Lieberman J A, Alvir J, Mukherjee S, Kane J M
Hillside Hospital, Division of Long Island Jewish Medical Center, Glen Oaks, NY.
Arch Gen Psychiatry. 1989 Oct;46(10):908-13. doi: 10.1001/archpsyc.1989.01810100050009.
Pathophysiologic theories postulate that tardive dyskinesia arises from the development of chemical denervation supersensitivity of dopamine receptors produced by chronic long-term neuroleptic treatment. To test a dopamine receptor modification strategy, 16 patients with tardive dyskinesia were assigned to treatment with a neuroleptic plus bromocriptine (a dopamine agonist) or placebo for 10 weeks in a rising-dose design. Patients were evaluated weekly during the 10-week treatment period and for 8 weeks after medication withdrawal. No significant treatment effect was found in tardive dyskinesia response in the overall sample. When patients were classified by tardive dyskinesia subtype, patients with choreoathetoid symptoms exhibited only slight improvement with active treatment, which persisted after drug withdrawal; patients with dystonic symptoms showed moderate improvement that was drug and dose dependent. The sustained administration of substantial doses of a dopamine agonist did not produce significant adverse effects, including behavioral toxic effects. These results, although not statistically significant, are of clinical and heuristic interest.
病理生理学理论假定，迟发性运动障碍源于长期使用抗精神病药物治疗导致多巴胺受体化学去神经超敏反应的发展。为了测试一种多巴胺受体修饰策略，16例迟发性运动障碍患者被分配接受抗精神病药物加溴隐亭（一种多巴胺激动剂）或安慰剂治疗，采用剂量递增设计，为期10周。在为期10周的治疗期间，患者每周接受评估，停药后评估8周。在整个样本中，未发现对迟发性运动障碍反应有显著的治疗效果。当根据迟发性运动障碍亚型对患者进行分类时，舞蹈指痉症症状患者在积极治疗后仅表现出轻微改善，停药后仍持续存在；肌张力障碍症状患者表现出中度改善，且与药物和剂量有关。持续给予大剂量多巴胺激动剂未产生显著不良反应，包括行为毒性作用。这些结果虽然无统计学意义，但具有临床和启发意义。
