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Thursday, May 8, 2008

rTMS not Effective for Depression

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.

After the review only one other randomized sham controlled trial was published about rTMS for depression.

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.

rTMS for Parkinson's disease and Dystonia?
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.

Nah, get out of here..........

There is now even deep TMS
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.

Or cTMS.
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 รข€“ the beginning of the end or the end of the beginning?. Psychological Medicine, 38(03) DOI: 10.1017/S0033291707001651

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