Progress in Neuro-Psychopharmacology and Biological Psychiatry
A double-blind sham controlled study of right prefrontal repetitive transcranial magnetic stimulation (rTMS): Therapeutic and cognitive effect in medication free unipolar depression during 4 weeks
Introduction
Since its introduction as a tool for investigating and mapping cortical functions (Barker and Freeston, 1985), transcranial magnetic stimulation (TMS) in psychiatry has been tested as a therapeutic tool in major depressive disorders (Höflich et al., 1993, Pascual-Leone et al., 1996, George et al., 2000, Dannon and Grunhaus, 2001, Grunhaus et al., 2002, Grunhaus et al., 2003).
TMS is a safe and non-invasive method. A brief and powerful magnetic current is generated by a small coil placed over the scalp. This magnetic flow passes unimpeded through the skull inducing a localised current which induces neuronal depolarisation of the cortex.
Numerous studies emphasize that stimulation at different frequencies may have divergent effects on neural activity. The prevailing hypothesis of the repetitive transmagnetic stimulation (rTMS) action mechanism is mainly based on its ability to modify cortical excitability, high frequencies having a facilitatory effect on neural activity while low frequencies produce an inhibitory effect.
Maeda et al. (2000) found asymmetric effect on cortical excitability, with left cortical excitability being lower than the right cortex during major depressive disorders.
In addition, a growing number of studies report antidepressant effect of rTMS. Several studies have proved the ability of high frequency repetitive TMS (rTMS) on the left dorsolateral prefrontal cortex to relieve depressive symptoms (Burt et al., 2002, Martin et al., 2002) and more rarely when the right side was stimulated.
Until now, most of these published studies are limited by either open-label design or the use of antidepressant drugs. Concerning the double-blind studies, we observed a lack of homogeneity in the selection criteria of depressive patients and TMS parameters, a short period of treatment by TMS (two weeks in general).
Recent technologic advances led to the development of magnetic stimulators that could stimulate faster than once per second (1 Hz). By convention, this is called repetitive transcranial magnetic stimulation (rTMS) with frequencies above 1 Hz being called high frequency and frequencies of 1 Hz or less being called low frequencies.
These reasons could partially explain the results of a recent meta-analysis (Burt et al., 2002). Klein et al. (1999) found positive results with right rTMS treatment in major depression in a two-week period of medication. The previous medical treatment was maintained in this study.
We decided to evaluate the efficacy of TMS in a homogenous population of depressed patients, treated only by TMS during one month. The primary objective of the study was to evaluate the efficacy of TMS in unipolar depression: the percentage of responders (> 50% HDRS reduction) after four weeks of active TMS treatment in depressed patients free of any antidepressive agent versus shamTMS.
Section snippets
Method and material
We performed a double-blind sham controlled study of the rTMS efficacy of the treatment of unipolar depression.
Description of the patients
27 patients responding to the criteria of the protocol were included and randomized in two groups: rTMS (N = 11) and sham TMS (N = 16,) (Table 1). The groups were comparable regarding demographic and clinical features: mean age of the global population was 37.78 years (± 11.27); age range 20 to 65 years. HDRS scores were comparable at day—1 (23.23 ± 2.83 and 22.9 ± 2.9, p > 0.05) for TMS and sham, respectively, p > 0.05) and at day 1 (22.08 ± 3.65 and 22.35 ± 2.7, p > 0.05) for TMS and sham, respectively.
Clinical results
In our
Discussion
It is one of first articles on the efficacy of the right rTMS (dorso prefrontal lateral cortex) tested over a period of 4 weeks in double-blind study for untreated and non resistant depressed patients. In most of the studies, the stimulations are localised in the left dorsolateral prefrontal cortex. The characteristics of our parameters are close to those used by Klein et al. (1999), except for the duration of treatment (one month versus 2 weeks) and the intensity (90% versus 110%). Klein et
Conclusion
Our study has shown an efficacy of right rTMS in free medication unipolar depression over a month. Nevertheless, our sample of patients is low and multicentric studies with homogenous parameters will be necessary to demonstrate the antidepressive action of TMS. Moreover, it is interesting to test in the future if brainsight could improve the clinical results and to compare both sides of TMS stimulation for therapeutic results.
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