Subthalamic Nucleus Stimulation in Severe Obsessive–Compulsive Disorder

Luc Mallet, M.D., Ph.D., Mircea Polosan, M.D., Nematollah Jaafari, M.D., Nicolas Baup, M.D., Marie-Laure Welter, M.D., Ph.D., Denys Fontaine, M.D., Ph.D., Sophie Tezenas du Montcel, M.D., Ph.D., Jérôme Yelnik, M.D., Isabelle Chéreau, M.D., Christophe Arbus, M.D., Sylvie Raoul, M.D., Ph.D., Bruno Aouizerate, M.D., Ph.D., Philippe Damier, M.D., Ph.D., Stephan Chabardès, M.D., Ph.D., Virginie Czernecki, Ph.D., Claire Ardouin, Ph.D., Marie-Odile Krebs, M.D., Ph.D., Eric Bardinet, Ph.D., Patrick Chaynes, M.D., Ph.D., Pierre Burbaud, M.D., Ph.D., Philippe Cornu, M.D., Philippe Derost, M.D., Thierry Bougerol, M.D., Ph.D., Benoit Bataille, M.D., Vianney Mattei, M.D., Didier Dormont, M.D., Ph.D., Bertrand Devaux, M.D., Marc Vérin, M.D., Ph.D., Jean-Luc Houeto, M.D., Ph.D., Pierre Pollak, M.D., Ph.D., Alim-Louis Benabid, M.D., Ph.D., Yves Agid, M.D., Ph.D., Paul Krack, M.D., Ph.D., Bruno Millet, M.D., Ph.D., Antoine Pelissolo, M.D., Ph.D., for the STOC Study Group

ABSTRACT

Background Severe, refractory obsessive–compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option.

Methods In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests.

Results After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [±SD], 19±8 vs. 28±7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56±14 vs. 43±8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events.

Conclusions These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377 [ClinicalTrials.gov] .)