This morning I was looking at some videos on TED. This made me wonder if and what kind of videos are online available about TMS. I was hoping to find an old video no one ever heard that I could use for my reseach but unfortunatelly that did not happen. I tried Youtube with the search “transcranial magnetic stimulation” and only a handful of interesting modern videos were the result. No old videos about guinea pigs in a magnetic stimulator came up. Nevertheless I will present the videos below. So if you might come across interesting videos or other information about TMS please let me know in the comments
Rapid Transcranial Magnetic Stimulation (rTMS) to the left prefrontal cortex is not more effective than sham rTMS for depression. This was the result of a recent published randomized controlled trial with 4 month follow-up.
rTMS is a non-invasive method to stimulate the brain. Weak electric currents are induced in the cortex of the brain by rapidly changing magnetic fields (electromagnetic induction). This way, brain activity can be triggered with minimal discomfort, no need for anesthesia, and no cognitive side-effects. Side effects of rTMS are: discomfort or pain from the stimulation of the scalp and associated nerves and muscles on the overlying skin and hearing from the loud click made by the TMS pulses.
The most recent Cochrane review concluded that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit. Since then (2002) 8 randomized controlled trials were published about rTMS and depression, you can read about these trials here.
Considering the outcome on the time point at week 4, Dr Shock is not very impressed by the results. For significant difference with the primary outcome 6 patients had to be excluded from the analysis. The mean difference between active and sham on the severity scales is in the range of 2-3 points, significant but hardly clinical relevant. Absolute figures on response and remission at week 4 are not given in this article. Remission rate at 6 weeks on the HAMD-17 was 15.5% increasing to 22.6% at week 9 with open labeled therapy. Not very impressive.
Since some previous studies used relatively non-intense stimulation parameters in the absence of a true placebo condition this trial used an intensive form of rTMS treatment:
Research physicians administered TMS at 110% resting MT (motor threshold) at frequency 10 Hz, in 5-second trains. Twenty trains were given each session with inter-train intervals of 55 seconds. Thus a total of 1000 TMS pulses were given per session and 10 000 per course.
In addition, very few reported meaningful follow-up data, in this study subjects were followed up for 4 months. To prevent unblinding placebo rTMS was delivered in the same way as real rTMS but using a purpose-built sham coil (Magstim Co.,Whitland, UK) that was visually identical to the real coil and made the same clicking sound but did not deliver a magnetic field to scalp or cortex.
And these are the results:
Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant grouprtime interaction (p=0.09) or group main effect (p=0.85) ; the mean difference in HAMD change scores wasx0.3 (95% CIx3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06) ; 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2) ; the mean difference in HAMD change scores was 2.9 (95% CI x0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters.
In a comment they still want us to believe that rTMS can be promising. In the comment comparison is mad with antidepressants and ECT but these treatments have been studied far more often resulting in not very great advantages but much more evidence and meta analysis with greater power. Moreover, as with other failing treatments in the past rTMS is studied in all kinds of diagnoses. rTMS for Stroke?
A study by a group out of the University of Cologne in Germany has demonstrated that rTMS over the unaffected motor cortex of patients that have had a stroke will make their use of the affected hand more efficient and quicker.
Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson’s disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects.
This specific technology can excite or inhibit more areas of the brain than conventional TMS. Regular TMS is basically limited the brain’s outer layer, the neocortex, and can only reach about 1 to 2 centimeters into the brain. So it is limited in its ability to affect many brain areas. The new deep tms can stimulate inner brain areas without inducing unbearable electromagnetic fields cortically. This device currently has almost magical properties and it is somewhat difficult to distinguish company hype from real clinical benefit. I’m not sure at this point how selective this targeting technique is. I think it will be fairly difficult to selectively turn on or off specific brain areas without having unintentional effects.
Researchers have developed a better way to manipulate a person’s brain functioning. They have created a new type of transcranial magnetic stimulation (TMS) device (called controllable pulse width TMS or cTMS for short) that will allow rectangular pulse shapes of the magnetic fields. This device will enable researchers to control the width of the magnetic pulse that passes through the subjects skull.
Will keep you posted on all this, will it help TMS?. Let me know in the comments what you think?
Mogg, A., Pluck, G., Eranti, S., Landau, S., Purvis, R., Brown, R., Curtis, V., Howard, R., Philpot, M., McLoughlin, D. (2008). A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Psychological Medicine, 38(03) DOI: 10.1017/S0033291707001663 Ebmeier, K., Herrmann, L. (2008). TMS â€“ the beginning of the end or the end of the beginning?. Psychological Medicine, 38(03) DOI: 10.1017/S0033291707001651
Another open labeled trial with rTMS. It is a continuation trial after a recent double-blind placebo controlled trial with rTMS.This study is discussed in a recent post on this blog: Finally some good news about rTMS?
Considering the outcome on the time point at week 4, Dr Shock is not very impressed by the results. For significant difference with the primary outcome 6 patients had to be excluded from the analysis. The mean difference between active and sham on the severity scales is in the range of 2-3 points, significant but hardly clinical relevant.
The NICE guidelines use a difference of 3 point or more as clinical significant.
Another open trial is unethical to my opinion in this stage of development of rTMS. Patients that were non responders on the double-blind sham controlled rTMS trial received an additional 6 weeks of active rTMS. The nonreponders on the active rTMS group also were continued on rTMS for 6 weeks. Both patients and investigators remained blind to prior treatment condition. The open label study had 2 phases: a 6 week antidepressant medication free acute phase treatment and a 3 week taper phase during which antidepressant medication was initiated. Patients received 5 rTMS sessions per week during 6 weeks followed by 3 times a week in week 7, 2 times a week in week 8 and once a week in the last week.
Results Patients who received sham in the preceding randomized controlled trial (N = 85), the mean reduction in MADRS scores after 6 weeks of open-label active TMS was -17.0. Further, at 6 weeks, 36 (42.4%) of these patients achieved response on the MADRS, and 17 patients (20.0%) remitted. Remission was defined as a score under 10 on the MADRS. For those patients who received and did not respond to active TMS in the preceding randomized controlled trial (N = 73), the mean reduction in MADRS scores was -12.5, and response and remission rates were 26.0% and 11.0%, respectively.
A well just to let you know, we will wait for another open label trial.
What is interesting to know is that in in the sham to rTMS treatment group, failure to only one antidepressant trial before rTMS resulted in a greater likelihood of response. If resistant to more antidepressants before rTMS predicted less favorable outcome.
When is there going to be a sham controlled trial without medication resistant depressive patients?
Avery, D.H. (2008). Transcranial magnetic stimulation in the acute treatment of major depressive disorder: clinical response in an open-label extension trial.. Journal of Clinical Psychiatry, 69(3), 441-451.