An estimate of placebo effect of repetitive transcranial magnetic stimulation in epilepsy

Abstract

Objective-Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool in epilepsy. In recent years, several open-label trials have shown an encouraging reduction in seizure frequency in patients with epilepsy. However, the data from controlled trials are mixed with respect to antiepileptic rTMS efficacy, and the field would benefit from further carefully controlled trials. Prior to initiating new trials, it is important assess the magnitude of the placebo effect of presently used sham rTMS methods.Methods-We systematically analyzed individual subject data from three placebo-controlled trials and measured the placebo effect at follow-up intervals of 2, 4, and 8 weeks after sham rTMS treatment. Given the relatively small subgroup sample size, placebo condition data were pooled for analysis.Results-Three methods for sham rTMS were employed in the reviewed studies: (1) coil positioning orthogonal to the scalp, (2) a spring-loaded sham coil, and (3) a double active-sham coil. The placebo response overall was consistently low across follow-up intervals, both for median change in seizure frequency (Kruskal-Wallis, P>0.4, df = 2) and for responder (defined as ≥50% seizure frequency reduction) rate (Fisher's exact rest, P>0.9, df = 2). The aggregate effect of the placebo condition was a 0-2% median seizure reduction rate and a responder rate of 16-20%.Conclusion-We anticipate that these data will contribute to future power analysis as well as selection and design of sham rTMS methods for controlled rTMS trials.

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies

“…Moreover, sham rTMS has been shown to have the potential for a low but detectable placebo effect. 35 Although both rTMS QP ( present data) and training 36 modalities can facilitate descending corticospinal pathways after neurologically-incomplete SCI, the functional outcome appears to be greater when two modalities (i.e. inputs) are combined, supporting the "more is better" concept.…”

A Randomized, Placebo-Controlled Trial of Repetitive Spinal Magnetic Stimulation in Lumbosacral Spondylotic Pain

“…Additionally with regard to placebo design, the relevance must be interpreted within the context of individual experimental findings. Previous investigators have compared tilting the coil at 90 degrees, similar to our method, and found that it is not to be inferior to a commercially available Magstim sham coil (Magstim, Whitland, UK) [8]. It has also been estimated systematically in TMS studies for epilepsy that the placebo effect, even with this orthogonal coil position, was similar to spring loaded or double active sham coils at 0% to 2% only [9].…”

Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy

“…Possibly illustrative of a network rather than a focal anti-epileptic effect is the more pronounced reduction in CPS compared to SPS following vertex stimulation in the study by Kinoshita et al, rather preventing the spread of aberrant activity within the brain than preventing epileptic activity from occurring at all [18]. A comparative review by Bae et al between 3 placebo-controlled studies did however identify superiority of targeted stimulation over nontargeted vertex stimulation (for review [61]; for separate RCTs [23,25,26]). Brighina et al explored the network approach by targeting the posterior cerebellar lobe with HF-rTMS and thereby addressing the cerebello-cortical network in order to induce diffuse inhibitory output to the cortex [14].…”

“…all involved investigators is difficult to achieve and often poorly described. However, pooled data from placebo conditions in 3 RCTs estimated a relatively small placebo effect, with a mean SZF reduction of 0-2% and a responder rate of 16-20% across placebo conditions most likely attributable to normal SZF variability (for review [61]; for separate RCTs [23,25,26]). Since objective outcome parameters like the number of IEDs are less affected by placebo effects, inclusion in future study designs is encouraged.…”