Treatment of Tardive Dyskinesia

Abstract

Although the new generation of atypical antipsychotic agents could some day eliminate concerns about tardive dyskinesia (TD), this disorder remains a significant clinical problem for both patients and physicians. Fortunately, many, if not most, cases of TD are mild. For patients with mild to moderate TD, therapeutic efforts are primarily directed at minimizing neuroleptic exposure or, when possible, changing to atypical agents. Most cases of TD do not seem to progress, suggesting that the risk of remaining on typical neuroleptics is probably small. Patients with moderate to severe forms of TD present greater challenges. These patients frequently require medication to suppress their dyskinesias. A variety of suppressive agents have been tried with limited success. No treatment strategy has emerged that is clearly superior or even successful in most patients. Increasing doses of typical neuroleptics may be useful for short-term suppression; however, the long-term efficacy and risk of this strategy have not been studied carefully. Data on atypical neuroleptics are scant. Clozapine's short-term suppressive effects seem, at best, weak, but patients may improve with long-term treatment. Medications with relatively few side effects that may have suppressive efficacy for some patients include calcium channel blockers, adrenergic antagonists, and vitamin E. Gamma-amino-butyric acid agonists agents and dopamine depleters are frequently useful, but have troubling side effects of their own. A variety of other medications have been employed, but are not well studied. For patients with tardive dystonia, anticholinergic agents or botulinum toxin has been particularly effective. Efforts to understand the neurobiology of TD may shed light on this persistent clinical conundrum.

Reversal of haloperidol-induced orofacial dyskinesia by quercetin, a bioflavonoid

“…Neuroleptics are extensively used in the treatment of schizophrenia and other affective disorders. TD, which occurs in 20-40% of patients taking chronic neuroleptic medication, is a major limitation of neuroleptic therapy (Egan et al 1997;Casey 2000;Kulkarni and Naidu 2001). In spite of its high frequency of occurrence, the pathophysiology of tardive dyskinesia remains elusive.…”

Tardive Dyskinesia in Geriatric Patients

“…Certain patientand treatment-related risk factors that increase the likelihood of developing TD have been identified (Box 3) [58,59]. How these factors confer vulnerability to TD remains largely unknown, and not all patients with these characteristics will develop TD.…”

“…Patient factors associated with TD include increased age, psychiatric diagnosis, female sex (particularly in elderly patients), diabetes, organic brain damage, development of other neurological side effects (e.g., extrapyramidal symptoms [EPS]), and the presence of negative symptoms of schizophrenia [59][60][61][62][63][64].…”

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

“…9 In addition, genetic susceptibility contributes to individual susceptibility to develop TD following antipsychotic exposure, 10 and despite methodological difficulties, family studies support a genetic component. 11,12 The pathogenesis of TD is unknown and may involve supersensitivity of the nigrostriatal pathway dopamine D2 receptors, 13 neuronal damage caused by free radical overproduction 14,15 and GABAergic system dysregulation. 16,17 Interestingly, several studies have shown that spontaneous movement disorders, mainly spontaneous dyskinesia, may be present in antipsychotic-naive schizophrenia patients and may represent an intrinsic neuromotor component of this disorder.…”