF‐rTMS studies between total amount of pulses and SMD, corrected for total number of sessions. (D): Meta‐regression of LF‐rTMS studies between total number of sessions and SMD, corrected for total amount of pulses. HF, high‐frequency; LF, low‐frequency; rTMS, repetitive transcranial magnetic stimulation; SMD, standardized mean difference.
FIGURE 3
FIGURE 3
Forest plot of the randomized clinical trials (RCTs) using a sham control arm. Using the SMD calculated between groups enables us to interpret these results corrected for sham‐effect. An effect size of 0.78 was found, which favors active treatment over sham rTMS treatment. CI, confidence interval; rTMS, repetitive transcranial magnetic stimulation; SMD, standardized mean difference.
FIGURE 4
FIGURE 4
Meta‐regressions between stimulation intensity and SMD, for both HF‐rTMS and LF‐rTMS. Regression analysis between the % MT and the SMD of the active HF‐rTMS (in red) and active LF‐rTMS (in blue). Statistical significance was reached when p < 0.05. HF, high‐frequency; LF, low‐frequency; rTMS, repetitive transcranial magnetic stimulation; SMD, standardized mean difference.
FIGURE 5
FIGURE 5
Funnel plot.
See this image and copyright information in PMC

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