Bilateral Deep Brain Stimulation of the Globus Pallidus to Treat Tardive Dyskinesia

Abstract

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 followup, bilateral globus pallidus deep brain stimulation seems to offer a much-needed new treatment option for disabling TD.

Contribution of Decreased Serotonin Release to the Antidyskinetic Effects of Deep Brain Stimulation in a Rodent Model of Tardive Dyskinesia: Comparison of the Subthalamic and Entopeduncular Nuclei

“…Moreover, this is the first study to examine the basal ganglia, and to attempt to elucidate the contribution of decreased 5-HT release to the motor effects of DBS. Clinically, both the STN and GPi have been used effectively to relieve symptoms of treatment-resistant TD and tardive dystonia (Damier et al, 2007;Sun et al, 2007). Our observation that EPN-DBS suppresses VCMs in this model despite its lack of effect on the 5-HT system further strengthens our conclusion that decreasing 5-HT is not a necessary component of the DBS therapeutic mechanism.…”

“…However, despite its widespread clinical application in movement disorders, the mechanisms underlying the antidyskinetic effects of DBS remain largely unknown. We have shown that STN-and EPN-DBS influence activity in a variety of brain regions at sites distal from the stimulation target (Creed et al, 2012), an observation that has also been made in the clinic (Su et al, 2001;Schulte et al, 2006;Damier et al, 2007). DBS also effects several neurotransmitter systems (Lee et al, 2006;Covey and Garris, 2009;Navailles et al, 2010;Feuerstein et al, 2011;Sgambato-Faure and Cenci, 2012).…”

“…Over the last decade, DBS applied to the subthalamic nucleus (STN) or internal globus pallidus (GPi) has been successfully used to treat several movement disorders (Lyons, 2011;Troster, 2009), including treatment-resistant tardive dyskinesia (TD). TD is a disorder induced by chronic therapy with classical antipsychotic drugs (Damier et al, 2007;Capelle et al, 2010), which is characterized by abnormal, involuntary movements of the head, neck, face and jaw, which can persist for a prolonged time after medication withdrawal (Casey, 1985(Casey, , 2004. While the GPi is the most common DBS target in cases of TD, the STN has also been shown to alleviate motor symptoms associated with chronic antipsychotic use (Zhang et al, 2006;Sun et al, 2007).…”

Long-term neuropsychiatric outcomes after pallidal stimulation in primary and secondary dystonia

“…11,14,39,40 GPi DBS was less effective in secondary dystonia, as expected. 17,30,31,37 Our study has several limitations. Individual follow-up times were variable.…”

“…17,30,31 These reports have been limited by the small sample size, the relatively short follow-up (#36 months), and the lack of use of psychiatric interviews to assess patients.…”