Chakos M H, Alvir J M, Woerner M G, Koreen A, Geisler S, Mayerhoff D, Sobel S, Kane J M, Borenstein M, Lieberman J A
Department of Psychiatry, Hillside Hospital, Long Island Jewish Medical Center, Albert Einstein College of Medicine, Glen Oaks, NY, USA.
Arch Gen Psychiatry. 1996 Apr;53(4):313-9. doi: 10.1001/archpsyc.1996.01830040049009.
There is controversy over whether tardive dyskinesia (TD) is solely a consequence of antipsychotic drug treatment or in part may reflect an intrinsic aspect of the disease process. Pathophysiologic factors could, independently or in concert with drug effects, lead to the development of dyskinetic signs.
We studied prospectively 118 patients in their first episode of psychosis who were treatment-naive or had less than 12 weeks of antipsychotic drug exposure at study entry. Patients received standardized antipsychotic drug treatment and were evaluated for up to 8 1/2 years with regular assessments of psychopathologic signs and symptoms and side effects.
The cumulative incidence of presumptive TD was 6.3% after 1 year of follow-up, 11.5% after 2 years, 13.7% after 3 years, and 17.5% after 4 years. Persistent TD had a cumulative incidence of 4.8% after 1 year, 7.2% after 2 years, and 15.6% after 4 years. Taken individually, both antipsychotic drug dose, entered as a time-dependent covariate, and poor response to treatment of the first psychotic episode were significant predicters of time to TD. When antipsychotic drug dose and treatment response were examined together, treatment responders had significantly lower hazards for presumptive TD than nonresponders (hazard ratio, 0.29; 95% confidence interval, 0.09 to 0.97). Dose was a trend-level predicter, with each 100-mg chlorpromazine equivalent unit increase in dose associated with a 5% increase in the hazard of presumptive TD (hazard ratio, 1.05; 95% confidence interval, 0.99 to 1.11).
Poor response to the treatment of a first episode of psychosis and, to a lesser extent, antipsychotic drug dose are important factors in the development of TD. This suggests that there may be a disease-related vulnerability to TD manifest with antipsychotic drug exposure. Potential pathophysiologic factors might include neurodevelopmentally induced structural neuropathologic characteristics, sensitization of nigrostriatal dopamine neurons, and the induction of glutamatergically mediated neurotoxic effects.
迟发性运动障碍（TD）是否仅仅是抗精神病药物治疗的结果，还是部分可能反映疾病过程的内在方面，目前存在争议。病理生理因素可能独立地或与药物作用协同导致运动障碍体征的出现。
我们前瞻性地研究了118例首次发作精神病的患者，这些患者在研究开始时未接受过治疗或抗精神病药物暴露少于12周。患者接受标准化抗精神病药物治疗，并进行长达8年半的评估，定期评估精神病理体征和症状以及副作用。
随访1年后推定TD的累积发病率为6.3%，2年后为11.5%，3年后为13.7%，4年后为17.5%。持续性TD的累积发病率1年后为4.8%，2年后为7.2%，4年后为15.6%。单独来看，作为时间依赖性协变量纳入的抗精神病药物剂量以及对首次精神病发作治疗反应不佳都是TD发生时间的重要预测因素。当同时检查抗精神病药物剂量和治疗反应时，治疗有反应者推定TD的风险显著低于无反应者（风险比，0.29；95%置信区间，0.09至0.97）。剂量是一个趋势水平的预测因素，每增加100毫克氯丙嗪等效单位的剂量，推定TD的风险增加5%（风险比，1.05；95%置信区间，0.99至1.11）。
对首次精神病发作治疗反应不佳以及在较小程度上抗精神病药物剂量是TD发生发展的重要因素。这表明可能存在与疾病相关的对TD的易感性，并在抗精神病药物暴露时显现出来。潜在的病理生理因素可能包括神经发育诱导的结构性神经病理特征、黑质纹状体多巴胺神经元的致敏作用以及谷氨酸介导的神经毒性作用的诱导。
