The search for a treatment of tardive dyskinesia has generally been guided by the putative biochemical mechanisms underlying the extrapyramidal disorders, but no markedly effective treatment has yet been found. The currently postulated mechanism in tardive dyskinesia involves namely an imbalance between the central dopamine-acetylcholine systems whose balance may also be influenced by neuroendocrine factors. The agents reported having some clinical efficacy in the management of this neurological complication act on these systems. The clinical investigation for the treatment of tardive dyskinesia is laborious and raises several problems that could account for the unpredictability and the discrepancies in results. These problems can be divided into three broad categories: patient variables, experimental treatment variables and methodological variables. These variables are discussed and some suggestions made.
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