Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 23399312 · doi:10.1017/S1461145712001691
What was done
A systematic review and meta-analysis of randomized, double-blind, sham-controlled trials evaluating blinding integrity in high-frequency (HF), low-frequency (LF), and bilateral repetitive transcranial magnetic stimulation (rTMS) for major depression. Databases (Medline, EMBASE, PsycINFO, Cochrane Central, Scopus) were searched from January 1995 to July 2012. The primary outcome was participants' ability to correctly guess their treatment assignment at study end, analyzed using random-effects risk differences (RD).
What was found
Data were obtained from 7 HF-rTMS trials (396 subjects) and 2 bilateral rTMS trials (93 subjects), averaging approximately 13 sessions; no LF-rTMS trials reported blinding data. In HF-rTMS trials, 52% of active and 59% of sham subjects correctly guessed their allocation (RD = -0.04; z = -0.51; p = 0.61). In bilateral rTMS trials, 63.3% of active and 57.5% of sham subjects correctly guessed (RD = 0.05; z = 0.49; p = 0.62). Angulation and sham coil methods produced similar blinding results in HF-rTMS trials.
Why it matters
These findings suggest that current sham rTMS protocols achieve acceptable participant blinding, mitigating concerns that efficacy outcomes in depression trials are artifacts of broken blinding.
Limits
Only 9 trials reported empirical blinding data, indicating widespread underreporting in rTMS literature. Bilateral rTMS had few participants (n = 93 across 2 trials), no data were available for LF-rTMS, and assessor or operator blinding integrity was not reported.
Cited by
- supports In rTMS clinical trials, sham stimulation effectively blinds participants so they cannot guess whether they received active or sham treatment.