© 2004 The Royal College of Psychiatrists
Correspondence |
Antidepressant effects of repetitive transcranial magnetic stimulation
Harborview Medical Center, University of Washington Medical Center, Department of Psychiatry and Behavioral Sciences, 325 Ninth Avenue, Box 359896, Seattle, WA 98104-2499, USA
Department of Psychiatry, University Hospital, Bonn, Germany
P.E.H. and D.A. have received research support from the US National Institute of Mental Health. D.A. has received research support from Philips, Inc., belongs to speakers’ bureaux at Cephalon, Wyeth Pharmaceuticals and Pfizer, and is a member of consultancy or advisory boards at Bristol-Myers-Squibb, Cyberonics, Eli Lilly, Inc., Forest Laboratories, Inc., GlaxoSmithKline, Janssen Pharmaceutica Products, Inc., Neuronetics, Inc. and UBC Pharma, Inc. T.E.S. has received research support from NV Organon, USA, Cyberonics, Inc. and Magstim, Inc., UK; belongs to speakers’ bureaux at NV Organon, USA, Eli Lilly and Company, Switzerland and Pfizer, Inc., Switzerland; and is a member of advisory boards at Otsuka Pharmaceuticals, USA and Janssen AG, Switzerland.
The report by Martin et al (2003) seems in conflict with previous meta-analyses of repetitive transcranial magnetic stimulation (rTMS) (Holtzheimer et al, 2001; McNamara et al, 2001; Burt et al, 2002). We wish to provide a broader context for interpreting these results.
The analysis by Martin et al was designed to minimise type 1 error – to identify the level of confidence that can be placed in purported antidepressant effects of rTMS. It combined only studies with similar methodologies, included only studies that met high standards of randomisation and blinding, and analysed only end-point depression ratings (rather than analysing change scores or controlling for baseline depression severity). With this approach, the review found a statistically significant effect size for high-frequency (> 1 Hz) rTMS applied to the left prefrontal cortex (– 0.35, 95% CI – 0.66 to – 0.04, P=0.03), but did not find evidence that antidepressant effects were clinically significant or that they persisted over time.
The other meta-analyses attempted to minimise type 2 error – to identify whether there is reason to believe that rTMS might have significant antidepressant properties warranting further investigation. They combined studies with different methodologies and calculated effect sizes based on changes in depression severity over time. Such a technique can be important when analysing studies where different treatment arms may start at different baselines. Using these analytic techniques, prior meta-analyses found effect sizes for high-frequency, left prefrontal rTMS ranging from 0.5 to 0.8, suggesting that rTMS does indeed have statistically significant antidepressant effects. However, these analyses all agree that the clinical significance of these effects is not yet established.
The results of the Martin et al review do not suggest at all that rTMS has no antidepressant effects. On the contrary, this methodologically rigorous review identifies statistically (but not clinically) significant, short-term antidepressant effects for 2 weeks of high-frequency, left prefrontal rTMS and recommends further studies to establish efficacy and identify optimal parameters. Even more importantly, numerous studies have shown that rTMS alters brain functioning, with effects ranging from altered gene expression in animals to modified cerebral perfusion in humans; in many cases, these effects are very similar to those seen with established antidepressant treatments.
With these points in mind, we offer the following recommendations to help guide use of rTMS in clinical and research settings.
- Given the small clinical effects seen with rTMS in studies to date, it does
not seem that rTMS is appropriate for widespread clinical use at this
time.
- Large, multi-site trials are warranted to clarify the antidepressant
effects of rTMS.
- Future studies of rTMS should incorporate several improvements in study
design, including appropriate (and well-documented) randomisation, adequate
blinding of subjects and therapists (probably requiring an improved sham
condition), and better assessment of the duration of any antidepressant
effects.
- More research should be directed at clarifying which patient and treatment
characteristics might lead to greater antidepressant effects with rTMS.
- More research should be directed at identifying and testing potential
mechanisms by which rTMS produces antidepressant effects.
REFERENCES
- Burt, T., Lisanby, S. H. & Sackeim, H. A. (2002) Neuropsychiatric applications of transcranial magnetic stimulation: a meta-analysis. International Journal of Neuropsychopharmacology, 5, 73 -103.
- Holtzheimer, P., Russo, J. & Avery, D. (2001) A metaanalysis of repetitive transcranial magnetic stimulation in the treatment of depression. Psychopharmacology Bulletin, 35, 149 -169.[Medline]
- Martin, J. L. R., Barbanoj, M. J., Schlaepfer, T. E., et
al (2003) Repetitive transcranial magnetic stimulation
for the treatment of depression: systematic review and meta-analysis.
British Journal of Psychiatry,
182, 480
-491.
[Abstract/Free Full Text] - McNamara, B., Ray, J. L., Arthurs, J., et al (2001) Transcranial magnetic stimulation for depression and other psychiatric disorders. Psychological Medicine, 31, 1141 -1146.[CrossRef][Medline]
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