Influence of prefrontal target region on the efficacy of repetitive transcranial magnetic stimulation in patients with medication-resistant depression: a [(18)F]-fluorodeoxyglucose PET and MRI study.
It is currently unknown whether the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) depends on specific characteristics of the stimulated frontal area, such as metabolic changes. We investigated the effect of high-frequency rTMS, administered over the most hypometabolic prefrontal area in depressed patients in a two-site, double-blind, randomized placebo-controlled add-on study. Forty-eight patients with medication-resistant major depression underwent magnetic resonance imaging and [(18)F]-fluorodeoxyglucose positron emission tomography (PET) in order to determine a target area for rTMS. After randomization to PET-guided (n = 16), standard (n = 18), or sham rTMS (n = 14) conditions, the patients received 10 sessions of 10-Hz rTMS (1600 pulses/session) at 90% motor threshold. Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores did not differ between PET-guided, standard and sham groups at 2-wk end-point. Exploratory comparison of left PET-guided (n = 9), right PET-guided, standard, and sham rTMS revealed significant effects. The highest improvement in MADRS scores was observed with left PET-guided (60 + or - 31%), significantly superior to sham (30 + or - 37%, p = 0.01) and right-guided (31 + or - 33%, p = 0.02) stimulation. Comparison between left PET-guided and standard rTMS (49 + or - 28%) was not significant (p = 0.12). Comparison between stimulation over dorsolateral prefrontal cortex (BA 9-46), stimulation of other areas, and sham rTMS was statistically significant. Stimulation over BA 9-46 region (n = 15) was superior to sham rTMS (p = 0.02). The results do not support the general hypothesis of increased antidepressant effects of high-frequency rTMS with prefrontal hypometabolism-related PET guidance. Nonetheless, whether metabolism and anatomy characteristics of left frontal area underneath the coil might account for an increase or speeding up of rTMS effects needs further investigation.
Paillère Martinot
Marie-Laure
ML
Inserm U797, CEA - INSERM U797 'Neuroimaging & Psychiatry', I2BM, IFR49. ml.paillere@cch.aphp.fr
Galinowski
André
A
Ringuenet
Damien
D
Gallarda
Thierry
T
Lefaucheur
Jean-Pascal
JP
Bellivier
Frank
F
Picq
Christine
C
Bruguière
Pascale
P
Mangin
Jean-François
JF
Rivière
Denis
D
Willer
Jean-Claude
JC
Falissard
Bruno
B
Leboyer
Marion
M
Olié
Jean-Pierre
JP
Artiges
Eric
E
Martinot
Jean-Luc
JL
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001931:Brain Mapping; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D050781:Transcranial Magnetic Stimulation / Q000379:methods* / Q000523:psychology; D016896:Treatment Outcome
D000928:Antidepressive Agents; D019788:Fluorodeoxyglucose F18