Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia

Philippe Damier, Stéphane Thobois, Tatiana Witjas, Emmanuel Cuny, Philippe Derost, Sylvie Raoul, Patrick Mertens, Jean-Claude Peragut, Jean-Jacques Lemaire, Pierre Burbaud, Jean-Michel Nguyen, Pierre-Michel Llorca, Olivier Rascol
Archives of General Psychiatry 2007, 64 (2): 170-6

CONTEXT: Tardive dyskinesia (TD) is a common and potentially disabling disorder induced by use of antipsychotic drugs for which medical treatment often gives disappointing results.

OBJECTIVE: To assess the efficacy of bilateral deep brain stimulation of the internal part of the globus pallidus to treat severe TD.

DESIGN: Prospective phase 2 multicenter study.

SETTING: Six French university hospitals. Patients Patients with severe TD refractory to medical treatment were studied to evaluate the severity of abnormal involuntary movements before and after 6 months of bilateral globus pallidus deep brain stimulation. A 2-step open Fleming procedure was used to avoid unnecessary accrual of patients. A successful outcome was defined as a decrease of more than 40% in the main outcome measure at 6 months. The early stopping rule was invoked if the number of successful outcomes in 10 patients was fewer than 2, or 5 or more. A double-blind evaluation in the presence and absence of stimulation was performed at 6 months after surgery. Main Outcome Measure Change in score on the Extrapyramidal Symptoms Rating Scale.

RESULTS: At 6 months after surgery, the Extrapyramidal Symptoms Rating Scale score had decreased compared with baseline by more than 40% (mean improvement, 61%; range, 44%-75%) in the first 10 patients included. In accord with the 2-step open Fleming procedure, we ended the trial at the first step and concluded that pallidal stimulation is an effective treatment for TD. The efficacy of the treatment was confirmed by a double-blind evaluation, with a mean decrease of 50% (range, 30%-66%) (P = .002) in the Extrapyramidal Symptoms Rating Scale score when stimulation was applied compared with the absence of stimulation. There were no marked changes in the patients' psychiatric status.

CONCLUSION: Although these results need to be confirmed in a larger group of patients with a longer follow-up, bilateral globus pallidus deep brain stimulation seems to offer a much-needed new treatment option for disabling TD.

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