Surgery for Tardive Dyskinesia

Abstract

Tardive dyskinesia (TD) is an often bothersome side effect of antipsychotic treatment. Medical treatment options are usually disappointing. A few single case reports have suggested some efficacy of lesionning surgery (i.e. pallidotomy or thalamotomy). A much greater number of series (including one controlled-study) have assessed the effects of deep brain stimulation applied to the internal globus pallidus. All of them have shown a marked improvement of motor symptoms without any major psychiatric side effects.

Introduction

Tardive dyskinesia (TD), consisting in a wide spectrum of abnormal involuntary movements (from dystonia to choreic-like movements), is an often bothersome side effect of a chronic antipsychotic treatment (for review, see Damier, 2009). For severe cases, medical treatment options are usually disappointing. The first option is to attempt withdrawing the antipsychotic drug if the psychiatric state of the patient permits it. However, in about half of the cases, TD persists even after more than a year without any intake of the incriminated drug. When the use of a neuroleptic is mandatory (e.g., for chronic psychotic diseases), a switch to an atypical neuroleptic such as clozapine is a useful option to consider. The risk of TD is indeed much lower with such a drug than with the classical antipsychotic (Correll et al., 2004). Several add-on treatments have also been proposed for reducing TD. Among them, tetrabenazine is probably the most effective but with the risk of inducing a depression or a parkinsonian syndrome (Kenney et al., 2007). Many other drugs (i.e., vitamin E, calcium channel blockers, noradrenergic antagonists, and benzodiazepines) have also shown to have some efficacy (Soares and McGrath, 1999) In many patients however, despite all these attempts, distressing TD may persist and lead to a severe disability.

Since the late 1980s, there has been a renewed interest in surgery for treating various movement disorders, such as Parkinson's disease, tremor or dystonia. Such a treatment consists in a focal brain lesion or in continuous deep brain stimulation, the currently preferred option due to the reversibility (the stimulation can be turned off if required) and the adaptability (the electrical parameters can be fine-tuned in order to obtain the best ratio between effectiveness and stimulation-induced side effects) of the treatment. Three main targets are used for treating movement disorders: the subthalamic nucleus for Parkinson's disease (Krack et al., 2003); the ventral intermediate nucleus of the thalamus for tremor (Benabid et al., 1993); and the sensorimotor part of the internal globus pallidus (GPi) for Parkinson's disease and for dystonia (Vidailhet et al., 2005). GPi stimulation and pallidotomy have shown to be effective to treat either generalized or focal primary dystonia. Its efficacy remains more controversial for secondary dystonias (Vidailhet et al., 2005, Vidailhet et al., 2009). Several studies have recently reported substantial benefits of the surgical treatment for severe TD. The results of lesioning surgery and deep brain stimulation in this indication are reviewed.